Obat antivirusObat antivirus

VirusVirusParasit intraseluler obligat dimana virus tersebut memanfaatkan

enzim-enzim metabolik dari sel inang ribosom inang untuk sintesis protein

Kehidupannya sangat tergantung pada sel inang Tak ada yang dapat dibuatnya tanpa sel inang

Struktur virusStruktur virusPartikel virus (virion) terdiri dari

bagian-bagian berikut

1048708 inti asam nukleat DNA or RNA1048708 sering terdapat enzim spesifik

virus1048708 ditutupi oleh protein ldquocapsidrdquo 1048708 kadang-kadang terdapat lipid

pada lapisan terluar ldquoenveloperdquo

Klasifikasi virusKlasifikasi virusDNA viruses

Contain an DNA genome Virus replication

ndash DNA polymerase Examples

ndash Herpes Virusndash Hepatitis B virusndash Epstein-Barr virus

RNA Viruses Contain an RNA genome Virus replication

ndash RNA-dependent RNA polymerasendash Reverse transcriptase

(Retroviruses) Examples

ndash Rubella virusndash Dengue fever virusHepatitis A

virusndash Hepatitis C virusndash HIVndash Influenza virus

Siklus hidup

1Attachment melekatnya virus pada reseptor yang terdapat pada permukaan sel inang

2Entry masuknya virus melewati membran sel inang 3Uncoating uncoating asam nukleat virus4Replication sintesis protein pengatur awal ( cth asam nukleat polimerase sintesis virus baru RNA or DNA sintesis protein pembentuk struktur5 Assembly (maturation) pematangan partikel virus 6 Release pelepasan dari sel

1 2 3

6

5

4

78

bull Banyak virus menginfeksi sel inang spesifik

bull Banyak infeksi virus bersifat self limiting tidak memerlukan pengobatan cth common cold yang disebabkan oleh rinovirus

bull Infeksi virus yang umum seperti influenza chicken pox mumps biasanya dapat diatasi oleh sistem imun tubuh

Virus lain dapat menyebabkan penyakit serius dan fatal sehingga memerlukan pengobatan yang agresif cth HIV (AIDS)

Poin penting

Virus Genera Nucleic Acid Clinical Illness

Adenovirus DNA URTIs Eye infections

Hepadnaviridae DNA Hepatitis B Cancer ()

Herpesvirus DNA Genital herpes Varicella Encephalitis Retinitis

Papillomavirus DNA Papilloma Cancer

Parvovirus DNA Erythema infectiosum

Arenavirus RNA Lymphocytic choriomeningitis

Bunyavirus RNA Encephalitis

Coronavirus RNA URTIs

Influenzavirus RNA Influenza

Paramyxovirus RNA Measles URTIs

Picornavirus RNA Poliomyelitis diarrhea URTIs

Retrovirus RNA Leukemia AIDS

Rhabdovirus RNA Rabies

Togavirus RNA Rubella Yellow fever

Virus Groups of Clinical Importance

Obat anti virusObat anti virus Vaksin sering digunakan untuk membangun

sistem kekebalan sebelum infeksi virus terjadi

Agar efektif antivirus harus dapat menghambat entry atau keluarya virus ke sel inang atau aktif di dalam sel inang

9

Tantangan terapi anti virus replikasi virus yang cepat menyebabkan

sulitnya mengembangkan anti virus yang efektif

Virus dapat bermutasi dengan cepat obat menjadi tidak efektif

Kesulitan obat menemukan virus tanpa mengganggu sel normal inang

10

ANTI-HERPES ANTI VZVANTI-HERPES ANTI VZV

HSV = herpes simplex virusHSV = herpes simplex virusVZV = Varicella Zoster virusVZV = Varicella Zoster virus

ACYCLOVIRACYCLOVIR

Aktif terhadap HSV1 HSV2 amp VZV Aktifitas lebih lemah terhadap EBV

(ebstein bar virus) CMV (cytomegalo virus)

Mekanisme kerjaMekanisme kerjaTiga tahap fosforilasi

FarmakokinetikFarmakokinetik BA oral 10-30 menurun dengan peningkatan

dosis BA relatif meningkat sampai 70 setelah

pemberian valasiklovir Terdistribusi luas pada cairan tubuh termasuk

cairan vesikuler dan CSF Terkonsentrasi di ASI cairan amnionik dan

plasenta Absorbsi perkutan rendah

Penggunaan dalam terapiPenggunaan dalam terapi

Herpes genital (awal dan kambuhan) ndash 200 mg 5xhari selama 10 hari ndash oralndash 5 mgkg per 8 jam ndash IVRecurrent 400 mg 2xhari atau 200 mg

3xhari

THERAPEUTIC USESTHERAPEUTIC USES

ACUTE HERPES ZOSTER (SHINGLES)SYSTEMIC ACYCLOVIR PROPHYLAXISHSV ENCEPHALITISVARICELLA ZOSTER VIRUS INFECTIONCMV PROPHYLAXIS

Efek sampingEfek samping

Sediaan topikal-iritasi mukosa dan rasa terbakar pada luka genital

ORAL ndash mual diare rash sakit kepala insufisiensi ginjal neurotoksisitas

IV- insufisiensi ginjal CNS

PENCICLOVIRPENCICLOVIR

Aktivitas dan potensi mirid dengan asiklovir terhadap HSV amp VZV

Aktif terhadap HBV (hepatiis B virus)

MKMK Menghambat sintesis DNA virus Awalnya difosforilasi oleh viral thymidine

kinase Penciclovir trifosfat merupakan inhibitor

kompetitif terhadap viral DNA polymerase Potensi 100 lebih rendah dibanding asiklovir

tapi berada pada konsentrasi yg lebih tinggi dan lebih lama dalam sel yang terinfeksi

Penggunaan dalam terapiPenggunaan dalam terapidosis 5 mgkg per 8-12 jam iv selama 7

hari seara dengan asiklovir utk infeksi mucocutaneous HSV

Sediaan Topical 1 penciclovir cream dioleskan tiap 2 jam 4 hari utk labial HSV

Efek sampingEfek samping

Mutagenik pada konsentrasi tinggi IO yang signifikan secara klinis tidak

teridentifikasi

DRUG MECHANISMVIRAL

SELECTIVITY

CLINICAL USE

VIRAL RESISTANCE

UNDESIRABLE SIDE EFFECTS

PHARMACOKINETICS

NOTES

Acylovir Metabolized by thymidine kinase to triphosphate

Herpes simplex 1 amp 2 varicella zoster

Produce abnormal thymidine kinase

Skin irritation burning crystalline nephropathy

IVPO Administer slowly CNS level=50 serum level Decrease dose w kidney dysfunction

Pencyclovir Oral HSV (coldsores)

Topical

Valacyclovir L-valyl ester of acyclovir converted to acyclovir

Herpes zoster (shingles)

Nausea headache PO Slightly better oral absorption than acyclovir

No clear advantage over acyclovir

Idoxuridine Phosphorylated metabolite incorporates into DNA causing strand breaks

Herpes simplex keratitis No effect on RNA viruses

Resistance develops

Photophobia irritation of conjunctiva amp eyelid

Eyedrops Drug is a halogenated derivative of deoxyuridine

Famciclovir Phosphorylated by viral thymidine kinase to penciclovir triiphosphate

Shortens duration of herpes zoster amp genital herpes

Minimal toxicity Headache

PO Decrease dose with renal dysfunction

Ganciclovir Metabolized by thymidine kinase to triphosphate Preferentially phosphorylated to active drug in CMV infected cells

CMV retinitis amp severe systemic CMV infections

Some resistant strains lack thymidine kinase Cannot activate drug

Granulocytopenia thrombocytopenia

IVPO Excreted unchanged in urine Decrease dose with renal dysfunction

Do not coadminister zidovudine (granulocytopenia) or imipenem-cilastatin (seizures)

ANTIVIRAL DRUGS ndash DNA amp RNA VIRUSES

Cidofovir Metabolized to diphosphate form Otherwise like ganciclovir

CMV retinitis Nephrotoxicity may be reduced by hydration amp coadministration of Probenicid Neutropenia

Foscarnet Analog of pyrophosphate Competes for pyrophosphate site in viral but not human DNA polymerase amp reverse transcriptase

CMV retinitis Does not need phosphorylation it is active against thymidine kinase ndashdeficient strains

Renal toxicity seizures hypocalcemia fever anemia diarrhea nausea

IV gt80 excreted unchanged in the urine CSF penetration variable Reduce dose with renal dysfunction

Deposited in bone amp teeth Hydrate patient during therapy to protect the kidney

Amantadine Prevents virus from entering susceptible cells

Treatment amp prophylaxis of influenza A

Depression CNS toxicity CHF orthostatic hypotension urinary retention

PO Excreted unmetabolized

Rimantadine Analog of amantadine inhibits viral uncoating

Prophylaxis in children

Fewer CNS side effects risk of seizure

PO Prolonged elimination w renal or hepatic dysfunction

Ribavirin Unknown mechanism

RSV Decreased pulmonary function

Aerosol administration Absorbed systemically

May precipitate in ventilator tubing

ANTI-INFLUENZAANTI-INFLUENZA

AMANTADINRIMANTADINAMANTADINRIMANTADIN Menghambat proses uncoating virus RNA

influenza A di dalam cell inang mencegah replikasi

Efektif menurunkan durasi gejala influenza jika diberikan dalam 48 jam setelah onset

FKFK

Absorpsi oral baikEkskresi dalam bentuk tak termetabolisme

di urinAmantadin dapat diekskresikan lewat ASI

Efek sampingEfek samping

Umum gangguan GI dan CNS minor (gugup light headanche susah konsentrasi insomnia mual nafsu makan berkurang)

Amantadin konsentrasi tinggi di plasma reaksi neurotoksik serius delirium kejang koma aritmia

Penggunaan terapiPenggunaan terapi

Pencegahan dan pengobatan influenza A 200 mghari dalam 1 atau 2 dosis

(pengobatan)Pencegahan harus dimulai ketika mulai

teridentifikasi pandemi virus 100mghari (4 ndash 8 minggu)

ZANAMIVIROSELTAMIVIRZANAMIVIROSELTAMIVIRPenghambat Neuroaminidase Menghambat replikasi influenza A amp B

FKFK

Diserap dengan cepat setelah pemberian oral (BA 80)

Eliminasi di ginjal dalam bentuk tak berubah

Berinterkasi dengan probenecid (meningkatkan T12 ndash 2x)

Efek sampingEfek samping

Mual rasa tak nyaman di lambung muntah lokal iritasi

Konsentrasi yang sangat tinggi berhungan dengan kematian (tikus)

ANTI-HEPATITISANTI-HEPATITIS

ADEFOVIRADEFOVIRSecara kompetitif menghambat HBV

DNA polymeraseMenghambat sintesis DNAEfek samping nefrotoksik pusing

diare ganggian abdomen)Pengobaan infeksi HBV kronis 10 mghari

INTERFERONINTERFERON Protein endogen yang dihasilkan dan dilepaskan

oleh sel sebagai respon terhadap patogen Menginduksi enzim menekan proliferasi aktivitas

imunomodulator dan menghambat replikasi virus Menghambat penetrasi dan amp uncoating Untuk pengobatan HBV amp HCV

ANTIRETROVIRAL ANTIRETROVIRAL AGENTSAGENTS

CURRENT ARV MEDICATIONSCURRENT ARV MEDICATIONS

NRTIbull Abacavir bull Didanosine bull Emtricitabine bull Lamivudine bull Stavudine bull Tenofovir bull Zidovudine

NNRTIbull Efavirenz bull Etravirine bull Nevirapine

PIbull Atazanavir bull Darunavir bull Fosamprenavir bull Indinavir bull Lopinavir bull Nelfinavirbull Ritonavir bull Saquinavir bull Tipranavir Fusion Inhibitorbull Enfuvirtide bull

Fixed-dose CombinationsbullZidovudine lamivudinebullZidovudinelamivudineabacavirbullAbacavirlamivudinebullEmtricitabinetenofovirbullEfavirenzemtricitabine tenofovir

DRUG MECHANISM amp VIRAL SELECTIVITY

CLINICAL USE

VIRAL RESISTANCE

UNDESIRABLE SIDE EFFECTS

PHARMACOKINETICS

NOTES

Zidovudine (AZT)

Thymidine analog is incorporated into DNA of human immunodeficiency viirus causing termination of the viral DNA chain

HIV Prevention of maternal-fetal transmission of HIV

Mutations in reverse transcriptase

Headaches nausea myalgias anemia neutropenia macrocytosis

PO Well absorbed rapidly metabolized by liver

Acetaminophen increases risk of hematologic toxicity

Didanosine (ddl)Zalcitabine (ddC)Lamivudine

-Metabolized intracellularly to dideoxynucleotide triphosphate that inhibits reverse transcriptase amp incorporates into viral DNA-Nucleotides fail to bind to ddATP bec it lacks free 3rsquo OH group

HIV Mutations in reverse transcriptase

Peripheral neuropathy pancreatitis diarrhea headache insomnia vomiting nausea rash abdominal pain

IVPO Partially metabolized in liver excreted in the urine Toxicity may be enhanced by renal or hepatic dysfunction

Limited utility as a single agent therapy because of viral resistance

Stavudine Metabolized to stavudine triphosphate wc inhibits HIV reverse transcriptase amp DNA polymerase Prevents DNA elongation

HIV Peripheral neuropathy

PO Not indicated for initial monotherapy of HIV

ANTIVIRAL DRUGS - RETROVIRUSES

RitonavirIndinavirSaquinavirNelfinavir

Inhibts HIV protease Results in immature virion

HIV Mutations in protease sequence reduce affinity of protease inhibitors

GI distress headache neurologic symptoms Indinavir associated w increase risk for kidney stones

PO Metabolized by P450 in liver Reduce dose in patients with liver disease Poor CNS penetration

Potentially serious drug interactions due to P450 competition

NevirapineDelavirdene

Nob-nucleoside inhibitor of HIV reverse transcriptase

HIV Never as monotherapy due to rapid development of resistance

Rapid resistance develops due to mutations in reverse transcriptase

Severe skin rash fever nausea headache

PO Well absorbed Nevirapine crosses placenta amp has better CNS penetration than Delavirdene

Delavirdene failed to show clinical efficacy when added to didanosine in clinical trial

• Obat antivirus
• Virus
• Struktur virus
• Klasifikasi virus
• PowerPoint Presentation
• Slide 6
• Slide 7
• Slide 8
• Obat anti virus
• Slide 10
• ANTI-HERPES ANTI VZV HSV = herpes simplex virus VZV = Varicella Zoster virus
• ACYCLOVIR
• Mekanisme kerja
• Farmakokinetik
• Penggunaan dalam terapi
• THERAPEUTIC USES
• Efek samping
• PENCICLOVIR
• MK
• Slide 20
• Slide 21
• Slide 22
• Slide 23
• ANTI-INFLUENZA
• AMANTADINRIMANTADIN
• FK
• Efek samping
• Penggunaan terapi
• ZANAMIVIROSELTAMIVIR
• Slide 30
• Slide 31
• ANTI-HEPATITIS
• ADEFOVIR
• INTERFERON
• ANTIRETROVIRAL AGENTS
• Slide 36
• CURRENT ARV MEDICATIONS
• Slide 38
• Slide 39
• Slide 40
• Slide 41

VirusVirusParasit intraseluler obligat dimana virus tersebut memanfaatkan

enzim-enzim metabolik dari sel inang ribosom inang untuk sintesis protein

Kehidupannya sangat tergantung pada sel inang Tak ada yang dapat dibuatnya tanpa sel inang

Struktur virusStruktur virusPartikel virus (virion) terdiri dari

bagian-bagian berikut

1048708 inti asam nukleat DNA or RNA1048708 sering terdapat enzim spesifik

virus1048708 ditutupi oleh protein ldquocapsidrdquo 1048708 kadang-kadang terdapat lipid

pada lapisan terluar ldquoenveloperdquo

Klasifikasi virusKlasifikasi virusDNA viruses

Contain an DNA genome Virus replication

ndash DNA polymerase Examples

ndash Herpes Virusndash Hepatitis B virusndash Epstein-Barr virus

RNA Viruses Contain an RNA genome Virus replication

ndash RNA-dependent RNA polymerasendash Reverse transcriptase

(Retroviruses) Examples

ndash Rubella virusndash Dengue fever virusHepatitis A

virusndash Hepatitis C virusndash HIVndash Influenza virus

Siklus hidup

1Attachment melekatnya virus pada reseptor yang terdapat pada permukaan sel inang

2Entry masuknya virus melewati membran sel inang 3Uncoating uncoating asam nukleat virus4Replication sintesis protein pengatur awal ( cth asam nukleat polimerase sintesis virus baru RNA or DNA sintesis protein pembentuk struktur5 Assembly (maturation) pematangan partikel virus 6 Release pelepasan dari sel

1 2 3

6

5

4

78

bull Banyak virus menginfeksi sel inang spesifik

bull Banyak infeksi virus bersifat self limiting tidak memerlukan pengobatan cth common cold yang disebabkan oleh rinovirus

bull Infeksi virus yang umum seperti influenza chicken pox mumps biasanya dapat diatasi oleh sistem imun tubuh

Virus lain dapat menyebabkan penyakit serius dan fatal sehingga memerlukan pengobatan yang agresif cth HIV (AIDS)

Poin penting

Virus Genera Nucleic Acid Clinical Illness

Adenovirus DNA URTIs Eye infections

Hepadnaviridae DNA Hepatitis B Cancer ()

Herpesvirus DNA Genital herpes Varicella Encephalitis Retinitis

Papillomavirus DNA Papilloma Cancer

Parvovirus DNA Erythema infectiosum

Arenavirus RNA Lymphocytic choriomeningitis

Bunyavirus RNA Encephalitis

Coronavirus RNA URTIs

Influenzavirus RNA Influenza

Paramyxovirus RNA Measles URTIs

Picornavirus RNA Poliomyelitis diarrhea URTIs

Retrovirus RNA Leukemia AIDS

Rhabdovirus RNA Rabies

Togavirus RNA Rubella Yellow fever

Virus Groups of Clinical Importance

Obat anti virusObat anti virus Vaksin sering digunakan untuk membangun

sistem kekebalan sebelum infeksi virus terjadi

Agar efektif antivirus harus dapat menghambat entry atau keluarya virus ke sel inang atau aktif di dalam sel inang

9

Tantangan terapi anti virus replikasi virus yang cepat menyebabkan

sulitnya mengembangkan anti virus yang efektif

Virus dapat bermutasi dengan cepat obat menjadi tidak efektif

Kesulitan obat menemukan virus tanpa mengganggu sel normal inang

10

ANTI-HERPES ANTI VZVANTI-HERPES ANTI VZV

HSV = herpes simplex virusHSV = herpes simplex virusVZV = Varicella Zoster virusVZV = Varicella Zoster virus

ACYCLOVIRACYCLOVIR

Aktif terhadap HSV1 HSV2 amp VZV Aktifitas lebih lemah terhadap EBV

(ebstein bar virus) CMV (cytomegalo virus)

Mekanisme kerjaMekanisme kerjaTiga tahap fosforilasi

FarmakokinetikFarmakokinetik BA oral 10-30 menurun dengan peningkatan

dosis BA relatif meningkat sampai 70 setelah

pemberian valasiklovir Terdistribusi luas pada cairan tubuh termasuk

cairan vesikuler dan CSF Terkonsentrasi di ASI cairan amnionik dan

plasenta Absorbsi perkutan rendah

Penggunaan dalam terapiPenggunaan dalam terapi

Herpes genital (awal dan kambuhan) ndash 200 mg 5xhari selama 10 hari ndash oralndash 5 mgkg per 8 jam ndash IVRecurrent 400 mg 2xhari atau 200 mg

3xhari

THERAPEUTIC USESTHERAPEUTIC USES

ACUTE HERPES ZOSTER (SHINGLES)SYSTEMIC ACYCLOVIR PROPHYLAXISHSV ENCEPHALITISVARICELLA ZOSTER VIRUS INFECTIONCMV PROPHYLAXIS

Efek sampingEfek samping

Sediaan topikal-iritasi mukosa dan rasa terbakar pada luka genital

ORAL ndash mual diare rash sakit kepala insufisiensi ginjal neurotoksisitas

IV- insufisiensi ginjal CNS

PENCICLOVIRPENCICLOVIR

Aktivitas dan potensi mirid dengan asiklovir terhadap HSV amp VZV

Aktif terhadap HBV (hepatiis B virus)

MKMK Menghambat sintesis DNA virus Awalnya difosforilasi oleh viral thymidine

kinase Penciclovir trifosfat merupakan inhibitor

kompetitif terhadap viral DNA polymerase Potensi 100 lebih rendah dibanding asiklovir

tapi berada pada konsentrasi yg lebih tinggi dan lebih lama dalam sel yang terinfeksi

Penggunaan dalam terapiPenggunaan dalam terapidosis 5 mgkg per 8-12 jam iv selama 7

hari seara dengan asiklovir utk infeksi mucocutaneous HSV

Sediaan Topical 1 penciclovir cream dioleskan tiap 2 jam 4 hari utk labial HSV

Efek sampingEfek samping

Mutagenik pada konsentrasi tinggi IO yang signifikan secara klinis tidak

teridentifikasi

DRUG MECHANISMVIRAL

SELECTIVITY

CLINICAL USE

VIRAL RESISTANCE

UNDESIRABLE SIDE EFFECTS

PHARMACOKINETICS

NOTES

Acylovir Metabolized by thymidine kinase to triphosphate

Herpes simplex 1 amp 2 varicella zoster

Produce abnormal thymidine kinase

Skin irritation burning crystalline nephropathy

IVPO Administer slowly CNS level=50 serum level Decrease dose w kidney dysfunction

Pencyclovir Oral HSV (coldsores)

Topical

Valacyclovir L-valyl ester of acyclovir converted to acyclovir

Herpes zoster (shingles)

Nausea headache PO Slightly better oral absorption than acyclovir

No clear advantage over acyclovir

Idoxuridine Phosphorylated metabolite incorporates into DNA causing strand breaks

Herpes simplex keratitis No effect on RNA viruses

Resistance develops

Photophobia irritation of conjunctiva amp eyelid

Eyedrops Drug is a halogenated derivative of deoxyuridine

Famciclovir Phosphorylated by viral thymidine kinase to penciclovir triiphosphate

Shortens duration of herpes zoster amp genital herpes

Minimal toxicity Headache

PO Decrease dose with renal dysfunction

Ganciclovir Metabolized by thymidine kinase to triphosphate Preferentially phosphorylated to active drug in CMV infected cells

CMV retinitis amp severe systemic CMV infections

Some resistant strains lack thymidine kinase Cannot activate drug

Granulocytopenia thrombocytopenia

IVPO Excreted unchanged in urine Decrease dose with renal dysfunction

Do not coadminister zidovudine (granulocytopenia) or imipenem-cilastatin (seizures)

ANTIVIRAL DRUGS ndash DNA amp RNA VIRUSES

Cidofovir Metabolized to diphosphate form Otherwise like ganciclovir

CMV retinitis Nephrotoxicity may be reduced by hydration amp coadministration of Probenicid Neutropenia

Foscarnet Analog of pyrophosphate Competes for pyrophosphate site in viral but not human DNA polymerase amp reverse transcriptase

CMV retinitis Does not need phosphorylation it is active against thymidine kinase ndashdeficient strains

Renal toxicity seizures hypocalcemia fever anemia diarrhea nausea

IV gt80 excreted unchanged in the urine CSF penetration variable Reduce dose with renal dysfunction

Deposited in bone amp teeth Hydrate patient during therapy to protect the kidney

Amantadine Prevents virus from entering susceptible cells

Treatment amp prophylaxis of influenza A

Depression CNS toxicity CHF orthostatic hypotension urinary retention

PO Excreted unmetabolized

Rimantadine Analog of amantadine inhibits viral uncoating

Prophylaxis in children

Fewer CNS side effects risk of seizure

PO Prolonged elimination w renal or hepatic dysfunction

Ribavirin Unknown mechanism

RSV Decreased pulmonary function

Aerosol administration Absorbed systemically

May precipitate in ventilator tubing

ANTI-INFLUENZAANTI-INFLUENZA

AMANTADINRIMANTADINAMANTADINRIMANTADIN Menghambat proses uncoating virus RNA

influenza A di dalam cell inang mencegah replikasi

Efektif menurunkan durasi gejala influenza jika diberikan dalam 48 jam setelah onset

FKFK

Absorpsi oral baikEkskresi dalam bentuk tak termetabolisme

di urinAmantadin dapat diekskresikan lewat ASI

Efek sampingEfek samping

Umum gangguan GI dan CNS minor (gugup light headanche susah konsentrasi insomnia mual nafsu makan berkurang)

Amantadin konsentrasi tinggi di plasma reaksi neurotoksik serius delirium kejang koma aritmia

Penggunaan terapiPenggunaan terapi

Pencegahan dan pengobatan influenza A 200 mghari dalam 1 atau 2 dosis

(pengobatan)Pencegahan harus dimulai ketika mulai

teridentifikasi pandemi virus 100mghari (4 ndash 8 minggu)

ZANAMIVIROSELTAMIVIRZANAMIVIROSELTAMIVIRPenghambat Neuroaminidase Menghambat replikasi influenza A amp B

FKFK

Diserap dengan cepat setelah pemberian oral (BA 80)

Eliminasi di ginjal dalam bentuk tak berubah

Berinterkasi dengan probenecid (meningkatkan T12 ndash 2x)

Efek sampingEfek samping

Mual rasa tak nyaman di lambung muntah lokal iritasi

Konsentrasi yang sangat tinggi berhungan dengan kematian (tikus)

ANTI-HEPATITISANTI-HEPATITIS

ADEFOVIRADEFOVIRSecara kompetitif menghambat HBV

DNA polymeraseMenghambat sintesis DNAEfek samping nefrotoksik pusing

diare ganggian abdomen)Pengobaan infeksi HBV kronis 10 mghari

INTERFERONINTERFERON Protein endogen yang dihasilkan dan dilepaskan

oleh sel sebagai respon terhadap patogen Menginduksi enzim menekan proliferasi aktivitas

imunomodulator dan menghambat replikasi virus Menghambat penetrasi dan amp uncoating Untuk pengobatan HBV amp HCV

ANTIRETROVIRAL ANTIRETROVIRAL AGENTSAGENTS

CURRENT ARV MEDICATIONSCURRENT ARV MEDICATIONS

NRTIbull Abacavir bull Didanosine bull Emtricitabine bull Lamivudine bull Stavudine bull Tenofovir bull Zidovudine

NNRTIbull Efavirenz bull Etravirine bull Nevirapine

PIbull Atazanavir bull Darunavir bull Fosamprenavir bull Indinavir bull Lopinavir bull Nelfinavirbull Ritonavir bull Saquinavir bull Tipranavir Fusion Inhibitorbull Enfuvirtide bull

Fixed-dose CombinationsbullZidovudine lamivudinebullZidovudinelamivudineabacavirbullAbacavirlamivudinebullEmtricitabinetenofovirbullEfavirenzemtricitabine tenofovir

DRUG MECHANISM amp VIRAL SELECTIVITY

CLINICAL USE

VIRAL RESISTANCE

UNDESIRABLE SIDE EFFECTS

PHARMACOKINETICS

NOTES

Zidovudine (AZT)

Thymidine analog is incorporated into DNA of human immunodeficiency viirus causing termination of the viral DNA chain

HIV Prevention of maternal-fetal transmission of HIV

Mutations in reverse transcriptase

Headaches nausea myalgias anemia neutropenia macrocytosis

PO Well absorbed rapidly metabolized by liver

Acetaminophen increases risk of hematologic toxicity

Didanosine (ddl)Zalcitabine (ddC)Lamivudine

-Metabolized intracellularly to dideoxynucleotide triphosphate that inhibits reverse transcriptase amp incorporates into viral DNA-Nucleotides fail to bind to ddATP bec it lacks free 3rsquo OH group

HIV Mutations in reverse transcriptase

Peripheral neuropathy pancreatitis diarrhea headache insomnia vomiting nausea rash abdominal pain

IVPO Partially metabolized in liver excreted in the urine Toxicity may be enhanced by renal or hepatic dysfunction

Limited utility as a single agent therapy because of viral resistance

Stavudine Metabolized to stavudine triphosphate wc inhibits HIV reverse transcriptase amp DNA polymerase Prevents DNA elongation

HIV Peripheral neuropathy

PO Not indicated for initial monotherapy of HIV

ANTIVIRAL DRUGS - RETROVIRUSES

RitonavirIndinavirSaquinavirNelfinavir

Inhibts HIV protease Results in immature virion

HIV Mutations in protease sequence reduce affinity of protease inhibitors

GI distress headache neurologic symptoms Indinavir associated w increase risk for kidney stones

PO Metabolized by P450 in liver Reduce dose in patients with liver disease Poor CNS penetration

Potentially serious drug interactions due to P450 competition

NevirapineDelavirdene

Nob-nucleoside inhibitor of HIV reverse transcriptase

HIV Never as monotherapy due to rapid development of resistance

Rapid resistance develops due to mutations in reverse transcriptase

Severe skin rash fever nausea headache

PO Well absorbed Nevirapine crosses placenta amp has better CNS penetration than Delavirdene

Delavirdene failed to show clinical efficacy when added to didanosine in clinical trial

• Obat antivirus
• Virus
• Struktur virus
• Klasifikasi virus
• PowerPoint Presentation
• Slide 6
• Slide 7
• Slide 8
• Obat anti virus
• Slide 10
• ANTI-HERPES ANTI VZV HSV = herpes simplex virus VZV = Varicella Zoster virus
• ACYCLOVIR
• Mekanisme kerja
• Farmakokinetik
• Penggunaan dalam terapi
• THERAPEUTIC USES
• Efek samping
• PENCICLOVIR
• MK
• Slide 20
• Slide 21
• Slide 22
• Slide 23
• ANTI-INFLUENZA
• AMANTADINRIMANTADIN
• FK
• Efek samping
• Penggunaan terapi
• ZANAMIVIROSELTAMIVIR
• Slide 30
• Slide 31
• ANTI-HEPATITIS
• ADEFOVIR
• INTERFERON
• ANTIRETROVIRAL AGENTS
• Slide 36
• CURRENT ARV MEDICATIONS
• Slide 38
• Slide 39
• Slide 40
• Slide 41

Struktur virusStruktur virusPartikel virus (virion) terdiri dari

bagian-bagian berikut

1048708 inti asam nukleat DNA or RNA1048708 sering terdapat enzim spesifik

virus1048708 ditutupi oleh protein ldquocapsidrdquo 1048708 kadang-kadang terdapat lipid

pada lapisan terluar ldquoenveloperdquo

Klasifikasi virusKlasifikasi virusDNA viruses

Contain an DNA genome Virus replication

ndash DNA polymerase Examples

ndash Herpes Virusndash Hepatitis B virusndash Epstein-Barr virus

RNA Viruses Contain an RNA genome Virus replication

ndash RNA-dependent RNA polymerasendash Reverse transcriptase

(Retroviruses) Examples

ndash Rubella virusndash Dengue fever virusHepatitis A

virusndash Hepatitis C virusndash HIVndash Influenza virus

Siklus hidup

1Attachment melekatnya virus pada reseptor yang terdapat pada permukaan sel inang

2Entry masuknya virus melewati membran sel inang 3Uncoating uncoating asam nukleat virus4Replication sintesis protein pengatur awal ( cth asam nukleat polimerase sintesis virus baru RNA or DNA sintesis protein pembentuk struktur5 Assembly (maturation) pematangan partikel virus 6 Release pelepasan dari sel

1 2 3

6

5

4

78

bull Banyak virus menginfeksi sel inang spesifik

bull Banyak infeksi virus bersifat self limiting tidak memerlukan pengobatan cth common cold yang disebabkan oleh rinovirus

bull Infeksi virus yang umum seperti influenza chicken pox mumps biasanya dapat diatasi oleh sistem imun tubuh

Virus lain dapat menyebabkan penyakit serius dan fatal sehingga memerlukan pengobatan yang agresif cth HIV (AIDS)

Poin penting

Virus Genera Nucleic Acid Clinical Illness

Adenovirus DNA URTIs Eye infections

Hepadnaviridae DNA Hepatitis B Cancer ()

Herpesvirus DNA Genital herpes Varicella Encephalitis Retinitis

Papillomavirus DNA Papilloma Cancer

Parvovirus DNA Erythema infectiosum

Arenavirus RNA Lymphocytic choriomeningitis

Bunyavirus RNA Encephalitis

Coronavirus RNA URTIs

Influenzavirus RNA Influenza

Paramyxovirus RNA Measles URTIs

Picornavirus RNA Poliomyelitis diarrhea URTIs

Retrovirus RNA Leukemia AIDS

Rhabdovirus RNA Rabies

Togavirus RNA Rubella Yellow fever

Virus Groups of Clinical Importance

Obat anti virusObat anti virus Vaksin sering digunakan untuk membangun

sistem kekebalan sebelum infeksi virus terjadi

Agar efektif antivirus harus dapat menghambat entry atau keluarya virus ke sel inang atau aktif di dalam sel inang

9

Tantangan terapi anti virus replikasi virus yang cepat menyebabkan

sulitnya mengembangkan anti virus yang efektif

Virus dapat bermutasi dengan cepat obat menjadi tidak efektif

Kesulitan obat menemukan virus tanpa mengganggu sel normal inang

10

ANTI-HERPES ANTI VZVANTI-HERPES ANTI VZV

HSV = herpes simplex virusHSV = herpes simplex virusVZV = Varicella Zoster virusVZV = Varicella Zoster virus

ACYCLOVIRACYCLOVIR

Aktif terhadap HSV1 HSV2 amp VZV Aktifitas lebih lemah terhadap EBV

(ebstein bar virus) CMV (cytomegalo virus)

Mekanisme kerjaMekanisme kerjaTiga tahap fosforilasi

FarmakokinetikFarmakokinetik BA oral 10-30 menurun dengan peningkatan

dosis BA relatif meningkat sampai 70 setelah

pemberian valasiklovir Terdistribusi luas pada cairan tubuh termasuk

cairan vesikuler dan CSF Terkonsentrasi di ASI cairan amnionik dan

plasenta Absorbsi perkutan rendah

Penggunaan dalam terapiPenggunaan dalam terapi

Herpes genital (awal dan kambuhan) ndash 200 mg 5xhari selama 10 hari ndash oralndash 5 mgkg per 8 jam ndash IVRecurrent 400 mg 2xhari atau 200 mg

3xhari

THERAPEUTIC USESTHERAPEUTIC USES

ACUTE HERPES ZOSTER (SHINGLES)SYSTEMIC ACYCLOVIR PROPHYLAXISHSV ENCEPHALITISVARICELLA ZOSTER VIRUS INFECTIONCMV PROPHYLAXIS

Efek sampingEfek samping

Sediaan topikal-iritasi mukosa dan rasa terbakar pada luka genital

ORAL ndash mual diare rash sakit kepala insufisiensi ginjal neurotoksisitas

IV- insufisiensi ginjal CNS

PENCICLOVIRPENCICLOVIR

Aktivitas dan potensi mirid dengan asiklovir terhadap HSV amp VZV

Aktif terhadap HBV (hepatiis B virus)

MKMK Menghambat sintesis DNA virus Awalnya difosforilasi oleh viral thymidine

kinase Penciclovir trifosfat merupakan inhibitor

kompetitif terhadap viral DNA polymerase Potensi 100 lebih rendah dibanding asiklovir

tapi berada pada konsentrasi yg lebih tinggi dan lebih lama dalam sel yang terinfeksi

Penggunaan dalam terapiPenggunaan dalam terapidosis 5 mgkg per 8-12 jam iv selama 7

hari seara dengan asiklovir utk infeksi mucocutaneous HSV

Sediaan Topical 1 penciclovir cream dioleskan tiap 2 jam 4 hari utk labial HSV

Efek sampingEfek samping

Mutagenik pada konsentrasi tinggi IO yang signifikan secara klinis tidak

teridentifikasi

DRUG MECHANISMVIRAL

SELECTIVITY

CLINICAL USE

VIRAL RESISTANCE

UNDESIRABLE SIDE EFFECTS

PHARMACOKINETICS

NOTES

Acylovir Metabolized by thymidine kinase to triphosphate

Herpes simplex 1 amp 2 varicella zoster

Produce abnormal thymidine kinase

Skin irritation burning crystalline nephropathy

IVPO Administer slowly CNS level=50 serum level Decrease dose w kidney dysfunction

Pencyclovir Oral HSV (coldsores)

Topical

Valacyclovir L-valyl ester of acyclovir converted to acyclovir

Herpes zoster (shingles)

Nausea headache PO Slightly better oral absorption than acyclovir

No clear advantage over acyclovir

Idoxuridine Phosphorylated metabolite incorporates into DNA causing strand breaks

Herpes simplex keratitis No effect on RNA viruses

Resistance develops

Photophobia irritation of conjunctiva amp eyelid

Eyedrops Drug is a halogenated derivative of deoxyuridine

Famciclovir Phosphorylated by viral thymidine kinase to penciclovir triiphosphate

Shortens duration of herpes zoster amp genital herpes

Minimal toxicity Headache

PO Decrease dose with renal dysfunction

Ganciclovir Metabolized by thymidine kinase to triphosphate Preferentially phosphorylated to active drug in CMV infected cells

CMV retinitis amp severe systemic CMV infections

Some resistant strains lack thymidine kinase Cannot activate drug

Granulocytopenia thrombocytopenia

IVPO Excreted unchanged in urine Decrease dose with renal dysfunction

Do not coadminister zidovudine (granulocytopenia) or imipenem-cilastatin (seizures)

ANTIVIRAL DRUGS ndash DNA amp RNA VIRUSES

Cidofovir Metabolized to diphosphate form Otherwise like ganciclovir

CMV retinitis Nephrotoxicity may be reduced by hydration amp coadministration of Probenicid Neutropenia

Foscarnet Analog of pyrophosphate Competes for pyrophosphate site in viral but not human DNA polymerase amp reverse transcriptase

CMV retinitis Does not need phosphorylation it is active against thymidine kinase ndashdeficient strains

Renal toxicity seizures hypocalcemia fever anemia diarrhea nausea

IV gt80 excreted unchanged in the urine CSF penetration variable Reduce dose with renal dysfunction

Deposited in bone amp teeth Hydrate patient during therapy to protect the kidney

Amantadine Prevents virus from entering susceptible cells

Treatment amp prophylaxis of influenza A

Depression CNS toxicity CHF orthostatic hypotension urinary retention

PO Excreted unmetabolized

Rimantadine Analog of amantadine inhibits viral uncoating

Prophylaxis in children

Fewer CNS side effects risk of seizure

PO Prolonged elimination w renal or hepatic dysfunction

Ribavirin Unknown mechanism

RSV Decreased pulmonary function

Aerosol administration Absorbed systemically

May precipitate in ventilator tubing

ANTI-INFLUENZAANTI-INFLUENZA

AMANTADINRIMANTADINAMANTADINRIMANTADIN Menghambat proses uncoating virus RNA

influenza A di dalam cell inang mencegah replikasi

Efektif menurunkan durasi gejala influenza jika diberikan dalam 48 jam setelah onset

FKFK

Absorpsi oral baikEkskresi dalam bentuk tak termetabolisme

di urinAmantadin dapat diekskresikan lewat ASI

Efek sampingEfek samping

Umum gangguan GI dan CNS minor (gugup light headanche susah konsentrasi insomnia mual nafsu makan berkurang)

Amantadin konsentrasi tinggi di plasma reaksi neurotoksik serius delirium kejang koma aritmia

Penggunaan terapiPenggunaan terapi

Pencegahan dan pengobatan influenza A 200 mghari dalam 1 atau 2 dosis

(pengobatan)Pencegahan harus dimulai ketika mulai

teridentifikasi pandemi virus 100mghari (4 ndash 8 minggu)

ZANAMIVIROSELTAMIVIRZANAMIVIROSELTAMIVIRPenghambat Neuroaminidase Menghambat replikasi influenza A amp B

FKFK

Diserap dengan cepat setelah pemberian oral (BA 80)

Eliminasi di ginjal dalam bentuk tak berubah

Berinterkasi dengan probenecid (meningkatkan T12 ndash 2x)

Efek sampingEfek samping

Mual rasa tak nyaman di lambung muntah lokal iritasi

Konsentrasi yang sangat tinggi berhungan dengan kematian (tikus)

ANTI-HEPATITISANTI-HEPATITIS

ADEFOVIRADEFOVIRSecara kompetitif menghambat HBV

DNA polymeraseMenghambat sintesis DNAEfek samping nefrotoksik pusing

diare ganggian abdomen)Pengobaan infeksi HBV kronis 10 mghari

INTERFERONINTERFERON Protein endogen yang dihasilkan dan dilepaskan

oleh sel sebagai respon terhadap patogen Menginduksi enzim menekan proliferasi aktivitas

imunomodulator dan menghambat replikasi virus Menghambat penetrasi dan amp uncoating Untuk pengobatan HBV amp HCV

ANTIRETROVIRAL ANTIRETROVIRAL AGENTSAGENTS

CURRENT ARV MEDICATIONSCURRENT ARV MEDICATIONS

NRTIbull Abacavir bull Didanosine bull Emtricitabine bull Lamivudine bull Stavudine bull Tenofovir bull Zidovudine

NNRTIbull Efavirenz bull Etravirine bull Nevirapine

PIbull Atazanavir bull Darunavir bull Fosamprenavir bull Indinavir bull Lopinavir bull Nelfinavirbull Ritonavir bull Saquinavir bull Tipranavir Fusion Inhibitorbull Enfuvirtide bull

Fixed-dose CombinationsbullZidovudine lamivudinebullZidovudinelamivudineabacavirbullAbacavirlamivudinebullEmtricitabinetenofovirbullEfavirenzemtricitabine tenofovir

DRUG MECHANISM amp VIRAL SELECTIVITY

CLINICAL USE

VIRAL RESISTANCE

UNDESIRABLE SIDE EFFECTS

PHARMACOKINETICS

NOTES

Zidovudine (AZT)

Thymidine analog is incorporated into DNA of human immunodeficiency viirus causing termination of the viral DNA chain

HIV Prevention of maternal-fetal transmission of HIV

Mutations in reverse transcriptase

Headaches nausea myalgias anemia neutropenia macrocytosis

PO Well absorbed rapidly metabolized by liver

Acetaminophen increases risk of hematologic toxicity

Didanosine (ddl)Zalcitabine (ddC)Lamivudine

-Metabolized intracellularly to dideoxynucleotide triphosphate that inhibits reverse transcriptase amp incorporates into viral DNA-Nucleotides fail to bind to ddATP bec it lacks free 3rsquo OH group

HIV Mutations in reverse transcriptase

Peripheral neuropathy pancreatitis diarrhea headache insomnia vomiting nausea rash abdominal pain

IVPO Partially metabolized in liver excreted in the urine Toxicity may be enhanced by renal or hepatic dysfunction

Limited utility as a single agent therapy because of viral resistance

Stavudine Metabolized to stavudine triphosphate wc inhibits HIV reverse transcriptase amp DNA polymerase Prevents DNA elongation

