Anti Fungi
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ANTIFUNGIANTIFUNGI
OLEHOLEH
WISNU SETYARI JWISNU SETYARI J
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ANTIFUNGI
MENGUBAHPERMEABILITAS
SEL MEMBRAN