HIV Peripheral neuropathy

PO Not indicated for initial monotherapy of HIV

ANTIVIRAL DRUGS - RETROVIRUSES

RitonavirIndinavirSaquinavirNelfinavir

Inhibts HIV protease Results in immature virion

HIV Mutations in protease sequence reduce affinity of protease inhibitors

GI distress headache neurologic symptoms Indinavir associated w increase risk for kidney stones

PO Metabolized by P450 in liver Reduce dose in patients with liver disease Poor CNS penetration

Potentially serious drug interactions due to P450 competition

NevirapineDelavirdene

Nob-nucleoside inhibitor of HIV reverse transcriptase

HIV Never as monotherapy due to rapid development of resistance

Rapid resistance develops due to mutations in reverse transcriptase

Severe skin rash fever nausea headache

PO Well absorbed Nevirapine crosses placenta amp has better CNS penetration than Delavirdene

Delavirdene failed to show clinical efficacy when added to didanosine in clinical trial

• Obat antivirus
• Virus
• Struktur virus
• Klasifikasi virus
• PowerPoint Presentation
• Slide 6
• Slide 7
• Slide 8
• Obat anti virus
• Slide 10
• ANTI-HERPES ANTI VZV HSV = herpes simplex virus VZV = Varicella Zoster virus
• ACYCLOVIR
• Mekanisme kerja
• Farmakokinetik
• Penggunaan dalam terapi
• THERAPEUTIC USES
• Efek samping
• PENCICLOVIR
• MK
• Slide 20
• Slide 21
• Slide 22
• Slide 23
• ANTI-INFLUENZA
• AMANTADINRIMANTADIN
• FK
• Efek samping
• Penggunaan terapi
• ZANAMIVIROSELTAMIVIR
• Slide 30
• Slide 31
• ANTI-HEPATITIS
• ADEFOVIR
• INTERFERON
• ANTIRETROVIRAL AGENTS
• Slide 36
• CURRENT ARV MEDICATIONS
• Slide 38
• Slide 39
• Slide 40
• Slide 41

Klasifikasi virusKlasifikasi virusDNA viruses

Contain an DNA genome Virus replication

ndash DNA polymerase Examples

ndash Herpes Virusndash Hepatitis B virusndash Epstein-Barr virus

RNA Viruses Contain an RNA genome Virus replication

ndash RNA-dependent RNA polymerasendash Reverse transcriptase

(Retroviruses) Examples

ndash Rubella virusndash Dengue fever virusHepatitis A

virusndash Hepatitis C virusndash HIVndash Influenza virus

Siklus hidup

1Attachment melekatnya virus pada reseptor yang terdapat pada permukaan sel inang

2Entry masuknya virus melewati membran sel inang 3Uncoating uncoating asam nukleat virus4Replication sintesis protein pengatur awal ( cth asam nukleat polimerase sintesis virus baru RNA or DNA sintesis protein pembentuk struktur5 Assembly (maturation) pematangan partikel virus 6 Release pelepasan dari sel

1 2 3

6

5

4

78

bull Banyak virus menginfeksi sel inang spesifik

bull Banyak infeksi virus bersifat self limiting tidak memerlukan pengobatan cth common cold yang disebabkan oleh rinovirus

bull Infeksi virus yang umum seperti influenza chicken pox mumps biasanya dapat diatasi oleh sistem imun tubuh

Virus lain dapat menyebabkan penyakit serius dan fatal sehingga memerlukan pengobatan yang agresif cth HIV (AIDS)

Poin penting

Virus Genera Nucleic Acid Clinical Illness

Adenovirus DNA URTIs Eye infections

Hepadnaviridae DNA Hepatitis B Cancer ()

Herpesvirus DNA Genital herpes Varicella Encephalitis Retinitis

Papillomavirus DNA Papilloma Cancer

Parvovirus DNA Erythema infectiosum

Arenavirus RNA Lymphocytic choriomeningitis

Bunyavirus RNA Encephalitis

Coronavirus RNA URTIs

Influenzavirus RNA Influenza

Paramyxovirus RNA Measles URTIs

Picornavirus RNA Poliomyelitis diarrhea URTIs

Retrovirus RNA Leukemia AIDS

Rhabdovirus RNA Rabies

Togavirus RNA Rubella Yellow fever

Virus Groups of Clinical Importance

Obat anti virusObat anti virus Vaksin sering digunakan untuk membangun

sistem kekebalan sebelum infeksi virus terjadi

Agar efektif antivirus harus dapat menghambat entry atau keluarya virus ke sel inang atau aktif di dalam sel inang

9

Tantangan terapi anti virus replikasi virus yang cepat menyebabkan

sulitnya mengembangkan anti virus yang efektif

Virus dapat bermutasi dengan cepat obat menjadi tidak efektif

Kesulitan obat menemukan virus tanpa mengganggu sel normal inang

10

ANTI-HERPES ANTI VZVANTI-HERPES ANTI VZV

HSV = herpes simplex virusHSV = herpes simplex virusVZV = Varicella Zoster virusVZV = Varicella Zoster virus

ACYCLOVIRACYCLOVIR

Aktif terhadap HSV1 HSV2 amp VZV Aktifitas lebih lemah terhadap EBV

(ebstein bar virus) CMV (cytomegalo virus)

Mekanisme kerjaMekanisme kerjaTiga tahap fosforilasi

FarmakokinetikFarmakokinetik BA oral 10-30 menurun dengan peningkatan

dosis BA relatif meningkat sampai 70 setelah

pemberian valasiklovir Terdistribusi luas pada cairan tubuh termasuk

cairan vesikuler dan CSF Terkonsentrasi di ASI cairan amnionik dan

plasenta Absorbsi perkutan rendah

Penggunaan dalam terapiPenggunaan dalam terapi

Herpes genital (awal dan kambuhan) ndash 200 mg 5xhari selama 10 hari ndash oralndash 5 mgkg per 8 jam ndash IVRecurrent 400 mg 2xhari atau 200 mg

3xhari

THERAPEUTIC USESTHERAPEUTIC USES

ACUTE HERPES ZOSTER (SHINGLES)SYSTEMIC ACYCLOVIR PROPHYLAXISHSV ENCEPHALITISVARICELLA ZOSTER VIRUS INFECTIONCMV PROPHYLAXIS

Efek sampingEfek samping

Sediaan topikal-iritasi mukosa dan rasa terbakar pada luka genital

ORAL ndash mual diare rash sakit kepala insufisiensi ginjal neurotoksisitas

IV- insufisiensi ginjal CNS

PENCICLOVIRPENCICLOVIR

Aktivitas dan potensi mirid dengan asiklovir terhadap HSV amp VZV

Aktif terhadap HBV (hepatiis B virus)

MKMK Menghambat sintesis DNA virus Awalnya difosforilasi oleh viral thymidine

kinase Penciclovir trifosfat merupakan inhibitor

kompetitif terhadap viral DNA polymerase Potensi 100 lebih rendah dibanding asiklovir

tapi berada pada konsentrasi yg lebih tinggi dan lebih lama dalam sel yang terinfeksi

Penggunaan dalam terapiPenggunaan dalam terapidosis 5 mgkg per 8-12 jam iv selama 7

hari seara dengan asiklovir utk infeksi mucocutaneous HSV

Sediaan Topical 1 penciclovir cream dioleskan tiap 2 jam 4 hari utk labial HSV

Efek sampingEfek samping

Mutagenik pada konsentrasi tinggi IO yang signifikan secara klinis tidak

teridentifikasi

DRUG MECHANISMVIRAL

SELECTIVITY

CLINICAL USE

VIRAL RESISTANCE

UNDESIRABLE SIDE EFFECTS

PHARMACOKINETICS

NOTES

Acylovir Metabolized by thymidine kinase to triphosphate

Herpes simplex 1 amp 2 varicella zoster

Produce abnormal thymidine kinase

Skin irritation burning crystalline nephropathy

IVPO Administer slowly CNS level=50 serum level Decrease dose w kidney dysfunction

Pencyclovir Oral HSV (coldsores)

Topical

Valacyclovir L-valyl ester of acyclovir converted to acyclovir

Herpes zoster (shingles)

Nausea headache PO Slightly better oral absorption than acyclovir

No clear advantage over acyclovir

Idoxuridine Phosphorylated metabolite incorporates into DNA causing strand breaks

Herpes simplex keratitis No effect on RNA viruses

Resistance develops

Photophobia irritation of conjunctiva amp eyelid

Eyedrops Drug is a halogenated derivative of deoxyuridine

Famciclovir Phosphorylated by viral thymidine kinase to penciclovir triiphosphate

Shortens duration of herpes zoster amp genital herpes

Minimal toxicity Headache

PO Decrease dose with renal dysfunction

Ganciclovir Metabolized by thymidine kinase to triphosphate Preferentially phosphorylated to active drug in CMV infected cells

CMV retinitis amp severe systemic CMV infections

Some resistant strains lack thymidine kinase Cannot activate drug

Granulocytopenia thrombocytopenia

IVPO Excreted unchanged in urine Decrease dose with renal dysfunction

Do not coadminister zidovudine (granulocytopenia) or imipenem-cilastatin (seizures)

ANTIVIRAL DRUGS ndash DNA amp RNA VIRUSES

Cidofovir Metabolized to diphosphate form Otherwise like ganciclovir

CMV retinitis Nephrotoxicity may be reduced by hydration amp coadministration of Probenicid Neutropenia

Foscarnet Analog of pyrophosphate Competes for pyrophosphate site in viral but not human DNA polymerase amp reverse transcriptase

CMV retinitis Does not need phosphorylation it is active against thymidine kinase ndashdeficient strains

Renal toxicity seizures hypocalcemia fever anemia diarrhea nausea

IV gt80 excreted unchanged in the urine CSF penetration variable Reduce dose with renal dysfunction

Deposited in bone amp teeth Hydrate patient during therapy to protect the kidney

Amantadine Prevents virus from entering susceptible cells

Treatment amp prophylaxis of influenza A

Depression CNS toxicity CHF orthostatic hypotension urinary retention

PO Excreted unmetabolized

Rimantadine Analog of amantadine inhibits viral uncoating

Prophylaxis in children

Fewer CNS side effects risk of seizure

PO Prolonged elimination w renal or hepatic dysfunction

Ribavirin Unknown mechanism

RSV Decreased pulmonary function

Aerosol administration Absorbed systemically

May precipitate in ventilator tubing

ANTI-INFLUENZAANTI-INFLUENZA

AMANTADINRIMANTADINAMANTADINRIMANTADIN Menghambat proses uncoating virus RNA

influenza A di dalam cell inang mencegah replikasi

Efektif menurunkan durasi gejala influenza jika diberikan dalam 48 jam setelah onset

FKFK

Absorpsi oral baikEkskresi dalam bentuk tak termetabolisme

di urinAmantadin dapat diekskresikan lewat ASI

Efek sampingEfek samping

Umum gangguan GI dan CNS minor (gugup light headanche susah konsentrasi insomnia mual nafsu makan berkurang)

Amantadin konsentrasi tinggi di plasma reaksi neurotoksik serius delirium kejang koma aritmia

Penggunaan terapiPenggunaan terapi

Pencegahan dan pengobatan influenza A 200 mghari dalam 1 atau 2 dosis

(pengobatan)Pencegahan harus dimulai ketika mulai

teridentifikasi pandemi virus 100mghari (4 ndash 8 minggu)

ZANAMIVIROSELTAMIVIRZANAMIVIROSELTAMIVIRPenghambat Neuroaminidase Menghambat replikasi influenza A amp B

FKFK

Diserap dengan cepat setelah pemberian oral (BA 80)

Eliminasi di ginjal dalam bentuk tak berubah

Berinterkasi dengan probenecid (meningkatkan T12 ndash 2x)

Efek sampingEfek samping

Mual rasa tak nyaman di lambung muntah lokal iritasi

Konsentrasi yang sangat tinggi berhungan dengan kematian (tikus)

ANTI-HEPATITISANTI-HEPATITIS

ADEFOVIRADEFOVIRSecara kompetitif menghambat HBV

DNA polymeraseMenghambat sintesis DNAEfek samping nefrotoksik pusing

diare ganggian abdomen)Pengobaan infeksi HBV kronis 10 mghari

INTERFERONINTERFERON Protein endogen yang dihasilkan dan dilepaskan

oleh sel sebagai respon terhadap patogen Menginduksi enzim menekan proliferasi aktivitas

imunomodulator dan menghambat replikasi virus Menghambat penetrasi dan amp uncoating Untuk pengobatan HBV amp HCV

ANTIRETROVIRAL ANTIRETROVIRAL AGENTSAGENTS

CURRENT ARV MEDICATIONSCURRENT ARV MEDICATIONS

NRTIbull Abacavir bull Didanosine bull Emtricitabine bull Lamivudine bull Stavudine bull Tenofovir bull Zidovudine

NNRTIbull Efavirenz bull Etravirine bull Nevirapine

PIbull Atazanavir bull Darunavir bull Fosamprenavir bull Indinavir bull Lopinavir bull Nelfinavirbull Ritonavir bull Saquinavir bull Tipranavir Fusion Inhibitorbull Enfuvirtide bull

Fixed-dose CombinationsbullZidovudine lamivudinebullZidovudinelamivudineabacavirbullAbacavirlamivudinebullEmtricitabinetenofovirbullEfavirenzemtricitabine tenofovir

DRUG MECHANISM amp VIRAL SELECTIVITY

CLINICAL USE

VIRAL RESISTANCE

UNDESIRABLE SIDE EFFECTS

PHARMACOKINETICS

NOTES

Zidovudine (AZT)

Thymidine analog is incorporated into DNA of human immunodeficiency viirus causing termination of the viral DNA chain

HIV Prevention of maternal-fetal transmission of HIV

Mutations in reverse transcriptase

Headaches nausea myalgias anemia neutropenia macrocytosis

PO Well absorbed rapidly metabolized by liver

Acetaminophen increases risk of hematologic toxicity

Didanosine (ddl)Zalcitabine (ddC)Lamivudine

-Metabolized intracellularly to dideoxynucleotide triphosphate that inhibits reverse transcriptase amp incorporates into viral DNA-Nucleotides fail to bind to ddATP bec it lacks free 3rsquo OH group

HIV Mutations in reverse transcriptase

Peripheral neuropathy pancreatitis diarrhea headache insomnia vomiting nausea rash abdominal pain

IVPO Partially metabolized in liver excreted in the urine Toxicity may be enhanced by renal or hepatic dysfunction

Limited utility as a single agent therapy because of viral resistance

Stavudine Metabolized to stavudine triphosphate wc inhibits HIV reverse transcriptase amp DNA polymerase Prevents DNA elongation

HIV Peripheral neuropathy

PO Not indicated for initial monotherapy of HIV

ANTIVIRAL DRUGS - RETROVIRUSES

RitonavirIndinavirSaquinavirNelfinavir

Inhibts HIV protease Results in immature virion

HIV Mutations in protease sequence reduce affinity of protease inhibitors

GI distress headache neurologic symptoms Indinavir associated w increase risk for kidney stones

PO Metabolized by P450 in liver Reduce dose in patients with liver disease Poor CNS penetration

Potentially serious drug interactions due to P450 competition

NevirapineDelavirdene

Nob-nucleoside inhibitor of HIV reverse transcriptase

HIV Never as monotherapy due to rapid development of resistance

Rapid resistance develops due to mutations in reverse transcriptase

Severe skin rash fever nausea headache

PO Well absorbed Nevirapine crosses placenta amp has better CNS penetration than Delavirdene

Delavirdene failed to show clinical efficacy when added to didanosine in clinical trial

• Obat antivirus
• Virus
• Struktur virus
• Klasifikasi virus
• PowerPoint Presentation
• Slide 6
• Slide 7
• Slide 8
• Obat anti virus
• Slide 10
• ANTI-HERPES ANTI VZV HSV = herpes simplex virus VZV = Varicella Zoster virus
• ACYCLOVIR
• Mekanisme kerja
• Farmakokinetik
• Penggunaan dalam terapi
• THERAPEUTIC USES
• Efek samping
• PENCICLOVIR
• MK
• Slide 20
• Slide 21
• Slide 22
• Slide 23
• ANTI-INFLUENZA
• AMANTADINRIMANTADIN
• FK
• Efek samping
• Penggunaan terapi
• ZANAMIVIROSELTAMIVIR
• Slide 30
• Slide 31
• ANTI-HEPATITIS
• ADEFOVIR
• INTERFERON
• ANTIRETROVIRAL AGENTS
• Slide 36
• CURRENT ARV MEDICATIONS
• Slide 38
• Slide 39
• Slide 40
• Slide 41

Siklus hidup

1Attachment melekatnya virus pada reseptor yang terdapat pada permukaan sel inang

2Entry masuknya virus melewati membran sel inang 3Uncoating uncoating asam nukleat virus4Replication sintesis protein pengatur awal ( cth asam nukleat polimerase sintesis virus baru RNA or DNA sintesis protein pembentuk struktur5 Assembly (maturation) pematangan partikel virus 6 Release pelepasan dari sel

1 2 3

6

5

4

78

bull Banyak virus menginfeksi sel inang spesifik

bull Banyak infeksi virus bersifat self limiting tidak memerlukan pengobatan cth common cold yang disebabkan oleh rinovirus

bull Infeksi virus yang umum seperti influenza chicken pox mumps biasanya dapat diatasi oleh sistem imun tubuh

Virus lain dapat menyebabkan penyakit serius dan fatal sehingga memerlukan pengobatan yang agresif cth HIV (AIDS)

Poin penting

Virus Genera Nucleic Acid Clinical Illness

Adenovirus DNA URTIs Eye infections

Hepadnaviridae DNA Hepatitis B Cancer ()

Herpesvirus DNA Genital herpes Varicella Encephalitis Retinitis

Papillomavirus DNA Papilloma Cancer

Parvovirus DNA Erythema infectiosum

Arenavirus RNA Lymphocytic choriomeningitis

Bunyavirus RNA Encephalitis

Coronavirus RNA URTIs

Influenzavirus RNA Influenza

Paramyxovirus RNA Measles URTIs

Picornavirus RNA Poliomyelitis diarrhea URTIs

Retrovirus RNA Leukemia AIDS

Rhabdovirus RNA Rabies

Togavirus RNA Rubella Yellow fever

Virus Groups of Clinical Importance

Obat anti virusObat anti virus Vaksin sering digunakan untuk membangun

sistem kekebalan sebelum infeksi virus terjadi

Agar efektif antivirus harus dapat menghambat entry atau keluarya virus ke sel inang atau aktif di dalam sel inang

9

Tantangan terapi anti virus replikasi virus yang cepat menyebabkan

sulitnya mengembangkan anti virus yang efektif

Virus dapat bermutasi dengan cepat obat menjadi tidak efektif

Kesulitan obat menemukan virus tanpa mengganggu sel normal inang

10

ANTI-HERPES ANTI VZVANTI-HERPES ANTI VZV

HSV = herpes simplex virusHSV = herpes simplex virusVZV = Varicella Zoster virusVZV = Varicella Zoster virus

ACYCLOVIRACYCLOVIR

Aktif terhadap HSV1 HSV2 amp VZV Aktifitas lebih lemah terhadap EBV

(ebstein bar virus) CMV (cytomegalo virus)

Mekanisme kerjaMekanisme kerjaTiga tahap fosforilasi

FarmakokinetikFarmakokinetik BA oral 10-30 menurun dengan peningkatan

dosis BA relatif meningkat sampai 70 setelah

pemberian valasiklovir Terdistribusi luas pada cairan tubuh termasuk

cairan vesikuler dan CSF Terkonsentrasi di ASI cairan amnionik dan

plasenta Absorbsi perkutan rendah

Penggunaan dalam terapiPenggunaan dalam terapi

Herpes genital (awal dan kambuhan) ndash 200 mg 5xhari selama 10 hari ndash oralndash 5 mgkg per 8 jam ndash IVRecurrent 400 mg 2xhari atau 200 mg

3xhari

THERAPEUTIC USESTHERAPEUTIC USES

ACUTE HERPES ZOSTER (SHINGLES)SYSTEMIC ACYCLOVIR PROPHYLAXISHSV ENCEPHALITISVARICELLA ZOSTER VIRUS INFECTIONCMV PROPHYLAXIS

Efek sampingEfek samping

Sediaan topikal-iritasi mukosa dan rasa terbakar pada luka genital

ORAL ndash mual diare rash sakit kepala insufisiensi ginjal neurotoksisitas

IV- insufisiensi ginjal CNS

PENCICLOVIRPENCICLOVIR

Aktivitas dan potensi mirid dengan asiklovir terhadap HSV amp VZV

Aktif terhadap HBV (hepatiis B virus)

MKMK Menghambat sintesis DNA virus Awalnya difosforilasi oleh viral thymidine

kinase Penciclovir trifosfat merupakan inhibitor

kompetitif terhadap viral DNA polymerase Potensi 100 lebih rendah dibanding asiklovir

tapi berada pada konsentrasi yg lebih tinggi dan lebih lama dalam sel yang terinfeksi

Penggunaan dalam terapiPenggunaan dalam terapidosis 5 mgkg per 8-12 jam iv selama 7

hari seara dengan asiklovir utk infeksi mucocutaneous HSV

Sediaan Topical 1 penciclovir cream dioleskan tiap 2 jam 4 hari utk labial HSV

Efek sampingEfek samping

Mutagenik pada konsentrasi tinggi IO yang signifikan secara klinis tidak

teridentifikasi

DRUG MECHANISMVIRAL

SELECTIVITY

CLINICAL USE

VIRAL RESISTANCE

UNDESIRABLE SIDE EFFECTS

PHARMACOKINETICS

NOTES

Acylovir Metabolized by thymidine kinase to triphosphate

Herpes simplex 1 amp 2 varicella zoster

Produce abnormal thymidine kinase

Skin irritation burning crystalline nephropathy

IVPO Administer slowly CNS level=50 serum level Decrease dose w kidney dysfunction

Pencyclovir Oral HSV (coldsores)

Topical

Valacyclovir L-valyl ester of acyclovir converted to acyclovir

Herpes zoster (shingles)

Nausea headache PO Slightly better oral absorption than acyclovir

No clear advantage over acyclovir

Idoxuridine Phosphorylated metabolite incorporates into DNA causing strand breaks

Herpes simplex keratitis No effect on RNA viruses

Resistance develops

Photophobia irritation of conjunctiva amp eyelid

Eyedrops Drug is a halogenated derivative of deoxyuridine

Famciclovir Phosphorylated by viral thymidine kinase to penciclovir triiphosphate

Shortens duration of herpes zoster amp genital herpes

Minimal toxicity Headache

PO Decrease dose with renal dysfunction

Ganciclovir Metabolized by thymidine kinase to triphosphate Preferentially phosphorylated to active drug in CMV infected cells

CMV retinitis amp severe systemic CMV infections

Some resistant strains lack thymidine kinase Cannot activate drug

Granulocytopenia thrombocytopenia

IVPO Excreted unchanged in urine Decrease dose with renal dysfunction

Do not coadminister zidovudine (granulocytopenia) or imipenem-cilastatin (seizures)

ANTIVIRAL DRUGS ndash DNA amp RNA VIRUSES

Cidofovir Metabolized to diphosphate form Otherwise like ganciclovir

CMV retinitis Nephrotoxicity may be reduced by hydration amp coadministration of Probenicid Neutropenia

Foscarnet Analog of pyrophosphate Competes for pyrophosphate site in viral but not human DNA polymerase amp reverse transcriptase

CMV retinitis Does not need phosphorylation it is active against thymidine kinase ndashdeficient strains

Renal toxicity seizures hypocalcemia fever anemia diarrhea nausea

IV gt80 excreted unchanged in the urine CSF penetration variable Reduce dose with renal dysfunction

Deposited in bone amp teeth Hydrate patient during therapy to protect the kidney

Amantadine Prevents virus from entering susceptible cells

Treatment amp prophylaxis of influenza A

Depression CNS toxicity CHF orthostatic hypotension urinary retention

PO Excreted unmetabolized

Rimantadine Analog of amantadine inhibits viral uncoating

Prophylaxis in children

Fewer CNS side effects risk of seizure

PO Prolonged elimination w renal or hepatic dysfunction

Ribavirin Unknown mechanism

RSV Decreased pulmonary function

Aerosol administration Absorbed systemically

May precipitate in ventilator tubing

ANTI-INFLUENZAANTI-INFLUENZA

AMANTADINRIMANTADINAMANTADINRIMANTADIN Menghambat proses uncoating virus RNA

influenza A di dalam cell inang mencegah replikasi

Efektif menurunkan durasi gejala influenza jika diberikan dalam 48 jam setelah onset

FKFK

Absorpsi oral baikEkskresi dalam bentuk tak termetabolisme

di urinAmantadin dapat diekskresikan lewat ASI

Efek sampingEfek samping

Umum gangguan GI dan CNS minor (gugup light headanche susah konsentrasi insomnia mual nafsu makan berkurang)

Amantadin konsentrasi tinggi di plasma reaksi neurotoksik serius delirium kejang koma aritmia

Penggunaan terapiPenggunaan terapi

Pencegahan dan pengobatan influenza A 200 mghari dalam 1 atau 2 dosis

(pengobatan)Pencegahan harus dimulai ketika mulai

teridentifikasi pandemi virus 100mghari (4 ndash 8 minggu)

ZANAMIVIROSELTAMIVIRZANAMIVIROSELTAMIVIRPenghambat Neuroaminidase Menghambat replikasi influenza A amp B

FKFK

Diserap dengan cepat setelah pemberian oral (BA 80)

Eliminasi di ginjal dalam bentuk tak berubah

Berinterkasi dengan probenecid (meningkatkan T12 ndash 2x)

Efek sampingEfek samping

Mual rasa tak nyaman di lambung muntah lokal iritasi

Konsentrasi yang sangat tinggi berhungan dengan kematian (tikus)

ANTI-HEPATITISANTI-HEPATITIS

ADEFOVIRADEFOVIRSecara kompetitif menghambat HBV

DNA polymeraseMenghambat sintesis DNAEfek samping nefrotoksik pusing

diare ganggian abdomen)Pengobaan infeksi HBV kronis 10 mghari

INTERFERONINTERFERON Protein endogen yang dihasilkan dan dilepaskan

oleh sel sebagai respon terhadap patogen Menginduksi enzim menekan proliferasi aktivitas

imunomodulator dan menghambat replikasi virus Menghambat penetrasi dan amp uncoating Untuk pengobatan HBV amp HCV

ANTIRETROVIRAL ANTIRETROVIRAL AGENTSAGENTS

CURRENT ARV MEDICATIONSCURRENT ARV MEDICATIONS

NRTIbull Abacavir bull Didanosine bull Emtricitabine bull Lamivudine bull Stavudine bull Tenofovir bull Zidovudine

NNRTIbull Efavirenz bull Etravirine bull Nevirapine

PIbull Atazanavir bull Darunavir bull Fosamprenavir bull Indinavir bull Lopinavir bull Nelfinavirbull Ritonavir bull Saquinavir bull Tipranavir Fusion Inhibitorbull Enfuvirtide bull

Fixed-dose CombinationsbullZidovudine lamivudinebullZidovudinelamivudineabacavirbullAbacavirlamivudinebullEmtricitabinetenofovirbullEfavirenzemtricitabine tenofovir

DRUG MECHANISM amp VIRAL SELECTIVITY

CLINICAL USE

VIRAL RESISTANCE

UNDESIRABLE SIDE EFFECTS

PHARMACOKINETICS

NOTES

Zidovudine (AZT)

Thymidine analog is incorporated into DNA of human immunodeficiency viirus causing termination of the viral DNA chain

HIV Prevention of maternal-fetal transmission of HIV

Mutations in reverse transcriptase

Headaches nausea myalgias anemia neutropenia macrocytosis

PO Well absorbed rapidly metabolized by liver

Acetaminophen increases risk of hematologic toxicity

Didanosine (ddl)Zalcitabine (ddC)Lamivudine

-Metabolized intracellularly to dideoxynucleotide triphosphate that inhibits reverse transcriptase amp incorporates into viral DNA-Nucleotides fail to bind to ddATP bec it lacks free 3rsquo OH group

HIV Mutations in reverse transcriptase

Peripheral neuropathy pancreatitis diarrhea headache insomnia vomiting nausea rash abdominal pain

IVPO Partially metabolized in liver excreted in the urine Toxicity may be enhanced by renal or hepatic dysfunction

Limited utility as a single agent therapy because of viral resistance

Stavudine Metabolized to stavudine triphosphate wc inhibits HIV reverse transcriptase amp DNA polymerase Prevents DNA elongation

HIV Peripheral neuropathy

PO Not indicated for initial monotherapy of HIV

ANTIVIRAL DRUGS - RETROVIRUSES

RitonavirIndinavirSaquinavirNelfinavir

Inhibts HIV protease Results in immature virion

HIV Mutations in protease sequence reduce affinity of protease inhibitors

GI distress headache neurologic symptoms Indinavir associated w increase risk for kidney stones

PO Metabolized by P450 in liver Reduce dose in patients with liver disease Poor CNS penetration

Potentially serious drug interactions due to P450 competition

NevirapineDelavirdene

Nob-nucleoside inhibitor of HIV reverse transcriptase

HIV Never as monotherapy due to rapid development of resistance

Rapid resistance develops due to mutations in reverse transcriptase

Severe skin rash fever nausea headache

PO Well absorbed Nevirapine crosses placenta amp has better CNS penetration than Delavirdene

Delavirdene failed to show clinical efficacy when added to didanosine in clinical trial

• Obat antivirus
• Virus
• Struktur virus
• Klasifikasi virus
• PowerPoint Presentation
• Slide 6
• Slide 7
• Slide 8
• Obat anti virus
• Slide 10
• ANTI-HERPES ANTI VZV HSV = herpes simplex virus VZV = Varicella Zoster virus
• ACYCLOVIR
• Mekanisme kerja
• Farmakokinetik
• Penggunaan dalam terapi
• THERAPEUTIC USES
• Efek samping
• PENCICLOVIR
• MK
• Slide 20
• Slide 21
• Slide 22
• Slide 23
• ANTI-INFLUENZA
• AMANTADINRIMANTADIN
• FK
• Efek samping
• Penggunaan terapi
• ZANAMIVIROSELTAMIVIR
• Slide 30
• Slide 31
• ANTI-HEPATITIS
• ADEFOVIR
• INTERFERON
• ANTIRETROVIRAL AGENTS
• Slide 36
• CURRENT ARV MEDICATIONS
• Slide 38
• Slide 39
• Slide 40
• Slide 41

1 2 3

6

5

4

78

bull Banyak virus menginfeksi sel inang spesifik

bull Banyak infeksi virus bersifat self limiting tidak memerlukan pengobatan cth common cold yang disebabkan oleh rinovirus

bull Infeksi virus yang umum seperti influenza chicken pox mumps biasanya dapat diatasi oleh sistem imun tubuh

Virus lain dapat menyebabkan penyakit serius dan fatal sehingga memerlukan pengobatan yang agresif cth HIV (AIDS)

Poin penting

Virus Genera Nucleic Acid Clinical Illness

Adenovirus DNA URTIs Eye infections

Hepadnaviridae DNA Hepatitis B Cancer ()

Herpesvirus DNA Genital herpes Varicella Encephalitis Retinitis

Papillomavirus DNA Papilloma Cancer

Parvovirus DNA Erythema infectiosum

Arenavirus RNA Lymphocytic choriomeningitis

Bunyavirus RNA Encephalitis

Coronavirus RNA URTIs

Influenzavirus RNA Influenza

Paramyxovirus RNA Measles URTIs

Picornavirus RNA Poliomyelitis diarrhea URTIs

Retrovirus RNA Leukemia AIDS

Rhabdovirus RNA Rabies

Togavirus RNA Rubella Yellow fever

Virus Groups of Clinical Importance

Obat anti virusObat anti virus Vaksin sering digunakan untuk membangun

sistem kekebalan sebelum infeksi virus terjadi

Agar efektif antivirus harus dapat menghambat entry atau keluarya virus ke sel inang atau aktif di dalam sel inang

9

Tantangan terapi anti virus replikasi virus yang cepat menyebabkan

sulitnya mengembangkan anti virus yang efektif

Virus dapat bermutasi dengan cepat obat menjadi tidak efektif

Kesulitan obat menemukan virus tanpa mengganggu sel normal inang

10

ANTI-HERPES ANTI VZVANTI-HERPES ANTI VZV

HSV = herpes simplex virusHSV = herpes simplex virusVZV = Varicella Zoster virusVZV = Varicella Zoster virus

ACYCLOVIRACYCLOVIR

Aktif terhadap HSV1 HSV2 amp VZV Aktifitas lebih lemah terhadap EBV

(ebstein bar virus) CMV (cytomegalo virus)

Mekanisme kerjaMekanisme kerjaTiga tahap fosforilasi

FarmakokinetikFarmakokinetik BA oral 10-30 menurun dengan peningkatan

dosis BA relatif meningkat sampai 70 setelah

pemberian valasiklovir Terdistribusi luas pada cairan tubuh termasuk

cairan vesikuler dan CSF Terkonsentrasi di ASI cairan amnionik dan

plasenta Absorbsi perkutan rendah

Penggunaan dalam terapiPenggunaan dalam terapi

Herpes genital (awal dan kambuhan) ndash 200 mg 5xhari selama 10 hari ndash oralndash 5 mgkg per 8 jam ndash IVRecurrent 400 mg 2xhari atau 200 mg

3xhari

THERAPEUTIC USESTHERAPEUTIC USES

ACUTE HERPES ZOSTER (SHINGLES)SYSTEMIC ACYCLOVIR PROPHYLAXISHSV ENCEPHALITISVARICELLA ZOSTER VIRUS INFECTIONCMV PROPHYLAXIS

Efek sampingEfek samping

Sediaan topikal-iritasi mukosa dan rasa terbakar pada luka genital

ORAL ndash mual diare rash sakit kepala insufisiensi ginjal neurotoksisitas

IV- insufisiensi ginjal CNS

PENCICLOVIRPENCICLOVIR

Aktivitas dan potensi mirid dengan asiklovir terhadap HSV amp VZV

Aktif terhadap HBV (hepatiis B virus)

MKMK Menghambat sintesis DNA virus Awalnya difosforilasi oleh viral thymidine

kinase Penciclovir trifosfat merupakan inhibitor

kompetitif terhadap viral DNA polymerase Potensi 100 lebih rendah dibanding asiklovir

tapi berada pada konsentrasi yg lebih tinggi dan lebih lama dalam sel yang terinfeksi

Penggunaan dalam terapiPenggunaan dalam terapidosis 5 mgkg per 8-12 jam iv selama 7

hari seara dengan asiklovir utk infeksi mucocutaneous HSV

Sediaan Topical 1 penciclovir cream dioleskan tiap 2 jam 4 hari utk labial HSV

Efek sampingEfek samping

Mutagenik pada konsentrasi tinggi IO yang signifikan secara klinis tidak

teridentifikasi

DRUG MECHANISMVIRAL

SELECTIVITY

CLINICAL USE

VIRAL RESISTANCE

UNDESIRABLE SIDE EFFECTS

PHARMACOKINETICS

NOTES

Acylovir Metabolized by thymidine kinase to triphosphate

Herpes simplex 1 amp 2 varicella zoster

Produce abnormal thymidine kinase

Skin irritation burning crystalline nephropathy

IVPO Administer slowly CNS level=50 serum level Decrease dose w kidney dysfunction

Pencyclovir Oral HSV (coldsores)

Topical

Valacyclovir L-valyl ester of acyclovir converted to acyclovir

Herpes zoster (shingles)

Nausea headache PO Slightly better oral absorption than acyclovir

No clear advantage over acyclovir

Idoxuridine Phosphorylated metabolite incorporates into DNA causing strand breaks

Herpes simplex keratitis No effect on RNA viruses

Resistance develops

Photophobia irritation of conjunctiva amp eyelid

Eyedrops Drug is a halogenated derivative of deoxyuridine

Famciclovir Phosphorylated by viral thymidine kinase to penciclovir triiphosphate

Shortens duration of herpes zoster amp genital herpes

Minimal toxicity Headache

PO Decrease dose with renal dysfunction

Ganciclovir Metabolized by thymidine kinase to triphosphate Preferentially phosphorylated to active drug in CMV infected cells

CMV retinitis amp severe systemic CMV infections

Some resistant strains lack thymidine kinase Cannot activate drug

Granulocytopenia thrombocytopenia

IVPO Excreted unchanged in urine Decrease dose with renal dysfunction

Do not coadminister zidovudine (granulocytopenia) or imipenem-cilastatin (seizures)

ANTIVIRAL DRUGS ndash DNA amp RNA VIRUSES

Cidofovir Metabolized to diphosphate form Otherwise like ganciclovir

CMV retinitis Nephrotoxicity may be reduced by hydration amp coadministration of Probenicid Neutropenia

Foscarnet Analog of pyrophosphate Competes for pyrophosphate site in viral but not human DNA polymerase amp reverse transcriptase

CMV retinitis Does not need phosphorylation it is active against thymidine kinase ndashdeficient strains

Renal toxicity seizures hypocalcemia fever anemia diarrhea nausea

IV gt80 excreted unchanged in the urine CSF penetration variable Reduce dose with renal dysfunction

Deposited in bone amp teeth Hydrate patient during therapy to protect the kidney

Amantadine Prevents virus from entering susceptible cells

Treatment amp prophylaxis of influenza A

Depression CNS toxicity CHF orthostatic hypotension urinary retention

PO Excreted unmetabolized

Rimantadine Analog of amantadine inhibits viral uncoating

Prophylaxis in children

Fewer CNS side effects risk of seizure

PO Prolonged elimination w renal or hepatic dysfunction

Ribavirin Unknown mechanism

RSV Decreased pulmonary function

Aerosol administration Absorbed systemically

May precipitate in ventilator tubing

ANTI-INFLUENZAANTI-INFLUENZA

AMANTADINRIMANTADINAMANTADINRIMANTADIN Menghambat proses uncoating virus RNA

influenza A di dalam cell inang mencegah replikasi

Efektif menurunkan durasi gejala influenza jika diberikan dalam 48 jam setelah onset

FKFK

Absorpsi oral baikEkskresi dalam bentuk tak termetabolisme

di urinAmantadin dapat diekskresikan lewat ASI

Efek sampingEfek samping

Umum gangguan GI dan CNS minor (gugup light headanche susah konsentrasi insomnia mual nafsu makan berkurang)

Amantadin konsentrasi tinggi di plasma reaksi neurotoksik serius delirium kejang koma aritmia

Penggunaan terapiPenggunaan terapi

Pencegahan dan pengobatan influenza A 200 mghari dalam 1 atau 2 dosis

(pengobatan)Pencegahan harus dimulai ketika mulai

teridentifikasi pandemi virus 100mghari (4 ndash 8 minggu)

ZANAMIVIROSELTAMIVIRZANAMIVIROSELTAMIVIRPenghambat Neuroaminidase Menghambat replikasi influenza A amp B

FKFK

Diserap dengan cepat setelah pemberian oral (BA 80)

Eliminasi di ginjal dalam bentuk tak berubah

Berinterkasi dengan probenecid (meningkatkan T12 ndash 2x)

Efek sampingEfek samping

Mual rasa tak nyaman di lambung muntah lokal iritasi

Konsentrasi yang sangat tinggi berhungan dengan kematian (tikus)

ANTI-HEPATITISANTI-HEPATITIS

ADEFOVIRADEFOVIRSecara kompetitif menghambat HBV

DNA polymeraseMenghambat sintesis DNAEfek samping nefrotoksik pusing

diare ganggian abdomen)Pengobaan infeksi HBV kronis 10 mghari

INTERFERONINTERFERON Protein endogen yang dihasilkan dan dilepaskan

oleh sel sebagai respon terhadap patogen Menginduksi enzim menekan proliferasi aktivitas

imunomodulator dan menghambat replikasi virus Menghambat penetrasi dan amp uncoating Untuk pengobatan HBV amp HCV

ANTIRETROVIRAL ANTIRETROVIRAL AGENTSAGENTS

CURRENT ARV MEDICATIONSCURRENT ARV MEDICATIONS

NRTIbull Abacavir bull Didanosine bull Emtricitabine bull Lamivudine bull Stavudine bull Tenofovir bull Zidovudine

NNRTIbull Efavirenz bull Etravirine bull Nevirapine

PIbull Atazanavir bull Darunavir bull Fosamprenavir bull Indinavir bull Lopinavir bull Nelfinavirbull Ritonavir bull Saquinavir bull Tipranavir Fusion Inhibitorbull Enfuvirtide bull

Fixed-dose CombinationsbullZidovudine lamivudinebullZidovudinelamivudineabacavirbullAbacavirlamivudinebullEmtricitabinetenofovirbullEfavirenzemtricitabine tenofovir

DRUG MECHANISM amp VIRAL SELECTIVITY

CLINICAL USE

VIRAL RESISTANCE

UNDESIRABLE SIDE EFFECTS

PHARMACOKINETICS

NOTES

Zidovudine (AZT)

Thymidine analog is incorporated into DNA of human immunodeficiency viirus causing termination of the viral DNA chain

HIV Prevention of maternal-fetal transmission of HIV

Mutations in reverse transcriptase

Headaches nausea myalgias anemia neutropenia macrocytosis

PO Well absorbed rapidly metabolized by liver

Acetaminophen increases risk of hematologic toxicity

Didanosine (ddl)Zalcitabine (ddC)Lamivudine

-Metabolized intracellularly to dideoxynucleotide triphosphate that inhibits reverse transcriptase amp incorporates into viral DNA-Nucleotides fail to bind to ddATP bec it lacks free 3rsquo OH group

HIV Mutations in reverse transcriptase

Peripheral neuropathy pancreatitis diarrhea headache insomnia vomiting nausea rash abdominal pain

IVPO Partially metabolized in liver excreted in the urine Toxicity may be enhanced by renal or hepatic dysfunction

Limited utility as a single agent therapy because of viral resistance

Stavudine Metabolized to stavudine triphosphate wc inhibits HIV reverse transcriptase amp DNA polymerase Prevents DNA elongation

HIV Peripheral neuropathy

PO Not indicated for initial monotherapy of HIV

ANTIVIRAL DRUGS - RETROVIRUSES

RitonavirIndinavirSaquinavirNelfinavir

Inhibts HIV protease Results in immature virion

HIV Mutations in protease sequence reduce affinity of protease inhibitors

GI distress headache neurologic symptoms Indinavir associated w increase risk for kidney stones

PO Metabolized by P450 in liver Reduce dose in patients with liver disease Poor CNS penetration

Potentially serious drug interactions due to P450 competition

NevirapineDelavirdene

Nob-nucleoside inhibitor of HIV reverse transcriptase

HIV Never as monotherapy due to rapid development of resistance

Rapid resistance develops due to mutations in reverse transcriptase

Severe skin rash fever nausea headache

PO Well absorbed Nevirapine crosses placenta amp has better CNS penetration than Delavirdene

Delavirdene failed to show clinical efficacy when added to didanosine in clinical trial

• Obat antivirus
• Virus
• Struktur virus
• Klasifikasi virus
• PowerPoint Presentation
• Slide 6
• Slide 7
• Slide 8
• Obat anti virus
• Slide 10
• ANTI-HERPES ANTI VZV HSV = herpes simplex virus VZV = Varicella Zoster virus
• ACYCLOVIR
• Mekanisme kerja
• Farmakokinetik
• Penggunaan dalam terapi
• THERAPEUTIC USES
• Efek samping
• PENCICLOVIR
• MK
• Slide 20
• Slide 21
• Slide 22
• Slide 23
• ANTI-INFLUENZA
• AMANTADINRIMANTADIN
• FK
• Efek samping
• Penggunaan terapi
• ZANAMIVIROSELTAMIVIR
• Slide 30
• Slide 31
• ANTI-HEPATITIS
• ADEFOVIR
• INTERFERON
• ANTIRETROVIRAL AGENTS
• Slide 36
• CURRENT ARV MEDICATIONS
• Slide 38
• Slide 39
• Slide 40
• Slide 41

bull Banyak virus menginfeksi sel inang spesifik

bull Banyak infeksi virus bersifat self limiting tidak memerlukan pengobatan cth common cold yang disebabkan oleh rinovirus

bull Infeksi virus yang umum seperti influenza chicken pox mumps biasanya dapat diatasi oleh sistem imun tubuh

Virus lain dapat menyebabkan penyakit serius dan fatal sehingga memerlukan pengobatan yang agresif cth HIV (AIDS)

Poin penting

Virus Genera Nucleic Acid Clinical Illness

Adenovirus DNA URTIs Eye infections

Hepadnaviridae DNA Hepatitis B Cancer ()

Herpesvirus DNA Genital herpes Varicella Encephalitis Retinitis

Papillomavirus DNA Papilloma Cancer

Parvovirus DNA Erythema infectiosum

Arenavirus RNA Lymphocytic choriomeningitis

Bunyavirus RNA Encephalitis

Coronavirus RNA URTIs

Influenzavirus RNA Influenza

Paramyxovirus RNA Measles URTIs

Picornavirus RNA Poliomyelitis diarrhea URTIs

Retrovirus RNA Leukemia AIDS

Rhabdovirus RNA Rabies

Togavirus RNA Rubella Yellow fever

Virus Groups of Clinical Importance

Obat anti virusObat anti virus Vaksin sering digunakan untuk membangun

sistem kekebalan sebelum infeksi virus terjadi

Agar efektif antivirus harus dapat menghambat entry atau keluarya virus ke sel inang atau aktif di dalam sel inang

9

Tantangan terapi anti virus replikasi virus yang cepat menyebabkan

sulitnya mengembangkan anti virus yang efektif

Virus dapat bermutasi dengan cepat obat menjadi tidak efektif

Kesulitan obat menemukan virus tanpa mengganggu sel normal inang

10

ANTI-HERPES ANTI VZVANTI-HERPES ANTI VZV

HSV = herpes simplex virusHSV = herpes simplex virusVZV = Varicella Zoster virusVZV = Varicella Zoster virus

ACYCLOVIRACYCLOVIR

Aktif terhadap HSV1 HSV2 amp VZV Aktifitas lebih lemah terhadap EBV

(ebstein bar virus) CMV (cytomegalo virus)

Mekanisme kerjaMekanisme kerjaTiga tahap fosforilasi

FarmakokinetikFarmakokinetik BA oral 10-30 menurun dengan peningkatan

dosis BA relatif meningkat sampai 70 setelah

pemberian valasiklovir Terdistribusi luas pada cairan tubuh termasuk

cairan vesikuler dan CSF Terkonsentrasi di ASI cairan amnionik dan

plasenta Absorbsi perkutan rendah

Penggunaan dalam terapiPenggunaan dalam terapi

Herpes genital (awal dan kambuhan) ndash 200 mg 5xhari selama 10 hari ndash oralndash 5 mgkg per 8 jam ndash IVRecurrent 400 mg 2xhari atau 200 mg

3xhari

THERAPEUTIC USESTHERAPEUTIC USES

ACUTE HERPES ZOSTER (SHINGLES)SYSTEMIC ACYCLOVIR PROPHYLAXISHSV ENCEPHALITISVARICELLA ZOSTER VIRUS INFECTIONCMV PROPHYLAXIS

Efek sampingEfek samping

Sediaan topikal-iritasi mukosa dan rasa terbakar pada luka genital

ORAL ndash mual diare rash sakit kepala insufisiensi ginjal neurotoksisitas

IV- insufisiensi ginjal CNS

PENCICLOVIRPENCICLOVIR

Aktivitas dan potensi mirid dengan asiklovir terhadap HSV amp VZV

Aktif terhadap HBV (hepatiis B virus)

MKMK Menghambat sintesis DNA virus Awalnya difosforilasi oleh viral thymidine

kinase Penciclovir trifosfat merupakan inhibitor

kompetitif terhadap viral DNA polymerase Potensi 100 lebih rendah dibanding asiklovir

tapi berada pada konsentrasi yg lebih tinggi dan lebih lama dalam sel yang terinfeksi

Penggunaan dalam terapiPenggunaan dalam terapidosis 5 mgkg per 8-12 jam iv selama 7

hari seara dengan asiklovir utk infeksi mucocutaneous HSV

Sediaan Topical 1 penciclovir cream dioleskan tiap 2 jam 4 hari utk labial HSV

Efek sampingEfek samping

Mutagenik pada konsentrasi tinggi IO yang signifikan secara klinis tidak

teridentifikasi

DRUG MECHANISMVIRAL

SELECTIVITY

CLINICAL USE

VIRAL RESISTANCE

UNDESIRABLE SIDE EFFECTS

PHARMACOKINETICS

NOTES

Acylovir Metabolized by thymidine kinase to triphosphate

Herpes simplex 1 amp 2 varicella zoster

Produce abnormal thymidine kinase

Skin irritation burning crystalline nephropathy

IVPO Administer slowly CNS level=50 serum level Decrease dose w kidney dysfunction

Pencyclovir Oral HSV (coldsores)

Topical

Valacyclovir L-valyl ester of acyclovir converted to acyclovir

Herpes zoster (shingles)

Nausea headache PO Slightly better oral absorption than acyclovir

No clear advantage over acyclovir

Idoxuridine Phosphorylated metabolite incorporates into DNA causing strand breaks

Herpes simplex keratitis No effect on RNA viruses

Resistance develops

Photophobia irritation of conjunctiva amp eyelid

Eyedrops Drug is a halogenated derivative of deoxyuridine

Famciclovir Phosphorylated by viral thymidine kinase to penciclovir triiphosphate

Shortens duration of herpes zoster amp genital herpes

Minimal toxicity Headache

PO Decrease dose with renal dysfunction

Ganciclovir Metabolized by thymidine kinase to triphosphate Preferentially phosphorylated to active drug in CMV infected cells

CMV retinitis amp severe systemic CMV infections

Some resistant strains lack thymidine kinase Cannot activate drug

Granulocytopenia thrombocytopenia

IVPO Excreted unchanged in urine Decrease dose with renal dysfunction

Do not coadminister zidovudine (granulocytopenia) or imipenem-cilastatin (seizures)

ANTIVIRAL DRUGS ndash DNA amp RNA VIRUSES

Cidofovir Metabolized to diphosphate form Otherwise like ganciclovir

CMV retinitis Nephrotoxicity may be reduced by hydration amp coadministration of Probenicid Neutropenia

Foscarnet Analog of pyrophosphate Competes for pyrophosphate site in viral but not human DNA polymerase amp reverse transcriptase

CMV retinitis Does not need phosphorylation it is active against thymidine kinase ndashdeficient strains

Renal toxicity seizures hypocalcemia fever anemia diarrhea nausea

IV gt80 excreted unchanged in the urine CSF penetration variable Reduce dose with renal dysfunction

Deposited in bone amp teeth Hydrate patient during therapy to protect the kidney

Amantadine Prevents virus from entering susceptible cells

Treatment amp prophylaxis of influenza A

Depression CNS toxicity CHF orthostatic hypotension urinary retention

PO Excreted unmetabolized

Rimantadine Analog of amantadine inhibits viral uncoating

Prophylaxis in children

Fewer CNS side effects risk of seizure

PO Prolonged elimination w renal or hepatic dysfunction

Ribavirin Unknown mechanism

RSV Decreased pulmonary function

Aerosol administration Absorbed systemically

May precipitate in ventilator tubing

ANTI-INFLUENZAANTI-INFLUENZA

AMANTADINRIMANTADINAMANTADINRIMANTADIN Menghambat proses uncoating virus RNA

influenza A di dalam cell inang mencegah replikasi

Efektif menurunkan durasi gejala influenza jika diberikan dalam 48 jam setelah onset

FKFK

Absorpsi oral baikEkskresi dalam bentuk tak termetabolisme

di urinAmantadin dapat diekskresikan lewat ASI

Efek sampingEfek samping

Umum gangguan GI dan CNS minor (gugup light headanche susah konsentrasi insomnia mual nafsu makan berkurang)

Amantadin konsentrasi tinggi di plasma reaksi neurotoksik serius delirium kejang koma aritmia

Penggunaan terapiPenggunaan terapi

Pencegahan dan pengobatan influenza A 200 mghari dalam 1 atau 2 dosis

(pengobatan)Pencegahan harus dimulai ketika mulai

teridentifikasi pandemi virus 100mghari (4 ndash 8 minggu)

ZANAMIVIROSELTAMIVIRZANAMIVIROSELTAMIVIRPenghambat Neuroaminidase Menghambat replikasi influenza A amp B

FKFK

Diserap dengan cepat setelah pemberian oral (BA 80)

Eliminasi di ginjal dalam bentuk tak berubah

Berinterkasi dengan probenecid (meningkatkan T12 ndash 2x)

Efek sampingEfek samping

Mual rasa tak nyaman di lambung muntah lokal iritasi

Konsentrasi yang sangat tinggi berhungan dengan kematian (tikus)

ANTI-HEPATITISANTI-HEPATITIS

ADEFOVIRADEFOVIRSecara kompetitif menghambat HBV

DNA polymeraseMenghambat sintesis DNAEfek samping nefrotoksik pusing

diare ganggian abdomen)Pengobaan infeksi HBV kronis 10 mghari

INTERFERONINTERFERON Protein endogen yang dihasilkan dan dilepaskan

oleh sel sebagai respon terhadap patogen Menginduksi enzim menekan proliferasi aktivitas

imunomodulator dan menghambat replikasi virus Menghambat penetrasi dan amp uncoating Untuk pengobatan HBV amp HCV

ANTIRETROVIRAL ANTIRETROVIRAL AGENTSAGENTS

CURRENT ARV MEDICATIONSCURRENT ARV MEDICATIONS

NRTIbull Abacavir bull Didanosine bull Emtricitabine bull Lamivudine bull Stavudine bull Tenofovir bull Zidovudine

NNRTIbull Efavirenz bull Etravirine bull Nevirapine

PIbull Atazanavir bull Darunavir bull Fosamprenavir bull Indinavir bull Lopinavir bull Nelfinavirbull Ritonavir bull Saquinavir bull Tipranavir Fusion Inhibitorbull Enfuvirtide bull

Fixed-dose CombinationsbullZidovudine lamivudinebullZidovudinelamivudineabacavirbullAbacavirlamivudinebullEmtricitabinetenofovirbullEfavirenzemtricitabine tenofovir

DRUG MECHANISM amp VIRAL SELECTIVITY

CLINICAL USE

VIRAL RESISTANCE

UNDESIRABLE SIDE EFFECTS

PHARMACOKINETICS

NOTES

Zidovudine (AZT)

Thymidine analog is incorporated into DNA of human immunodeficiency viirus causing termination of the viral DNA chain

HIV Prevention of maternal-fetal transmission of HIV

Mutations in reverse transcriptase

Headaches nausea myalgias anemia neutropenia macrocytosis

PO Well absorbed rapidly metabolized by liver

Acetaminophen increases risk of hematologic toxicity

Didanosine (ddl)Zalcitabine (ddC)Lamivudine

-Metabolized intracellularly to dideoxynucleotide triphosphate that inhibits reverse transcriptase amp incorporates into viral DNA-Nucleotides fail to bind to ddATP bec it lacks free 3rsquo OH group

HIV Mutations in reverse transcriptase

Peripheral neuropathy pancreatitis diarrhea headache insomnia vomiting nausea rash abdominal pain

IVPO Partially metabolized in liver excreted in the urine Toxicity may be enhanced by renal or hepatic dysfunction

Limited utility as a single agent therapy because of viral resistance

Stavudine Metabolized to stavudine triphosphate wc inhibits HIV reverse transcriptase amp DNA polymerase Prevents DNA elongation

HIV Peripheral neuropathy

PO Not indicated for initial monotherapy of HIV

ANTIVIRAL DRUGS - RETROVIRUSES

RitonavirIndinavirSaquinavirNelfinavir

Inhibts HIV protease Results in immature virion

HIV Mutations in protease sequence reduce affinity of protease inhibitors

GI distress headache neurologic symptoms Indinavir associated w increase risk for kidney stones

PO Metabolized by P450 in liver Reduce dose in patients with liver disease Poor CNS penetration

Potentially serious drug interactions due to P450 competition

NevirapineDelavirdene

Nob-nucleoside inhibitor of HIV reverse transcriptase

HIV Never as monotherapy due to rapid development of resistance

Rapid resistance develops due to mutations in reverse transcriptase

Severe skin rash fever nausea headache

PO Well absorbed Nevirapine crosses placenta amp has better CNS penetration than Delavirdene

Delavirdene failed to show clinical efficacy when added to didanosine in clinical trial

• Obat antivirus
• Virus
• Struktur virus
• Klasifikasi virus
• PowerPoint Presentation
• Slide 6
• Slide 7
• Slide 8
• Obat anti virus
• Slide 10
• ANTI-HERPES ANTI VZV HSV = herpes simplex virus VZV = Varicella Zoster virus
• ACYCLOVIR
• Mekanisme kerja
• Farmakokinetik
• Penggunaan dalam terapi
• THERAPEUTIC USES
• Efek samping
• PENCICLOVIR
• MK
• Slide 20
• Slide 21
• Slide 22
• Slide 23
• ANTI-INFLUENZA
• AMANTADINRIMANTADIN
• FK
• Efek samping
• Penggunaan terapi
• ZANAMIVIROSELTAMIVIR
• Slide 30
• Slide 31
• ANTI-HEPATITIS
• ADEFOVIR
• INTERFERON
• ANTIRETROVIRAL AGENTS
• Slide 36
• CURRENT ARV MEDICATIONS
• Slide 38
• Slide 39
• Slide 40
• Slide 41

Virus Genera Nucleic Acid Clinical Illness

Adenovirus DNA URTIs Eye infections

Hepadnaviridae DNA Hepatitis B Cancer ()

Herpesvirus DNA Genital herpes Varicella Encephalitis Retinitis

Papillomavirus DNA Papilloma Cancer

Parvovirus DNA Erythema infectiosum

Arenavirus RNA Lymphocytic choriomeningitis

Bunyavirus RNA Encephalitis

Coronavirus RNA URTIs

Influenzavirus RNA Influenza

Paramyxovirus RNA Measles URTIs

Picornavirus RNA Poliomyelitis diarrhea URTIs

Retrovirus RNA Leukemia AIDS

Rhabdovirus RNA Rabies

Togavirus RNA Rubella Yellow fever

Virus Groups of Clinical Importance

Obat anti virusObat anti virus Vaksin sering digunakan untuk membangun

sistem kekebalan sebelum infeksi virus terjadi

Agar efektif antivirus harus dapat menghambat entry atau keluarya virus ke sel inang atau aktif di dalam sel inang

9

Tantangan terapi anti virus replikasi virus yang cepat menyebabkan

sulitnya mengembangkan anti virus yang efektif

Virus dapat bermutasi dengan cepat obat menjadi tidak efektif

Kesulitan obat menemukan virus tanpa mengganggu sel normal inang

10

ANTI-HERPES ANTI VZVANTI-HERPES ANTI VZV

HSV = herpes simplex virusHSV = herpes simplex virusVZV = Varicella Zoster virusVZV = Varicella Zoster virus

ACYCLOVIRACYCLOVIR

Aktif terhadap HSV1 HSV2 amp VZV Aktifitas lebih lemah terhadap EBV

(ebstein bar virus) CMV (cytomegalo virus)

Mekanisme kerjaMekanisme kerjaTiga tahap fosforilasi

FarmakokinetikFarmakokinetik BA oral 10-30 menurun dengan peningkatan

dosis BA relatif meningkat sampai 70 setelah

pemberian valasiklovir Terdistribusi luas pada cairan tubuh termasuk

cairan vesikuler dan CSF Terkonsentrasi di ASI cairan amnionik dan

plasenta Absorbsi perkutan rendah

Penggunaan dalam terapiPenggunaan dalam terapi

Herpes genital (awal dan kambuhan) ndash 200 mg 5xhari selama 10 hari ndash oralndash 5 mgkg per 8 jam ndash IVRecurrent 400 mg 2xhari atau 200 mg

3xhari

THERAPEUTIC USESTHERAPEUTIC USES

ACUTE HERPES ZOSTER (SHINGLES)SYSTEMIC ACYCLOVIR PROPHYLAXISHSV ENCEPHALITISVARICELLA ZOSTER VIRUS INFECTIONCMV PROPHYLAXIS

Efek sampingEfek samping

Sediaan topikal-iritasi mukosa dan rasa terbakar pada luka genital

ORAL ndash mual diare rash sakit kepala insufisiensi ginjal neurotoksisitas

IV- insufisiensi ginjal CNS

PENCICLOVIRPENCICLOVIR

Aktivitas dan potensi mirid dengan asiklovir terhadap HSV amp VZV

Aktif terhadap HBV (hepatiis B virus)

MKMK Menghambat sintesis DNA virus Awalnya difosforilasi oleh viral thymidine

kinase Penciclovir trifosfat merupakan inhibitor

kompetitif terhadap viral DNA polymerase Potensi 100 lebih rendah dibanding asiklovir

tapi berada pada konsentrasi yg lebih tinggi dan lebih lama dalam sel yang terinfeksi

Penggunaan dalam terapiPenggunaan dalam terapidosis 5 mgkg per 8-12 jam iv selama 7

hari seara dengan asiklovir utk infeksi mucocutaneous HSV

Sediaan Topical 1 penciclovir cream dioleskan tiap 2 jam 4 hari utk labial HSV

Efek sampingEfek samping

Mutagenik pada konsentrasi tinggi IO yang signifikan secara klinis tidak

teridentifikasi

DRUG MECHANISMVIRAL

SELECTIVITY

CLINICAL USE

VIRAL RESISTANCE

UNDESIRABLE SIDE EFFECTS

PHARMACOKINETICS

NOTES

Acylovir Metabolized by thymidine kinase to triphosphate

Herpes simplex 1 amp 2 varicella zoster

Produce abnormal thymidine kinase

Skin irritation burning crystalline nephropathy

IVPO Administer slowly CNS level=50 serum level Decrease dose w kidney dysfunction

Pencyclovir Oral HSV (coldsores)

Topical

Valacyclovir L-valyl ester of acyclovir converted to acyclovir

Herpes zoster (shingles)

Nausea headache PO Slightly better oral absorption than acyclovir

No clear advantage over acyclovir

Idoxuridine Phosphorylated metabolite incorporates into DNA causing strand breaks

Herpes simplex keratitis No effect on RNA viruses

Resistance develops

Photophobia irritation of conjunctiva amp eyelid

Eyedrops Drug is a halogenated derivative of deoxyuridine

Famciclovir Phosphorylated by viral thymidine kinase to penciclovir triiphosphate

Shortens duration of herpes zoster amp genital herpes

Minimal toxicity Headache

PO Decrease dose with renal dysfunction

Ganciclovir Metabolized by thymidine kinase to triphosphate Preferentially phosphorylated to active drug in CMV infected cells

CMV retinitis amp severe systemic CMV infections

Some resistant strains lack thymidine kinase Cannot activate drug

Granulocytopenia thrombocytopenia

IVPO Excreted unchanged in urine Decrease dose with renal dysfunction

Do not coadminister zidovudine (granulocytopenia) or imipenem-cilastatin (seizures)

ANTIVIRAL DRUGS ndash DNA amp RNA VIRUSES

Cidofovir Metabolized to diphosphate form Otherwise like ganciclovir

CMV retinitis Nephrotoxicity may be reduced by hydration amp coadministration of Probenicid Neutropenia

Foscarnet Analog of pyrophosphate Competes for pyrophosphate site in viral but not human DNA polymerase amp reverse transcriptase

CMV retinitis Does not need phosphorylation it is active against thymidine kinase ndashdeficient strains

Renal toxicity seizures hypocalcemia fever anemia diarrhea nausea

IV gt80 excreted unchanged in the urine CSF penetration variable Reduce dose with renal dysfunction

Deposited in bone amp teeth Hydrate patient during therapy to protect the kidney

Amantadine Prevents virus from entering susceptible cells

Treatment amp prophylaxis of influenza A

Depression CNS toxicity CHF orthostatic hypotension urinary retention

PO Excreted unmetabolized

Rimantadine Analog of amantadine inhibits viral uncoating

Prophylaxis in children

Fewer CNS side effects risk of seizure

PO Prolonged elimination w renal or hepatic dysfunction

Ribavirin Unknown mechanism

RSV Decreased pulmonary function

Aerosol administration Absorbed systemically

May precipitate in ventilator tubing

ANTI-INFLUENZAANTI-INFLUENZA

AMANTADINRIMANTADINAMANTADINRIMANTADIN Menghambat proses uncoating virus RNA

influenza A di dalam cell inang mencegah replikasi

Efektif menurunkan durasi gejala influenza jika diberikan dalam 48 jam setelah onset

FKFK

Absorpsi oral baikEkskresi dalam bentuk tak termetabolisme

di urinAmantadin dapat diekskresikan lewat ASI

Efek sampingEfek samping

Umum gangguan GI dan CNS minor (gugup light headanche susah konsentrasi insomnia mual nafsu makan berkurang)

Amantadin konsentrasi tinggi di plasma reaksi neurotoksik serius delirium kejang koma aritmia

Penggunaan terapiPenggunaan terapi

Pencegahan dan pengobatan influenza A 200 mghari dalam 1 atau 2 dosis

(pengobatan)Pencegahan harus dimulai ketika mulai

teridentifikasi pandemi virus 100mghari (4 ndash 8 minggu)

ZANAMIVIROSELTAMIVIRZANAMIVIROSELTAMIVIRPenghambat Neuroaminidase Menghambat replikasi influenza A amp B

FKFK

Diserap dengan cepat setelah pemberian oral (BA 80)

Eliminasi di ginjal dalam bentuk tak berubah

Berinterkasi dengan probenecid (meningkatkan T12 ndash 2x)

Efek sampingEfek samping

Mual rasa tak nyaman di lambung muntah lokal iritasi

Konsentrasi yang sangat tinggi berhungan dengan kematian (tikus)

ANTI-HEPATITISANTI-HEPATITIS

ADEFOVIRADEFOVIRSecara kompetitif menghambat HBV

DNA polymeraseMenghambat sintesis DNAEfek samping nefrotoksik pusing

diare ganggian abdomen)Pengobaan infeksi HBV kronis 10 mghari

INTERFERONINTERFERON Protein endogen yang dihasilkan dan dilepaskan

oleh sel sebagai respon terhadap patogen Menginduksi enzim menekan proliferasi aktivitas

imunomodulator dan menghambat replikasi virus Menghambat penetrasi dan amp uncoating Untuk pengobatan HBV amp HCV

ANTIRETROVIRAL ANTIRETROVIRAL AGENTSAGENTS

CURRENT ARV MEDICATIONSCURRENT ARV MEDICATIONS

NRTIbull Abacavir bull Didanosine bull Emtricitabine bull Lamivudine bull Stavudine bull Tenofovir bull Zidovudine

NNRTIbull Efavirenz bull Etravirine bull Nevirapine

PIbull Atazanavir bull Darunavir bull Fosamprenavir bull Indinavir bull Lopinavir bull Nelfinavirbull Ritonavir bull Saquinavir bull Tipranavir Fusion Inhibitorbull Enfuvirtide bull

Fixed-dose CombinationsbullZidovudine lamivudinebullZidovudinelamivudineabacavirbullAbacavirlamivudinebullEmtricitabinetenofovirbullEfavirenzemtricitabine tenofovir

DRUG MECHANISM amp VIRAL SELECTIVITY

CLINICAL USE

VIRAL RESISTANCE

UNDESIRABLE SIDE EFFECTS

PHARMACOKINETICS

NOTES

Zidovudine (AZT)

Thymidine analog is incorporated into DNA of human immunodeficiency viirus causing termination of the viral DNA chain

HIV Prevention of maternal-fetal transmission of HIV

Mutations in reverse transcriptase

Headaches nausea myalgias anemia neutropenia macrocytosis

PO Well absorbed rapidly metabolized by liver

Acetaminophen increases risk of hematologic toxicity

Didanosine (ddl)Zalcitabine (ddC)Lamivudine

-Metabolized intracellularly to dideoxynucleotide triphosphate that inhibits reverse transcriptase amp incorporates into viral DNA-Nucleotides fail to bind to ddATP bec it lacks free 3rsquo OH group

HIV Mutations in reverse transcriptase

Peripheral neuropathy pancreatitis diarrhea headache insomnia vomiting nausea rash abdominal pain

IVPO Partially metabolized in liver excreted in the urine Toxicity may be enhanced by renal or hepatic dysfunction

Limited utility as a single agent therapy because of viral resistance

Stavudine Metabolized to stavudine triphosphate wc inhibits HIV reverse transcriptase amp DNA polymerase Prevents DNA elongation

HIV Peripheral neuropathy

PO Not indicated for initial monotherapy of HIV

ANTIVIRAL DRUGS - RETROVIRUSES

RitonavirIndinavirSaquinavirNelfinavir

Inhibts HIV protease Results in immature virion

HIV Mutations in protease sequence reduce affinity of protease inhibitors

GI distress headache neurologic symptoms Indinavir associated w increase risk for kidney stones

PO Metabolized by P450 in liver Reduce dose in patients with liver disease Poor CNS penetration

Potentially serious drug interactions due to P450 competition

NevirapineDelavirdene

Nob-nucleoside inhibitor of HIV reverse transcriptase

HIV Never as monotherapy due to rapid development of resistance

Rapid resistance develops due to mutations in reverse transcriptase

Severe skin rash fever nausea headache

PO Well absorbed Nevirapine crosses placenta amp has better CNS penetration than Delavirdene

Delavirdene failed to show clinical efficacy when added to didanosine in clinical trial

• Obat antivirus
• Virus
• Struktur virus
• Klasifikasi virus
• PowerPoint Presentation
• Slide 6
• Slide 7
• Slide 8
• Obat anti virus
• Slide 10
• ANTI-HERPES ANTI VZV HSV = herpes simplex virus VZV = Varicella Zoster virus
• ACYCLOVIR
• Mekanisme kerja
• Farmakokinetik
• Penggunaan dalam terapi
• THERAPEUTIC USES
• Efek samping
• PENCICLOVIR
• MK
• Slide 20
• Slide 21
• Slide 22
• Slide 23
• ANTI-INFLUENZA
• AMANTADINRIMANTADIN
• FK
• Efek samping
• Penggunaan terapi
• ZANAMIVIROSELTAMIVIR
• Slide 30
• Slide 31
• ANTI-HEPATITIS
• ADEFOVIR
• INTERFERON
• ANTIRETROVIRAL AGENTS
• Slide 36
• CURRENT ARV MEDICATIONS
• Slide 38
• Slide 39
• Slide 40
• Slide 41

Obat anti virusObat anti virus Vaksin sering digunakan untuk membangun

sistem kekebalan sebelum infeksi virus terjadi

Agar efektif antivirus harus dapat menghambat entry atau keluarya virus ke sel inang atau aktif di dalam sel inang

9

Tantangan terapi anti virus replikasi virus yang cepat menyebabkan

sulitnya mengembangkan anti virus yang efektif

Virus dapat bermutasi dengan cepat obat menjadi tidak efektif

Kesulitan obat menemukan virus tanpa mengganggu sel normal inang

10

ANTI-HERPES ANTI VZVANTI-HERPES ANTI VZV

HSV = herpes simplex virusHSV = herpes simplex virusVZV = Varicella Zoster virusVZV = Varicella Zoster virus

ACYCLOVIRACYCLOVIR

Aktif terhadap HSV1 HSV2 amp VZV Aktifitas lebih lemah terhadap EBV

(ebstein bar virus) CMV (cytomegalo virus)

Mekanisme kerjaMekanisme kerjaTiga tahap fosforilasi

FarmakokinetikFarmakokinetik BA oral 10-30 menurun dengan peningkatan

dosis BA relatif meningkat sampai 70 setelah

pemberian valasiklovir Terdistribusi luas pada cairan tubuh termasuk

cairan vesikuler dan CSF Terkonsentrasi di ASI cairan amnionik dan

plasenta Absorbsi perkutan rendah

Penggunaan dalam terapiPenggunaan dalam terapi

Herpes genital (awal dan kambuhan) ndash 200 mg 5xhari selama 10 hari ndash oralndash 5 mgkg per 8 jam ndash IVRecurrent 400 mg 2xhari atau 200 mg

3xhari

THERAPEUTIC USESTHERAPEUTIC USES

ACUTE HERPES ZOSTER (SHINGLES)SYSTEMIC ACYCLOVIR PROPHYLAXISHSV ENCEPHALITISVARICELLA ZOSTER VIRUS INFECTIONCMV PROPHYLAXIS

Efek sampingEfek samping

Sediaan topikal-iritasi mukosa dan rasa terbakar pada luka genital

ORAL ndash mual diare rash sakit kepala insufisiensi ginjal neurotoksisitas

IV- insufisiensi ginjal CNS

PENCICLOVIRPENCICLOVIR

Aktivitas dan potensi mirid dengan asiklovir terhadap HSV amp VZV

Aktif terhadap HBV (hepatiis B virus)

MKMK Menghambat sintesis DNA virus Awalnya difosforilasi oleh viral thymidine

kinase Penciclovir trifosfat merupakan inhibitor

kompetitif terhadap viral DNA polymerase Potensi 100 lebih rendah dibanding asiklovir

tapi berada pada konsentrasi yg lebih tinggi dan lebih lama dalam sel yang terinfeksi

Penggunaan dalam terapiPenggunaan dalam terapidosis 5 mgkg per 8-12 jam iv selama 7

hari seara dengan asiklovir utk infeksi mucocutaneous HSV

Sediaan Topical 1 penciclovir cream dioleskan tiap 2 jam 4 hari utk labial HSV

Efek sampingEfek samping

Mutagenik pada konsentrasi tinggi IO yang signifikan secara klinis tidak

teridentifikasi

DRUG MECHANISMVIRAL

SELECTIVITY

CLINICAL USE

VIRAL RESISTANCE

UNDESIRABLE SIDE EFFECTS

PHARMACOKINETICS

NOTES

Acylovir Metabolized by thymidine kinase to triphosphate

Herpes simplex 1 amp 2 varicella zoster

Produce abnormal thymidine kinase

Skin irritation burning crystalline nephropathy

IVPO Administer slowly CNS level=50 serum level Decrease dose w kidney dysfunction

Pencyclovir Oral HSV (coldsores)

Topical

Valacyclovir L-valyl ester of acyclovir converted to acyclovir

Herpes zoster (shingles)

Nausea headache PO Slightly better oral absorption than acyclovir

No clear advantage over acyclovir

Idoxuridine Phosphorylated metabolite incorporates into DNA causing strand breaks

Herpes simplex keratitis No effect on RNA viruses

Resistance develops

Photophobia irritation of conjunctiva amp eyelid

Eyedrops Drug is a halogenated derivative of deoxyuridine

Famciclovir Phosphorylated by viral thymidine kinase to penciclovir triiphosphate

Shortens duration of herpes zoster amp genital herpes

Minimal toxicity Headache

PO Decrease dose with renal dysfunction

Ganciclovir Metabolized by thymidine kinase to triphosphate Preferentially phosphorylated to active drug in CMV infected cells

CMV retinitis amp severe systemic CMV infections

Some resistant strains lack thymidine kinase Cannot activate drug

Granulocytopenia thrombocytopenia

IVPO Excreted unchanged in urine Decrease dose with renal dysfunction

Do not coadminister zidovudine (granulocytopenia) or imipenem-cilastatin (seizures)

ANTIVIRAL DRUGS ndash DNA amp RNA VIRUSES

Cidofovir Metabolized to diphosphate form Otherwise like ganciclovir

CMV retinitis Nephrotoxicity may be reduced by hydration amp coadministration of Probenicid Neutropenia

Foscarnet Analog of pyrophosphate Competes for pyrophosphate site in viral but not human DNA polymerase amp reverse transcriptase

CMV retinitis Does not need phosphorylation it is active against thymidine kinase ndashdeficient strains

Renal toxicity seizures hypocalcemia fever anemia diarrhea nausea

IV gt80 excreted unchanged in the urine CSF penetration variable Reduce dose with renal dysfunction

Deposited in bone amp teeth Hydrate patient during therapy to protect the kidney

Amantadine Prevents virus from entering susceptible cells

Treatment amp prophylaxis of influenza A

Depression CNS toxicity CHF orthostatic hypotension urinary retention

PO Excreted unmetabolized

Rimantadine Analog of amantadine inhibits viral uncoating

Prophylaxis in children

Fewer CNS side effects risk of seizure

PO Prolonged elimination w renal or hepatic dysfunction

Ribavirin Unknown mechanism

RSV Decreased pulmonary function

Aerosol administration Absorbed systemically

May precipitate in ventilator tubing

ANTI-INFLUENZAANTI-INFLUENZA

AMANTADINRIMANTADINAMANTADINRIMANTADIN Menghambat proses uncoating virus RNA

influenza A di dalam cell inang mencegah replikasi

Efektif menurunkan durasi gejala influenza jika diberikan dalam 48 jam setelah onset

FKFK

Absorpsi oral baikEkskresi dalam bentuk tak termetabolisme

di urinAmantadin dapat diekskresikan lewat ASI

Efek sampingEfek samping

Umum gangguan GI dan CNS minor (gugup light headanche susah konsentrasi insomnia mual nafsu makan berkurang)

Amantadin konsentrasi tinggi di plasma reaksi neurotoksik serius delirium kejang koma aritmia

Penggunaan terapiPenggunaan terapi

Pencegahan dan pengobatan influenza A 200 mghari dalam 1 atau 2 dosis

(pengobatan)Pencegahan harus dimulai ketika mulai

teridentifikasi pandemi virus 100mghari (4 ndash 8 minggu)

ZANAMIVIROSELTAMIVIRZANAMIVIROSELTAMIVIRPenghambat Neuroaminidase Menghambat replikasi influenza A amp B

FKFK

Diserap dengan cepat setelah pemberian oral (BA 80)

Eliminasi di ginjal dalam bentuk tak berubah

Berinterkasi dengan probenecid (meningkatkan T12 ndash 2x)

Efek sampingEfek samping

Mual rasa tak nyaman di lambung muntah lokal iritasi

Konsentrasi yang sangat tinggi berhungan dengan kematian (tikus)

ANTI-HEPATITISANTI-HEPATITIS

ADEFOVIRADEFOVIRSecara kompetitif menghambat HBV

DNA polymeraseMenghambat sintesis DNAEfek samping nefrotoksik pusing

diare ganggian abdomen)Pengobaan infeksi HBV kronis 10 mghari

INTERFERONINTERFERON Protein endogen yang dihasilkan dan dilepaskan

oleh sel sebagai respon terhadap patogen Menginduksi enzim menekan proliferasi aktivitas

imunomodulator dan menghambat replikasi virus Menghambat penetrasi dan amp uncoating Untuk pengobatan HBV amp HCV

ANTIRETROVIRAL ANTIRETROVIRAL AGENTSAGENTS

CURRENT ARV MEDICATIONSCURRENT ARV MEDICATIONS

NRTIbull Abacavir bull Didanosine bull Emtricitabine bull Lamivudine bull Stavudine bull Tenofovir bull Zidovudine

NNRTIbull Efavirenz bull Etravirine bull Nevirapine

PIbull Atazanavir bull Darunavir bull Fosamprenavir bull Indinavir bull Lopinavir bull Nelfinavirbull Ritonavir bull Saquinavir bull Tipranavir Fusion Inhibitorbull Enfuvirtide bull

Fixed-dose CombinationsbullZidovudine lamivudinebullZidovudinelamivudineabacavirbullAbacavirlamivudinebullEmtricitabinetenofovirbullEfavirenzemtricitabine tenofovir

DRUG MECHANISM amp VIRAL SELECTIVITY

CLINICAL USE

VIRAL RESISTANCE

UNDESIRABLE SIDE EFFECTS

PHARMACOKINETICS

NOTES

Zidovudine (AZT)

Thymidine analog is incorporated into DNA of human immunodeficiency viirus causing termination of the viral DNA chain

HIV Prevention of maternal-fetal transmission of HIV

Mutations in reverse transcriptase

Headaches nausea myalgias anemia neutropenia macrocytosis

PO Well absorbed rapidly metabolized by liver

Acetaminophen increases risk of hematologic toxicity

Didanosine (ddl)Zalcitabine (ddC)Lamivudine

-Metabolized intracellularly to dideoxynucleotide triphosphate that inhibits reverse transcriptase amp incorporates into viral DNA-Nucleotides fail to bind to ddATP bec it lacks free 3rsquo OH group

HIV Mutations in reverse transcriptase

Peripheral neuropathy pancreatitis diarrhea headache insomnia vomiting nausea rash abdominal pain

IVPO Partially metabolized in liver excreted in the urine Toxicity may be enhanced by renal or hepatic dysfunction

Limited utility as a single agent therapy because of viral resistance

Stavudine Metabolized to stavudine triphosphate wc inhibits HIV reverse transcriptase amp DNA polymerase Prevents DNA elongation

HIV Peripheral neuropathy

PO Not indicated for initial monotherapy of HIV

ANTIVIRAL DRUGS - RETROVIRUSES

RitonavirIndinavirSaquinavirNelfinavir

Inhibts HIV protease Results in immature virion

HIV Mutations in protease sequence reduce affinity of protease inhibitors

GI distress headache neurologic symptoms Indinavir associated w increase risk for kidney stones

PO Metabolized by P450 in liver Reduce dose in patients with liver disease Poor CNS penetration

Potentially serious drug interactions due to P450 competition

NevirapineDelavirdene

Nob-nucleoside inhibitor of HIV reverse transcriptase

HIV Never as monotherapy due to rapid development of resistance

Rapid resistance develops due to mutations in reverse transcriptase

Severe skin rash fever nausea headache

PO Well absorbed Nevirapine crosses placenta amp has better CNS penetration than Delavirdene

Delavirdene failed to show clinical efficacy when added to didanosine in clinical trial

• Obat antivirus
• Virus
• Struktur virus
• Klasifikasi virus
• PowerPoint Presentation
• Slide 6
• Slide 7
• Slide 8
• Obat anti virus
• Slide 10
• ANTI-HERPES ANTI VZV HSV = herpes simplex virus VZV = Varicella Zoster virus
• ACYCLOVIR
• Mekanisme kerja
• Farmakokinetik
• Penggunaan dalam terapi
• THERAPEUTIC USES
• Efek samping
• PENCICLOVIR
• MK
• Slide 20
• Slide 21
• Slide 22
• Slide 23
• ANTI-INFLUENZA
• AMANTADINRIMANTADIN
• FK
• Efek samping
• Penggunaan terapi
• ZANAMIVIROSELTAMIVIR
• Slide 30
• Slide 31
• ANTI-HEPATITIS
• ADEFOVIR
• INTERFERON
• ANTIRETROVIRAL AGENTS
• Slide 36
• CURRENT ARV MEDICATIONS
• Slide 38
• Slide 39
• Slide 40
• Slide 41

Tantangan terapi anti virus replikasi virus yang cepat menyebabkan

sulitnya mengembangkan anti virus yang efektif

Virus dapat bermutasi dengan cepat obat menjadi tidak efektif

Kesulitan obat menemukan virus tanpa mengganggu sel normal inang

10

ANTI-HERPES ANTI VZVANTI-HERPES ANTI VZV

HSV = herpes simplex virusHSV = herpes simplex virusVZV = Varicella Zoster virusVZV = Varicella Zoster virus

ACYCLOVIRACYCLOVIR

Aktif terhadap HSV1 HSV2 amp VZV Aktifitas lebih lemah terhadap EBV

(ebstein bar virus) CMV (cytomegalo virus)

Mekanisme kerjaMekanisme kerjaTiga tahap fosforilasi

FarmakokinetikFarmakokinetik BA oral 10-30 menurun dengan peningkatan

dosis BA relatif meningkat sampai 70 setelah

pemberian valasiklovir Terdistribusi luas pada cairan tubuh termasuk

cairan vesikuler dan CSF Terkonsentrasi di ASI cairan amnionik dan

plasenta Absorbsi perkutan rendah

Penggunaan dalam terapiPenggunaan dalam terapi

Herpes genital (awal dan kambuhan) ndash 200 mg 5xhari selama 10 hari ndash oralndash 5 mgkg per 8 jam ndash IVRecurrent 400 mg 2xhari atau 200 mg

3xhari

THERAPEUTIC USESTHERAPEUTIC USES

ACUTE HERPES ZOSTER (SHINGLES)SYSTEMIC ACYCLOVIR PROPHYLAXISHSV ENCEPHALITISVARICELLA ZOSTER VIRUS INFECTIONCMV PROPHYLAXIS

Efek sampingEfek samping

Sediaan topikal-iritasi mukosa dan rasa terbakar pada luka genital

ORAL ndash mual diare rash sakit kepala insufisiensi ginjal neurotoksisitas

IV- insufisiensi ginjal CNS

PENCICLOVIRPENCICLOVIR

Aktivitas dan potensi mirid dengan asiklovir terhadap HSV amp VZV

Aktif terhadap HBV (hepatiis B virus)

MKMK Menghambat sintesis DNA virus Awalnya difosforilasi oleh viral thymidine

kinase Penciclovir trifosfat merupakan inhibitor

kompetitif terhadap viral DNA polymerase Potensi 100 lebih rendah dibanding asiklovir

tapi berada pada konsentrasi yg lebih tinggi dan lebih lama dalam sel yang terinfeksi

Penggunaan dalam terapiPenggunaan dalam terapidosis 5 mgkg per 8-12 jam iv selama 7

hari seara dengan asiklovir utk infeksi mucocutaneous HSV

Sediaan Topical 1 penciclovir cream dioleskan tiap 2 jam 4 hari utk labial HSV

Efek sampingEfek samping

Mutagenik pada konsentrasi tinggi IO yang signifikan secara klinis tidak

teridentifikasi

DRUG MECHANISMVIRAL

SELECTIVITY

CLINICAL USE

VIRAL RESISTANCE

UNDESIRABLE SIDE EFFECTS

PHARMACOKINETICS

NOTES

Acylovir Metabolized by thymidine kinase to triphosphate

Herpes simplex 1 amp 2 varicella zoster

Produce abnormal thymidine kinase

Skin irritation burning crystalline nephropathy

IVPO Administer slowly CNS level=50 serum level Decrease dose w kidney dysfunction

Pencyclovir Oral HSV (coldsores)

Topical

Valacyclovir L-valyl ester of acyclovir converted to acyclovir

Herpes zoster (shingles)

Nausea headache PO Slightly better oral absorption than acyclovir

No clear advantage over acyclovir

Idoxuridine Phosphorylated metabolite incorporates into DNA causing strand breaks

Herpes simplex keratitis No effect on RNA viruses

Resistance develops

Photophobia irritation of conjunctiva amp eyelid

Eyedrops Drug is a halogenated derivative of deoxyuridine

Famciclovir Phosphorylated by viral thymidine kinase to penciclovir triiphosphate

Shortens duration of herpes zoster amp genital herpes

Minimal toxicity Headache

PO Decrease dose with renal dysfunction

Ganciclovir Metabolized by thymidine kinase to triphosphate Preferentially phosphorylated to active drug in CMV infected cells

CMV retinitis amp severe systemic CMV infections

Some resistant strains lack thymidine kinase Cannot activate drug

Granulocytopenia thrombocytopenia

IVPO Excreted unchanged in urine Decrease dose with renal dysfunction

Do not coadminister zidovudine (granulocytopenia) or imipenem-cilastatin (seizures)

ANTIVIRAL DRUGS ndash DNA amp RNA VIRUSES

Cidofovir Metabolized to diphosphate form Otherwise like ganciclovir

CMV retinitis Nephrotoxicity may be reduced by hydration amp coadministration of Probenicid Neutropenia

Foscarnet Analog of pyrophosphate Competes for pyrophosphate site in viral but not human DNA polymerase amp reverse transcriptase

CMV retinitis Does not need phosphorylation it is active against thymidine kinase ndashdeficient strains

Renal toxicity seizures hypocalcemia fever anemia diarrhea nausea

IV gt80 excreted unchanged in the urine CSF penetration variable Reduce dose with renal dysfunction

Deposited in bone amp teeth Hydrate patient during therapy to protect the kidney

Amantadine Prevents virus from entering susceptible cells

Treatment amp prophylaxis of influenza A

Depression CNS toxicity CHF orthostatic hypotension urinary retention

PO Excreted unmetabolized

Rimantadine Analog of amantadine inhibits viral uncoating

Prophylaxis in children

Fewer CNS side effects risk of seizure

PO Prolonged elimination w renal or hepatic dysfunction

Ribavirin Unknown mechanism

RSV Decreased pulmonary function

Aerosol administration Absorbed systemically

May precipitate in ventilator tubing

ANTI-INFLUENZAANTI-INFLUENZA

AMANTADINRIMANTADINAMANTADINRIMANTADIN Menghambat proses uncoating virus RNA

influenza A di dalam cell inang mencegah replikasi

Efektif menurunkan durasi gejala influenza jika diberikan dalam 48 jam setelah onset

FKFK

Absorpsi oral baikEkskresi dalam bentuk tak termetabolisme

di urinAmantadin dapat diekskresikan lewat ASI

Efek sampingEfek samping

Umum gangguan GI dan CNS minor (gugup light headanche susah konsentrasi insomnia mual nafsu makan berkurang)

Amantadin konsentrasi tinggi di plasma reaksi neurotoksik serius delirium kejang koma aritmia

Penggunaan terapiPenggunaan terapi

Pencegahan dan pengobatan influenza A 200 mghari dalam 1 atau 2 dosis

(pengobatan)Pencegahan harus dimulai ketika mulai

teridentifikasi pandemi virus 100mghari (4 ndash 8 minggu)

ZANAMIVIROSELTAMIVIRZANAMIVIROSELTAMIVIRPenghambat Neuroaminidase Menghambat replikasi influenza A amp B

FKFK

Diserap dengan cepat setelah pemberian oral (BA 80)

Eliminasi di ginjal dalam bentuk tak berubah

Berinterkasi dengan probenecid (meningkatkan T12 ndash 2x)

Efek sampingEfek samping

Mual rasa tak nyaman di lambung muntah lokal iritasi

Konsentrasi yang sangat tinggi berhungan dengan kematian (tikus)

ANTI-HEPATITISANTI-HEPATITIS

ADEFOVIRADEFOVIRSecara kompetitif menghambat HBV

DNA polymeraseMenghambat sintesis DNAEfek samping nefrotoksik pusing

diare ganggian abdomen)Pengobaan infeksi HBV kronis 10 mghari

INTERFERONINTERFERON Protein endogen yang dihasilkan dan dilepaskan

oleh sel sebagai respon terhadap patogen Menginduksi enzim menekan proliferasi aktivitas

imunomodulator dan menghambat replikasi virus Menghambat penetrasi dan amp uncoating Untuk pengobatan HBV amp HCV

ANTIRETROVIRAL ANTIRETROVIRAL AGENTSAGENTS

CURRENT ARV MEDICATIONSCURRENT ARV MEDICATIONS

NRTIbull Abacavir bull Didanosine bull Emtricitabine bull Lamivudine bull Stavudine bull Tenofovir bull Zidovudine

NNRTIbull Efavirenz bull Etravirine bull Nevirapine

PIbull Atazanavir bull Darunavir bull Fosamprenavir bull Indinavir bull Lopinavir bull Nelfinavirbull Ritonavir bull Saquinavir bull Tipranavir Fusion Inhibitorbull Enfuvirtide bull

Fixed-dose CombinationsbullZidovudine lamivudinebullZidovudinelamivudineabacavirbullAbacavirlamivudinebullEmtricitabinetenofovirbullEfavirenzemtricitabine tenofovir

DRUG MECHANISM amp VIRAL SELECTIVITY

CLINICAL USE

VIRAL RESISTANCE

UNDESIRABLE SIDE EFFECTS

PHARMACOKINETICS

NOTES

Zidovudine (AZT)

Thymidine analog is incorporated into DNA of human immunodeficiency viirus causing termination of the viral DNA chain

HIV Prevention of maternal-fetal transmission of HIV

Mutations in reverse transcriptase

Headaches nausea myalgias anemia neutropenia macrocytosis

PO Well absorbed rapidly metabolized by liver

Acetaminophen increases risk of hematologic toxicity

Didanosine (ddl)Zalcitabine (ddC)Lamivudine

-Metabolized intracellularly to dideoxynucleotide triphosphate that inhibits reverse transcriptase amp incorporates into viral DNA-Nucleotides fail to bind to ddATP bec it lacks free 3rsquo OH group

HIV Mutations in reverse transcriptase

Peripheral neuropathy pancreatitis diarrhea headache insomnia vomiting nausea rash abdominal pain

IVPO Partially metabolized in liver excreted in the urine Toxicity may be enhanced by renal or hepatic dysfunction

Limited utility as a single agent therapy because of viral resistance

Stavudine Metabolized to stavudine triphosphate wc inhibits HIV reverse transcriptase amp DNA polymerase Prevents DNA elongation

HIV Peripheral neuropathy

PO Not indicated for initial monotherapy of HIV

ANTIVIRAL DRUGS - RETROVIRUSES

RitonavirIndinavirSaquinavirNelfinavir

Inhibts HIV protease Results in immature virion

HIV Mutations in protease sequence reduce affinity of protease inhibitors

GI distress headache neurologic symptoms Indinavir associated w increase risk for kidney stones

PO Metabolized by P450 in liver Reduce dose in patients with liver disease Poor CNS penetration

Potentially serious drug interactions due to P450 competition

NevirapineDelavirdene

Nob-nucleoside inhibitor of HIV reverse transcriptase

HIV Never as monotherapy due to rapid development of resistance

Rapid resistance develops due to mutations in reverse transcriptase

Severe skin rash fever nausea headache

PO Well absorbed Nevirapine crosses placenta amp has better CNS penetration than Delavirdene

Delavirdene failed to show clinical efficacy when added to didanosine in clinical trial

• Obat antivirus
• Virus
• Struktur virus
• Klasifikasi virus
• PowerPoint Presentation
• Slide 6
• Slide 7
• Slide 8
• Obat anti virus
• Slide 10
• ANTI-HERPES ANTI VZV HSV = herpes simplex virus VZV = Varicella Zoster virus
• ACYCLOVIR
• Mekanisme kerja
• Farmakokinetik
• Penggunaan dalam terapi
• THERAPEUTIC USES
• Efek samping
• PENCICLOVIR
• MK
• Slide 20
• Slide 21
• Slide 22
• Slide 23
• ANTI-INFLUENZA
• AMANTADINRIMANTADIN
• FK
• Efek samping
• Penggunaan terapi
• ZANAMIVIROSELTAMIVIR
• Slide 30
• Slide 31
• ANTI-HEPATITIS
• ADEFOVIR
• INTERFERON
• ANTIRETROVIRAL AGENTS
• Slide 36
• CURRENT ARV MEDICATIONS
• Slide 38
• Slide 39
• Slide 40
• Slide 41

ANTI-HERPES ANTI VZVANTI-HERPES ANTI VZV

HSV = herpes simplex virusHSV = herpes simplex virusVZV = Varicella Zoster virusVZV = Varicella Zoster virus

ACYCLOVIRACYCLOVIR

Aktif terhadap HSV1 HSV2 amp VZV Aktifitas lebih lemah terhadap EBV

(ebstein bar virus) CMV (cytomegalo virus)

Mekanisme kerjaMekanisme kerjaTiga tahap fosforilasi

FarmakokinetikFarmakokinetik BA oral 10-30 menurun dengan peningkatan

dosis BA relatif meningkat sampai 70 setelah

pemberian valasiklovir Terdistribusi luas pada cairan tubuh termasuk

cairan vesikuler dan CSF Terkonsentrasi di ASI cairan amnionik dan

plasenta Absorbsi perkutan rendah

Penggunaan dalam terapiPenggunaan dalam terapi

Herpes genital (awal dan kambuhan) ndash 200 mg 5xhari selama 10 hari ndash oralndash 5 mgkg per 8 jam ndash IVRecurrent 400 mg 2xhari atau 200 mg

3xhari

THERAPEUTIC USESTHERAPEUTIC USES

ACUTE HERPES ZOSTER (SHINGLES)SYSTEMIC ACYCLOVIR PROPHYLAXISHSV ENCEPHALITISVARICELLA ZOSTER VIRUS INFECTIONCMV PROPHYLAXIS

Efek sampingEfek samping

Sediaan topikal-iritasi mukosa dan rasa terbakar pada luka genital

ORAL ndash mual diare rash sakit kepala insufisiensi ginjal neurotoksisitas

IV- insufisiensi ginjal CNS

PENCICLOVIRPENCICLOVIR

Aktivitas dan potensi mirid dengan asiklovir terhadap HSV amp VZV

Aktif terhadap HBV (hepatiis B virus)

MKMK Menghambat sintesis DNA virus Awalnya difosforilasi oleh viral thymidine

kinase Penciclovir trifosfat merupakan inhibitor

kompetitif terhadap viral DNA polymerase Potensi 100 lebih rendah dibanding asiklovir

tapi berada pada konsentrasi yg lebih tinggi dan lebih lama dalam sel yang terinfeksi

Penggunaan dalam terapiPenggunaan dalam terapidosis 5 mgkg per 8-12 jam iv selama 7

hari seara dengan asiklovir utk infeksi mucocutaneous HSV

Sediaan Topical 1 penciclovir cream dioleskan tiap 2 jam 4 hari utk labial HSV

Efek sampingEfek samping

Mutagenik pada konsentrasi tinggi IO yang signifikan secara klinis tidak

teridentifikasi

DRUG MECHANISMVIRAL

SELECTIVITY

CLINICAL USE

VIRAL RESISTANCE

UNDESIRABLE SIDE EFFECTS

PHARMACOKINETICS

NOTES

Acylovir Metabolized by thymidine kinase to triphosphate

Herpes simplex 1 amp 2 varicella zoster

Produce abnormal thymidine kinase

Skin irritation burning crystalline nephropathy

IVPO Administer slowly CNS level=50 serum level Decrease dose w kidney dysfunction

Pencyclovir Oral HSV (coldsores)

Topical

Valacyclovir L-valyl ester of acyclovir converted to acyclovir

Herpes zoster (shingles)

Nausea headache PO Slightly better oral absorption than acyclovir

No clear advantage over acyclovir

Idoxuridine Phosphorylated metabolite incorporates into DNA causing strand breaks

Herpes simplex keratitis No effect on RNA viruses

Resistance develops

Photophobia irritation of conjunctiva amp eyelid

Eyedrops Drug is a halogenated derivative of deoxyuridine

Famciclovir Phosphorylated by viral thymidine kinase to penciclovir triiphosphate

Shortens duration of herpes zoster amp genital herpes

Minimal toxicity Headache

PO Decrease dose with renal dysfunction

Ganciclovir Metabolized by thymidine kinase to triphosphate Preferentially phosphorylated to active drug in CMV infected cells

CMV retinitis amp severe systemic CMV infections

Some resistant strains lack thymidine kinase Cannot activate drug

Granulocytopenia thrombocytopenia

IVPO Excreted unchanged in urine Decrease dose with renal dysfunction

Do not coadminister zidovudine (granulocytopenia) or imipenem-cilastatin (seizures)

ANTIVIRAL DRUGS ndash DNA amp RNA VIRUSES

Cidofovir Metabolized to diphosphate form Otherwise like ganciclovir

CMV retinitis Nephrotoxicity may be reduced by hydration amp coadministration of Probenicid Neutropenia

Foscarnet Analog of pyrophosphate Competes for pyrophosphate site in viral but not human DNA polymerase amp reverse transcriptase

CMV retinitis Does not need phosphorylation it is active against thymidine kinase ndashdeficient strains

Renal toxicity seizures hypocalcemia fever anemia diarrhea nausea

IV gt80 excreted unchanged in the urine CSF penetration variable Reduce dose with renal dysfunction

Deposited in bone amp teeth Hydrate patient during therapy to protect the kidney

Amantadine Prevents virus from entering susceptible cells

Treatment amp prophylaxis of influenza A

Depression CNS toxicity CHF orthostatic hypotension urinary retention

PO Excreted unmetabolized

Rimantadine Analog of amantadine inhibits viral uncoating

Prophylaxis in children

Fewer CNS side effects risk of seizure

PO Prolonged elimination w renal or hepatic dysfunction

Ribavirin Unknown mechanism

RSV Decreased pulmonary function

Aerosol administration Absorbed systemically

May precipitate in ventilator tubing

ANTI-INFLUENZAANTI-INFLUENZA

AMANTADINRIMANTADINAMANTADINRIMANTADIN Menghambat proses uncoating virus RNA

influenza A di dalam cell inang mencegah replikasi

Efektif menurunkan durasi gejala influenza jika diberikan dalam 48 jam setelah onset

FKFK

Absorpsi oral baikEkskresi dalam bentuk tak termetabolisme

di urinAmantadin dapat diekskresikan lewat ASI

Efek sampingEfek samping

Umum gangguan GI dan CNS minor (gugup light headanche susah konsentrasi insomnia mual nafsu makan berkurang)

Amantadin konsentrasi tinggi di plasma reaksi neurotoksik serius delirium kejang koma aritmia

Penggunaan terapiPenggunaan terapi

Pencegahan dan pengobatan influenza A 200 mghari dalam 1 atau 2 dosis

(pengobatan)Pencegahan harus dimulai ketika mulai

teridentifikasi pandemi virus 100mghari (4 ndash 8 minggu)

ZANAMIVIROSELTAMIVIRZANAMIVIROSELTAMIVIRPenghambat Neuroaminidase Menghambat replikasi influenza A amp B

FKFK

Diserap dengan cepat setelah pemberian oral (BA 80)

Eliminasi di ginjal dalam bentuk tak berubah

Berinterkasi dengan probenecid (meningkatkan T12 ndash 2x)

Efek sampingEfek samping

Mual rasa tak nyaman di lambung muntah lokal iritasi

Konsentrasi yang sangat tinggi berhungan dengan kematian (tikus)

ANTI-HEPATITISANTI-HEPATITIS

ADEFOVIRADEFOVIRSecara kompetitif menghambat HBV

DNA polymeraseMenghambat sintesis DNAEfek samping nefrotoksik pusing

diare ganggian abdomen)Pengobaan infeksi HBV kronis 10 mghari

INTERFERONINTERFERON Protein endogen yang dihasilkan dan dilepaskan

oleh sel sebagai respon terhadap patogen Menginduksi enzim menekan proliferasi aktivitas

imunomodulator dan menghambat replikasi virus Menghambat penetrasi dan amp uncoating Untuk pengobatan HBV amp HCV

ANTIRETROVIRAL ANTIRETROVIRAL AGENTSAGENTS

CURRENT ARV MEDICATIONSCURRENT ARV MEDICATIONS

NRTIbull Abacavir bull Didanosine bull Emtricitabine bull Lamivudine bull Stavudine bull Tenofovir bull Zidovudine

NNRTIbull Efavirenz bull Etravirine bull Nevirapine

PIbull Atazanavir bull Darunavir bull Fosamprenavir bull Indinavir bull Lopinavir bull Nelfinavirbull Ritonavir bull Saquinavir bull Tipranavir Fusion Inhibitorbull Enfuvirtide bull

Fixed-dose CombinationsbullZidovudine lamivudinebullZidovudinelamivudineabacavirbullAbacavirlamivudinebullEmtricitabinetenofovirbullEfavirenzemtricitabine tenofovir

DRUG MECHANISM amp VIRAL SELECTIVITY

CLINICAL USE

VIRAL RESISTANCE

UNDESIRABLE SIDE EFFECTS

PHARMACOKINETICS

NOTES

Zidovudine (AZT)

Thymidine analog is incorporated into DNA of human immunodeficiency viirus causing termination of the viral DNA chain

HIV Prevention of maternal-fetal transmission of HIV

Mutations in reverse transcriptase

Headaches nausea myalgias anemia neutropenia macrocytosis

PO Well absorbed rapidly metabolized by liver

Acetaminophen increases risk of hematologic toxicity

Didanosine (ddl)Zalcitabine (ddC)Lamivudine

-Metabolized intracellularly to dideoxynucleotide triphosphate that inhibits reverse transcriptase amp incorporates into viral DNA-Nucleotides fail to bind to ddATP bec it lacks free 3rsquo OH group

HIV Mutations in reverse transcriptase

Peripheral neuropathy pancreatitis diarrhea headache insomnia vomiting nausea rash abdominal pain

IVPO Partially metabolized in liver excreted in the urine Toxicity may be enhanced by renal or hepatic dysfunction

Limited utility as a single agent therapy because of viral resistance

Stavudine Metabolized to stavudine triphosphate wc inhibits HIV reverse transcriptase amp DNA polymerase Prevents DNA elongation

HIV Peripheral neuropathy

PO Not indicated for initial monotherapy of HIV

ANTIVIRAL DRUGS - RETROVIRUSES

RitonavirIndinavirSaquinavirNelfinavir

Inhibts HIV protease Results in immature virion

HIV Mutations in protease sequence reduce affinity of protease inhibitors

GI distress headache neurologic symptoms Indinavir associated w increase risk for kidney stones

PO Metabolized by P450 in liver Reduce dose in patients with liver disease Poor CNS penetration

Potentially serious drug interactions due to P450 competition

NevirapineDelavirdene

Nob-nucleoside inhibitor of HIV reverse transcriptase

HIV Never as monotherapy due to rapid development of resistance

Rapid resistance develops due to mutations in reverse transcriptase

Severe skin rash fever nausea headache

PO Well absorbed Nevirapine crosses placenta amp has better CNS penetration than Delavirdene

Delavirdene failed to show clinical efficacy when added to didanosine in clinical trial

• Obat antivirus
• Virus
• Struktur virus
• Klasifikasi virus
• PowerPoint Presentation
• Slide 6
• Slide 7
• Slide 8
• Obat anti virus
• Slide 10
• ANTI-HERPES ANTI VZV HSV = herpes simplex virus VZV = Varicella Zoster virus
• ACYCLOVIR
• Mekanisme kerja
• Farmakokinetik
• Penggunaan dalam terapi
• THERAPEUTIC USES
• Efek samping
• PENCICLOVIR
• MK
• Slide 20
• Slide 21
• Slide 22
• Slide 23
• ANTI-INFLUENZA
• AMANTADINRIMANTADIN
• FK
• Efek samping
• Penggunaan terapi
• ZANAMIVIROSELTAMIVIR
• Slide 30
• Slide 31
• ANTI-HEPATITIS
• ADEFOVIR
• INTERFERON
• ANTIRETROVIRAL AGENTS
• Slide 36
• CURRENT ARV MEDICATIONS
• Slide 38
• Slide 39
• Slide 40
• Slide 41

ACYCLOVIRACYCLOVIR

Aktif terhadap HSV1 HSV2 amp VZV Aktifitas lebih lemah terhadap EBV

(ebstein bar virus) CMV (cytomegalo virus)

Mekanisme kerjaMekanisme kerjaTiga tahap fosforilasi

FarmakokinetikFarmakokinetik BA oral 10-30 menurun dengan peningkatan

dosis BA relatif meningkat sampai 70 setelah

pemberian valasiklovir Terdistribusi luas pada cairan tubuh termasuk

cairan vesikuler dan CSF Terkonsentrasi di ASI cairan amnionik dan

plasenta Absorbsi perkutan rendah

Penggunaan dalam terapiPenggunaan dalam terapi

Herpes genital (awal dan kambuhan) ndash 200 mg 5xhari selama 10 hari ndash oralndash 5 mgkg per 8 jam ndash IVRecurrent 400 mg 2xhari atau 200 mg

3xhari

THERAPEUTIC USESTHERAPEUTIC USES

ACUTE HERPES ZOSTER (SHINGLES)SYSTEMIC ACYCLOVIR PROPHYLAXISHSV ENCEPHALITISVARICELLA ZOSTER VIRUS INFECTIONCMV PROPHYLAXIS

Efek sampingEfek samping

Sediaan topikal-iritasi mukosa dan rasa terbakar pada luka genital

ORAL ndash mual diare rash sakit kepala insufisiensi ginjal neurotoksisitas

IV- insufisiensi ginjal CNS

PENCICLOVIRPENCICLOVIR

Aktivitas dan potensi mirid dengan asiklovir terhadap HSV amp VZV

Aktif terhadap HBV (hepatiis B virus)

MKMK Menghambat sintesis DNA virus Awalnya difosforilasi oleh viral thymidine

kinase Penciclovir trifosfat merupakan inhibitor

kompetitif terhadap viral DNA polymerase Potensi 100 lebih rendah dibanding asiklovir

tapi berada pada konsentrasi yg lebih tinggi dan lebih lama dalam sel yang terinfeksi

Penggunaan dalam terapiPenggunaan dalam terapidosis 5 mgkg per 8-12 jam iv selama 7

hari seara dengan asiklovir utk infeksi mucocutaneous HSV

Sediaan Topical 1 penciclovir cream dioleskan tiap 2 jam 4 hari utk labial HSV

Efek sampingEfek samping

Mutagenik pada konsentrasi tinggi IO yang signifikan secara klinis tidak

teridentifikasi

DRUG MECHANISMVIRAL

SELECTIVITY

CLINICAL USE

VIRAL RESISTANCE

UNDESIRABLE SIDE EFFECTS

PHARMACOKINETICS

NOTES

Acylovir Metabolized by thymidine kinase to triphosphate

Herpes simplex 1 amp 2 varicella zoster

Produce abnormal thymidine kinase

Skin irritation burning crystalline nephropathy

IVPO Administer slowly CNS level=50 serum level Decrease dose w kidney dysfunction

Pencyclovir Oral HSV (coldsores)

Topical

Valacyclovir L-valyl ester of acyclovir converted to acyclovir

Herpes zoster (shingles)

Nausea headache PO Slightly better oral absorption than acyclovir

No clear advantage over acyclovir

Idoxuridine Phosphorylated metabolite incorporates into DNA causing strand breaks

Herpes simplex keratitis No effect on RNA viruses

Resistance develops

Photophobia irritation of conjunctiva amp eyelid

Eyedrops Drug is a halogenated derivative of deoxyuridine

Famciclovir Phosphorylated by viral thymidine kinase to penciclovir triiphosphate

Shortens duration of herpes zoster amp genital herpes

Minimal toxicity Headache

PO Decrease dose with renal dysfunction

Ganciclovir Metabolized by thymidine kinase to triphosphate Preferentially phosphorylated to active drug in CMV infected cells

CMV retinitis amp severe systemic CMV infections

Some resistant strains lack thymidine kinase Cannot activate drug

Granulocytopenia thrombocytopenia

IVPO Excreted unchanged in urine Decrease dose with renal dysfunction

Do not coadminister zidovudine (granulocytopenia) or imipenem-cilastatin (seizures)

ANTIVIRAL DRUGS ndash DNA amp RNA VIRUSES

Cidofovir Metabolized to diphosphate form Otherwise like ganciclovir

CMV retinitis Nephrotoxicity may be reduced by hydration amp coadministration of Probenicid Neutropenia

Foscarnet Analog of pyrophosphate Competes for pyrophosphate site in viral but not human DNA polymerase amp reverse transcriptase

CMV retinitis Does not need phosphorylation it is active against thymidine kinase ndashdeficient strains

Renal toxicity seizures hypocalcemia fever anemia diarrhea nausea

IV gt80 excreted unchanged in the urine CSF penetration variable Reduce dose with renal dysfunction

Deposited in bone amp teeth Hydrate patient during therapy to protect the kidney

Amantadine Prevents virus from entering susceptible cells

Treatment amp prophylaxis of influenza A

Depression CNS toxicity CHF orthostatic hypotension urinary retention

PO Excreted unmetabolized

Rimantadine Analog of amantadine inhibits viral uncoating

Prophylaxis in children

Fewer CNS side effects risk of seizure

PO Prolonged elimination w renal or hepatic dysfunction

Ribavirin Unknown mechanism

RSV Decreased pulmonary function

Aerosol administration Absorbed systemically

May precipitate in ventilator tubing

ANTI-INFLUENZAANTI-INFLUENZA

AMANTADINRIMANTADINAMANTADINRIMANTADIN Menghambat proses uncoating virus RNA

influenza A di dalam cell inang mencegah replikasi

Efektif menurunkan durasi gejala influenza jika diberikan dalam 48 jam setelah onset

FKFK

Absorpsi oral baikEkskresi dalam bentuk tak termetabolisme

di urinAmantadin dapat diekskresikan lewat ASI

Efek sampingEfek samping

Umum gangguan GI dan CNS minor (gugup light headanche susah konsentrasi insomnia mual nafsu makan berkurang)

Amantadin konsentrasi tinggi di plasma reaksi neurotoksik serius delirium kejang koma aritmia

Penggunaan terapiPenggunaan terapi

Pencegahan dan pengobatan influenza A 200 mghari dalam 1 atau 2 dosis

(pengobatan)Pencegahan harus dimulai ketika mulai

teridentifikasi pandemi virus 100mghari (4 ndash 8 minggu)

ZANAMIVIROSELTAMIVIRZANAMIVIROSELTAMIVIRPenghambat Neuroaminidase Menghambat replikasi influenza A amp B

FKFK

Diserap dengan cepat setelah pemberian oral (BA 80)

Eliminasi di ginjal dalam bentuk tak berubah

Berinterkasi dengan probenecid (meningkatkan T12 ndash 2x)

Efek sampingEfek samping

Mual rasa tak nyaman di lambung muntah lokal iritasi

Konsentrasi yang sangat tinggi berhungan dengan kematian (tikus)

ANTI-HEPATITISANTI-HEPATITIS

ADEFOVIRADEFOVIRSecara kompetitif menghambat HBV

DNA polymeraseMenghambat sintesis DNAEfek samping nefrotoksik pusing

diare ganggian abdomen)Pengobaan infeksi HBV kronis 10 mghari

INTERFERONINTERFERON Protein endogen yang dihasilkan dan dilepaskan

oleh sel sebagai respon terhadap patogen Menginduksi enzim menekan proliferasi aktivitas

imunomodulator dan menghambat replikasi virus Menghambat penetrasi dan amp uncoating Untuk pengobatan HBV amp HCV

ANTIRETROVIRAL ANTIRETROVIRAL AGENTSAGENTS

CURRENT ARV MEDICATIONSCURRENT ARV MEDICATIONS

NRTIbull Abacavir bull Didanosine bull Emtricitabine bull Lamivudine bull Stavudine bull Tenofovir bull Zidovudine

NNRTIbull Efavirenz bull Etravirine bull Nevirapine

PIbull Atazanavir bull Darunavir bull Fosamprenavir bull Indinavir bull Lopinavir bull Nelfinavirbull Ritonavir bull Saquinavir bull Tipranavir Fusion Inhibitorbull Enfuvirtide bull

Fixed-dose CombinationsbullZidovudine lamivudinebullZidovudinelamivudineabacavirbullAbacavirlamivudinebullEmtricitabinetenofovirbullEfavirenzemtricitabine tenofovir

DRUG MECHANISM amp VIRAL SELECTIVITY

CLINICAL USE

VIRAL RESISTANCE

UNDESIRABLE SIDE EFFECTS

PHARMACOKINETICS

NOTES

Zidovudine (AZT)

Thymidine analog is incorporated into DNA of human immunodeficiency viirus causing termination of the viral DNA chain

HIV Prevention of maternal-fetal transmission of HIV

Mutations in reverse transcriptase

Headaches nausea myalgias anemia neutropenia macrocytosis

PO Well absorbed rapidly metabolized by liver

Acetaminophen increases risk of hematologic toxicity

Didanosine (ddl)Zalcitabine (ddC)Lamivudine

-Metabolized intracellularly to dideoxynucleotide triphosphate that inhibits reverse transcriptase amp incorporates into viral DNA-Nucleotides fail to bind to ddATP bec it lacks free 3rsquo OH group

HIV Mutations in reverse transcriptase

Peripheral neuropathy pancreatitis diarrhea headache insomnia vomiting nausea rash abdominal pain

IVPO Partially metabolized in liver excreted in the urine Toxicity may be enhanced by renal or hepatic dysfunction

Limited utility as a single agent therapy because of viral resistance

Stavudine Metabolized to stavudine triphosphate wc inhibits HIV reverse transcriptase amp DNA polymerase Prevents DNA elongation

HIV Peripheral neuropathy

PO Not indicated for initial monotherapy of HIV

ANTIVIRAL DRUGS - RETROVIRUSES

RitonavirIndinavirSaquinavirNelfinavir

Inhibts HIV protease Results in immature virion

HIV Mutations in protease sequence reduce affinity of protease inhibitors

GI distress headache neurologic symptoms Indinavir associated w increase risk for kidney stones

PO Metabolized by P450 in liver Reduce dose in patients with liver disease Poor CNS penetration

Potentially serious drug interactions due to P450 competition

NevirapineDelavirdene

Nob-nucleoside inhibitor of HIV reverse transcriptase

HIV Never as monotherapy due to rapid development of resistance

Rapid resistance develops due to mutations in reverse transcriptase

Severe skin rash fever nausea headache

PO Well absorbed Nevirapine crosses placenta amp has better CNS penetration than Delavirdene

Delavirdene failed to show clinical efficacy when added to didanosine in clinical trial

• Obat antivirus
• Virus
• Struktur virus
• Klasifikasi virus
• PowerPoint Presentation
• Slide 6
• Slide 7
• Slide 8
• Obat anti virus
• Slide 10
• ANTI-HERPES ANTI VZV HSV = herpes simplex virus VZV = Varicella Zoster virus
• ACYCLOVIR
• Mekanisme kerja
• Farmakokinetik
• Penggunaan dalam terapi
• THERAPEUTIC USES
• Efek samping
• PENCICLOVIR
• MK
• Slide 20
• Slide 21
• Slide 22
• Slide 23
• ANTI-INFLUENZA
• AMANTADINRIMANTADIN
• FK
• Efek samping
• Penggunaan terapi
• ZANAMIVIROSELTAMIVIR
• Slide 30
• Slide 31
• ANTI-HEPATITIS
• ADEFOVIR
• INTERFERON
• ANTIRETROVIRAL AGENTS
• Slide 36
• CURRENT ARV MEDICATIONS
• Slide 38
• Slide 39
• Slide 40
• Slide 41

Mekanisme kerjaMekanisme kerjaTiga tahap fosforilasi

FarmakokinetikFarmakokinetik BA oral 10-30 menurun dengan peningkatan

dosis BA relatif meningkat sampai 70 setelah

pemberian valasiklovir Terdistribusi luas pada cairan tubuh termasuk

cairan vesikuler dan CSF Terkonsentrasi di ASI cairan amnionik dan

plasenta Absorbsi perkutan rendah

Penggunaan dalam terapiPenggunaan dalam terapi

Herpes genital (awal dan kambuhan) ndash 200 mg 5xhari selama 10 hari ndash oralndash 5 mgkg per 8 jam ndash IVRecurrent 400 mg 2xhari atau 200 mg

3xhari

THERAPEUTIC USESTHERAPEUTIC USES

ACUTE HERPES ZOSTER (SHINGLES)SYSTEMIC ACYCLOVIR PROPHYLAXISHSV ENCEPHALITISVARICELLA ZOSTER VIRUS INFECTIONCMV PROPHYLAXIS

Efek sampingEfek samping

Sediaan topikal-iritasi mukosa dan rasa terbakar pada luka genital

ORAL ndash mual diare rash sakit kepala insufisiensi ginjal neurotoksisitas

IV- insufisiensi ginjal CNS

PENCICLOVIRPENCICLOVIR

Aktivitas dan potensi mirid dengan asiklovir terhadap HSV amp VZV

Aktif terhadap HBV (hepatiis B virus)

MKMK Menghambat sintesis DNA virus Awalnya difosforilasi oleh viral thymidine

kinase Penciclovir trifosfat merupakan inhibitor

kompetitif terhadap viral DNA polymerase Potensi 100 lebih rendah dibanding asiklovir

tapi berada pada konsentrasi yg lebih tinggi dan lebih lama dalam sel yang terinfeksi

Penggunaan dalam terapiPenggunaan dalam terapidosis 5 mgkg per 8-12 jam iv selama 7

hari seara dengan asiklovir utk infeksi mucocutaneous HSV

Sediaan Topical 1 penciclovir cream dioleskan tiap 2 jam 4 hari utk labial HSV

Efek sampingEfek samping

Mutagenik pada konsentrasi tinggi IO yang signifikan secara klinis tidak

teridentifikasi

DRUG MECHANISMVIRAL

SELECTIVITY

CLINICAL USE

VIRAL RESISTANCE

UNDESIRABLE SIDE EFFECTS

PHARMACOKINETICS

NOTES

Acylovir Metabolized by thymidine kinase to triphosphate

Herpes simplex 1 amp 2 varicella zoster

Produce abnormal thymidine kinase

Skin irritation burning crystalline nephropathy

IVPO Administer slowly CNS level=50 serum level Decrease dose w kidney dysfunction

Pencyclovir Oral HSV (coldsores)

Topical

Valacyclovir L-valyl ester of acyclovir converted to acyclovir

Herpes zoster (shingles)

Nausea headache PO Slightly better oral absorption than acyclovir

No clear advantage over acyclovir

Idoxuridine Phosphorylated metabolite incorporates into DNA causing strand breaks

Herpes simplex keratitis No effect on RNA viruses

Resistance develops

Photophobia irritation of conjunctiva amp eyelid

Eyedrops Drug is a halogenated derivative of deoxyuridine

Famciclovir Phosphorylated by viral thymidine kinase to penciclovir triiphosphate

Shortens duration of herpes zoster amp genital herpes

Minimal toxicity Headache

PO Decrease dose with renal dysfunction

Ganciclovir Metabolized by thymidine kinase to triphosphate Preferentially phosphorylated to active drug in CMV infected cells

CMV retinitis amp severe systemic CMV infections

Some resistant strains lack thymidine kinase Cannot activate drug

Granulocytopenia thrombocytopenia

IVPO Excreted unchanged in urine Decrease dose with renal dysfunction

Do not coadminister zidovudine (granulocytopenia) or imipenem-cilastatin (seizures)

ANTIVIRAL DRUGS ndash DNA amp RNA VIRUSES

Cidofovir Metabolized to diphosphate form Otherwise like ganciclovir

CMV retinitis Nephrotoxicity may be reduced by hydration amp coadministration of Probenicid Neutropenia

Foscarnet Analog of pyrophosphate Competes for pyrophosphate site in viral but not human DNA polymerase amp reverse transcriptase

CMV retinitis Does not need phosphorylation it is active against thymidine kinase ndashdeficient strains

Renal toxicity seizures hypocalcemia fever anemia diarrhea nausea

IV gt80 excreted unchanged in the urine CSF penetration variable Reduce dose with renal dysfunction

Deposited in bone amp teeth Hydrate patient during therapy to protect the kidney

Amantadine Prevents virus from entering susceptible cells

Treatment amp prophylaxis of influenza A

Depression CNS toxicity CHF orthostatic hypotension urinary retention

PO Excreted unmetabolized

Rimantadine Analog of amantadine inhibits viral uncoating

Prophylaxis in children

Fewer CNS side effects risk of seizure

PO Prolonged elimination w renal or hepatic dysfunction

Ribavirin Unknown mechanism

RSV Decreased pulmonary function

Aerosol administration Absorbed systemically

May precipitate in ventilator tubing

ANTI-INFLUENZAANTI-INFLUENZA

AMANTADINRIMANTADINAMANTADINRIMANTADIN Menghambat proses uncoating virus RNA

influenza A di dalam cell inang mencegah replikasi

Efektif menurunkan durasi gejala influenza jika diberikan dalam 48 jam setelah onset

FKFK

Absorpsi oral baikEkskresi dalam bentuk tak termetabolisme

di urinAmantadin dapat diekskresikan lewat ASI

Efek sampingEfek samping

Umum gangguan GI dan CNS minor (gugup light headanche susah konsentrasi insomnia mual nafsu makan berkurang)

Amantadin konsentrasi tinggi di plasma reaksi neurotoksik serius delirium kejang koma aritmia

Penggunaan terapiPenggunaan terapi

Pencegahan dan pengobatan influenza A 200 mghari dalam 1 atau 2 dosis

(pengobatan)Pencegahan harus dimulai ketika mulai

teridentifikasi pandemi virus 100mghari (4 ndash 8 minggu)

ZANAMIVIROSELTAMIVIRZANAMIVIROSELTAMIVIRPenghambat Neuroaminidase Menghambat replikasi influenza A amp B

FKFK

Diserap dengan cepat setelah pemberian oral (BA 80)

Eliminasi di ginjal dalam bentuk tak berubah

Berinterkasi dengan probenecid (meningkatkan T12 ndash 2x)

Efek sampingEfek samping

Mual rasa tak nyaman di lambung muntah lokal iritasi

Konsentrasi yang sangat tinggi berhungan dengan kematian (tikus)

ANTI-HEPATITISANTI-HEPATITIS

ADEFOVIRADEFOVIRSecara kompetitif menghambat HBV

DNA polymeraseMenghambat sintesis DNAEfek samping nefrotoksik pusing

diare ganggian abdomen)Pengobaan infeksi HBV kronis 10 mghari

INTERFERONINTERFERON Protein endogen yang dihasilkan dan dilepaskan

oleh sel sebagai respon terhadap patogen Menginduksi enzim menekan proliferasi aktivitas

imunomodulator dan menghambat replikasi virus Menghambat penetrasi dan amp uncoating Untuk pengobatan HBV amp HCV

ANTIRETROVIRAL ANTIRETROVIRAL AGENTSAGENTS

CURRENT ARV MEDICATIONSCURRENT ARV MEDICATIONS

NRTIbull Abacavir bull Didanosine bull Emtricitabine bull Lamivudine bull Stavudine bull Tenofovir bull Zidovudine

NNRTIbull Efavirenz bull Etravirine bull Nevirapine

PIbull Atazanavir bull Darunavir bull Fosamprenavir bull Indinavir bull Lopinavir bull Nelfinavirbull Ritonavir bull Saquinavir bull Tipranavir Fusion Inhibitorbull Enfuvirtide bull

Fixed-dose CombinationsbullZidovudine lamivudinebullZidovudinelamivudineabacavirbullAbacavirlamivudinebullEmtricitabinetenofovirbullEfavirenzemtricitabine tenofovir

DRUG MECHANISM amp VIRAL SELECTIVITY

CLINICAL USE

VIRAL RESISTANCE

UNDESIRABLE SIDE EFFECTS

PHARMACOKINETICS

NOTES

Zidovudine (AZT)

Thymidine analog is incorporated into DNA of human immunodeficiency viirus causing termination of the viral DNA chain

HIV Prevention of maternal-fetal transmission of HIV

Mutations in reverse transcriptase

Headaches nausea myalgias anemia neutropenia macrocytosis

PO Well absorbed rapidly metabolized by liver

Acetaminophen increases risk of hematologic toxicity

Didanosine (ddl)Zalcitabine (ddC)Lamivudine

-Metabolized intracellularly to dideoxynucleotide triphosphate that inhibits reverse transcriptase amp incorporates into viral DNA-Nucleotides fail to bind to ddATP bec it lacks free 3rsquo OH group

HIV Mutations in reverse transcriptase

Peripheral neuropathy pancreatitis diarrhea headache insomnia vomiting nausea rash abdominal pain

IVPO Partially metabolized in liver excreted in the urine Toxicity may be enhanced by renal or hepatic dysfunction

Limited utility as a single agent therapy because of viral resistance

Stavudine Metabolized to stavudine triphosphate wc inhibits HIV reverse transcriptase amp DNA polymerase Prevents DNA elongation

HIV Peripheral neuropathy

PO Not indicated for initial monotherapy of HIV

ANTIVIRAL DRUGS - RETROVIRUSES

RitonavirIndinavirSaquinavirNelfinavir

Inhibts HIV protease Results in immature virion

HIV Mutations in protease sequence reduce affinity of protease inhibitors

GI distress headache neurologic symptoms Indinavir associated w increase risk for kidney stones

PO Metabolized by P450 in liver Reduce dose in patients with liver disease Poor CNS penetration

Potentially serious drug interactions due to P450 competition

NevirapineDelavirdene

Nob-nucleoside inhibitor of HIV reverse transcriptase

HIV Never as monotherapy due to rapid development of resistance

Rapid resistance develops due to mutations in reverse transcriptase

Severe skin rash fever nausea headache

PO Well absorbed Nevirapine crosses placenta amp has better CNS penetration than Delavirdene

Delavirdene failed to show clinical efficacy when added to didanosine in clinical trial

• Obat antivirus
• Virus
• Struktur virus
• Klasifikasi virus
• PowerPoint Presentation
• Slide 6
• Slide 7
• Slide 8
• Obat anti virus
• Slide 10
• ANTI-HERPES ANTI VZV HSV = herpes simplex virus VZV = Varicella Zoster virus
• ACYCLOVIR
• Mekanisme kerja
• Farmakokinetik
• Penggunaan dalam terapi
• THERAPEUTIC USES
• Efek samping
• PENCICLOVIR
• MK
• Slide 20
• Slide 21
• Slide 22
• Slide 23
• ANTI-INFLUENZA
• AMANTADINRIMANTADIN
• FK
• Efek samping
• Penggunaan terapi
• ZANAMIVIROSELTAMIVIR
• Slide 30
• Slide 31
• ANTI-HEPATITIS
• ADEFOVIR
• INTERFERON
• ANTIRETROVIRAL AGENTS
• Slide 36
• CURRENT ARV MEDICATIONS
• Slide 38
• Slide 39
• Slide 40
• Slide 41

FarmakokinetikFarmakokinetik BA oral 10-30 menurun dengan peningkatan

dosis BA relatif meningkat sampai 70 setelah

pemberian valasiklovir Terdistribusi luas pada cairan tubuh termasuk

cairan vesikuler dan CSF Terkonsentrasi di ASI cairan amnionik dan

plasenta Absorbsi perkutan rendah

Penggunaan dalam terapiPenggunaan dalam terapi

Herpes genital (awal dan kambuhan) ndash 200 mg 5xhari selama 10 hari ndash oralndash 5 mgkg per 8 jam ndash IVRecurrent 400 mg 2xhari atau 200 mg

3xhari

THERAPEUTIC USESTHERAPEUTIC USES

ACUTE HERPES ZOSTER (SHINGLES)SYSTEMIC ACYCLOVIR PROPHYLAXISHSV ENCEPHALITISVARICELLA ZOSTER VIRUS INFECTIONCMV PROPHYLAXIS

Efek sampingEfek samping

Sediaan topikal-iritasi mukosa dan rasa terbakar pada luka genital

ORAL ndash mual diare rash sakit kepala insufisiensi ginjal neurotoksisitas

IV- insufisiensi ginjal CNS

PENCICLOVIRPENCICLOVIR

Aktivitas dan potensi mirid dengan asiklovir terhadap HSV amp VZV

Aktif terhadap HBV (hepatiis B virus)

MKMK Menghambat sintesis DNA virus Awalnya difosforilasi oleh viral thymidine

kinase Penciclovir trifosfat merupakan inhibitor

kompetitif terhadap viral DNA polymerase Potensi 100 lebih rendah dibanding asiklovir

tapi berada pada konsentrasi yg lebih tinggi dan lebih lama dalam sel yang terinfeksi

Penggunaan dalam terapiPenggunaan dalam terapidosis 5 mgkg per 8-12 jam iv selama 7

hari seara dengan asiklovir utk infeksi mucocutaneous HSV

Sediaan Topical 1 penciclovir cream dioleskan tiap 2 jam 4 hari utk labial HSV

Efek sampingEfek samping

Mutagenik pada konsentrasi tinggi IO yang signifikan secara klinis tidak

teridentifikasi

DRUG MECHANISMVIRAL

SELECTIVITY

CLINICAL USE

VIRAL RESISTANCE

UNDESIRABLE SIDE EFFECTS

PHARMACOKINETICS

NOTES

Acylovir Metabolized by thymidine kinase to triphosphate

Herpes simplex 1 amp 2 varicella zoster

Produce abnormal thymidine kinase

Skin irritation burning crystalline nephropathy

IVPO Administer slowly CNS level=50 serum level Decrease dose w kidney dysfunction

Pencyclovir Oral HSV (coldsores)

Topical

Valacyclovir L-valyl ester of acyclovir converted to acyclovir

Herpes zoster (shingles)

Nausea headache PO Slightly better oral absorption than acyclovir

No clear advantage over acyclovir

Idoxuridine Phosphorylated metabolite incorporates into DNA causing strand breaks

Herpes simplex keratitis No effect on RNA viruses

Resistance develops

Photophobia irritation of conjunctiva amp eyelid

Eyedrops Drug is a halogenated derivative of deoxyuridine

Famciclovir Phosphorylated by viral thymidine kinase to penciclovir triiphosphate

Shortens duration of herpes zoster amp genital herpes

Minimal toxicity Headache

PO Decrease dose with renal dysfunction

Ganciclovir Metabolized by thymidine kinase to triphosphate Preferentially phosphorylated to active drug in CMV infected cells

CMV retinitis amp severe systemic CMV infections

Some resistant strains lack thymidine kinase Cannot activate drug

Granulocytopenia thrombocytopenia

IVPO Excreted unchanged in urine Decrease dose with renal dysfunction

Do not coadminister zidovudine (granulocytopenia) or imipenem-cilastatin (seizures)

ANTIVIRAL DRUGS ndash DNA amp RNA VIRUSES

Cidofovir Metabolized to diphosphate form Otherwise like ganciclovir

CMV retinitis Nephrotoxicity may be reduced by hydration amp coadministration of Probenicid Neutropenia

Foscarnet Analog of pyrophosphate Competes for pyrophosphate site in viral but not human DNA polymerase amp reverse transcriptase

CMV retinitis Does not need phosphorylation it is active against thymidine kinase ndashdeficient strains

Renal toxicity seizures hypocalcemia fever anemia diarrhea nausea

IV gt80 excreted unchanged in the urine CSF penetration variable Reduce dose with renal dysfunction

Deposited in bone amp teeth Hydrate patient during therapy to protect the kidney

Amantadine Prevents virus from entering susceptible cells

Treatment amp prophylaxis of influenza A

Depression CNS toxicity CHF orthostatic hypotension urinary retention

PO Excreted unmetabolized

Rimantadine Analog of amantadine inhibits viral uncoating

Prophylaxis in children

Fewer CNS side effects risk of seizure

PO Prolonged elimination w renal or hepatic dysfunction

Ribavirin Unknown mechanism

RSV Decreased pulmonary function

Aerosol administration Absorbed systemically

May precipitate in ventilator tubing

ANTI-INFLUENZAANTI-INFLUENZA

AMANTADINRIMANTADINAMANTADINRIMANTADIN Menghambat proses uncoating virus RNA

influenza A di dalam cell inang mencegah replikasi

Efektif menurunkan durasi gejala influenza jika diberikan dalam 48 jam setelah onset

FKFK

Absorpsi oral baikEkskresi dalam bentuk tak termetabolisme

di urinAmantadin dapat diekskresikan lewat ASI

Efek sampingEfek samping

Umum gangguan GI dan CNS minor (gugup light headanche susah konsentrasi insomnia mual nafsu makan berkurang)

Amantadin konsentrasi tinggi di plasma reaksi neurotoksik serius delirium kejang koma aritmia

Penggunaan terapiPenggunaan terapi

Pencegahan dan pengobatan influenza A 200 mghari dalam 1 atau 2 dosis

(pengobatan)Pencegahan harus dimulai ketika mulai

teridentifikasi pandemi virus 100mghari (4 ndash 8 minggu)

ZANAMIVIROSELTAMIVIRZANAMIVIROSELTAMIVIRPenghambat Neuroaminidase Menghambat replikasi influenza A amp B

FKFK

Diserap dengan cepat setelah pemberian oral (BA 80)

Eliminasi di ginjal dalam bentuk tak berubah

Berinterkasi dengan probenecid (meningkatkan T12 ndash 2x)

Efek sampingEfek samping

Mual rasa tak nyaman di lambung muntah lokal iritasi

Konsentrasi yang sangat tinggi berhungan dengan kematian (tikus)

ANTI-HEPATITISANTI-HEPATITIS

ADEFOVIRADEFOVIRSecara kompetitif menghambat HBV

DNA polymeraseMenghambat sintesis DNAEfek samping nefrotoksik pusing

diare ganggian abdomen)Pengobaan infeksi HBV kronis 10 mghari

INTERFERONINTERFERON Protein endogen yang dihasilkan dan dilepaskan

oleh sel sebagai respon terhadap patogen Menginduksi enzim menekan proliferasi aktivitas

imunomodulator dan menghambat replikasi virus Menghambat penetrasi dan amp uncoating Untuk pengobatan HBV amp HCV

ANTIRETROVIRAL ANTIRETROVIRAL AGENTSAGENTS

CURRENT ARV MEDICATIONSCURRENT ARV MEDICATIONS

NRTIbull Abacavir bull Didanosine bull Emtricitabine bull Lamivudine bull Stavudine bull Tenofovir bull Zidovudine

NNRTIbull Efavirenz bull Etravirine bull Nevirapine

PIbull Atazanavir bull Darunavir bull Fosamprenavir bull Indinavir bull Lopinavir bull Nelfinavirbull Ritonavir bull Saquinavir bull Tipranavir Fusion Inhibitorbull Enfuvirtide bull

Fixed-dose CombinationsbullZidovudine lamivudinebullZidovudinelamivudineabacavirbullAbacavirlamivudinebullEmtricitabinetenofovirbullEfavirenzemtricitabine tenofovir

DRUG MECHANISM amp VIRAL SELECTIVITY

CLINICAL USE

VIRAL RESISTANCE

UNDESIRABLE SIDE EFFECTS

PHARMACOKINETICS

NOTES

Zidovudine (AZT)

Thymidine analog is incorporated into DNA of human immunodeficiency viirus causing termination of the viral DNA chain

HIV Prevention of maternal-fetal transmission of HIV

Mutations in reverse transcriptase

Headaches nausea myalgias anemia neutropenia macrocytosis

PO Well absorbed rapidly metabolized by liver

Acetaminophen increases risk of hematologic toxicity

Didanosine (ddl)Zalcitabine (ddC)Lamivudine

-Metabolized intracellularly to dideoxynucleotide triphosphate that inhibits reverse transcriptase amp incorporates into viral DNA-Nucleotides fail to bind to ddATP bec it lacks free 3rsquo OH group

HIV Mutations in reverse transcriptase

Peripheral neuropathy pancreatitis diarrhea headache insomnia vomiting nausea rash abdominal pain

IVPO Partially metabolized in liver excreted in the urine Toxicity may be enhanced by renal or hepatic dysfunction

Limited utility as a single agent therapy because of viral resistance

Stavudine Metabolized to stavudine triphosphate wc inhibits HIV reverse transcriptase amp DNA polymerase Prevents DNA elongation

HIV Peripheral neuropathy

PO Not indicated for initial monotherapy of HIV

ANTIVIRAL DRUGS - RETROVIRUSES

RitonavirIndinavirSaquinavirNelfinavir

Inhibts HIV protease Results in immature virion

HIV Mutations in protease sequence reduce affinity of protease inhibitors

GI distress headache neurologic symptoms Indinavir associated w increase risk for kidney stones

PO Metabolized by P450 in liver Reduce dose in patients with liver disease Poor CNS penetration

Potentially serious drug interactions due to P450 competition

NevirapineDelavirdene

Nob-nucleoside inhibitor of HIV reverse transcriptase

HIV Never as monotherapy due to rapid development of resistance

Rapid resistance develops due to mutations in reverse transcriptase

Severe skin rash fever nausea headache

PO Well absorbed Nevirapine crosses placenta amp has better CNS penetration than Delavirdene

Delavirdene failed to show clinical efficacy when added to didanosine in clinical trial

• Obat antivirus
• Virus
• Struktur virus
• Klasifikasi virus
• PowerPoint Presentation
• Slide 6
• Slide 7
• Slide 8
• Obat anti virus
• Slide 10
• ANTI-HERPES ANTI VZV HSV = herpes simplex virus VZV = Varicella Zoster virus
• ACYCLOVIR
• Mekanisme kerja
• Farmakokinetik
• Penggunaan dalam terapi
• THERAPEUTIC USES
• Efek samping
• PENCICLOVIR
• MK
• Slide 20
• Slide 21
• Slide 22
• Slide 23
• ANTI-INFLUENZA
• AMANTADINRIMANTADIN
• FK
• Efek samping
• Penggunaan terapi
• ZANAMIVIROSELTAMIVIR
• Slide 30
• Slide 31
• ANTI-HEPATITIS
• ADEFOVIR
• INTERFERON
• ANTIRETROVIRAL AGENTS
• Slide 36
• CURRENT ARV MEDICATIONS
• Slide 38
• Slide 39
• Slide 40
• Slide 41

Penggunaan dalam terapiPenggunaan dalam terapi

Herpes genital (awal dan kambuhan) ndash 200 mg 5xhari selama 10 hari ndash oralndash 5 mgkg per 8 jam ndash IVRecurrent 400 mg 2xhari atau 200 mg

3xhari

THERAPEUTIC USESTHERAPEUTIC USES

ACUTE HERPES ZOSTER (SHINGLES)SYSTEMIC ACYCLOVIR PROPHYLAXISHSV ENCEPHALITISVARICELLA ZOSTER VIRUS INFECTIONCMV PROPHYLAXIS

Efek sampingEfek samping

Sediaan topikal-iritasi mukosa dan rasa terbakar pada luka genital

ORAL ndash mual diare rash sakit kepala insufisiensi ginjal neurotoksisitas

IV- insufisiensi ginjal CNS

PENCICLOVIRPENCICLOVIR

Aktivitas dan potensi mirid dengan asiklovir terhadap HSV amp VZV

Aktif terhadap HBV (hepatiis B virus)

MKMK Menghambat sintesis DNA virus Awalnya difosforilasi oleh viral thymidine

kinase Penciclovir trifosfat merupakan inhibitor

kompetitif terhadap viral DNA polymerase Potensi 100 lebih rendah dibanding asiklovir

tapi berada pada konsentrasi yg lebih tinggi dan lebih lama dalam sel yang terinfeksi

Penggunaan dalam terapiPenggunaan dalam terapidosis 5 mgkg per 8-12 jam iv selama 7

hari seara dengan asiklovir utk infeksi mucocutaneous HSV

Sediaan Topical 1 penciclovir cream dioleskan tiap 2 jam 4 hari utk labial HSV

Efek sampingEfek samping

Mutagenik pada konsentrasi tinggi IO yang signifikan secara klinis tidak

teridentifikasi

DRUG MECHANISMVIRAL

SELECTIVITY

CLINICAL USE

VIRAL RESISTANCE

UNDESIRABLE SIDE EFFECTS

PHARMACOKINETICS

NOTES

Acylovir Metabolized by thymidine kinase to triphosphate

Herpes simplex 1 amp 2 varicella zoster

Produce abnormal thymidine kinase

Skin irritation burning crystalline nephropathy

IVPO Administer slowly CNS level=50 serum level Decrease dose w kidney dysfunction

Pencyclovir Oral HSV (coldsores)

Topical

Valacyclovir L-valyl ester of acyclovir converted to acyclovir

Herpes zoster (shingles)

Nausea headache PO Slightly better oral absorption than acyclovir

No clear advantage over acyclovir

Idoxuridine Phosphorylated metabolite incorporates into DNA causing strand breaks

Herpes simplex keratitis No effect on RNA viruses

Resistance develops

Photophobia irritation of conjunctiva amp eyelid

Eyedrops Drug is a halogenated derivative of deoxyuridine

Famciclovir Phosphorylated by viral thymidine kinase to penciclovir triiphosphate

Shortens duration of herpes zoster amp genital herpes

Minimal toxicity Headache

PO Decrease dose with renal dysfunction

Ganciclovir Metabolized by thymidine kinase to triphosphate Preferentially phosphorylated to active drug in CMV infected cells

CMV retinitis amp severe systemic CMV infections

Some resistant strains lack thymidine kinase Cannot activate drug

Granulocytopenia thrombocytopenia

IVPO Excreted unchanged in urine Decrease dose with renal dysfunction

Do not coadminister zidovudine (granulocytopenia) or imipenem-cilastatin (seizures)

ANTIVIRAL DRUGS ndash DNA amp RNA VIRUSES

Cidofovir Metabolized to diphosphate form Otherwise like ganciclovir

CMV retinitis Nephrotoxicity may be reduced by hydration amp coadministration of Probenicid Neutropenia

Foscarnet Analog of pyrophosphate Competes for pyrophosphate site in viral but not human DNA polymerase amp reverse transcriptase

CMV retinitis Does not need phosphorylation it is active against thymidine kinase ndashdeficient strains

Renal toxicity seizures hypocalcemia fever anemia diarrhea nausea

IV gt80 excreted unchanged in the urine CSF penetration variable Reduce dose with renal dysfunction

Deposited in bone amp teeth Hydrate patient during therapy to protect the kidney

Amantadine Prevents virus from entering susceptible cells

Treatment amp prophylaxis of influenza A

Depression CNS toxicity CHF orthostatic hypotension urinary retention

PO Excreted unmetabolized

Rimantadine Analog of amantadine inhibits viral uncoating

Prophylaxis in children

Fewer CNS side effects risk of seizure

PO Prolonged elimination w renal or hepatic dysfunction

Ribavirin Unknown mechanism

RSV Decreased pulmonary function

Aerosol administration Absorbed systemically

May precipitate in ventilator tubing

ANTI-INFLUENZAANTI-INFLUENZA

AMANTADINRIMANTADINAMANTADINRIMANTADIN Menghambat proses uncoating virus RNA

influenza A di dalam cell inang mencegah replikasi

Efektif menurunkan durasi gejala influenza jika diberikan dalam 48 jam setelah onset

FKFK

Absorpsi oral baikEkskresi dalam bentuk tak termetabolisme

di urinAmantadin dapat diekskresikan lewat ASI

Efek sampingEfek samping

Umum gangguan GI dan CNS minor (gugup light headanche susah konsentrasi insomnia mual nafsu makan berkurang)

Amantadin konsentrasi tinggi di plasma reaksi neurotoksik serius delirium kejang koma aritmia

Penggunaan terapiPenggunaan terapi

Pencegahan dan pengobatan influenza A 200 mghari dalam 1 atau 2 dosis

(pengobatan)Pencegahan harus dimulai ketika mulai

teridentifikasi pandemi virus 100mghari (4 ndash 8 minggu)

ZANAMIVIROSELTAMIVIRZANAMIVIROSELTAMIVIRPenghambat Neuroaminidase Menghambat replikasi influenza A amp B

FKFK

Diserap dengan cepat setelah pemberian oral (BA 80)

Eliminasi di ginjal dalam bentuk tak berubah

Berinterkasi dengan probenecid (meningkatkan T12 ndash 2x)

Efek sampingEfek samping

Mual rasa tak nyaman di lambung muntah lokal iritasi

Konsentrasi yang sangat tinggi berhungan dengan kematian (tikus)

ANTI-HEPATITISANTI-HEPATITIS

ADEFOVIRADEFOVIRSecara kompetitif menghambat HBV

DNA polymeraseMenghambat sintesis DNAEfek samping nefrotoksik pusing

diare ganggian abdomen)Pengobaan infeksi HBV kronis 10 mghari

INTERFERONINTERFERON Protein endogen yang dihasilkan dan dilepaskan

oleh sel sebagai respon terhadap patogen Menginduksi enzim menekan proliferasi aktivitas

imunomodulator dan menghambat replikasi virus Menghambat penetrasi dan amp uncoating Untuk pengobatan HBV amp HCV

ANTIRETROVIRAL ANTIRETROVIRAL AGENTSAGENTS

CURRENT ARV MEDICATIONSCURRENT ARV MEDICATIONS

NRTIbull Abacavir bull Didanosine bull Emtricitabine bull Lamivudine bull Stavudine bull Tenofovir bull Zidovudine

NNRTIbull Efavirenz bull Etravirine bull Nevirapine

PIbull Atazanavir bull Darunavir bull Fosamprenavir bull Indinavir bull Lopinavir bull Nelfinavirbull Ritonavir bull Saquinavir bull Tipranavir Fusion Inhibitorbull Enfuvirtide bull

Fixed-dose CombinationsbullZidovudine lamivudinebullZidovudinelamivudineabacavirbullAbacavirlamivudinebullEmtricitabinetenofovirbullEfavirenzemtricitabine tenofovir

DRUG MECHANISM amp VIRAL SELECTIVITY

CLINICAL USE

VIRAL RESISTANCE

UNDESIRABLE SIDE EFFECTS

PHARMACOKINETICS

NOTES

Zidovudine (AZT)

Thymidine analog is incorporated into DNA of human immunodeficiency viirus causing termination of the viral DNA chain

HIV Prevention of maternal-fetal transmission of HIV

Mutations in reverse transcriptase

Headaches nausea myalgias anemia neutropenia macrocytosis

PO Well absorbed rapidly metabolized by liver

Acetaminophen increases risk of hematologic toxicity

Didanosine (ddl)Zalcitabine (ddC)Lamivudine

-Metabolized intracellularly to dideoxynucleotide triphosphate that inhibits reverse transcriptase amp incorporates into viral DNA-Nucleotides fail to bind to ddATP bec it lacks free 3rsquo OH group

HIV Mutations in reverse transcriptase

Peripheral neuropathy pancreatitis diarrhea headache insomnia vomiting nausea rash abdominal pain

IVPO Partially metabolized in liver excreted in the urine Toxicity may be enhanced by renal or hepatic dysfunction

Limited utility as a single agent therapy because of viral resistance

Stavudine Metabolized to stavudine triphosphate wc inhibits HIV reverse transcriptase amp DNA polymerase Prevents DNA elongation

HIV Peripheral neuropathy

PO Not indicated for initial monotherapy of HIV

ANTIVIRAL DRUGS - RETROVIRUSES

RitonavirIndinavirSaquinavirNelfinavir

Inhibts HIV protease Results in immature virion

HIV Mutations in protease sequence reduce affinity of protease inhibitors

GI distress headache neurologic symptoms Indinavir associated w increase risk for kidney stones

PO Metabolized by P450 in liver Reduce dose in patients with liver disease Poor CNS penetration

Potentially serious drug interactions due to P450 competition

NevirapineDelavirdene

Nob-nucleoside inhibitor of HIV reverse transcriptase

HIV Never as monotherapy due to rapid development of resistance

Rapid resistance develops due to mutations in reverse transcriptase

Severe skin rash fever nausea headache

PO Well absorbed Nevirapine crosses placenta amp has better CNS penetration than Delavirdene

Delavirdene failed to show clinical efficacy when added to didanosine in clinical trial

• Obat antivirus
• Virus
• Struktur virus
• Klasifikasi virus
• PowerPoint Presentation
• Slide 6
• Slide 7
• Slide 8
• Obat anti virus
• Slide 10
• ANTI-HERPES ANTI VZV HSV = herpes simplex virus VZV = Varicella Zoster virus
• ACYCLOVIR
• Mekanisme kerja
• Farmakokinetik
• Penggunaan dalam terapi
• THERAPEUTIC USES
• Efek samping
• PENCICLOVIR
• MK
• Slide 20
• Slide 21
• Slide 22
• Slide 23
• ANTI-INFLUENZA
• AMANTADINRIMANTADIN
• FK
• Efek samping
• Penggunaan terapi
• ZANAMIVIROSELTAMIVIR
• Slide 30
• Slide 31
• ANTI-HEPATITIS
• ADEFOVIR
• INTERFERON
• ANTIRETROVIRAL AGENTS
• Slide 36
• CURRENT ARV MEDICATIONS
• Slide 38
• Slide 39
• Slide 40
• Slide 41

THERAPEUTIC USESTHERAPEUTIC USES

ACUTE HERPES ZOSTER (SHINGLES)SYSTEMIC ACYCLOVIR PROPHYLAXISHSV ENCEPHALITISVARICELLA ZOSTER VIRUS INFECTIONCMV PROPHYLAXIS

Efek sampingEfek samping

Sediaan topikal-iritasi mukosa dan rasa terbakar pada luka genital

ORAL ndash mual diare rash sakit kepala insufisiensi ginjal neurotoksisitas

IV- insufisiensi ginjal CNS

PENCICLOVIRPENCICLOVIR

Aktivitas dan potensi mirid dengan asiklovir terhadap HSV amp VZV

Aktif terhadap HBV (hepatiis B virus)

MKMK Menghambat sintesis DNA virus Awalnya difosforilasi oleh viral thymidine

kinase Penciclovir trifosfat merupakan inhibitor

kompetitif terhadap viral DNA polymerase Potensi 100 lebih rendah dibanding asiklovir

tapi berada pada konsentrasi yg lebih tinggi dan lebih lama dalam sel yang terinfeksi

Penggunaan dalam terapiPenggunaan dalam terapidosis 5 mgkg per 8-12 jam iv selama 7

hari seara dengan asiklovir utk infeksi mucocutaneous HSV

Sediaan Topical 1 penciclovir cream dioleskan tiap 2 jam 4 hari utk labial HSV

Efek sampingEfek samping

Mutagenik pada konsentrasi tinggi IO yang signifikan secara klinis tidak

teridentifikasi

DRUG MECHANISMVIRAL

SELECTIVITY

CLINICAL USE

VIRAL RESISTANCE

UNDESIRABLE SIDE EFFECTS

PHARMACOKINETICS

NOTES

Acylovir Metabolized by thymidine kinase to triphosphate

Herpes simplex 1 amp 2 varicella zoster

Produce abnormal thymidine kinase

Skin irritation burning crystalline nephropathy

IVPO Administer slowly CNS level=50 serum level Decrease dose w kidney dysfunction

Pencyclovir Oral HSV (coldsores)

Topical

Valacyclovir L-valyl ester of acyclovir converted to acyclovir

Herpes zoster (shingles)

Nausea headache PO Slightly better oral absorption than acyclovir

No clear advantage over acyclovir

Idoxuridine Phosphorylated metabolite incorporates into DNA causing strand breaks

Herpes simplex keratitis No effect on RNA viruses

Resistance develops

Photophobia irritation of conjunctiva amp eyelid

Eyedrops Drug is a halogenated derivative of deoxyuridine

Famciclovir Phosphorylated by viral thymidine kinase to penciclovir triiphosphate

Shortens duration of herpes zoster amp genital herpes

Minimal toxicity Headache

PO Decrease dose with renal dysfunction

Ganciclovir Metabolized by thymidine kinase to triphosphate Preferentially phosphorylated to active drug in CMV infected cells

CMV retinitis amp severe systemic CMV infections

Some resistant strains lack thymidine kinase Cannot activate drug

Granulocytopenia thrombocytopenia

IVPO Excreted unchanged in urine Decrease dose with renal dysfunction

Do not coadminister zidovudine (granulocytopenia) or imipenem-cilastatin (seizures)

ANTIVIRAL DRUGS ndash DNA amp RNA VIRUSES

Cidofovir Metabolized to diphosphate form Otherwise like ganciclovir

CMV retinitis Nephrotoxicity may be reduced by hydration amp coadministration of Probenicid Neutropenia

Foscarnet Analog of pyrophosphate Competes for pyrophosphate site in viral but not human DNA polymerase amp reverse transcriptase

CMV retinitis Does not need phosphorylation it is active against thymidine kinase ndashdeficient strains

Renal toxicity seizures hypocalcemia fever anemia diarrhea nausea

IV gt80 excreted unchanged in the urine CSF penetration variable Reduce dose with renal dysfunction

Deposited in bone amp teeth Hydrate patient during therapy to protect the kidney

Amantadine Prevents virus from entering susceptible cells

Treatment amp prophylaxis of influenza A

Depression CNS toxicity CHF orthostatic hypotension urinary retention

PO Excreted unmetabolized

Rimantadine Analog of amantadine inhibits viral uncoating

Prophylaxis in children

Fewer CNS side effects risk of seizure

PO Prolonged elimination w renal or hepatic dysfunction

Ribavirin Unknown mechanism

RSV Decreased pulmonary function

Aerosol administration Absorbed systemically

May precipitate in ventilator tubing

ANTI-INFLUENZAANTI-INFLUENZA

AMANTADINRIMANTADINAMANTADINRIMANTADIN Menghambat proses uncoating virus RNA

influenza A di dalam cell inang mencegah replikasi

Efektif menurunkan durasi gejala influenza jika diberikan dalam 48 jam setelah onset

FKFK

Absorpsi oral baikEkskresi dalam bentuk tak termetabolisme

di urinAmantadin dapat diekskresikan lewat ASI

Efek sampingEfek samping

Umum gangguan GI dan CNS minor (gugup light headanche susah konsentrasi insomnia mual nafsu makan berkurang)

Amantadin konsentrasi tinggi di plasma reaksi neurotoksik serius delirium kejang koma aritmia

Penggunaan terapiPenggunaan terapi

Pencegahan dan pengobatan influenza A 200 mghari dalam 1 atau 2 dosis

(pengobatan)Pencegahan harus dimulai ketika mulai

teridentifikasi pandemi virus 100mghari (4 ndash 8 minggu)

ZANAMIVIROSELTAMIVIRZANAMIVIROSELTAMIVIRPenghambat Neuroaminidase Menghambat replikasi influenza A amp B

FKFK

Diserap dengan cepat setelah pemberian oral (BA 80)

Eliminasi di ginjal dalam bentuk tak berubah

Berinterkasi dengan probenecid (meningkatkan T12 ndash 2x)

Efek sampingEfek samping

Mual rasa tak nyaman di lambung muntah lokal iritasi

Konsentrasi yang sangat tinggi berhungan dengan kematian (tikus)

ANTI-HEPATITISANTI-HEPATITIS

ADEFOVIRADEFOVIRSecara kompetitif menghambat HBV

DNA polymeraseMenghambat sintesis DNAEfek samping nefrotoksik pusing

diare ganggian abdomen)Pengobaan infeksi HBV kronis 10 mghari

INTERFERONINTERFERON Protein endogen yang dihasilkan dan dilepaskan

oleh sel sebagai respon terhadap patogen Menginduksi enzim menekan proliferasi aktivitas

imunomodulator dan menghambat replikasi virus Menghambat penetrasi dan amp uncoating Untuk pengobatan HBV amp HCV

ANTIRETROVIRAL ANTIRETROVIRAL AGENTSAGENTS

CURRENT ARV MEDICATIONSCURRENT ARV MEDICATIONS

NRTIbull Abacavir bull Didanosine bull Emtricitabine bull Lamivudine bull Stavudine bull Tenofovir bull Zidovudine

NNRTIbull Efavirenz bull Etravirine bull Nevirapine

PIbull Atazanavir bull Darunavir bull Fosamprenavir bull Indinavir bull Lopinavir bull Nelfinavirbull Ritonavir bull Saquinavir bull Tipranavir Fusion Inhibitorbull Enfuvirtide bull

Fixed-dose CombinationsbullZidovudine lamivudinebullZidovudinelamivudineabacavirbullAbacavirlamivudinebullEmtricitabinetenofovirbullEfavirenzemtricitabine tenofovir

DRUG MECHANISM amp VIRAL SELECTIVITY

CLINICAL USE

VIRAL RESISTANCE

UNDESIRABLE SIDE EFFECTS

PHARMACOKINETICS

NOTES

Zidovudine (AZT)

Thymidine analog is incorporated into DNA of human immunodeficiency viirus causing termination of the viral DNA chain

HIV Prevention of maternal-fetal transmission of HIV

Mutations in reverse transcriptase

Headaches nausea myalgias anemia neutropenia macrocytosis

PO Well absorbed rapidly metabolized by liver

Acetaminophen increases risk of hematologic toxicity

Didanosine (ddl)Zalcitabine (ddC)Lamivudine

-Metabolized intracellularly to dideoxynucleotide triphosphate that inhibits reverse transcriptase amp incorporates into viral DNA-Nucleotides fail to bind to ddATP bec it lacks free 3rsquo OH group

HIV Mutations in reverse transcriptase

Peripheral neuropathy pancreatitis diarrhea headache insomnia vomiting nausea rash abdominal pain

IVPO Partially metabolized in liver excreted in the urine Toxicity may be enhanced by renal or hepatic dysfunction

Limited utility as a single agent therapy because of viral resistance

Stavudine Metabolized to stavudine triphosphate wc inhibits HIV reverse transcriptase amp DNA polymerase Prevents DNA elongation

HIV Peripheral neuropathy

PO Not indicated for initial monotherapy of HIV

ANTIVIRAL DRUGS - RETROVIRUSES

RitonavirIndinavirSaquinavirNelfinavir

Inhibts HIV protease Results in immature virion

HIV Mutations in protease sequence reduce affinity of protease inhibitors

GI distress headache neurologic symptoms Indinavir associated w increase risk for kidney stones

PO Metabolized by P450 in liver Reduce dose in patients with liver disease Poor CNS penetration

Potentially serious drug interactions due to P450 competition

NevirapineDelavirdene

Nob-nucleoside inhibitor of HIV reverse transcriptase

HIV Never as monotherapy due to rapid development of resistance

Rapid resistance develops due to mutations in reverse transcriptase

Severe skin rash fever nausea headache

PO Well absorbed Nevirapine crosses placenta amp has better CNS penetration than Delavirdene

Delavirdene failed to show clinical efficacy when added to didanosine in clinical trial

• Obat antivirus
• Virus
• Struktur virus
• Klasifikasi virus
• PowerPoint Presentation
• Slide 6
• Slide 7
• Slide 8
• Obat anti virus
• Slide 10
• ANTI-HERPES ANTI VZV HSV = herpes simplex virus VZV = Varicella Zoster virus
• ACYCLOVIR
• Mekanisme kerja
• Farmakokinetik
• Penggunaan dalam terapi
• THERAPEUTIC USES
• Efek samping
• PENCICLOVIR
• MK
• Slide 20
• Slide 21
• Slide 22
• Slide 23
• ANTI-INFLUENZA
• AMANTADINRIMANTADIN
• FK
• Efek samping
• Penggunaan terapi
• ZANAMIVIROSELTAMIVIR
• Slide 30
• Slide 31
• ANTI-HEPATITIS
• ADEFOVIR
• INTERFERON
• ANTIRETROVIRAL AGENTS
• Slide 36
• CURRENT ARV MEDICATIONS
• Slide 38
• Slide 39
• Slide 40
• Slide 41

Efek sampingEfek samping

Sediaan topikal-iritasi mukosa dan rasa terbakar pada luka genital

ORAL ndash mual diare rash sakit kepala insufisiensi ginjal neurotoksisitas

IV- insufisiensi ginjal CNS

PENCICLOVIRPENCICLOVIR

Aktivitas dan potensi mirid dengan asiklovir terhadap HSV amp VZV

Aktif terhadap HBV (hepatiis B virus)

MKMK Menghambat sintesis DNA virus Awalnya difosforilasi oleh viral thymidine

kinase Penciclovir trifosfat merupakan inhibitor

kompetitif terhadap viral DNA polymerase Potensi 100 lebih rendah dibanding asiklovir

tapi berada pada konsentrasi yg lebih tinggi dan lebih lama dalam sel yang terinfeksi

Penggunaan dalam terapiPenggunaan dalam terapidosis 5 mgkg per 8-12 jam iv selama 7

hari seara dengan asiklovir utk infeksi mucocutaneous HSV

Sediaan Topical 1 penciclovir cream dioleskan tiap 2 jam 4 hari utk labial HSV

Efek sampingEfek samping

Mutagenik pada konsentrasi tinggi IO yang signifikan secara klinis tidak

teridentifikasi

DRUG MECHANISMVIRAL

SELECTIVITY

CLINICAL USE

VIRAL RESISTANCE

UNDESIRABLE SIDE EFFECTS

PHARMACOKINETICS

NOTES

Acylovir Metabolized by thymidine kinase to triphosphate

Herpes simplex 1 amp 2 varicella zoster

Produce abnormal thymidine kinase

Skin irritation burning crystalline nephropathy

IVPO Administer slowly CNS level=50 serum level Decrease dose w kidney dysfunction

Pencyclovir Oral HSV (coldsores)

Topical

Valacyclovir L-valyl ester of acyclovir converted to acyclovir

Herpes zoster (shingles)

Nausea headache PO Slightly better oral absorption than acyclovir

No clear advantage over acyclovir

Idoxuridine Phosphorylated metabolite incorporates into DNA causing strand breaks

Herpes simplex keratitis No effect on RNA viruses

Resistance develops

Photophobia irritation of conjunctiva amp eyelid

Eyedrops Drug is a halogenated derivative of deoxyuridine

Famciclovir Phosphorylated by viral thymidine kinase to penciclovir triiphosphate

Shortens duration of herpes zoster amp genital herpes

Minimal toxicity Headache

PO Decrease dose with renal dysfunction

Ganciclovir Metabolized by thymidine kinase to triphosphate Preferentially phosphorylated to active drug in CMV infected cells

CMV retinitis amp severe systemic CMV infections

Some resistant strains lack thymidine kinase Cannot activate drug

Granulocytopenia thrombocytopenia

IVPO Excreted unchanged in urine Decrease dose with renal dysfunction

Do not coadminister zidovudine (granulocytopenia) or imipenem-cilastatin (seizures)

ANTIVIRAL DRUGS ndash DNA amp RNA VIRUSES

Cidofovir Metabolized to diphosphate form Otherwise like ganciclovir

CMV retinitis Nephrotoxicity may be reduced by hydration amp coadministration of Probenicid Neutropenia

Foscarnet Analog of pyrophosphate Competes for pyrophosphate site in viral but not human DNA polymerase amp reverse transcriptase

CMV retinitis Does not need phosphorylation it is active against thymidine kinase ndashdeficient strains

Renal toxicity seizures hypocalcemia fever anemia diarrhea nausea

IV gt80 excreted unchanged in the urine CSF penetration variable Reduce dose with renal dysfunction

Deposited in bone amp teeth Hydrate patient during therapy to protect the kidney

Amantadine Prevents virus from entering susceptible cells

Treatment amp prophylaxis of influenza A

Depression CNS toxicity CHF orthostatic hypotension urinary retention

PO Excreted unmetabolized

Rimantadine Analog of amantadine inhibits viral uncoating

Prophylaxis in children

Fewer CNS side effects risk of seizure

PO Prolonged elimination w renal or hepatic dysfunction

Ribavirin Unknown mechanism

RSV Decreased pulmonary function

Aerosol administration Absorbed systemically

May precipitate in ventilator tubing

ANTI-INFLUENZAANTI-INFLUENZA

AMANTADINRIMANTADINAMANTADINRIMANTADIN Menghambat proses uncoating virus RNA

influenza A di dalam cell inang mencegah replikasi

Efektif menurunkan durasi gejala influenza jika diberikan dalam 48 jam setelah onset

FKFK

Absorpsi oral baikEkskresi dalam bentuk tak termetabolisme

di urinAmantadin dapat diekskresikan lewat ASI

Efek sampingEfek samping

Umum gangguan GI dan CNS minor (gugup light headanche susah konsentrasi insomnia mual nafsu makan berkurang)

Amantadin konsentrasi tinggi di plasma reaksi neurotoksik serius delirium kejang koma aritmia

Penggunaan terapiPenggunaan terapi

Pencegahan dan pengobatan influenza A 200 mghari dalam 1 atau 2 dosis

(pengobatan)Pencegahan harus dimulai ketika mulai

teridentifikasi pandemi virus 100mghari (4 ndash 8 minggu)

ZANAMIVIROSELTAMIVIRZANAMIVIROSELTAMIVIRPenghambat Neuroaminidase Menghambat replikasi influenza A amp B

FKFK

Diserap dengan cepat setelah pemberian oral (BA 80)

Eliminasi di ginjal dalam bentuk tak berubah

Berinterkasi dengan probenecid (meningkatkan T12 ndash 2x)

Efek sampingEfek samping

Mual rasa tak nyaman di lambung muntah lokal iritasi

Konsentrasi yang sangat tinggi berhungan dengan kematian (tikus)

ANTI-HEPATITISANTI-HEPATITIS

ADEFOVIRADEFOVIRSecara kompetitif menghambat HBV

DNA polymeraseMenghambat sintesis DNAEfek samping nefrotoksik pusing

diare ganggian abdomen)Pengobaan infeksi HBV kronis 10 mghari

INTERFERONINTERFERON Protein endogen yang dihasilkan dan dilepaskan

oleh sel sebagai respon terhadap patogen Menginduksi enzim menekan proliferasi aktivitas

imunomodulator dan menghambat replikasi virus Menghambat penetrasi dan amp uncoating Untuk pengobatan HBV amp HCV

ANTIRETROVIRAL ANTIRETROVIRAL AGENTSAGENTS

CURRENT ARV MEDICATIONSCURRENT ARV MEDICATIONS

NRTIbull Abacavir bull Didanosine bull Emtricitabine bull Lamivudine bull Stavudine bull Tenofovir bull Zidovudine

NNRTIbull Efavirenz bull Etravirine bull Nevirapine

PIbull Atazanavir bull Darunavir bull Fosamprenavir bull Indinavir bull Lopinavir bull Nelfinavirbull Ritonavir bull Saquinavir bull Tipranavir Fusion Inhibitorbull Enfuvirtide bull

Fixed-dose CombinationsbullZidovudine lamivudinebullZidovudinelamivudineabacavirbullAbacavirlamivudinebullEmtricitabinetenofovirbullEfavirenzemtricitabine tenofovir

DRUG MECHANISM amp VIRAL SELECTIVITY

CLINICAL USE

VIRAL RESISTANCE

UNDESIRABLE SIDE EFFECTS

PHARMACOKINETICS

NOTES

Zidovudine (AZT)

Thymidine analog is incorporated into DNA of human immunodeficiency viirus causing termination of the viral DNA chain

HIV Prevention of maternal-fetal transmission of HIV

Mutations in reverse transcriptase

Headaches nausea myalgias anemia neutropenia macrocytosis

PO Well absorbed rapidly metabolized by liver

Acetaminophen increases risk of hematologic toxicity

Didanosine (ddl)Zalcitabine (ddC)Lamivudine

-Metabolized intracellularly to dideoxynucleotide triphosphate that inhibits reverse transcriptase amp incorporates into viral DNA-Nucleotides fail to bind to ddATP bec it lacks free 3rsquo OH group

HIV Mutations in reverse transcriptase

Peripheral neuropathy pancreatitis diarrhea headache insomnia vomiting nausea rash abdominal pain

IVPO Partially metabolized in liver excreted in the urine Toxicity may be enhanced by renal or hepatic dysfunction

Limited utility as a single agent therapy because of viral resistance

Stavudine Metabolized to stavudine triphosphate wc inhibits HIV reverse transcriptase amp DNA polymerase Prevents DNA elongation

HIV Peripheral neuropathy

PO Not indicated for initial monotherapy of HIV

ANTIVIRAL DRUGS - RETROVIRUSES

RitonavirIndinavirSaquinavirNelfinavir

Inhibts HIV protease Results in immature virion

HIV Mutations in protease sequence reduce affinity of protease inhibitors

GI distress headache neurologic symptoms Indinavir associated w increase risk for kidney stones

PO Metabolized by P450 in liver Reduce dose in patients with liver disease Poor CNS penetration

Potentially serious drug interactions due to P450 competition

NevirapineDelavirdene

Nob-nucleoside inhibitor of HIV reverse transcriptase

HIV Never as monotherapy due to rapid development of resistance

Rapid resistance develops due to mutations in reverse transcriptase

Severe skin rash fever nausea headache

PO Well absorbed Nevirapine crosses placenta amp has better CNS penetration than Delavirdene

Delavirdene failed to show clinical efficacy when added to didanosine in clinical trial

• Obat antivirus
• Virus
• Struktur virus
• Klasifikasi virus
• PowerPoint Presentation
• Slide 6
• Slide 7
• Slide 8
• Obat anti virus
• Slide 10
• ANTI-HERPES ANTI VZV HSV = herpes simplex virus VZV = Varicella Zoster virus
• ACYCLOVIR
• Mekanisme kerja
• Farmakokinetik
• Penggunaan dalam terapi
• THERAPEUTIC USES
• Efek samping
• PENCICLOVIR
• MK
• Slide 20
• Slide 21
• Slide 22
• Slide 23
• ANTI-INFLUENZA
• AMANTADINRIMANTADIN
• FK
• Efek samping
• Penggunaan terapi
• ZANAMIVIROSELTAMIVIR
• Slide 30
• Slide 31
• ANTI-HEPATITIS
• ADEFOVIR
• INTERFERON
• ANTIRETROVIRAL AGENTS
• Slide 36
• CURRENT ARV MEDICATIONS
• Slide 38
• Slide 39
• Slide 40
• Slide 41

PENCICLOVIRPENCICLOVIR

Aktivitas dan potensi mirid dengan asiklovir terhadap HSV amp VZV

Aktif terhadap HBV (hepatiis B virus)

MKMK Menghambat sintesis DNA virus Awalnya difosforilasi oleh viral thymidine

kinase Penciclovir trifosfat merupakan inhibitor

kompetitif terhadap viral DNA polymerase Potensi 100 lebih rendah dibanding asiklovir

tapi berada pada konsentrasi yg lebih tinggi dan lebih lama dalam sel yang terinfeksi

Penggunaan dalam terapiPenggunaan dalam terapidosis 5 mgkg per 8-12 jam iv selama 7

hari seara dengan asiklovir utk infeksi mucocutaneous HSV

Sediaan Topical 1 penciclovir cream dioleskan tiap 2 jam 4 hari utk labial HSV

Efek sampingEfek samping

Mutagenik pada konsentrasi tinggi IO yang signifikan secara klinis tidak

teridentifikasi

DRUG MECHANISMVIRAL

SELECTIVITY

CLINICAL USE

VIRAL RESISTANCE

UNDESIRABLE SIDE EFFECTS

PHARMACOKINETICS

NOTES

Acylovir Metabolized by thymidine kinase to triphosphate

Herpes simplex 1 amp 2 varicella zoster

Produce abnormal thymidine kinase

Skin irritation burning crystalline nephropathy

IVPO Administer slowly CNS level=50 serum level Decrease dose w kidney dysfunction

Pencyclovir Oral HSV (coldsores)

Topical

Valacyclovir L-valyl ester of acyclovir converted to acyclovir

Herpes zoster (shingles)

Nausea headache PO Slightly better oral absorption than acyclovir

No clear advantage over acyclovir

Idoxuridine Phosphorylated metabolite incorporates into DNA causing strand breaks

Herpes simplex keratitis No effect on RNA viruses

Resistance develops

Photophobia irritation of conjunctiva amp eyelid

Eyedrops Drug is a halogenated derivative of deoxyuridine

Famciclovir Phosphorylated by viral thymidine kinase to penciclovir triiphosphate

Shortens duration of herpes zoster amp genital herpes

Minimal toxicity Headache

PO Decrease dose with renal dysfunction

Ganciclovir Metabolized by thymidine kinase to triphosphate Preferentially phosphorylated to active drug in CMV infected cells

CMV retinitis amp severe systemic CMV infections

Some resistant strains lack thymidine kinase Cannot activate drug

Granulocytopenia thrombocytopenia

IVPO Excreted unchanged in urine Decrease dose with renal dysfunction

Do not coadminister zidovudine (granulocytopenia) or imipenem-cilastatin (seizures)

ANTIVIRAL DRUGS ndash DNA amp RNA VIRUSES

Cidofovir Metabolized to diphosphate form Otherwise like ganciclovir

CMV retinitis Nephrotoxicity may be reduced by hydration amp coadministration of Probenicid Neutropenia

Foscarnet Analog of pyrophosphate Competes for pyrophosphate site in viral but not human DNA polymerase amp reverse transcriptase

CMV retinitis Does not need phosphorylation it is active against thymidine kinase ndashdeficient strains

Renal toxicity seizures hypocalcemia fever anemia diarrhea nausea

IV gt80 excreted unchanged in the urine CSF penetration variable Reduce dose with renal dysfunction

Deposited in bone amp teeth Hydrate patient during therapy to protect the kidney

Amantadine Prevents virus from entering susceptible cells

Treatment amp prophylaxis of influenza A

Depression CNS toxicity CHF orthostatic hypotension urinary retention

PO Excreted unmetabolized

Rimantadine Analog of amantadine inhibits viral uncoating

Prophylaxis in children

Fewer CNS side effects risk of seizure

PO Prolonged elimination w renal or hepatic dysfunction

Ribavirin Unknown mechanism

RSV Decreased pulmonary function

Aerosol administration Absorbed systemically

May precipitate in ventilator tubing

ANTI-INFLUENZAANTI-INFLUENZA

AMANTADINRIMANTADINAMANTADINRIMANTADIN Menghambat proses uncoating virus RNA

influenza A di dalam cell inang mencegah replikasi

Efektif menurunkan durasi gejala influenza jika diberikan dalam 48 jam setelah onset

FKFK

Absorpsi oral baikEkskresi dalam bentuk tak termetabolisme

di urinAmantadin dapat diekskresikan lewat ASI

Efek sampingEfek samping

Umum gangguan GI dan CNS minor (gugup light headanche susah konsentrasi insomnia mual nafsu makan berkurang)

Amantadin konsentrasi tinggi di plasma reaksi neurotoksik serius delirium kejang koma aritmia

Penggunaan terapiPenggunaan terapi

Pencegahan dan pengobatan influenza A 200 mghari dalam 1 atau 2 dosis

(pengobatan)Pencegahan harus dimulai ketika mulai

teridentifikasi pandemi virus 100mghari (4 ndash 8 minggu)

ZANAMIVIROSELTAMIVIRZANAMIVIROSELTAMIVIRPenghambat Neuroaminidase Menghambat replikasi influenza A amp B

FKFK

Diserap dengan cepat setelah pemberian oral (BA 80)

Eliminasi di ginjal dalam bentuk tak berubah

Berinterkasi dengan probenecid (meningkatkan T12 ndash 2x)

Efek sampingEfek samping

Mual rasa tak nyaman di lambung muntah lokal iritasi

Konsentrasi yang sangat tinggi berhungan dengan kematian (tikus)

ANTI-HEPATITISANTI-HEPATITIS

ADEFOVIRADEFOVIRSecara kompetitif menghambat HBV

DNA polymeraseMenghambat sintesis DNAEfek samping nefrotoksik pusing

diare ganggian abdomen)Pengobaan infeksi HBV kronis 10 mghari

INTERFERONINTERFERON Protein endogen yang dihasilkan dan dilepaskan

oleh sel sebagai respon terhadap patogen Menginduksi enzim menekan proliferasi aktivitas

imunomodulator dan menghambat replikasi virus Menghambat penetrasi dan amp uncoating Untuk pengobatan HBV amp HCV

ANTIRETROVIRAL ANTIRETROVIRAL AGENTSAGENTS

CURRENT ARV MEDICATIONSCURRENT ARV MEDICATIONS

NRTIbull Abacavir bull Didanosine bull Emtricitabine bull Lamivudine bull Stavudine bull Tenofovir bull Zidovudine

NNRTIbull Efavirenz bull Etravirine bull Nevirapine

PIbull Atazanavir bull Darunavir bull Fosamprenavir bull Indinavir bull Lopinavir bull Nelfinavirbull Ritonavir bull Saquinavir bull Tipranavir Fusion Inhibitorbull Enfuvirtide bull

Fixed-dose CombinationsbullZidovudine lamivudinebullZidovudinelamivudineabacavirbullAbacavirlamivudinebullEmtricitabinetenofovirbullEfavirenzemtricitabine tenofovir

DRUG MECHANISM amp VIRAL SELECTIVITY

CLINICAL USE

VIRAL RESISTANCE

UNDESIRABLE SIDE EFFECTS

PHARMACOKINETICS

NOTES

Zidovudine (AZT)

Thymidine analog is incorporated into DNA of human immunodeficiency viirus causing termination of the viral DNA chain

HIV Prevention of maternal-fetal transmission of HIV

Mutations in reverse transcriptase

Headaches nausea myalgias anemia neutropenia macrocytosis

PO Well absorbed rapidly metabolized by liver

Acetaminophen increases risk of hematologic toxicity

Didanosine (ddl)Zalcitabine (ddC)Lamivudine

-Metabolized intracellularly to dideoxynucleotide triphosphate that inhibits reverse transcriptase amp incorporates into viral DNA-Nucleotides fail to bind to ddATP bec it lacks free 3rsquo OH group

HIV Mutations in reverse transcriptase

Peripheral neuropathy pancreatitis diarrhea headache insomnia vomiting nausea rash abdominal pain

IVPO Partially metabolized in liver excreted in the urine Toxicity may be enhanced by renal or hepatic dysfunction

Limited utility as a single agent therapy because of viral resistance

Stavudine Metabolized to stavudine triphosphate wc inhibits HIV reverse transcriptase amp DNA polymerase Prevents DNA elongation

HIV Peripheral neuropathy

PO Not indicated for initial monotherapy of HIV

ANTIVIRAL DRUGS - RETROVIRUSES

RitonavirIndinavirSaquinavirNelfinavir

Inhibts HIV protease Results in immature virion

HIV Mutations in protease sequence reduce affinity of protease inhibitors

GI distress headache neurologic symptoms Indinavir associated w increase risk for kidney stones

PO Metabolized by P450 in liver Reduce dose in patients with liver disease Poor CNS penetration

Potentially serious drug interactions due to P450 competition

NevirapineDelavirdene

Nob-nucleoside inhibitor of HIV reverse transcriptase

HIV Never as monotherapy due to rapid development of resistance

Rapid resistance develops due to mutations in reverse transcriptase

Severe skin rash fever nausea headache

PO Well absorbed Nevirapine crosses placenta amp has better CNS penetration than Delavirdene

Delavirdene failed to show clinical efficacy when added to didanosine in clinical trial

• Obat antivirus
• Virus
• Struktur virus
• Klasifikasi virus
• PowerPoint Presentation
• Slide 6
• Slide 7
• Slide 8
• Obat anti virus
• Slide 10
• ANTI-HERPES ANTI VZV HSV = herpes simplex virus VZV = Varicella Zoster virus
• ACYCLOVIR
• Mekanisme kerja
• Farmakokinetik
• Penggunaan dalam terapi
• THERAPEUTIC USES
• Efek samping
• PENCICLOVIR
• MK
• Slide 20
• Slide 21
• Slide 22
• Slide 23
• ANTI-INFLUENZA
• AMANTADINRIMANTADIN
• FK
• Efek samping
• Penggunaan terapi
• ZANAMIVIROSELTAMIVIR
• Slide 30
• Slide 31
• ANTI-HEPATITIS
• ADEFOVIR
• INTERFERON
• ANTIRETROVIRAL AGENTS
• Slide 36
• CURRENT ARV MEDICATIONS
• Slide 38
• Slide 39
• Slide 40
• Slide 41

MKMK Menghambat sintesis DNA virus Awalnya difosforilasi oleh viral thymidine

kinase Penciclovir trifosfat merupakan inhibitor

kompetitif terhadap viral DNA polymerase Potensi 100 lebih rendah dibanding asiklovir

tapi berada pada konsentrasi yg lebih tinggi dan lebih lama dalam sel yang terinfeksi

Penggunaan dalam terapiPenggunaan dalam terapidosis 5 mgkg per 8-12 jam iv selama 7

hari seara dengan asiklovir utk infeksi mucocutaneous HSV

Sediaan Topical 1 penciclovir cream dioleskan tiap 2 jam 4 hari utk labial HSV

Efek sampingEfek samping

Mutagenik pada konsentrasi tinggi IO yang signifikan secara klinis tidak

teridentifikasi

DRUG MECHANISMVIRAL

SELECTIVITY

CLINICAL USE

VIRAL RESISTANCE

UNDESIRABLE SIDE EFFECTS

PHARMACOKINETICS

NOTES

Acylovir Metabolized by thymidine kinase to triphosphate

Herpes simplex 1 amp 2 varicella zoster

Produce abnormal thymidine kinase

Skin irritation burning crystalline nephropathy

IVPO Administer slowly CNS level=50 serum level Decrease dose w kidney dysfunction

Pencyclovir Oral HSV (coldsores)

Topical

Valacyclovir L-valyl ester of acyclovir converted to acyclovir

Herpes zoster (shingles)

Nausea headache PO Slightly better oral absorption than acyclovir

No clear advantage over acyclovir

Idoxuridine Phosphorylated metabolite incorporates into DNA causing strand breaks

Herpes simplex keratitis No effect on RNA viruses

Resistance develops

Photophobia irritation of conjunctiva amp eyelid

Eyedrops Drug is a halogenated derivative of deoxyuridine

Famciclovir Phosphorylated by viral thymidine kinase to penciclovir triiphosphate

Shortens duration of herpes zoster amp genital herpes

Minimal toxicity Headache

PO Decrease dose with renal dysfunction

Ganciclovir Metabolized by thymidine kinase to triphosphate Preferentially phosphorylated to active drug in CMV infected cells

CMV retinitis amp severe systemic CMV infections

Some resistant strains lack thymidine kinase Cannot activate drug

Granulocytopenia thrombocytopenia

IVPO Excreted unchanged in urine Decrease dose with renal dysfunction

Do not coadminister zidovudine (granulocytopenia) or imipenem-cilastatin (seizures)

ANTIVIRAL DRUGS ndash DNA amp RNA VIRUSES

Cidofovir Metabolized to diphosphate form Otherwise like ganciclovir

CMV retinitis Nephrotoxicity may be reduced by hydration amp coadministration of Probenicid Neutropenia

Foscarnet Analog of pyrophosphate Competes for pyrophosphate site in viral but not human DNA polymerase amp reverse transcriptase

CMV retinitis Does not need phosphorylation it is active against thymidine kinase ndashdeficient strains

Renal toxicity seizures hypocalcemia fever anemia diarrhea nausea

IV gt80 excreted unchanged in the urine CSF penetration variable Reduce dose with renal dysfunction

Deposited in bone amp teeth Hydrate patient during therapy to protect the kidney

Amantadine Prevents virus from entering susceptible cells

Treatment amp prophylaxis of influenza A

Depression CNS toxicity CHF orthostatic hypotension urinary retention

PO Excreted unmetabolized

Rimantadine Analog of amantadine inhibits viral uncoating

Prophylaxis in children

Fewer CNS side effects risk of seizure

PO Prolonged elimination w renal or hepatic dysfunction

Ribavirin Unknown mechanism

RSV Decreased pulmonary function

Aerosol administration Absorbed systemically

May precipitate in ventilator tubing

ANTI-INFLUENZAANTI-INFLUENZA

AMANTADINRIMANTADINAMANTADINRIMANTADIN Menghambat proses uncoating virus RNA

influenza A di dalam cell inang mencegah replikasi

Efektif menurunkan durasi gejala influenza jika diberikan dalam 48 jam setelah onset

FKFK

Absorpsi oral baikEkskresi dalam bentuk tak termetabolisme

di urinAmantadin dapat diekskresikan lewat ASI

Efek sampingEfek samping

Umum gangguan GI dan CNS minor (gugup light headanche susah konsentrasi insomnia mual nafsu makan berkurang)

Amantadin konsentrasi tinggi di plasma reaksi neurotoksik serius delirium kejang koma aritmia

Penggunaan terapiPenggunaan terapi

Pencegahan dan pengobatan influenza A 200 mghari dalam 1 atau 2 dosis

(pengobatan)Pencegahan harus dimulai ketika mulai

teridentifikasi pandemi virus 100mghari (4 ndash 8 minggu)

ZANAMIVIROSELTAMIVIRZANAMIVIROSELTAMIVIRPenghambat Neuroaminidase Menghambat replikasi influenza A amp B

FKFK

Diserap dengan cepat setelah pemberian oral (BA 80)

Eliminasi di ginjal dalam bentuk tak berubah

Berinterkasi dengan probenecid (meningkatkan T12 ndash 2x)

Efek sampingEfek samping

Mual rasa tak nyaman di lambung muntah lokal iritasi

Konsentrasi yang sangat tinggi berhungan dengan kematian (tikus)

ANTI-HEPATITISANTI-HEPATITIS

ADEFOVIRADEFOVIRSecara kompetitif menghambat HBV

DNA polymeraseMenghambat sintesis DNAEfek samping nefrotoksik pusing

diare ganggian abdomen)Pengobaan infeksi HBV kronis 10 mghari

INTERFERONINTERFERON Protein endogen yang dihasilkan dan dilepaskan

oleh sel sebagai respon terhadap patogen Menginduksi enzim menekan proliferasi aktivitas

imunomodulator dan menghambat replikasi virus Menghambat penetrasi dan amp uncoating Untuk pengobatan HBV amp HCV

ANTIRETROVIRAL ANTIRETROVIRAL AGENTSAGENTS

CURRENT ARV MEDICATIONSCURRENT ARV MEDICATIONS

NRTIbull Abacavir bull Didanosine bull Emtricitabine bull Lamivudine bull Stavudine bull Tenofovir bull Zidovudine

NNRTIbull Efavirenz bull Etravirine bull Nevirapine

PIbull Atazanavir bull Darunavir bull Fosamprenavir bull Indinavir bull Lopinavir bull Nelfinavirbull Ritonavir bull Saquinavir bull Tipranavir Fusion Inhibitorbull Enfuvirtide bull

Fixed-dose CombinationsbullZidovudine lamivudinebullZidovudinelamivudineabacavirbullAbacavirlamivudinebullEmtricitabinetenofovirbullEfavirenzemtricitabine tenofovir

DRUG MECHANISM amp VIRAL SELECTIVITY

CLINICAL USE

VIRAL RESISTANCE

UNDESIRABLE SIDE EFFECTS

PHARMACOKINETICS

NOTES

Zidovudine (AZT)

Thymidine analog is incorporated into DNA of human immunodeficiency viirus causing termination of the viral DNA chain

HIV Prevention of maternal-fetal transmission of HIV

Mutations in reverse transcriptase

Headaches nausea myalgias anemia neutropenia macrocytosis

PO Well absorbed rapidly metabolized by liver

Acetaminophen increases risk of hematologic toxicity

Didanosine (ddl)Zalcitabine (ddC)Lamivudine

-Metabolized intracellularly to dideoxynucleotide triphosphate that inhibits reverse transcriptase amp incorporates into viral DNA-Nucleotides fail to bind to ddATP bec it lacks free 3rsquo OH group

HIV Mutations in reverse transcriptase

Peripheral neuropathy pancreatitis diarrhea headache insomnia vomiting nausea rash abdominal pain

IVPO Partially metabolized in liver excreted in the urine Toxicity may be enhanced by renal or hepatic dysfunction

Limited utility as a single agent therapy because of viral resistance

Stavudine Metabolized to stavudine triphosphate wc inhibits HIV reverse transcriptase amp DNA polymerase Prevents DNA elongation

HIV Peripheral neuropathy

PO Not indicated for initial monotherapy of HIV

ANTIVIRAL DRUGS - RETROVIRUSES

RitonavirIndinavirSaquinavirNelfinavir

Inhibts HIV protease Results in immature virion

HIV Mutations in protease sequence reduce affinity of protease inhibitors

GI distress headache neurologic symptoms Indinavir associated w increase risk for kidney stones

PO Metabolized by P450 in liver Reduce dose in patients with liver disease Poor CNS penetration

Potentially serious drug interactions due to P450 competition

NevirapineDelavirdene

Nob-nucleoside inhibitor of HIV reverse transcriptase

HIV Never as monotherapy due to rapid development of resistance

Rapid resistance develops due to mutations in reverse transcriptase

Severe skin rash fever nausea headache

PO Well absorbed Nevirapine crosses placenta amp has better CNS penetration than Delavirdene

Delavirdene failed to show clinical efficacy when added to didanosine in clinical trial

• Obat antivirus
• Virus
• Struktur virus
• Klasifikasi virus
• PowerPoint Presentation
• Slide 6
• Slide 7
• Slide 8
• Obat anti virus
• Slide 10
• ANTI-HERPES ANTI VZV HSV = herpes simplex virus VZV = Varicella Zoster virus
• ACYCLOVIR
• Mekanisme kerja
• Farmakokinetik
• Penggunaan dalam terapi
• THERAPEUTIC USES
• Efek samping
• PENCICLOVIR
• MK
• Slide 20
• Slide 21
• Slide 22
• Slide 23
• ANTI-INFLUENZA
• AMANTADINRIMANTADIN
• FK
• Efek samping
• Penggunaan terapi
• ZANAMIVIROSELTAMIVIR
• Slide 30
• Slide 31
• ANTI-HEPATITIS
• ADEFOVIR
• INTERFERON
• ANTIRETROVIRAL AGENTS
• Slide 36
• CURRENT ARV MEDICATIONS
• Slide 38
• Slide 39
• Slide 40
• Slide 41

Penggunaan dalam terapiPenggunaan dalam terapidosis 5 mgkg per 8-12 jam iv selama 7

hari seara dengan asiklovir utk infeksi mucocutaneous HSV

Sediaan Topical 1 penciclovir cream dioleskan tiap 2 jam 4 hari utk labial HSV

Efek sampingEfek samping

Mutagenik pada konsentrasi tinggi IO yang signifikan secara klinis tidak

teridentifikasi

DRUG MECHANISMVIRAL

SELECTIVITY

CLINICAL USE

VIRAL RESISTANCE

UNDESIRABLE SIDE EFFECTS

PHARMACOKINETICS

NOTES

Acylovir Metabolized by thymidine kinase to triphosphate

Herpes simplex 1 amp 2 varicella zoster

Produce abnormal thymidine kinase

Skin irritation burning crystalline nephropathy

IVPO Administer slowly CNS level=50 serum level Decrease dose w kidney dysfunction

Pencyclovir Oral HSV (coldsores)

Topical

Valacyclovir L-valyl ester of acyclovir converted to acyclovir

Herpes zoster (shingles)

Nausea headache PO Slightly better oral absorption than acyclovir

No clear advantage over acyclovir

Idoxuridine Phosphorylated metabolite incorporates into DNA causing strand breaks

Herpes simplex keratitis No effect on RNA viruses

Resistance develops

Photophobia irritation of conjunctiva amp eyelid

Eyedrops Drug is a halogenated derivative of deoxyuridine

Famciclovir Phosphorylated by viral thymidine kinase to penciclovir triiphosphate

Shortens duration of herpes zoster amp genital herpes

Minimal toxicity Headache

PO Decrease dose with renal dysfunction

Ganciclovir Metabolized by thymidine kinase to triphosphate Preferentially phosphorylated to active drug in CMV infected cells

CMV retinitis amp severe systemic CMV infections

Some resistant strains lack thymidine kinase Cannot activate drug

Granulocytopenia thrombocytopenia

IVPO Excreted unchanged in urine Decrease dose with renal dysfunction

Do not coadminister zidovudine (granulocytopenia) or imipenem-cilastatin (seizures)

ANTIVIRAL DRUGS ndash DNA amp RNA VIRUSES

Cidofovir Metabolized to diphosphate form Otherwise like ganciclovir

CMV retinitis Nephrotoxicity may be reduced by hydration amp coadministration of Probenicid Neutropenia

Foscarnet Analog of pyrophosphate Competes for pyrophosphate site in viral but not human DNA polymerase amp reverse transcriptase

CMV retinitis Does not need phosphorylation it is active against thymidine kinase ndashdeficient strains

Renal toxicity seizures hypocalcemia fever anemia diarrhea nausea

IV gt80 excreted unchanged in the urine CSF penetration variable Reduce dose with renal dysfunction

Deposited in bone amp teeth Hydrate patient during therapy to protect the kidney

Amantadine Prevents virus from entering susceptible cells

Treatment amp prophylaxis of influenza A

Depression CNS toxicity CHF orthostatic hypotension urinary retention

PO Excreted unmetabolized

Rimantadine Analog of amantadine inhibits viral uncoating

Prophylaxis in children

Fewer CNS side effects risk of seizure

PO Prolonged elimination w renal or hepatic dysfunction

Ribavirin Unknown mechanism

RSV Decreased pulmonary function

Aerosol administration Absorbed systemically

May precipitate in ventilator tubing

ANTI-INFLUENZAANTI-INFLUENZA

AMANTADINRIMANTADINAMANTADINRIMANTADIN Menghambat proses uncoating virus RNA

influenza A di dalam cell inang mencegah replikasi

Efektif menurunkan durasi gejala influenza jika diberikan dalam 48 jam setelah onset

FKFK

Absorpsi oral baikEkskresi dalam bentuk tak termetabolisme

di urinAmantadin dapat diekskresikan lewat ASI

Efek sampingEfek samping

Umum gangguan GI dan CNS minor (gugup light headanche susah konsentrasi insomnia mual nafsu makan berkurang)

Amantadin konsentrasi tinggi di plasma reaksi neurotoksik serius delirium kejang koma aritmia

Penggunaan terapiPenggunaan terapi

Pencegahan dan pengobatan influenza A 200 mghari dalam 1 atau 2 dosis

(pengobatan)Pencegahan harus dimulai ketika mulai

teridentifikasi pandemi virus 100mghari (4 ndash 8 minggu)

ZANAMIVIROSELTAMIVIRZANAMIVIROSELTAMIVIRPenghambat Neuroaminidase Menghambat replikasi influenza A amp B

FKFK

Diserap dengan cepat setelah pemberian oral (BA 80)

Eliminasi di ginjal dalam bentuk tak berubah

Berinterkasi dengan probenecid (meningkatkan T12 ndash 2x)

Efek sampingEfek samping

Mual rasa tak nyaman di lambung muntah lokal iritasi

Konsentrasi yang sangat tinggi berhungan dengan kematian (tikus)

ANTI-HEPATITISANTI-HEPATITIS

ADEFOVIRADEFOVIRSecara kompetitif menghambat HBV

DNA polymeraseMenghambat sintesis DNAEfek samping nefrotoksik pusing

diare ganggian abdomen)Pengobaan infeksi HBV kronis 10 mghari

INTERFERONINTERFERON Protein endogen yang dihasilkan dan dilepaskan

oleh sel sebagai respon terhadap patogen Menginduksi enzim menekan proliferasi aktivitas

imunomodulator dan menghambat replikasi virus Menghambat penetrasi dan amp uncoating Untuk pengobatan HBV amp HCV

ANTIRETROVIRAL ANTIRETROVIRAL AGENTSAGENTS

CURRENT ARV MEDICATIONSCURRENT ARV MEDICATIONS

NRTIbull Abacavir bull Didanosine bull Emtricitabine bull Lamivudine bull Stavudine bull Tenofovir bull Zidovudine

NNRTIbull Efavirenz bull Etravirine bull Nevirapine

PIbull Atazanavir bull Darunavir bull Fosamprenavir bull Indinavir bull Lopinavir bull Nelfinavirbull Ritonavir bull Saquinavir bull Tipranavir Fusion Inhibitorbull Enfuvirtide bull

Fixed-dose CombinationsbullZidovudine lamivudinebullZidovudinelamivudineabacavirbullAbacavirlamivudinebullEmtricitabinetenofovirbullEfavirenzemtricitabine tenofovir

DRUG MECHANISM amp VIRAL SELECTIVITY

CLINICAL USE

VIRAL RESISTANCE

UNDESIRABLE SIDE EFFECTS

PHARMACOKINETICS

NOTES

Zidovudine (AZT)

Thymidine analog is incorporated into DNA of human immunodeficiency viirus causing termination of the viral DNA chain

HIV Prevention of maternal-fetal transmission of HIV

Mutations in reverse transcriptase

Headaches nausea myalgias anemia neutropenia macrocytosis

PO Well absorbed rapidly metabolized by liver

Acetaminophen increases risk of hematologic toxicity

Didanosine (ddl)Zalcitabine (ddC)Lamivudine

-Metabolized intracellularly to dideoxynucleotide triphosphate that inhibits reverse transcriptase amp incorporates into viral DNA-Nucleotides fail to bind to ddATP bec it lacks free 3rsquo OH group

HIV Mutations in reverse transcriptase

Peripheral neuropathy pancreatitis diarrhea headache insomnia vomiting nausea rash abdominal pain

IVPO Partially metabolized in liver excreted in the urine Toxicity may be enhanced by renal or hepatic dysfunction

Limited utility as a single agent therapy because of viral resistance

Stavudine Metabolized to stavudine triphosphate wc inhibits HIV reverse transcriptase amp DNA polymerase Prevents DNA elongation

HIV Peripheral neuropathy

PO Not indicated for initial monotherapy of HIV

ANTIVIRAL DRUGS - RETROVIRUSES

RitonavirIndinavirSaquinavirNelfinavir

Inhibts HIV protease Results in immature virion

HIV Mutations in protease sequence reduce affinity of protease inhibitors

GI distress headache neurologic symptoms Indinavir associated w increase risk for kidney stones

PO Metabolized by P450 in liver Reduce dose in patients with liver disease Poor CNS penetration

Potentially serious drug interactions due to P450 competition

NevirapineDelavirdene

Nob-nucleoside inhibitor of HIV reverse transcriptase

HIV Never as monotherapy due to rapid development of resistance

Rapid resistance develops due to mutations in reverse transcriptase

Severe skin rash fever nausea headache

PO Well absorbed Nevirapine crosses placenta amp has better CNS penetration than Delavirdene

Delavirdene failed to show clinical efficacy when added to didanosine in clinical trial

• Obat antivirus
• Virus
• Struktur virus
• Klasifikasi virus
• PowerPoint Presentation
• Slide 6
• Slide 7
• Slide 8
• Obat anti virus
• Slide 10
• ANTI-HERPES ANTI VZV HSV = herpes simplex virus VZV = Varicella Zoster virus
• ACYCLOVIR
• Mekanisme kerja
• Farmakokinetik
• Penggunaan dalam terapi
• THERAPEUTIC USES
• Efek samping
• PENCICLOVIR
• MK
• Slide 20
• Slide 21
• Slide 22
• Slide 23
• ANTI-INFLUENZA
• AMANTADINRIMANTADIN
• FK
• Efek samping
• Penggunaan terapi
• ZANAMIVIROSELTAMIVIR
• Slide 30
• Slide 31
• ANTI-HEPATITIS
• ADEFOVIR
• INTERFERON
• ANTIRETROVIRAL AGENTS
• Slide 36
• CURRENT ARV MEDICATIONS
• Slide 38
• Slide 39
• Slide 40
• Slide 41

Efek sampingEfek samping

Mutagenik pada konsentrasi tinggi IO yang signifikan secara klinis tidak

teridentifikasi

DRUG MECHANISMVIRAL

SELECTIVITY

CLINICAL USE

VIRAL RESISTANCE

UNDESIRABLE SIDE EFFECTS

PHARMACOKINETICS

NOTES

Acylovir Metabolized by thymidine kinase to triphosphate

Herpes simplex 1 amp 2 varicella zoster

Produce abnormal thymidine kinase

Skin irritation burning crystalline nephropathy

IVPO Administer slowly CNS level=50 serum level Decrease dose w kidney dysfunction

Pencyclovir Oral HSV (coldsores)

Topical

Valacyclovir L-valyl ester of acyclovir converted to acyclovir

Herpes zoster (shingles)

Nausea headache PO Slightly better oral absorption than acyclovir

No clear advantage over acyclovir

Idoxuridine Phosphorylated metabolite incorporates into DNA causing strand breaks

Herpes simplex keratitis No effect on RNA viruses

Resistance develops

Photophobia irritation of conjunctiva amp eyelid

Eyedrops Drug is a halogenated derivative of deoxyuridine

Famciclovir Phosphorylated by viral thymidine kinase to penciclovir triiphosphate

Shortens duration of herpes zoster amp genital herpes

Minimal toxicity Headache

PO Decrease dose with renal dysfunction

Ganciclovir Metabolized by thymidine kinase to triphosphate Preferentially phosphorylated to active drug in CMV infected cells

CMV retinitis amp severe systemic CMV infections

Some resistant strains lack thymidine kinase Cannot activate drug

Granulocytopenia thrombocytopenia

IVPO Excreted unchanged in urine Decrease dose with renal dysfunction

Do not coadminister zidovudine (granulocytopenia) or imipenem-cilastatin (seizures)

ANTIVIRAL DRUGS ndash DNA amp RNA VIRUSES

Cidofovir Metabolized to diphosphate form Otherwise like ganciclovir

CMV retinitis Nephrotoxicity may be reduced by hydration amp coadministration of Probenicid Neutropenia

Foscarnet Analog of pyrophosphate Competes for pyrophosphate site in viral but not human DNA polymerase amp reverse transcriptase

CMV retinitis Does not need phosphorylation it is active against thymidine kinase ndashdeficient strains

Renal toxicity seizures hypocalcemia fever anemia diarrhea nausea

IV gt80 excreted unchanged in the urine CSF penetration variable Reduce dose with renal dysfunction

Deposited in bone amp teeth Hydrate patient during therapy to protect the kidney

Amantadine Prevents virus from entering susceptible cells

Treatment amp prophylaxis of influenza A

Depression CNS toxicity CHF orthostatic hypotension urinary retention

PO Excreted unmetabolized

Rimantadine Analog of amantadine inhibits viral uncoating

Prophylaxis in children

Fewer CNS side effects risk of seizure

PO Prolonged elimination w renal or hepatic dysfunction

Ribavirin Unknown mechanism

RSV Decreased pulmonary function

Aerosol administration Absorbed systemically

May precipitate in ventilator tubing

ANTI-INFLUENZAANTI-INFLUENZA

AMANTADINRIMANTADINAMANTADINRIMANTADIN Menghambat proses uncoating virus RNA

influenza A di dalam cell inang mencegah replikasi

Efektif menurunkan durasi gejala influenza jika diberikan dalam 48 jam setelah onset

FKFK

Absorpsi oral baikEkskresi dalam bentuk tak termetabolisme

di urinAmantadin dapat diekskresikan lewat ASI

Efek sampingEfek samping

Umum gangguan GI dan CNS minor (gugup light headanche susah konsentrasi insomnia mual nafsu makan berkurang)

Amantadin konsentrasi tinggi di plasma reaksi neurotoksik serius delirium kejang koma aritmia

Penggunaan terapiPenggunaan terapi

Pencegahan dan pengobatan influenza A 200 mghari dalam 1 atau 2 dosis

(pengobatan)Pencegahan harus dimulai ketika mulai

teridentifikasi pandemi virus 100mghari (4 ndash 8 minggu)

ZANAMIVIROSELTAMIVIRZANAMIVIROSELTAMIVIRPenghambat Neuroaminidase Menghambat replikasi influenza A amp B

FKFK

Diserap dengan cepat setelah pemberian oral (BA 80)

Eliminasi di ginjal dalam bentuk tak berubah

Berinterkasi dengan probenecid (meningkatkan T12 ndash 2x)

Efek sampingEfek samping

Mual rasa tak nyaman di lambung muntah lokal iritasi

Konsentrasi yang sangat tinggi berhungan dengan kematian (tikus)

ANTI-HEPATITISANTI-HEPATITIS

ADEFOVIRADEFOVIRSecara kompetitif menghambat HBV

DNA polymeraseMenghambat sintesis DNAEfek samping nefrotoksik pusing

diare ganggian abdomen)Pengobaan infeksi HBV kronis 10 mghari

INTERFERONINTERFERON Protein endogen yang dihasilkan dan dilepaskan

oleh sel sebagai respon terhadap patogen Menginduksi enzim menekan proliferasi aktivitas

imunomodulator dan menghambat replikasi virus Menghambat penetrasi dan amp uncoating Untuk pengobatan HBV amp HCV

ANTIRETROVIRAL ANTIRETROVIRAL AGENTSAGENTS

CURRENT ARV MEDICATIONSCURRENT ARV MEDICATIONS

NRTIbull Abacavir bull Didanosine bull Emtricitabine bull Lamivudine bull Stavudine bull Tenofovir bull Zidovudine

NNRTIbull Efavirenz bull Etravirine bull Nevirapine

PIbull Atazanavir bull Darunavir bull Fosamprenavir bull Indinavir bull Lopinavir bull Nelfinavirbull Ritonavir bull Saquinavir bull Tipranavir Fusion Inhibitorbull Enfuvirtide bull

Fixed-dose CombinationsbullZidovudine lamivudinebullZidovudinelamivudineabacavirbullAbacavirlamivudinebullEmtricitabinetenofovirbullEfavirenzemtricitabine tenofovir

DRUG MECHANISM amp VIRAL SELECTIVITY

CLINICAL USE

VIRAL RESISTANCE

UNDESIRABLE SIDE EFFECTS

PHARMACOKINETICS

NOTES

Zidovudine (AZT)

Thymidine analog is incorporated into DNA of human immunodeficiency viirus causing termination of the viral DNA chain

HIV Prevention of maternal-fetal transmission of HIV

Mutations in reverse transcriptase

Headaches nausea myalgias anemia neutropenia macrocytosis

PO Well absorbed rapidly metabolized by liver

Acetaminophen increases risk of hematologic toxicity

Didanosine (ddl)Zalcitabine (ddC)Lamivudine

-Metabolized intracellularly to dideoxynucleotide triphosphate that inhibits reverse transcriptase amp incorporates into viral DNA-Nucleotides fail to bind to ddATP bec it lacks free 3rsquo OH group

HIV Mutations in reverse transcriptase

Peripheral neuropathy pancreatitis diarrhea headache insomnia vomiting nausea rash abdominal pain

IVPO Partially metabolized in liver excreted in the urine Toxicity may be enhanced by renal or hepatic dysfunction

Limited utility as a single agent therapy because of viral resistance

Stavudine Metabolized to stavudine triphosphate wc inhibits HIV reverse transcriptase amp DNA polymerase Prevents DNA elongation

HIV Peripheral neuropathy

PO Not indicated for initial monotherapy of HIV

ANTIVIRAL DRUGS - RETROVIRUSES

RitonavirIndinavirSaquinavirNelfinavir

Inhibts HIV protease Results in immature virion

HIV Mutations in protease sequence reduce affinity of protease inhibitors

GI distress headache neurologic symptoms Indinavir associated w increase risk for kidney stones

PO Metabolized by P450 in liver Reduce dose in patients with liver disease Poor CNS penetration

Potentially serious drug interactions due to P450 competition

NevirapineDelavirdene

Nob-nucleoside inhibitor of HIV reverse transcriptase

HIV Never as monotherapy due to rapid development of resistance

Rapid resistance develops due to mutations in reverse transcriptase

Severe skin rash fever nausea headache

PO Well absorbed Nevirapine crosses placenta amp has better CNS penetration than Delavirdene

Delavirdene failed to show clinical efficacy when added to didanosine in clinical trial

• Obat antivirus
• Virus
• Struktur virus
• Klasifikasi virus
• PowerPoint Presentation
• Slide 6
• Slide 7
• Slide 8
• Obat anti virus
• Slide 10
• ANTI-HERPES ANTI VZV HSV = herpes simplex virus VZV = Varicella Zoster virus
• ACYCLOVIR
• Mekanisme kerja
• Farmakokinetik
• Penggunaan dalam terapi
• THERAPEUTIC USES
• Efek samping
• PENCICLOVIR
• MK
• Slide 20
• Slide 21
• Slide 22
• Slide 23
• ANTI-INFLUENZA
• AMANTADINRIMANTADIN
• FK
• Efek samping
• Penggunaan terapi
• ZANAMIVIROSELTAMIVIR
• Slide 30
• Slide 31
• ANTI-HEPATITIS
• ADEFOVIR
• INTERFERON
• ANTIRETROVIRAL AGENTS
• Slide 36
• CURRENT ARV MEDICATIONS
• Slide 38
• Slide 39
• Slide 40
• Slide 41

DRUG MECHANISMVIRAL

SELECTIVITY

CLINICAL USE

VIRAL RESISTANCE

UNDESIRABLE SIDE EFFECTS

PHARMACOKINETICS

NOTES

Acylovir Metabolized by thymidine kinase to triphosphate

Herpes simplex 1 amp 2 varicella zoster

Produce abnormal thymidine kinase

Skin irritation burning crystalline nephropathy

IVPO Administer slowly CNS level=50 serum level Decrease dose w kidney dysfunction

Pencyclovir Oral HSV (coldsores)

Topical

Valacyclovir L-valyl ester of acyclovir converted to acyclovir

Herpes zoster (shingles)

Nausea headache PO Slightly better oral absorption than acyclovir

No clear advantage over acyclovir

Idoxuridine Phosphorylated metabolite incorporates into DNA causing strand breaks

Herpes simplex keratitis No effect on RNA viruses

Resistance develops

Photophobia irritation of conjunctiva amp eyelid

Eyedrops Drug is a halogenated derivative of deoxyuridine

Famciclovir Phosphorylated by viral thymidine kinase to penciclovir triiphosphate

Shortens duration of herpes zoster amp genital herpes

Minimal toxicity Headache

PO Decrease dose with renal dysfunction

Ganciclovir Metabolized by thymidine kinase to triphosphate Preferentially phosphorylated to active drug in CMV infected cells

CMV retinitis amp severe systemic CMV infections

Some resistant strains lack thymidine kinase Cannot activate drug

Granulocytopenia thrombocytopenia

IVPO Excreted unchanged in urine Decrease dose with renal dysfunction

Do not coadminister zidovudine (granulocytopenia) or imipenem-cilastatin (seizures)

ANTIVIRAL DRUGS ndash DNA amp RNA VIRUSES

Cidofovir Metabolized to diphosphate form Otherwise like ganciclovir

CMV retinitis Nephrotoxicity may be reduced by hydration amp coadministration of Probenicid Neutropenia

Foscarnet Analog of pyrophosphate Competes for pyrophosphate site in viral but not human DNA polymerase amp reverse transcriptase

CMV retinitis Does not need phosphorylation it is active against thymidine kinase ndashdeficient strains

Renal toxicity seizures hypocalcemia fever anemia diarrhea nausea

IV gt80 excreted unchanged in the urine CSF penetration variable Reduce dose with renal dysfunction

Deposited in bone amp teeth Hydrate patient during therapy to protect the kidney

Amantadine Prevents virus from entering susceptible cells

Treatment amp prophylaxis of influenza A

Depression CNS toxicity CHF orthostatic hypotension urinary retention

PO Excreted unmetabolized

Rimantadine Analog of amantadine inhibits viral uncoating

Prophylaxis in children

Fewer CNS side effects risk of seizure

PO Prolonged elimination w renal or hepatic dysfunction

Ribavirin Unknown mechanism

RSV Decreased pulmonary function

Aerosol administration Absorbed systemically

May precipitate in ventilator tubing

ANTI-INFLUENZAANTI-INFLUENZA

AMANTADINRIMANTADINAMANTADINRIMANTADIN Menghambat proses uncoating virus RNA

influenza A di dalam cell inang mencegah replikasi

Efektif menurunkan durasi gejala influenza jika diberikan dalam 48 jam setelah onset

FKFK

Absorpsi oral baikEkskresi dalam bentuk tak termetabolisme

di urinAmantadin dapat diekskresikan lewat ASI

Efek sampingEfek samping

Umum gangguan GI dan CNS minor (gugup light headanche susah konsentrasi insomnia mual nafsu makan berkurang)

Amantadin konsentrasi tinggi di plasma reaksi neurotoksik serius delirium kejang koma aritmia

Penggunaan terapiPenggunaan terapi

Pencegahan dan pengobatan influenza A 200 mghari dalam 1 atau 2 dosis

(pengobatan)Pencegahan harus dimulai ketika mulai

teridentifikasi pandemi virus 100mghari (4 ndash 8 minggu)

ZANAMIVIROSELTAMIVIRZANAMIVIROSELTAMIVIRPenghambat Neuroaminidase Menghambat replikasi influenza A amp B

FKFK

Diserap dengan cepat setelah pemberian oral (BA 80)

Eliminasi di ginjal dalam bentuk tak berubah

Berinterkasi dengan probenecid (meningkatkan T12 ndash 2x)

Efek sampingEfek samping

Mual rasa tak nyaman di lambung muntah lokal iritasi

Konsentrasi yang sangat tinggi berhungan dengan kematian (tikus)

ANTI-HEPATITISANTI-HEPATITIS

ADEFOVIRADEFOVIRSecara kompetitif menghambat HBV

DNA polymeraseMenghambat sintesis DNAEfek samping nefrotoksik pusing

diare ganggian abdomen)Pengobaan infeksi HBV kronis 10 mghari

INTERFERONINTERFERON Protein endogen yang dihasilkan dan dilepaskan

oleh sel sebagai respon terhadap patogen Menginduksi enzim menekan proliferasi aktivitas

imunomodulator dan menghambat replikasi virus Menghambat penetrasi dan amp uncoating Untuk pengobatan HBV amp HCV

ANTIRETROVIRAL ANTIRETROVIRAL AGENTSAGENTS

CURRENT ARV MEDICATIONSCURRENT ARV MEDICATIONS

NRTIbull Abacavir bull Didanosine bull Emtricitabine bull Lamivudine bull Stavudine bull Tenofovir bull Zidovudine

NNRTIbull Efavirenz bull Etravirine bull Nevirapine

PIbull Atazanavir bull Darunavir bull Fosamprenavir bull Indinavir bull Lopinavir bull Nelfinavirbull Ritonavir bull Saquinavir bull Tipranavir Fusion Inhibitorbull Enfuvirtide bull

Fixed-dose CombinationsbullZidovudine lamivudinebullZidovudinelamivudineabacavirbullAbacavirlamivudinebullEmtricitabinetenofovirbullEfavirenzemtricitabine tenofovir

DRUG MECHANISM amp VIRAL SELECTIVITY

CLINICAL USE

VIRAL RESISTANCE

UNDESIRABLE SIDE EFFECTS

PHARMACOKINETICS

NOTES

Zidovudine (AZT)

Thymidine analog is incorporated into DNA of human immunodeficiency viirus causing termination of the viral DNA chain

HIV Prevention of maternal-fetal transmission of HIV

Mutations in reverse transcriptase

Headaches nausea myalgias anemia neutropenia macrocytosis

PO Well absorbed rapidly metabolized by liver

Acetaminophen increases risk of hematologic toxicity

Didanosine (ddl)Zalcitabine (ddC)Lamivudine

-Metabolized intracellularly to dideoxynucleotide triphosphate that inhibits reverse transcriptase amp incorporates into viral DNA-Nucleotides fail to bind to ddATP bec it lacks free 3rsquo OH group

HIV Mutations in reverse transcriptase

Peripheral neuropathy pancreatitis diarrhea headache insomnia vomiting nausea rash abdominal pain

IVPO Partially metabolized in liver excreted in the urine Toxicity may be enhanced by renal or hepatic dysfunction

Limited utility as a single agent therapy because of viral resistance

Stavudine Metabolized to stavudine triphosphate wc inhibits HIV reverse transcriptase amp DNA polymerase Prevents DNA elongation

HIV Peripheral neuropathy

PO Not indicated for initial monotherapy of HIV

ANTIVIRAL DRUGS - RETROVIRUSES

RitonavirIndinavirSaquinavirNelfinavir

Inhibts HIV protease Results in immature virion

HIV Mutations in protease sequence reduce affinity of protease inhibitors

GI distress headache neurologic symptoms Indinavir associated w increase risk for kidney stones

PO Metabolized by P450 in liver Reduce dose in patients with liver disease Poor CNS penetration

Potentially serious drug interactions due to P450 competition

NevirapineDelavirdene

Nob-nucleoside inhibitor of HIV reverse transcriptase

HIV Never as monotherapy due to rapid development of resistance

Rapid resistance develops due to mutations in reverse transcriptase

Severe skin rash fever nausea headache

PO Well absorbed Nevirapine crosses placenta amp has better CNS penetration than Delavirdene

Delavirdene failed to show clinical efficacy when added to didanosine in clinical trial

• Obat antivirus
• Virus
• Struktur virus
• Klasifikasi virus
• PowerPoint Presentation
• Slide 6
• Slide 7
• Slide 8
• Obat anti virus
• Slide 10
• ANTI-HERPES ANTI VZV HSV = herpes simplex virus VZV = Varicella Zoster virus
• ACYCLOVIR
• Mekanisme kerja
• Farmakokinetik
• Penggunaan dalam terapi
• THERAPEUTIC USES
• Efek samping
• PENCICLOVIR
• MK
• Slide 20
• Slide 21
• Slide 22
• Slide 23
• ANTI-INFLUENZA
• AMANTADINRIMANTADIN
• FK
• Efek samping
• Penggunaan terapi
• ZANAMIVIROSELTAMIVIR
• Slide 30
• Slide 31
• ANTI-HEPATITIS
• ADEFOVIR
• INTERFERON
• ANTIRETROVIRAL AGENTS
• Slide 36
• CURRENT ARV MEDICATIONS
• Slide 38
• Slide 39
• Slide 40
• Slide 41

Cidofovir Metabolized to diphosphate form Otherwise like ganciclovir

CMV retinitis Nephrotoxicity may be reduced by hydration amp coadministration of Probenicid Neutropenia

Foscarnet Analog of pyrophosphate Competes for pyrophosphate site in viral but not human DNA polymerase amp reverse transcriptase

CMV retinitis Does not need phosphorylation it is active against thymidine kinase ndashdeficient strains

Renal toxicity seizures hypocalcemia fever anemia diarrhea nausea

IV gt80 excreted unchanged in the urine CSF penetration variable Reduce dose with renal dysfunction

Deposited in bone amp teeth Hydrate patient during therapy to protect the kidney

Amantadine Prevents virus from entering susceptible cells

Treatment amp prophylaxis of influenza A

Depression CNS toxicity CHF orthostatic hypotension urinary retention

PO Excreted unmetabolized

Rimantadine Analog of amantadine inhibits viral uncoating

Prophylaxis in children

Fewer CNS side effects risk of seizure

PO Prolonged elimination w renal or hepatic dysfunction

Ribavirin Unknown mechanism

RSV Decreased pulmonary function

Aerosol administration Absorbed systemically

May precipitate in ventilator tubing

ANTI-INFLUENZAANTI-INFLUENZA

AMANTADINRIMANTADINAMANTADINRIMANTADIN Menghambat proses uncoating virus RNA

influenza A di dalam cell inang mencegah replikasi

Efektif menurunkan durasi gejala influenza jika diberikan dalam 48 jam setelah onset

FKFK

Absorpsi oral baikEkskresi dalam bentuk tak termetabolisme

di urinAmantadin dapat diekskresikan lewat ASI

Efek sampingEfek samping

Umum gangguan GI dan CNS minor (gugup light headanche susah konsentrasi insomnia mual nafsu makan berkurang)

Amantadin konsentrasi tinggi di plasma reaksi neurotoksik serius delirium kejang koma aritmia

Penggunaan terapiPenggunaan terapi

Pencegahan dan pengobatan influenza A 200 mghari dalam 1 atau 2 dosis

(pengobatan)Pencegahan harus dimulai ketika mulai

teridentifikasi pandemi virus 100mghari (4 ndash 8 minggu)

ZANAMIVIROSELTAMIVIRZANAMIVIROSELTAMIVIRPenghambat Neuroaminidase Menghambat replikasi influenza A amp B

FKFK

Diserap dengan cepat setelah pemberian oral (BA 80)

Eliminasi di ginjal dalam bentuk tak berubah

Berinterkasi dengan probenecid (meningkatkan T12 ndash 2x)

Efek sampingEfek samping

Mual rasa tak nyaman di lambung muntah lokal iritasi

Konsentrasi yang sangat tinggi berhungan dengan kematian (tikus)

ANTI-HEPATITISANTI-HEPATITIS

ADEFOVIRADEFOVIRSecara kompetitif menghambat HBV

DNA polymeraseMenghambat sintesis DNAEfek samping nefrotoksik pusing

diare ganggian abdomen)Pengobaan infeksi HBV kronis 10 mghari

INTERFERONINTERFERON Protein endogen yang dihasilkan dan dilepaskan

oleh sel sebagai respon terhadap patogen Menginduksi enzim menekan proliferasi aktivitas

imunomodulator dan menghambat replikasi virus Menghambat penetrasi dan amp uncoating Untuk pengobatan HBV amp HCV

ANTIRETROVIRAL ANTIRETROVIRAL AGENTSAGENTS

CURRENT ARV MEDICATIONSCURRENT ARV MEDICATIONS

NRTIbull Abacavir bull Didanosine bull Emtricitabine bull Lamivudine bull Stavudine bull Tenofovir bull Zidovudine

NNRTIbull Efavirenz bull Etravirine bull Nevirapine

PIbull Atazanavir bull Darunavir bull Fosamprenavir bull Indinavir bull Lopinavir bull Nelfinavirbull Ritonavir bull Saquinavir bull Tipranavir Fusion Inhibitorbull Enfuvirtide bull

Fixed-dose CombinationsbullZidovudine lamivudinebullZidovudinelamivudineabacavirbullAbacavirlamivudinebullEmtricitabinetenofovirbullEfavirenzemtricitabine tenofovir

DRUG MECHANISM amp VIRAL SELECTIVITY

CLINICAL USE

VIRAL RESISTANCE

UNDESIRABLE SIDE EFFECTS

PHARMACOKINETICS

NOTES

Zidovudine (AZT)

Thymidine analog is incorporated into DNA of human immunodeficiency viirus causing termination of the viral DNA chain

HIV Prevention of maternal-fetal transmission of HIV

Mutations in reverse transcriptase

Headaches nausea myalgias anemia neutropenia macrocytosis

PO Well absorbed rapidly metabolized by liver

Acetaminophen increases risk of hematologic toxicity

Didanosine (ddl)Zalcitabine (ddC)Lamivudine

-Metabolized intracellularly to dideoxynucleotide triphosphate that inhibits reverse transcriptase amp incorporates into viral DNA-Nucleotides fail to bind to ddATP bec it lacks free 3rsquo OH group

HIV Mutations in reverse transcriptase

Peripheral neuropathy pancreatitis diarrhea headache insomnia vomiting nausea rash abdominal pain

IVPO Partially metabolized in liver excreted in the urine Toxicity may be enhanced by renal or hepatic dysfunction

Limited utility as a single agent therapy because of viral resistance

Stavudine Metabolized to stavudine triphosphate wc inhibits HIV reverse transcriptase amp DNA polymerase Prevents DNA elongation

HIV Peripheral neuropathy

PO Not indicated for initial monotherapy of HIV

ANTIVIRAL DRUGS - RETROVIRUSES

RitonavirIndinavirSaquinavirNelfinavir

Inhibts HIV protease Results in immature virion

HIV Mutations in protease sequence reduce affinity of protease inhibitors

GI distress headache neurologic symptoms Indinavir associated w increase risk for kidney stones

PO Metabolized by P450 in liver Reduce dose in patients with liver disease Poor CNS penetration

Potentially serious drug interactions due to P450 competition

NevirapineDelavirdene

Nob-nucleoside inhibitor of HIV reverse transcriptase

HIV Never as monotherapy due to rapid development of resistance

Rapid resistance develops due to mutations in reverse transcriptase

Severe skin rash fever nausea headache

PO Well absorbed Nevirapine crosses placenta amp has better CNS penetration than Delavirdene

Delavirdene failed to show clinical efficacy when added to didanosine in clinical trial

• Obat antivirus
• Virus
• Struktur virus
• Klasifikasi virus
• PowerPoint Presentation
• Slide 6
• Slide 7
• Slide 8
• Obat anti virus
• Slide 10
• ANTI-HERPES ANTI VZV HSV = herpes simplex virus VZV = Varicella Zoster virus
• ACYCLOVIR
• Mekanisme kerja
• Farmakokinetik
• Penggunaan dalam terapi
• THERAPEUTIC USES
• Efek samping
• PENCICLOVIR
• MK
• Slide 20
• Slide 21
• Slide 22
• Slide 23
• ANTI-INFLUENZA
• AMANTADINRIMANTADIN
• FK
• Efek samping
• Penggunaan terapi
• ZANAMIVIROSELTAMIVIR
• Slide 30
• Slide 31
• ANTI-HEPATITIS
• ADEFOVIR
• INTERFERON
• ANTIRETROVIRAL AGENTS
• Slide 36
• CURRENT ARV MEDICATIONS
• Slide 38
• Slide 39
• Slide 40
• Slide 41

ANTI-INFLUENZAANTI-INFLUENZA

AMANTADINRIMANTADINAMANTADINRIMANTADIN Menghambat proses uncoating virus RNA

influenza A di dalam cell inang mencegah replikasi

Efektif menurunkan durasi gejala influenza jika diberikan dalam 48 jam setelah onset

FKFK

Absorpsi oral baikEkskresi dalam bentuk tak termetabolisme

di urinAmantadin dapat diekskresikan lewat ASI

Efek sampingEfek samping

Umum gangguan GI dan CNS minor (gugup light headanche susah konsentrasi insomnia mual nafsu makan berkurang)

Amantadin konsentrasi tinggi di plasma reaksi neurotoksik serius delirium kejang koma aritmia

Penggunaan terapiPenggunaan terapi

Pencegahan dan pengobatan influenza A 200 mghari dalam 1 atau 2 dosis

(pengobatan)Pencegahan harus dimulai ketika mulai

teridentifikasi pandemi virus 100mghari (4 ndash 8 minggu)

ZANAMIVIROSELTAMIVIRZANAMIVIROSELTAMIVIRPenghambat Neuroaminidase Menghambat replikasi influenza A amp B

FKFK

Diserap dengan cepat setelah pemberian oral (BA 80)

Eliminasi di ginjal dalam bentuk tak berubah

Berinterkasi dengan probenecid (meningkatkan T12 ndash 2x)

Efek sampingEfek samping

Mual rasa tak nyaman di lambung muntah lokal iritasi

Konsentrasi yang sangat tinggi berhungan dengan kematian (tikus)

ANTI-HEPATITISANTI-HEPATITIS

ADEFOVIRADEFOVIRSecara kompetitif menghambat HBV

DNA polymeraseMenghambat sintesis DNAEfek samping nefrotoksik pusing

diare ganggian abdomen)Pengobaan infeksi HBV kronis 10 mghari

INTERFERONINTERFERON Protein endogen yang dihasilkan dan dilepaskan

oleh sel sebagai respon terhadap patogen Menginduksi enzim menekan proliferasi aktivitas

imunomodulator dan menghambat replikasi virus Menghambat penetrasi dan amp uncoating Untuk pengobatan HBV amp HCV

ANTIRETROVIRAL ANTIRETROVIRAL AGENTSAGENTS

CURRENT ARV MEDICATIONSCURRENT ARV MEDICATIONS

NRTIbull Abacavir bull Didanosine bull Emtricitabine bull Lamivudine bull Stavudine bull Tenofovir bull Zidovudine

NNRTIbull Efavirenz bull Etravirine bull Nevirapine

PIbull Atazanavir bull Darunavir bull Fosamprenavir bull Indinavir bull Lopinavir bull Nelfinavirbull Ritonavir bull Saquinavir bull Tipranavir Fusion Inhibitorbull Enfuvirtide bull

Fixed-dose CombinationsbullZidovudine lamivudinebullZidovudinelamivudineabacavirbullAbacavirlamivudinebullEmtricitabinetenofovirbullEfavirenzemtricitabine tenofovir

DRUG MECHANISM amp VIRAL SELECTIVITY

CLINICAL USE

VIRAL RESISTANCE

UNDESIRABLE SIDE EFFECTS

PHARMACOKINETICS

NOTES

Zidovudine (AZT)

Thymidine analog is incorporated into DNA of human immunodeficiency viirus causing termination of the viral DNA chain

HIV Prevention of maternal-fetal transmission of HIV

Mutations in reverse transcriptase

Headaches nausea myalgias anemia neutropenia macrocytosis

PO Well absorbed rapidly metabolized by liver

Acetaminophen increases risk of hematologic toxicity

Didanosine (ddl)Zalcitabine (ddC)Lamivudine

-Metabolized intracellularly to dideoxynucleotide triphosphate that inhibits reverse transcriptase amp incorporates into viral DNA-Nucleotides fail to bind to ddATP bec it lacks free 3rsquo OH group

HIV Mutations in reverse transcriptase

Peripheral neuropathy pancreatitis diarrhea headache insomnia vomiting nausea rash abdominal pain

IVPO Partially metabolized in liver excreted in the urine Toxicity may be enhanced by renal or hepatic dysfunction

Limited utility as a single agent therapy because of viral resistance

Stavudine Metabolized to stavudine triphosphate wc inhibits HIV reverse transcriptase amp DNA polymerase Prevents DNA elongation

HIV Peripheral neuropathy

PO Not indicated for initial monotherapy of HIV

ANTIVIRAL DRUGS - RETROVIRUSES

RitonavirIndinavirSaquinavirNelfinavir

Inhibts HIV protease Results in immature virion

HIV Mutations in protease sequence reduce affinity of protease inhibitors

GI distress headache neurologic symptoms Indinavir associated w increase risk for kidney stones

PO Metabolized by P450 in liver Reduce dose in patients with liver disease Poor CNS penetration

Potentially serious drug interactions due to P450 competition

NevirapineDelavirdene

Nob-nucleoside inhibitor of HIV reverse transcriptase

HIV Never as monotherapy due to rapid development of resistance

Rapid resistance develops due to mutations in reverse transcriptase

Severe skin rash fever nausea headache

PO Well absorbed Nevirapine crosses placenta amp has better CNS penetration than Delavirdene

Delavirdene failed to show clinical efficacy when added to didanosine in clinical trial

• Obat antivirus
• Virus
• Struktur virus
• Klasifikasi virus
• PowerPoint Presentation
• Slide 6
• Slide 7
• Slide 8
• Obat anti virus
• Slide 10
• ANTI-HERPES ANTI VZV HSV = herpes simplex virus VZV = Varicella Zoster virus
• ACYCLOVIR
• Mekanisme kerja
• Farmakokinetik
• Penggunaan dalam terapi
• THERAPEUTIC USES
• Efek samping
• PENCICLOVIR
• MK
• Slide 20
• Slide 21
• Slide 22
• Slide 23
• ANTI-INFLUENZA
• AMANTADINRIMANTADIN
• FK
• Efek samping
• Penggunaan terapi
• ZANAMIVIROSELTAMIVIR
• Slide 30
• Slide 31
• ANTI-HEPATITIS
• ADEFOVIR
• INTERFERON
• ANTIRETROVIRAL AGENTS
• Slide 36
• CURRENT ARV MEDICATIONS
• Slide 38
• Slide 39
• Slide 40
• Slide 41

AMANTADINRIMANTADINAMANTADINRIMANTADIN Menghambat proses uncoating virus RNA

influenza A di dalam cell inang mencegah replikasi

Efektif menurunkan durasi gejala influenza jika diberikan dalam 48 jam setelah onset

FKFK

Absorpsi oral baikEkskresi dalam bentuk tak termetabolisme

di urinAmantadin dapat diekskresikan lewat ASI

Efek sampingEfek samping

Umum gangguan GI dan CNS minor (gugup light headanche susah konsentrasi insomnia mual nafsu makan berkurang)

Amantadin konsentrasi tinggi di plasma reaksi neurotoksik serius delirium kejang koma aritmia

Penggunaan terapiPenggunaan terapi

Pencegahan dan pengobatan influenza A 200 mghari dalam 1 atau 2 dosis

(pengobatan)Pencegahan harus dimulai ketika mulai

teridentifikasi pandemi virus 100mghari (4 ndash 8 minggu)

ZANAMIVIROSELTAMIVIRZANAMIVIROSELTAMIVIRPenghambat Neuroaminidase Menghambat replikasi influenza A amp B

FKFK

Diserap dengan cepat setelah pemberian oral (BA 80)

Eliminasi di ginjal dalam bentuk tak berubah

Berinterkasi dengan probenecid (meningkatkan T12 ndash 2x)

Efek sampingEfek samping

Mual rasa tak nyaman di lambung muntah lokal iritasi

Konsentrasi yang sangat tinggi berhungan dengan kematian (tikus)

ANTI-HEPATITISANTI-HEPATITIS

ADEFOVIRADEFOVIRSecara kompetitif menghambat HBV

DNA polymeraseMenghambat sintesis DNAEfek samping nefrotoksik pusing

diare ganggian abdomen)Pengobaan infeksi HBV kronis 10 mghari

INTERFERONINTERFERON Protein endogen yang dihasilkan dan dilepaskan

oleh sel sebagai respon terhadap patogen Menginduksi enzim menekan proliferasi aktivitas

imunomodulator dan menghambat replikasi virus Menghambat penetrasi dan amp uncoating Untuk pengobatan HBV amp HCV

ANTIRETROVIRAL ANTIRETROVIRAL AGENTSAGENTS

CURRENT ARV MEDICATIONSCURRENT ARV MEDICATIONS

NRTIbull Abacavir bull Didanosine bull Emtricitabine bull Lamivudine bull Stavudine bull Tenofovir bull Zidovudine

NNRTIbull Efavirenz bull Etravirine bull Nevirapine

PIbull Atazanavir bull Darunavir bull Fosamprenavir bull Indinavir bull Lopinavir bull Nelfinavirbull Ritonavir bull Saquinavir bull Tipranavir Fusion Inhibitorbull Enfuvirtide bull

Fixed-dose CombinationsbullZidovudine lamivudinebullZidovudinelamivudineabacavirbullAbacavirlamivudinebullEmtricitabinetenofovirbullEfavirenzemtricitabine tenofovir

DRUG MECHANISM amp VIRAL SELECTIVITY

CLINICAL USE

VIRAL RESISTANCE

UNDESIRABLE SIDE EFFECTS

PHARMACOKINETICS

NOTES

Zidovudine (AZT)

Thymidine analog is incorporated into DNA of human immunodeficiency viirus causing termination of the viral DNA chain

HIV Prevention of maternal-fetal transmission of HIV

Mutations in reverse transcriptase

Headaches nausea myalgias anemia neutropenia macrocytosis

PO Well absorbed rapidly metabolized by liver

Acetaminophen increases risk of hematologic toxicity

Didanosine (ddl)Zalcitabine (ddC)Lamivudine

-Metabolized intracellularly to dideoxynucleotide triphosphate that inhibits reverse transcriptase amp incorporates into viral DNA-Nucleotides fail to bind to ddATP bec it lacks free 3rsquo OH group

HIV Mutations in reverse transcriptase

Peripheral neuropathy pancreatitis diarrhea headache insomnia vomiting nausea rash abdominal pain

IVPO Partially metabolized in liver excreted in the urine Toxicity may be enhanced by renal or hepatic dysfunction

Limited utility as a single agent therapy because of viral resistance

Stavudine Metabolized to stavudine triphosphate wc inhibits HIV reverse transcriptase amp DNA polymerase Prevents DNA elongation

HIV Peripheral neuropathy

PO Not indicated for initial monotherapy of HIV

ANTIVIRAL DRUGS - RETROVIRUSES

RitonavirIndinavirSaquinavirNelfinavir

Inhibts HIV protease Results in immature virion

HIV Mutations in protease sequence reduce affinity of protease inhibitors

GI distress headache neurologic symptoms Indinavir associated w increase risk for kidney stones

PO Metabolized by P450 in liver Reduce dose in patients with liver disease Poor CNS penetration

Potentially serious drug interactions due to P450 competition

NevirapineDelavirdene

Nob-nucleoside inhibitor of HIV reverse transcriptase

HIV Never as monotherapy due to rapid development of resistance

Rapid resistance develops due to mutations in reverse transcriptase

Severe skin rash fever nausea headache

PO Well absorbed Nevirapine crosses placenta amp has better CNS penetration than Delavirdene

Delavirdene failed to show clinical efficacy when added to didanosine in clinical trial

• Obat antivirus
• Virus
• Struktur virus
• Klasifikasi virus
• PowerPoint Presentation
• Slide 6
• Slide 7
• Slide 8
• Obat anti virus
• Slide 10
• ANTI-HERPES ANTI VZV HSV = herpes simplex virus VZV = Varicella Zoster virus
• ACYCLOVIR
• Mekanisme kerja
• Farmakokinetik
• Penggunaan dalam terapi
• THERAPEUTIC USES
• Efek samping
• PENCICLOVIR
• MK
• Slide 20
• Slide 21
• Slide 22
• Slide 23
• ANTI-INFLUENZA
• AMANTADINRIMANTADIN
• FK
• Efek samping
• Penggunaan terapi
• ZANAMIVIROSELTAMIVIR
• Slide 30
• Slide 31
• ANTI-HEPATITIS
• ADEFOVIR
• INTERFERON
• ANTIRETROVIRAL AGENTS
• Slide 36
• CURRENT ARV MEDICATIONS
• Slide 38
• Slide 39
• Slide 40
• Slide 41

FKFK

Absorpsi oral baikEkskresi dalam bentuk tak termetabolisme

di urinAmantadin dapat diekskresikan lewat ASI

Efek sampingEfek samping

Umum gangguan GI dan CNS minor (gugup light headanche susah konsentrasi insomnia mual nafsu makan berkurang)

Amantadin konsentrasi tinggi di plasma reaksi neurotoksik serius delirium kejang koma aritmia

Penggunaan terapiPenggunaan terapi

Pencegahan dan pengobatan influenza A 200 mghari dalam 1 atau 2 dosis

(pengobatan)Pencegahan harus dimulai ketika mulai

teridentifikasi pandemi virus 100mghari (4 ndash 8 minggu)

ZANAMIVIROSELTAMIVIRZANAMIVIROSELTAMIVIRPenghambat Neuroaminidase Menghambat replikasi influenza A amp B

FKFK

Diserap dengan cepat setelah pemberian oral (BA 80)

Eliminasi di ginjal dalam bentuk tak berubah

Berinterkasi dengan probenecid (meningkatkan T12 ndash 2x)

Efek sampingEfek samping

Mual rasa tak nyaman di lambung muntah lokal iritasi

Konsentrasi yang sangat tinggi berhungan dengan kematian (tikus)

ANTI-HEPATITISANTI-HEPATITIS

ADEFOVIRADEFOVIRSecara kompetitif menghambat HBV

DNA polymeraseMenghambat sintesis DNAEfek samping nefrotoksik pusing

diare ganggian abdomen)Pengobaan infeksi HBV kronis 10 mghari

INTERFERONINTERFERON Protein endogen yang dihasilkan dan dilepaskan

oleh sel sebagai respon terhadap patogen Menginduksi enzim menekan proliferasi aktivitas

imunomodulator dan menghambat replikasi virus Menghambat penetrasi dan amp uncoating Untuk pengobatan HBV amp HCV

ANTIRETROVIRAL ANTIRETROVIRAL AGENTSAGENTS

CURRENT ARV MEDICATIONSCURRENT ARV MEDICATIONS

NRTIbull Abacavir bull Didanosine bull Emtricitabine bull Lamivudine bull Stavudine bull Tenofovir bull Zidovudine

NNRTIbull Efavirenz bull Etravirine bull Nevirapine

PIbull Atazanavir bull Darunavir bull Fosamprenavir bull Indinavir bull Lopinavir bull Nelfinavirbull Ritonavir bull Saquinavir bull Tipranavir Fusion Inhibitorbull Enfuvirtide bull

Fixed-dose CombinationsbullZidovudine lamivudinebullZidovudinelamivudineabacavirbullAbacavirlamivudinebullEmtricitabinetenofovirbullEfavirenzemtricitabine tenofovir

DRUG MECHANISM amp VIRAL SELECTIVITY

CLINICAL USE

VIRAL RESISTANCE

UNDESIRABLE SIDE EFFECTS

PHARMACOKINETICS

NOTES

Zidovudine (AZT)

Thymidine analog is incorporated into DNA of human immunodeficiency viirus causing termination of the viral DNA chain

HIV Prevention of maternal-fetal transmission of HIV

Mutations in reverse transcriptase

Headaches nausea myalgias anemia neutropenia macrocytosis

PO Well absorbed rapidly metabolized by liver

Acetaminophen increases risk of hematologic toxicity

Didanosine (ddl)Zalcitabine (ddC)Lamivudine

-Metabolized intracellularly to dideoxynucleotide triphosphate that inhibits reverse transcriptase amp incorporates into viral DNA-Nucleotides fail to bind to ddATP bec it lacks free 3rsquo OH group

HIV Mutations in reverse transcriptase

Peripheral neuropathy pancreatitis diarrhea headache insomnia vomiting nausea rash abdominal pain

IVPO Partially metabolized in liver excreted in the urine Toxicity may be enhanced by renal or hepatic dysfunction

Limited utility as a single agent therapy because of viral resistance

Stavudine Metabolized to stavudine triphosphate wc inhibits HIV reverse transcriptase amp DNA polymerase Prevents DNA elongation

HIV Peripheral neuropathy

PO Not indicated for initial monotherapy of HIV

ANTIVIRAL DRUGS - RETROVIRUSES

RitonavirIndinavirSaquinavirNelfinavir

Inhibts HIV protease Results in immature virion

HIV Mutations in protease sequence reduce affinity of protease inhibitors

GI distress headache neurologic symptoms Indinavir associated w increase risk for kidney stones

PO Metabolized by P450 in liver Reduce dose in patients with liver disease Poor CNS penetration

Potentially serious drug interactions due to P450 competition

NevirapineDelavirdene

Nob-nucleoside inhibitor of HIV reverse transcriptase

HIV Never as monotherapy due to rapid development of resistance

Rapid resistance develops due to mutations in reverse transcriptase

Severe skin rash fever nausea headache

PO Well absorbed Nevirapine crosses placenta amp has better CNS penetration than Delavirdene

Delavirdene failed to show clinical efficacy when added to didanosine in clinical trial

• Obat antivirus
• Virus
• Struktur virus
• Klasifikasi virus
• PowerPoint Presentation
• Slide 6
• Slide 7
• Slide 8
• Obat anti virus
• Slide 10
• ANTI-HERPES ANTI VZV HSV = herpes simplex virus VZV = Varicella Zoster virus
• ACYCLOVIR
• Mekanisme kerja
• Farmakokinetik
• Penggunaan dalam terapi
• THERAPEUTIC USES
• Efek samping
• PENCICLOVIR
• MK
• Slide 20
• Slide 21
• Slide 22
• Slide 23
• ANTI-INFLUENZA
• AMANTADINRIMANTADIN
• FK
• Efek samping
• Penggunaan terapi
• ZANAMIVIROSELTAMIVIR
• Slide 30
• Slide 31
• ANTI-HEPATITIS
• ADEFOVIR
• INTERFERON
• ANTIRETROVIRAL AGENTS
• Slide 36
• CURRENT ARV MEDICATIONS
• Slide 38
• Slide 39
• Slide 40
• Slide 41

Efek sampingEfek samping

Umum gangguan GI dan CNS minor (gugup light headanche susah konsentrasi insomnia mual nafsu makan berkurang)

Amantadin konsentrasi tinggi di plasma reaksi neurotoksik serius delirium kejang koma aritmia

Penggunaan terapiPenggunaan terapi

Pencegahan dan pengobatan influenza A 200 mghari dalam 1 atau 2 dosis

(pengobatan)Pencegahan harus dimulai ketika mulai

teridentifikasi pandemi virus 100mghari (4 ndash 8 minggu)

ZANAMIVIROSELTAMIVIRZANAMIVIROSELTAMIVIRPenghambat Neuroaminidase Menghambat replikasi influenza A amp B

FKFK

Diserap dengan cepat setelah pemberian oral (BA 80)

Eliminasi di ginjal dalam bentuk tak berubah

Berinterkasi dengan probenecid (meningkatkan T12 ndash 2x)

Efek sampingEfek samping

Mual rasa tak nyaman di lambung muntah lokal iritasi

Konsentrasi yang sangat tinggi berhungan dengan kematian (tikus)

ANTI-HEPATITISANTI-HEPATITIS

ADEFOVIRADEFOVIRSecara kompetitif menghambat HBV

DNA polymeraseMenghambat sintesis DNAEfek samping nefrotoksik pusing

diare ganggian abdomen)Pengobaan infeksi HBV kronis 10 mghari

INTERFERONINTERFERON Protein endogen yang dihasilkan dan dilepaskan

oleh sel sebagai respon terhadap patogen Menginduksi enzim menekan proliferasi aktivitas

imunomodulator dan menghambat replikasi virus Menghambat penetrasi dan amp uncoating Untuk pengobatan HBV amp HCV

ANTIRETROVIRAL ANTIRETROVIRAL AGENTSAGENTS

CURRENT ARV MEDICATIONSCURRENT ARV MEDICATIONS

NRTIbull Abacavir bull Didanosine bull Emtricitabine bull Lamivudine bull Stavudine bull Tenofovir bull Zidovudine

NNRTIbull Efavirenz bull Etravirine bull Nevirapine

PIbull Atazanavir bull Darunavir bull Fosamprenavir bull Indinavir bull Lopinavir bull Nelfinavirbull Ritonavir bull Saquinavir bull Tipranavir Fusion Inhibitorbull Enfuvirtide bull

Fixed-dose CombinationsbullZidovudine lamivudinebullZidovudinelamivudineabacavirbullAbacavirlamivudinebullEmtricitabinetenofovirbullEfavirenzemtricitabine tenofovir

DRUG MECHANISM amp VIRAL SELECTIVITY

CLINICAL USE

VIRAL RESISTANCE

UNDESIRABLE SIDE EFFECTS

PHARMACOKINETICS

NOTES

Zidovudine (AZT)

Thymidine analog is incorporated into DNA of human immunodeficiency viirus causing termination of the viral DNA chain

HIV Prevention of maternal-fetal transmission of HIV

Mutations in reverse transcriptase

Headaches nausea myalgias anemia neutropenia macrocytosis

PO Well absorbed rapidly metabolized by liver

Acetaminophen increases risk of hematologic toxicity

Didanosine (ddl)Zalcitabine (ddC)Lamivudine

-Metabolized intracellularly to dideoxynucleotide triphosphate that inhibits reverse transcriptase amp incorporates into viral DNA-Nucleotides fail to bind to ddATP bec it lacks free 3rsquo OH group

HIV Mutations in reverse transcriptase

Peripheral neuropathy pancreatitis diarrhea headache insomnia vomiting nausea rash abdominal pain

IVPO Partially metabolized in liver excreted in the urine Toxicity may be enhanced by renal or hepatic dysfunction

Limited utility as a single agent therapy because of viral resistance

Stavudine Metabolized to stavudine triphosphate wc inhibits HIV reverse transcriptase amp DNA polymerase Prevents DNA elongation

HIV Peripheral neuropathy

PO Not indicated for initial monotherapy of HIV

ANTIVIRAL DRUGS - RETROVIRUSES

RitonavirIndinavirSaquinavirNelfinavir

Inhibts HIV protease Results in immature virion

HIV Mutations in protease sequence reduce affinity of protease inhibitors

GI distress headache neurologic symptoms Indinavir associated w increase risk for kidney stones

PO Metabolized by P450 in liver Reduce dose in patients with liver disease Poor CNS penetration

Potentially serious drug interactions due to P450 competition

NevirapineDelavirdene

Nob-nucleoside inhibitor of HIV reverse transcriptase

HIV Never as monotherapy due to rapid development of resistance

Rapid resistance develops due to mutations in reverse transcriptase

Severe skin rash fever nausea headache

PO Well absorbed Nevirapine crosses placenta amp has better CNS penetration than Delavirdene

Delavirdene failed to show clinical efficacy when added to didanosine in clinical trial

• Obat antivirus
• Virus
• Struktur virus
• Klasifikasi virus
• PowerPoint Presentation
• Slide 6
• Slide 7
• Slide 8
• Obat anti virus
• Slide 10
• ANTI-HERPES ANTI VZV HSV = herpes simplex virus VZV = Varicella Zoster virus
• ACYCLOVIR
• Mekanisme kerja
• Farmakokinetik
• Penggunaan dalam terapi
• THERAPEUTIC USES
• Efek samping
• PENCICLOVIR
• MK
• Slide 20
• Slide 21
• Slide 22
• Slide 23
• ANTI-INFLUENZA
• AMANTADINRIMANTADIN
• FK
• Efek samping
• Penggunaan terapi
• ZANAMIVIROSELTAMIVIR
• Slide 30
• Slide 31
• ANTI-HEPATITIS
• ADEFOVIR
• INTERFERON
• ANTIRETROVIRAL AGENTS
• Slide 36
• CURRENT ARV MEDICATIONS
• Slide 38
• Slide 39
• Slide 40
• Slide 41

Penggunaan terapiPenggunaan terapi

Pencegahan dan pengobatan influenza A 200 mghari dalam 1 atau 2 dosis

(pengobatan)Pencegahan harus dimulai ketika mulai

teridentifikasi pandemi virus 100mghari (4 ndash 8 minggu)

ZANAMIVIROSELTAMIVIRZANAMIVIROSELTAMIVIRPenghambat Neuroaminidase Menghambat replikasi influenza A amp B

FKFK

Diserap dengan cepat setelah pemberian oral (BA 80)

Eliminasi di ginjal dalam bentuk tak berubah

Berinterkasi dengan probenecid (meningkatkan T12 ndash 2x)

Efek sampingEfek samping

Mual rasa tak nyaman di lambung muntah lokal iritasi

Konsentrasi yang sangat tinggi berhungan dengan kematian (tikus)

ANTI-HEPATITISANTI-HEPATITIS

ADEFOVIRADEFOVIRSecara kompetitif menghambat HBV

DNA polymeraseMenghambat sintesis DNAEfek samping nefrotoksik pusing

diare ganggian abdomen)Pengobaan infeksi HBV kronis 10 mghari

INTERFERONINTERFERON Protein endogen yang dihasilkan dan dilepaskan

oleh sel sebagai respon terhadap patogen Menginduksi enzim menekan proliferasi aktivitas

imunomodulator dan menghambat replikasi virus Menghambat penetrasi dan amp uncoating Untuk pengobatan HBV amp HCV

ANTIRETROVIRAL ANTIRETROVIRAL AGENTSAGENTS

CURRENT ARV MEDICATIONSCURRENT ARV MEDICATIONS

NRTIbull Abacavir bull Didanosine bull Emtricitabine bull Lamivudine bull Stavudine bull Tenofovir bull Zidovudine

NNRTIbull Efavirenz bull Etravirine bull Nevirapine

PIbull Atazanavir bull Darunavir bull Fosamprenavir bull Indinavir bull Lopinavir bull Nelfinavirbull Ritonavir bull Saquinavir bull Tipranavir Fusion Inhibitorbull Enfuvirtide bull

Fixed-dose CombinationsbullZidovudine lamivudinebullZidovudinelamivudineabacavirbullAbacavirlamivudinebullEmtricitabinetenofovirbullEfavirenzemtricitabine tenofovir

DRUG MECHANISM amp VIRAL SELECTIVITY

CLINICAL USE

VIRAL RESISTANCE

UNDESIRABLE SIDE EFFECTS

PHARMACOKINETICS

NOTES

Zidovudine (AZT)

Thymidine analog is incorporated into DNA of human immunodeficiency viirus causing termination of the viral DNA chain

HIV Prevention of maternal-fetal transmission of HIV

Mutations in reverse transcriptase

Headaches nausea myalgias anemia neutropenia macrocytosis

PO Well absorbed rapidly metabolized by liver

Acetaminophen increases risk of hematologic toxicity

Didanosine (ddl)Zalcitabine (ddC)Lamivudine

-Metabolized intracellularly to dideoxynucleotide triphosphate that inhibits reverse transcriptase amp incorporates into viral DNA-Nucleotides fail to bind to ddATP bec it lacks free 3rsquo OH group

HIV Mutations in reverse transcriptase

Peripheral neuropathy pancreatitis diarrhea headache insomnia vomiting nausea rash abdominal pain

IVPO Partially metabolized in liver excreted in the urine Toxicity may be enhanced by renal or hepatic dysfunction

Limited utility as a single agent therapy because of viral resistance

Stavudine Metabolized to stavudine triphosphate wc inhibits HIV reverse transcriptase amp DNA polymerase Prevents DNA elongation

HIV Peripheral neuropathy

PO Not indicated for initial monotherapy of HIV

ANTIVIRAL DRUGS - RETROVIRUSES

RitonavirIndinavirSaquinavirNelfinavir

Inhibts HIV protease Results in immature virion

HIV Mutations in protease sequence reduce affinity of protease inhibitors

GI distress headache neurologic symptoms Indinavir associated w increase risk for kidney stones

PO Metabolized by P450 in liver Reduce dose in patients with liver disease Poor CNS penetration

Potentially serious drug interactions due to P450 competition

NevirapineDelavirdene

Nob-nucleoside inhibitor of HIV reverse transcriptase

HIV Never as monotherapy due to rapid development of resistance

Rapid resistance develops due to mutations in reverse transcriptase

Severe skin rash fever nausea headache

PO Well absorbed Nevirapine crosses placenta amp has better CNS penetration than Delavirdene

Delavirdene failed to show clinical efficacy when added to didanosine in clinical trial

• Obat antivirus
• Virus
• Struktur virus
• Klasifikasi virus
• PowerPoint Presentation
• Slide 6
• Slide 7
• Slide 8
• Obat anti virus
• Slide 10
• ANTI-HERPES ANTI VZV HSV = herpes simplex virus VZV = Varicella Zoster virus
• ACYCLOVIR
• Mekanisme kerja
• Farmakokinetik
• Penggunaan dalam terapi
• THERAPEUTIC USES
• Efek samping
• PENCICLOVIR
• MK
• Slide 20
• Slide 21
• Slide 22
• Slide 23
• ANTI-INFLUENZA
• AMANTADINRIMANTADIN
• FK
• Efek samping
• Penggunaan terapi
• ZANAMIVIROSELTAMIVIR
• Slide 30
• Slide 31
• ANTI-HEPATITIS
• ADEFOVIR
• INTERFERON
• ANTIRETROVIRAL AGENTS
• Slide 36
• CURRENT ARV MEDICATIONS
• Slide 38
• Slide 39
• Slide 40
• Slide 41

ZANAMIVIROSELTAMIVIRZANAMIVIROSELTAMIVIRPenghambat Neuroaminidase Menghambat replikasi influenza A amp B

FKFK

Diserap dengan cepat setelah pemberian oral (BA 80)

Eliminasi di ginjal dalam bentuk tak berubah

Berinterkasi dengan probenecid (meningkatkan T12 ndash 2x)

Efek sampingEfek samping

Mual rasa tak nyaman di lambung muntah lokal iritasi

Konsentrasi yang sangat tinggi berhungan dengan kematian (tikus)

ANTI-HEPATITISANTI-HEPATITIS

ADEFOVIRADEFOVIRSecara kompetitif menghambat HBV

DNA polymeraseMenghambat sintesis DNAEfek samping nefrotoksik pusing

diare ganggian abdomen)Pengobaan infeksi HBV kronis 10 mghari

INTERFERONINTERFERON Protein endogen yang dihasilkan dan dilepaskan

oleh sel sebagai respon terhadap patogen Menginduksi enzim menekan proliferasi aktivitas

imunomodulator dan menghambat replikasi virus Menghambat penetrasi dan amp uncoating Untuk pengobatan HBV amp HCV

ANTIRETROVIRAL ANTIRETROVIRAL AGENTSAGENTS

CURRENT ARV MEDICATIONSCURRENT ARV MEDICATIONS

NRTIbull Abacavir bull Didanosine bull Emtricitabine bull Lamivudine bull Stavudine bull Tenofovir bull Zidovudine

NNRTIbull Efavirenz bull Etravirine bull Nevirapine

PIbull Atazanavir bull Darunavir bull Fosamprenavir bull Indinavir bull Lopinavir bull Nelfinavirbull Ritonavir bull Saquinavir bull Tipranavir Fusion Inhibitorbull Enfuvirtide bull

Fixed-dose CombinationsbullZidovudine lamivudinebullZidovudinelamivudineabacavirbullAbacavirlamivudinebullEmtricitabinetenofovirbullEfavirenzemtricitabine tenofovir

DRUG MECHANISM amp VIRAL SELECTIVITY

CLINICAL USE

VIRAL RESISTANCE

UNDESIRABLE SIDE EFFECTS

PHARMACOKINETICS

NOTES

Zidovudine (AZT)

Thymidine analog is incorporated into DNA of human immunodeficiency viirus causing termination of the viral DNA chain

HIV Prevention of maternal-fetal transmission of HIV

Mutations in reverse transcriptase

Headaches nausea myalgias anemia neutropenia macrocytosis

PO Well absorbed rapidly metabolized by liver

Acetaminophen increases risk of hematologic toxicity

Didanosine (ddl)Zalcitabine (ddC)Lamivudine

-Metabolized intracellularly to dideoxynucleotide triphosphate that inhibits reverse transcriptase amp incorporates into viral DNA-Nucleotides fail to bind to ddATP bec it lacks free 3rsquo OH group

HIV Mutations in reverse transcriptase

Peripheral neuropathy pancreatitis diarrhea headache insomnia vomiting nausea rash abdominal pain

IVPO Partially metabolized in liver excreted in the urine Toxicity may be enhanced by renal or hepatic dysfunction

Limited utility as a single agent therapy because of viral resistance

Stavudine Metabolized to stavudine triphosphate wc inhibits HIV reverse transcriptase amp DNA polymerase Prevents DNA elongation

HIV Peripheral neuropathy

PO Not indicated for initial monotherapy of HIV

ANTIVIRAL DRUGS - RETROVIRUSES

RitonavirIndinavirSaquinavirNelfinavir

Inhibts HIV protease Results in immature virion

HIV Mutations in protease sequence reduce affinity of protease inhibitors

GI distress headache neurologic symptoms Indinavir associated w increase risk for kidney stones

PO Metabolized by P450 in liver Reduce dose in patients with liver disease Poor CNS penetration

Potentially serious drug interactions due to P450 competition

NevirapineDelavirdene

Nob-nucleoside inhibitor of HIV reverse transcriptase

HIV Never as monotherapy due to rapid development of resistance

Rapid resistance develops due to mutations in reverse transcriptase

Severe skin rash fever nausea headache

PO Well absorbed Nevirapine crosses placenta amp has better CNS penetration than Delavirdene

Delavirdene failed to show clinical efficacy when added to didanosine in clinical trial

• Obat antivirus
• Virus
• Struktur virus
• Klasifikasi virus
• PowerPoint Presentation
• Slide 6
• Slide 7
• Slide 8
• Obat anti virus
• Slide 10
• ANTI-HERPES ANTI VZV HSV = herpes simplex virus VZV = Varicella Zoster virus
• ACYCLOVIR
• Mekanisme kerja
• Farmakokinetik
• Penggunaan dalam terapi
• THERAPEUTIC USES
• Efek samping
• PENCICLOVIR
• MK
• Slide 20
• Slide 21
• Slide 22
• Slide 23
• ANTI-INFLUENZA
• AMANTADINRIMANTADIN
• FK
• Efek samping
• Penggunaan terapi
• ZANAMIVIROSELTAMIVIR
• Slide 30
• Slide 31
• ANTI-HEPATITIS
• ADEFOVIR
• INTERFERON
• ANTIRETROVIRAL AGENTS
• Slide 36
• CURRENT ARV MEDICATIONS
• Slide 38
• Slide 39
• Slide 40
• Slide 41

FKFK

Diserap dengan cepat setelah pemberian oral (BA 80)

Eliminasi di ginjal dalam bentuk tak berubah

Berinterkasi dengan probenecid (meningkatkan T12 ndash 2x)

Efek sampingEfek samping

Mual rasa tak nyaman di lambung muntah lokal iritasi

Konsentrasi yang sangat tinggi berhungan dengan kematian (tikus)

ANTI-HEPATITISANTI-HEPATITIS

ADEFOVIRADEFOVIRSecara kompetitif menghambat HBV

DNA polymeraseMenghambat sintesis DNAEfek samping nefrotoksik pusing

diare ganggian abdomen)Pengobaan infeksi HBV kronis 10 mghari

INTERFERONINTERFERON Protein endogen yang dihasilkan dan dilepaskan

oleh sel sebagai respon terhadap patogen Menginduksi enzim menekan proliferasi aktivitas

imunomodulator dan menghambat replikasi virus Menghambat penetrasi dan amp uncoating Untuk pengobatan HBV amp HCV

ANTIRETROVIRAL ANTIRETROVIRAL AGENTSAGENTS

CURRENT ARV MEDICATIONSCURRENT ARV MEDICATIONS

NRTIbull Abacavir bull Didanosine bull Emtricitabine bull Lamivudine bull Stavudine bull Tenofovir bull Zidovudine

NNRTIbull Efavirenz bull Etravirine bull Nevirapine

PIbull Atazanavir bull Darunavir bull Fosamprenavir bull Indinavir bull Lopinavir bull Nelfinavirbull Ritonavir bull Saquinavir bull Tipranavir Fusion Inhibitorbull Enfuvirtide bull

Fixed-dose CombinationsbullZidovudine lamivudinebullZidovudinelamivudineabacavirbullAbacavirlamivudinebullEmtricitabinetenofovirbullEfavirenzemtricitabine tenofovir

DRUG MECHANISM amp VIRAL SELECTIVITY

CLINICAL USE

VIRAL RESISTANCE

UNDESIRABLE SIDE EFFECTS

PHARMACOKINETICS

NOTES

Zidovudine (AZT)

Thymidine analog is incorporated into DNA of human immunodeficiency viirus causing termination of the viral DNA chain

HIV Prevention of maternal-fetal transmission of HIV

Mutations in reverse transcriptase

Headaches nausea myalgias anemia neutropenia macrocytosis

PO Well absorbed rapidly metabolized by liver

Acetaminophen increases risk of hematologic toxicity

Didanosine (ddl)Zalcitabine (ddC)Lamivudine

-Metabolized intracellularly to dideoxynucleotide triphosphate that inhibits reverse transcriptase amp incorporates into viral DNA-Nucleotides fail to bind to ddATP bec it lacks free 3rsquo OH group

HIV Mutations in reverse transcriptase

Peripheral neuropathy pancreatitis diarrhea headache insomnia vomiting nausea rash abdominal pain

IVPO Partially metabolized in liver excreted in the urine Toxicity may be enhanced by renal or hepatic dysfunction

Limited utility as a single agent therapy because of viral resistance

Stavudine Metabolized to stavudine triphosphate wc inhibits HIV reverse transcriptase amp DNA polymerase Prevents DNA elongation

HIV Peripheral neuropathy

PO Not indicated for initial monotherapy of HIV

ANTIVIRAL DRUGS - RETROVIRUSES

RitonavirIndinavirSaquinavirNelfinavir

Inhibts HIV protease Results in immature virion

HIV Mutations in protease sequence reduce affinity of protease inhibitors

GI distress headache neurologic symptoms Indinavir associated w increase risk for kidney stones

PO Metabolized by P450 in liver Reduce dose in patients with liver disease Poor CNS penetration

Potentially serious drug interactions due to P450 competition

NevirapineDelavirdene

Nob-nucleoside inhibitor of HIV reverse transcriptase

HIV Never as monotherapy due to rapid development of resistance

Rapid resistance develops due to mutations in reverse transcriptase

Severe skin rash fever nausea headache

PO Well absorbed Nevirapine crosses placenta amp has better CNS penetration than Delavirdene

Delavirdene failed to show clinical efficacy when added to didanosine in clinical trial

• Obat antivirus
• Virus
• Struktur virus
• Klasifikasi virus
• PowerPoint Presentation
• Slide 6
• Slide 7
• Slide 8
• Obat anti virus
• Slide 10
• ANTI-HERPES ANTI VZV HSV = herpes simplex virus VZV = Varicella Zoster virus
• ACYCLOVIR
• Mekanisme kerja
• Farmakokinetik
• Penggunaan dalam terapi
• THERAPEUTIC USES
• Efek samping
• PENCICLOVIR
• MK
• Slide 20
• Slide 21
• Slide 22
• Slide 23
• ANTI-INFLUENZA
• AMANTADINRIMANTADIN
• FK
• Efek samping
• Penggunaan terapi
• ZANAMIVIROSELTAMIVIR
• Slide 30
• Slide 31
• ANTI-HEPATITIS
• ADEFOVIR
• INTERFERON
• ANTIRETROVIRAL AGENTS
• Slide 36
• CURRENT ARV MEDICATIONS
• Slide 38
• Slide 39
• Slide 40
• Slide 41

Efek sampingEfek samping

Mual rasa tak nyaman di lambung muntah lokal iritasi

Konsentrasi yang sangat tinggi berhungan dengan kematian (tikus)

ANTI-HEPATITISANTI-HEPATITIS

ADEFOVIRADEFOVIRSecara kompetitif menghambat HBV

DNA polymeraseMenghambat sintesis DNAEfek samping nefrotoksik pusing

diare ganggian abdomen)Pengobaan infeksi HBV kronis 10 mghari

INTERFERONINTERFERON Protein endogen yang dihasilkan dan dilepaskan

oleh sel sebagai respon terhadap patogen Menginduksi enzim menekan proliferasi aktivitas

imunomodulator dan menghambat replikasi virus Menghambat penetrasi dan amp uncoating Untuk pengobatan HBV amp HCV

ANTIRETROVIRAL ANTIRETROVIRAL AGENTSAGENTS

CURRENT ARV MEDICATIONSCURRENT ARV MEDICATIONS

NRTIbull Abacavir bull Didanosine bull Emtricitabine bull Lamivudine bull Stavudine bull Tenofovir bull Zidovudine

NNRTIbull Efavirenz bull Etravirine bull Nevirapine

PIbull Atazanavir bull Darunavir bull Fosamprenavir bull Indinavir bull Lopinavir bull Nelfinavirbull Ritonavir bull Saquinavir bull Tipranavir Fusion Inhibitorbull Enfuvirtide bull

Fixed-dose CombinationsbullZidovudine lamivudinebullZidovudinelamivudineabacavirbullAbacavirlamivudinebullEmtricitabinetenofovirbullEfavirenzemtricitabine tenofovir

DRUG MECHANISM amp VIRAL SELECTIVITY

CLINICAL USE

VIRAL RESISTANCE

UNDESIRABLE SIDE EFFECTS

PHARMACOKINETICS

NOTES

Zidovudine (AZT)

Thymidine analog is incorporated into DNA of human immunodeficiency viirus causing termination of the viral DNA chain

HIV Prevention of maternal-fetal transmission of HIV

Mutations in reverse transcriptase

Headaches nausea myalgias anemia neutropenia macrocytosis

PO Well absorbed rapidly metabolized by liver

Acetaminophen increases risk of hematologic toxicity

Didanosine (ddl)Zalcitabine (ddC)Lamivudine

-Metabolized intracellularly to dideoxynucleotide triphosphate that inhibits reverse transcriptase amp incorporates into viral DNA-Nucleotides fail to bind to ddATP bec it lacks free 3rsquo OH group

HIV Mutations in reverse transcriptase

Peripheral neuropathy pancreatitis diarrhea headache insomnia vomiting nausea rash abdominal pain

IVPO Partially metabolized in liver excreted in the urine Toxicity may be enhanced by renal or hepatic dysfunction

Limited utility as a single agent therapy because of viral resistance

Stavudine Metabolized to stavudine triphosphate wc inhibits HIV reverse transcriptase amp DNA polymerase Prevents DNA elongation

HIV Peripheral neuropathy

PO Not indicated for initial monotherapy of HIV

ANTIVIRAL DRUGS - RETROVIRUSES

RitonavirIndinavirSaquinavirNelfinavir

Inhibts HIV protease Results in immature virion

HIV Mutations in protease sequence reduce affinity of protease inhibitors

GI distress headache neurologic symptoms Indinavir associated w increase risk for kidney stones

PO Metabolized by P450 in liver Reduce dose in patients with liver disease Poor CNS penetration

Potentially serious drug interactions due to P450 competition

NevirapineDelavirdene

Nob-nucleoside inhibitor of HIV reverse transcriptase

HIV Never as monotherapy due to rapid development of resistance

Rapid resistance develops due to mutations in reverse transcriptase

Severe skin rash fever nausea headache

PO Well absorbed Nevirapine crosses placenta amp has better CNS penetration than Delavirdene

Delavirdene failed to show clinical efficacy when added to didanosine in clinical trial

• Obat antivirus
• Virus
• Struktur virus
• Klasifikasi virus
• PowerPoint Presentation
• Slide 6
• Slide 7
• Slide 8
• Obat anti virus
• Slide 10
• ANTI-HERPES ANTI VZV HSV = herpes simplex virus VZV = Varicella Zoster virus
• ACYCLOVIR
• Mekanisme kerja
• Farmakokinetik
• Penggunaan dalam terapi
• THERAPEUTIC USES
• Efek samping
• PENCICLOVIR
• MK
• Slide 20
• Slide 21
• Slide 22
• Slide 23
• ANTI-INFLUENZA
• AMANTADINRIMANTADIN
• FK
• Efek samping
• Penggunaan terapi
• ZANAMIVIROSELTAMIVIR
• Slide 30
• Slide 31
• ANTI-HEPATITIS
• ADEFOVIR
• INTERFERON
• ANTIRETROVIRAL AGENTS
• Slide 36
• CURRENT ARV MEDICATIONS
• Slide 38
• Slide 39
• Slide 40
• Slide 41

ANTI-HEPATITISANTI-HEPATITIS

ADEFOVIRADEFOVIRSecara kompetitif menghambat HBV

DNA polymeraseMenghambat sintesis DNAEfek samping nefrotoksik pusing

diare ganggian abdomen)Pengobaan infeksi HBV kronis 10 mghari

INTERFERONINTERFERON Protein endogen yang dihasilkan dan dilepaskan

oleh sel sebagai respon terhadap patogen Menginduksi enzim menekan proliferasi aktivitas

imunomodulator dan menghambat replikasi virus Menghambat penetrasi dan amp uncoating Untuk pengobatan HBV amp HCV

ANTIRETROVIRAL ANTIRETROVIRAL AGENTSAGENTS

CURRENT ARV MEDICATIONSCURRENT ARV MEDICATIONS

NRTIbull Abacavir bull Didanosine bull Emtricitabine bull Lamivudine bull Stavudine bull Tenofovir bull Zidovudine

NNRTIbull Efavirenz bull Etravirine bull Nevirapine

PIbull Atazanavir bull Darunavir bull Fosamprenavir bull Indinavir bull Lopinavir bull Nelfinavirbull Ritonavir bull Saquinavir bull Tipranavir Fusion Inhibitorbull Enfuvirtide bull

Fixed-dose CombinationsbullZidovudine lamivudinebullZidovudinelamivudineabacavirbullAbacavirlamivudinebullEmtricitabinetenofovirbullEfavirenzemtricitabine tenofovir

DRUG MECHANISM amp VIRAL SELECTIVITY

CLINICAL USE

VIRAL RESISTANCE

UNDESIRABLE SIDE EFFECTS

PHARMACOKINETICS

NOTES

Zidovudine (AZT)

Thymidine analog is incorporated into DNA of human immunodeficiency viirus causing termination of the viral DNA chain

HIV Prevention of maternal-fetal transmission of HIV

Mutations in reverse transcriptase

Headaches nausea myalgias anemia neutropenia macrocytosis

PO Well absorbed rapidly metabolized by liver

Acetaminophen increases risk of hematologic toxicity

Didanosine (ddl)Zalcitabine (ddC)Lamivudine

-Metabolized intracellularly to dideoxynucleotide triphosphate that inhibits reverse transcriptase amp incorporates into viral DNA-Nucleotides fail to bind to ddATP bec it lacks free 3rsquo OH group

HIV Mutations in reverse transcriptase

Peripheral neuropathy pancreatitis diarrhea headache insomnia vomiting nausea rash abdominal pain

IVPO Partially metabolized in liver excreted in the urine Toxicity may be enhanced by renal or hepatic dysfunction

Limited utility as a single agent therapy because of viral resistance

Stavudine Metabolized to stavudine triphosphate wc inhibits HIV reverse transcriptase amp DNA polymerase Prevents DNA elongation

HIV Peripheral neuropathy

PO Not indicated for initial monotherapy of HIV

ANTIVIRAL DRUGS - RETROVIRUSES

RitonavirIndinavirSaquinavirNelfinavir

Inhibts HIV protease Results in immature virion

HIV Mutations in protease sequence reduce affinity of protease inhibitors

GI distress headache neurologic symptoms Indinavir associated w increase risk for kidney stones

PO Metabolized by P450 in liver Reduce dose in patients with liver disease Poor CNS penetration

Potentially serious drug interactions due to P450 competition

NevirapineDelavirdene

Nob-nucleoside inhibitor of HIV reverse transcriptase

HIV Never as monotherapy due to rapid development of resistance

Rapid resistance develops due to mutations in reverse transcriptase

Severe skin rash fever nausea headache

PO Well absorbed Nevirapine crosses placenta amp has better CNS penetration than Delavirdene

Delavirdene failed to show clinical efficacy when added to didanosine in clinical trial

• Obat antivirus
• Virus
• Struktur virus
• Klasifikasi virus
• PowerPoint Presentation
• Slide 6
• Slide 7
• Slide 8
• Obat anti virus
• Slide 10
• ANTI-HERPES ANTI VZV HSV = herpes simplex virus VZV = Varicella Zoster virus
• ACYCLOVIR
• Mekanisme kerja
• Farmakokinetik
• Penggunaan dalam terapi
• THERAPEUTIC USES
• Efek samping
• PENCICLOVIR
• MK
• Slide 20
• Slide 21
• Slide 22
• Slide 23
• ANTI-INFLUENZA
• AMANTADINRIMANTADIN
• FK
• Efek samping
• Penggunaan terapi
• ZANAMIVIROSELTAMIVIR
• Slide 30
• Slide 31
• ANTI-HEPATITIS
• ADEFOVIR
• INTERFERON
• ANTIRETROVIRAL AGENTS
• Slide 36
• CURRENT ARV MEDICATIONS
• Slide 38
• Slide 39
• Slide 40
• Slide 41

ADEFOVIRADEFOVIRSecara kompetitif menghambat HBV

DNA polymeraseMenghambat sintesis DNAEfek samping nefrotoksik pusing

diare ganggian abdomen)Pengobaan infeksi HBV kronis 10 mghari

INTERFERONINTERFERON Protein endogen yang dihasilkan dan dilepaskan

oleh sel sebagai respon terhadap patogen Menginduksi enzim menekan proliferasi aktivitas

imunomodulator dan menghambat replikasi virus Menghambat penetrasi dan amp uncoating Untuk pengobatan HBV amp HCV

ANTIRETROVIRAL ANTIRETROVIRAL AGENTSAGENTS

CURRENT ARV MEDICATIONSCURRENT ARV MEDICATIONS

NRTIbull Abacavir bull Didanosine bull Emtricitabine bull Lamivudine bull Stavudine bull Tenofovir bull Zidovudine

NNRTIbull Efavirenz bull Etravirine bull Nevirapine

PIbull Atazanavir bull Darunavir bull Fosamprenavir bull Indinavir bull Lopinavir bull Nelfinavirbull Ritonavir bull Saquinavir bull Tipranavir Fusion Inhibitorbull Enfuvirtide bull

Fixed-dose CombinationsbullZidovudine lamivudinebullZidovudinelamivudineabacavirbullAbacavirlamivudinebullEmtricitabinetenofovirbullEfavirenzemtricitabine tenofovir

DRUG MECHANISM amp VIRAL SELECTIVITY

CLINICAL USE

VIRAL RESISTANCE

UNDESIRABLE SIDE EFFECTS

PHARMACOKINETICS

NOTES

Zidovudine (AZT)

Thymidine analog is incorporated into DNA of human immunodeficiency viirus causing termination of the viral DNA chain

HIV Prevention of maternal-fetal transmission of HIV

Mutations in reverse transcriptase

Headaches nausea myalgias anemia neutropenia macrocytosis

PO Well absorbed rapidly metabolized by liver

Acetaminophen increases risk of hematologic toxicity

Didanosine (ddl)Zalcitabine (ddC)Lamivudine

-Metabolized intracellularly to dideoxynucleotide triphosphate that inhibits reverse transcriptase amp incorporates into viral DNA-Nucleotides fail to bind to ddATP bec it lacks free 3rsquo OH group

HIV Mutations in reverse transcriptase

Peripheral neuropathy pancreatitis diarrhea headache insomnia vomiting nausea rash abdominal pain

IVPO Partially metabolized in liver excreted in the urine Toxicity may be enhanced by renal or hepatic dysfunction

Limited utility as a single agent therapy because of viral resistance

Stavudine Metabolized to stavudine triphosphate wc inhibits HIV reverse transcriptase amp DNA polymerase Prevents DNA elongation

HIV Peripheral neuropathy

PO Not indicated for initial monotherapy of HIV

ANTIVIRAL DRUGS - RETROVIRUSES

RitonavirIndinavirSaquinavirNelfinavir

Inhibts HIV protease Results in immature virion

HIV Mutations in protease sequence reduce affinity of protease inhibitors

GI distress headache neurologic symptoms Indinavir associated w increase risk for kidney stones

PO Metabolized by P450 in liver Reduce dose in patients with liver disease Poor CNS penetration

Potentially serious drug interactions due to P450 competition

NevirapineDelavirdene

Nob-nucleoside inhibitor of HIV reverse transcriptase

HIV Never as monotherapy due to rapid development of resistance

Rapid resistance develops due to mutations in reverse transcriptase

Severe skin rash fever nausea headache

PO Well absorbed Nevirapine crosses placenta amp has better CNS penetration than Delavirdene

Delavirdene failed to show clinical efficacy when added to didanosine in clinical trial

• Obat antivirus
• Virus
• Struktur virus
• Klasifikasi virus
• PowerPoint Presentation
• Slide 6
• Slide 7
• Slide 8
• Obat anti virus
• Slide 10
• ANTI-HERPES ANTI VZV HSV = herpes simplex virus VZV = Varicella Zoster virus
• ACYCLOVIR
• Mekanisme kerja
• Farmakokinetik
• Penggunaan dalam terapi
• THERAPEUTIC USES
• Efek samping
• PENCICLOVIR
• MK
• Slide 20
• Slide 21
• Slide 22
• Slide 23
• ANTI-INFLUENZA
• AMANTADINRIMANTADIN
• FK
• Efek samping
• Penggunaan terapi
• ZANAMIVIROSELTAMIVIR
• Slide 30
• Slide 31
• ANTI-HEPATITIS
• ADEFOVIR
• INTERFERON
• ANTIRETROVIRAL AGENTS
• Slide 36
• CURRENT ARV MEDICATIONS
• Slide 38
• Slide 39
• Slide 40
• Slide 41

INTERFERONINTERFERON Protein endogen yang dihasilkan dan dilepaskan

oleh sel sebagai respon terhadap patogen Menginduksi enzim menekan proliferasi aktivitas

imunomodulator dan menghambat replikasi virus Menghambat penetrasi dan amp uncoating Untuk pengobatan HBV amp HCV

ANTIRETROVIRAL ANTIRETROVIRAL AGENTSAGENTS

CURRENT ARV MEDICATIONSCURRENT ARV MEDICATIONS

NRTIbull Abacavir bull Didanosine bull Emtricitabine bull Lamivudine bull Stavudine bull Tenofovir bull Zidovudine

NNRTIbull Efavirenz bull Etravirine bull Nevirapine

PIbull Atazanavir bull Darunavir bull Fosamprenavir bull Indinavir bull Lopinavir bull Nelfinavirbull Ritonavir bull Saquinavir bull Tipranavir Fusion Inhibitorbull Enfuvirtide bull

Fixed-dose CombinationsbullZidovudine lamivudinebullZidovudinelamivudineabacavirbullAbacavirlamivudinebullEmtricitabinetenofovirbullEfavirenzemtricitabine tenofovir

DRUG MECHANISM amp VIRAL SELECTIVITY

CLINICAL USE

VIRAL RESISTANCE

UNDESIRABLE SIDE EFFECTS

PHARMACOKINETICS

NOTES

Zidovudine (AZT)

Thymidine analog is incorporated into DNA of human immunodeficiency viirus causing termination of the viral DNA chain

HIV Prevention of maternal-fetal transmission of HIV

Mutations in reverse transcriptase

Headaches nausea myalgias anemia neutropenia macrocytosis

PO Well absorbed rapidly metabolized by liver

Acetaminophen increases risk of hematologic toxicity

Didanosine (ddl)Zalcitabine (ddC)Lamivudine

-Metabolized intracellularly to dideoxynucleotide triphosphate that inhibits reverse transcriptase amp incorporates into viral DNA-Nucleotides fail to bind to ddATP bec it lacks free 3rsquo OH group

HIV Mutations in reverse transcriptase

Peripheral neuropathy pancreatitis diarrhea headache insomnia vomiting nausea rash abdominal pain

IVPO Partially metabolized in liver excreted in the urine Toxicity may be enhanced by renal or hepatic dysfunction

Limited utility as a single agent therapy because of viral resistance

Stavudine Metabolized to stavudine triphosphate wc inhibits HIV reverse transcriptase amp DNA polymerase Prevents DNA elongation

HIV Peripheral neuropathy

PO Not indicated for initial monotherapy of HIV

ANTIVIRAL DRUGS - RETROVIRUSES

RitonavirIndinavirSaquinavirNelfinavir

Inhibts HIV protease Results in immature virion

HIV Mutations in protease sequence reduce affinity of protease inhibitors

GI distress headache neurologic symptoms Indinavir associated w increase risk for kidney stones

PO Metabolized by P450 in liver Reduce dose in patients with liver disease Poor CNS penetration

Potentially serious drug interactions due to P450 competition

NevirapineDelavirdene

Nob-nucleoside inhibitor of HIV reverse transcriptase

HIV Never as monotherapy due to rapid development of resistance

Rapid resistance develops due to mutations in reverse transcriptase

Severe skin rash fever nausea headache

PO Well absorbed Nevirapine crosses placenta amp has better CNS penetration than Delavirdene

Delavirdene failed to show clinical efficacy when added to didanosine in clinical trial

• Obat antivirus
• Virus
• Struktur virus
• Klasifikasi virus
• PowerPoint Presentation
• Slide 6
• Slide 7
• Slide 8
• Obat anti virus
• Slide 10
• ANTI-HERPES ANTI VZV HSV = herpes simplex virus VZV = Varicella Zoster virus
• ACYCLOVIR
• Mekanisme kerja
• Farmakokinetik
• Penggunaan dalam terapi
• THERAPEUTIC USES
• Efek samping
• PENCICLOVIR
• MK
• Slide 20
• Slide 21
• Slide 22
• Slide 23
• ANTI-INFLUENZA
• AMANTADINRIMANTADIN
• FK
• Efek samping
• Penggunaan terapi
• ZANAMIVIROSELTAMIVIR
• Slide 30
• Slide 31
• ANTI-HEPATITIS
• ADEFOVIR
• INTERFERON
• ANTIRETROVIRAL AGENTS
• Slide 36
• CURRENT ARV MEDICATIONS
• Slide 38
• Slide 39
• Slide 40
• Slide 41

ANTIRETROVIRAL ANTIRETROVIRAL AGENTSAGENTS

CURRENT ARV MEDICATIONSCURRENT ARV MEDICATIONS

NRTIbull Abacavir bull Didanosine bull Emtricitabine bull Lamivudine bull Stavudine bull Tenofovir bull Zidovudine

NNRTIbull Efavirenz bull Etravirine bull Nevirapine

PIbull Atazanavir bull Darunavir bull Fosamprenavir bull Indinavir bull Lopinavir bull Nelfinavirbull Ritonavir bull Saquinavir bull Tipranavir Fusion Inhibitorbull Enfuvirtide bull

Fixed-dose CombinationsbullZidovudine lamivudinebullZidovudinelamivudineabacavirbullAbacavirlamivudinebullEmtricitabinetenofovirbullEfavirenzemtricitabine tenofovir

DRUG MECHANISM amp VIRAL SELECTIVITY

CLINICAL USE

VIRAL RESISTANCE

UNDESIRABLE SIDE EFFECTS

PHARMACOKINETICS

NOTES

Zidovudine (AZT)

Thymidine analog is incorporated into DNA of human immunodeficiency viirus causing termination of the viral DNA chain

HIV Prevention of maternal-fetal transmission of HIV

Mutations in reverse transcriptase

Headaches nausea myalgias anemia neutropenia macrocytosis

PO Well absorbed rapidly metabolized by liver

Acetaminophen increases risk of hematologic toxicity

Didanosine (ddl)Zalcitabine (ddC)Lamivudine

-Metabolized intracellularly to dideoxynucleotide triphosphate that inhibits reverse transcriptase amp incorporates into viral DNA-Nucleotides fail to bind to ddATP bec it lacks free 3rsquo OH group

HIV Mutations in reverse transcriptase

Peripheral neuropathy pancreatitis diarrhea headache insomnia vomiting nausea rash abdominal pain

IVPO Partially metabolized in liver excreted in the urine Toxicity may be enhanced by renal or hepatic dysfunction

Limited utility as a single agent therapy because of viral resistance

Stavudine Metabolized to stavudine triphosphate wc inhibits HIV reverse transcriptase amp DNA polymerase Prevents DNA elongation

HIV Peripheral neuropathy

PO Not indicated for initial monotherapy of HIV

ANTIVIRAL DRUGS - RETROVIRUSES

RitonavirIndinavirSaquinavirNelfinavir

Inhibts HIV protease Results in immature virion

HIV Mutations in protease sequence reduce affinity of protease inhibitors

GI distress headache neurologic symptoms Indinavir associated w increase risk for kidney stones

PO Metabolized by P450 in liver Reduce dose in patients with liver disease Poor CNS penetration

Potentially serious drug interactions due to P450 competition

NevirapineDelavirdene

Nob-nucleoside inhibitor of HIV reverse transcriptase

HIV Never as monotherapy due to rapid development of resistance

Rapid resistance develops due to mutations in reverse transcriptase

Severe skin rash fever nausea headache

PO Well absorbed Nevirapine crosses placenta amp has better CNS penetration than Delavirdene

Delavirdene failed to show clinical efficacy when added to didanosine in clinical trial

• Obat antivirus
• Virus
• Struktur virus
• Klasifikasi virus
• PowerPoint Presentation
• Slide 6
• Slide 7
• Slide 8
• Obat anti virus
• Slide 10
• ANTI-HERPES ANTI VZV HSV = herpes simplex virus VZV = Varicella Zoster virus
• ACYCLOVIR
• Mekanisme kerja
• Farmakokinetik
• Penggunaan dalam terapi
• THERAPEUTIC USES
• Efek samping
• PENCICLOVIR
• MK
• Slide 20
• Slide 21
• Slide 22
• Slide 23
• ANTI-INFLUENZA
• AMANTADINRIMANTADIN
• FK
• Efek samping
• Penggunaan terapi
• ZANAMIVIROSELTAMIVIR
• Slide 30
• Slide 31
• ANTI-HEPATITIS
• ADEFOVIR
• INTERFERON
• ANTIRETROVIRAL AGENTS
• Slide 36
• CURRENT ARV MEDICATIONS
• Slide 38
• Slide 39
• Slide 40
• Slide 41

CURRENT ARV MEDICATIONSCURRENT ARV MEDICATIONS

NRTIbull Abacavir bull Didanosine bull Emtricitabine bull Lamivudine bull Stavudine bull Tenofovir bull Zidovudine

NNRTIbull Efavirenz bull Etravirine bull Nevirapine

PIbull Atazanavir bull Darunavir bull Fosamprenavir bull Indinavir bull Lopinavir bull Nelfinavirbull Ritonavir bull Saquinavir bull Tipranavir Fusion Inhibitorbull Enfuvirtide bull

Fixed-dose CombinationsbullZidovudine lamivudinebullZidovudinelamivudineabacavirbullAbacavirlamivudinebullEmtricitabinetenofovirbullEfavirenzemtricitabine tenofovir

DRUG MECHANISM amp VIRAL SELECTIVITY

CLINICAL USE

VIRAL RESISTANCE

UNDESIRABLE SIDE EFFECTS

PHARMACOKINETICS

NOTES

Zidovudine (AZT)

Thymidine analog is incorporated into DNA of human immunodeficiency viirus causing termination of the viral DNA chain

HIV Prevention of maternal-fetal transmission of HIV

Mutations in reverse transcriptase

Headaches nausea myalgias anemia neutropenia macrocytosis

PO Well absorbed rapidly metabolized by liver

Acetaminophen increases risk of hematologic toxicity

Didanosine (ddl)Zalcitabine (ddC)Lamivudine

-Metabolized intracellularly to dideoxynucleotide triphosphate that inhibits reverse transcriptase amp incorporates into viral DNA-Nucleotides fail to bind to ddATP bec it lacks free 3rsquo OH group

HIV Mutations in reverse transcriptase

Peripheral neuropathy pancreatitis diarrhea headache insomnia vomiting nausea rash abdominal pain

IVPO Partially metabolized in liver excreted in the urine Toxicity may be enhanced by renal or hepatic dysfunction

Limited utility as a single agent therapy because of viral resistance

Stavudine Metabolized to stavudine triphosphate wc inhibits HIV reverse transcriptase amp DNA polymerase Prevents DNA elongation

HIV Peripheral neuropathy

PO Not indicated for initial monotherapy of HIV

ANTIVIRAL DRUGS - RETROVIRUSES

RitonavirIndinavirSaquinavirNelfinavir

Inhibts HIV protease Results in immature virion

HIV Mutations in protease sequence reduce affinity of protease inhibitors

GI distress headache neurologic symptoms Indinavir associated w increase risk for kidney stones

PO Metabolized by P450 in liver Reduce dose in patients with liver disease Poor CNS penetration

Potentially serious drug interactions due to P450 competition

NevirapineDelavirdene

Nob-nucleoside inhibitor of HIV reverse transcriptase

HIV Never as monotherapy due to rapid development of resistance

Rapid resistance develops due to mutations in reverse transcriptase

Severe skin rash fever nausea headache

PO Well absorbed Nevirapine crosses placenta amp has better CNS penetration than Delavirdene

Delavirdene failed to show clinical efficacy when added to didanosine in clinical trial

• Obat antivirus
• Virus
• Struktur virus
• Klasifikasi virus
• PowerPoint Presentation
• Slide 6
• Slide 7
• Slide 8
• Obat anti virus
• Slide 10
• ANTI-HERPES ANTI VZV HSV = herpes simplex virus VZV = Varicella Zoster virus
• ACYCLOVIR
• Mekanisme kerja
• Farmakokinetik
• Penggunaan dalam terapi
• THERAPEUTIC USES
• Efek samping
• PENCICLOVIR
• MK
• Slide 20
• Slide 21
• Slide 22
• Slide 23
• ANTI-INFLUENZA
• AMANTADINRIMANTADIN
• FK
• Efek samping
• Penggunaan terapi
• ZANAMIVIROSELTAMIVIR
• Slide 30
• Slide 31
• ANTI-HEPATITIS
• ADEFOVIR
• INTERFERON
• ANTIRETROVIRAL AGENTS
• Slide 36
• CURRENT ARV MEDICATIONS
• Slide 38
• Slide 39
• Slide 40
• Slide 41

DRUG MECHANISM amp VIRAL SELECTIVITY

CLINICAL USE

VIRAL RESISTANCE

UNDESIRABLE SIDE EFFECTS

PHARMACOKINETICS

NOTES

Zidovudine (AZT)

Thymidine analog is incorporated into DNA of human immunodeficiency viirus causing termination of the viral DNA chain

HIV Prevention of maternal-fetal transmission of HIV

Mutations in reverse transcriptase

Headaches nausea myalgias anemia neutropenia macrocytosis

PO Well absorbed rapidly metabolized by liver

Acetaminophen increases risk of hematologic toxicity

Didanosine (ddl)Zalcitabine (ddC)Lamivudine

-Metabolized intracellularly to dideoxynucleotide triphosphate that inhibits reverse transcriptase amp incorporates into viral DNA-Nucleotides fail to bind to ddATP bec it lacks free 3rsquo OH group

HIV Mutations in reverse transcriptase

Peripheral neuropathy pancreatitis diarrhea headache insomnia vomiting nausea rash abdominal pain

IVPO Partially metabolized in liver excreted in the urine Toxicity may be enhanced by renal or hepatic dysfunction

Limited utility as a single agent therapy because of viral resistance

Stavudine Metabolized to stavudine triphosphate wc inhibits HIV reverse transcriptase amp DNA polymerase Prevents DNA elongation

HIV Peripheral neuropathy

PO Not indicated for initial monotherapy of HIV

ANTIVIRAL DRUGS - RETROVIRUSES

RitonavirIndinavirSaquinavirNelfinavir

Inhibts HIV protease Results in immature virion

HIV Mutations in protease sequence reduce affinity of protease inhibitors

GI distress headache neurologic symptoms Indinavir associated w increase risk for kidney stones

PO Metabolized by P450 in liver Reduce dose in patients with liver disease Poor CNS penetration

Potentially serious drug interactions due to P450 competition

NevirapineDelavirdene

Nob-nucleoside inhibitor of HIV reverse transcriptase

HIV Never as monotherapy due to rapid development of resistance

Rapid resistance develops due to mutations in reverse transcriptase

Severe skin rash fever nausea headache

PO Well absorbed Nevirapine crosses placenta amp has better CNS penetration than Delavirdene

Delavirdene failed to show clinical efficacy when added to didanosine in clinical trial

• Obat antivirus
• Virus
• Struktur virus
• Klasifikasi virus
• PowerPoint Presentation
• Slide 6
• Slide 7
• Slide 8
• Obat anti virus
• Slide 10
• ANTI-HERPES ANTI VZV HSV = herpes simplex virus VZV = Varicella Zoster virus
• ACYCLOVIR
• Mekanisme kerja
• Farmakokinetik
• Penggunaan dalam terapi
• THERAPEUTIC USES
• Efek samping
• PENCICLOVIR
• MK
• Slide 20
• Slide 21
• Slide 22
• Slide 23
• ANTI-INFLUENZA
• AMANTADINRIMANTADIN
• FK
• Efek samping
• Penggunaan terapi
• ZANAMIVIROSELTAMIVIR
• Slide 30
• Slide 31
• ANTI-HEPATITIS
• ADEFOVIR
• INTERFERON
• ANTIRETROVIRAL AGENTS
• Slide 36
• CURRENT ARV MEDICATIONS
• Slide 38
• Slide 39
• Slide 40
• Slide 41

RitonavirIndinavirSaquinavirNelfinavir

Inhibts HIV protease Results in immature virion

HIV Mutations in protease sequence reduce affinity of protease inhibitors

GI distress headache neurologic symptoms Indinavir associated w increase risk for kidney stones

PO Metabolized by P450 in liver Reduce dose in patients with liver disease Poor CNS penetration

Potentially serious drug interactions due to P450 competition

NevirapineDelavirdene

Nob-nucleoside inhibitor of HIV reverse transcriptase

HIV Never as monotherapy due to rapid development of resistance

Rapid resistance develops due to mutations in reverse transcriptase

Severe skin rash fever nausea headache

PO Well absorbed Nevirapine crosses placenta amp has better CNS penetration than Delavirdene

Delavirdene failed to show clinical efficacy when added to didanosine in clinical trial

• Obat antivirus
• Virus
• Struktur virus
• Klasifikasi virus
• PowerPoint Presentation
• Slide 6
• Slide 7
• Slide 8
• Obat anti virus
• Slide 10
• ANTI-HERPES ANTI VZV HSV = herpes simplex virus VZV = Varicella Zoster virus
• ACYCLOVIR
• Mekanisme kerja
• Farmakokinetik
• Penggunaan dalam terapi
• THERAPEUTIC USES
• Efek samping
• PENCICLOVIR
• MK
• Slide 20
• Slide 21
• Slide 22
• Slide 23
• ANTI-INFLUENZA
• AMANTADINRIMANTADIN
• FK
• Efek samping
• Penggunaan terapi
• ZANAMIVIROSELTAMIVIR
• Slide 30
• Slide 31
• ANTI-HEPATITIS
• ADEFOVIR
• INTERFERON
• ANTIRETROVIRAL AGENTS
• Slide 36
• CURRENT ARV MEDICATIONS
• Slide 38
• Slide 39
• Slide 40
• Slide 41

• Obat antivirus
• Virus
• Struktur virus
• Klasifikasi virus
• PowerPoint Presentation
• Slide 6
• Slide 7
• Slide 8
• Obat anti virus
• Slide 10
• ANTI-HERPES ANTI VZV HSV = herpes simplex virus VZV = Varicella Zoster virus
• ACYCLOVIR
• Mekanisme kerja
• Farmakokinetik
• Penggunaan dalam terapi
• THERAPEUTIC USES
• Efek samping
• PENCICLOVIR
• MK
• Slide 20
• Slide 21
• Slide 22
• Slide 23
• ANTI-INFLUENZA
• AMANTADINRIMANTADIN
• FK
• Efek samping
• Penggunaan terapi
• ZANAMIVIROSELTAMIVIR
• Slide 30
• Slide 31
• ANTI-HEPATITIS
• ADEFOVIR
• INTERFERON
• ANTIRETROVIRAL AGENTS
• Slide 36
• CURRENT ARV MEDICATIONS
• Slide 38
• Slide 39
• Slide 40
• Slide 41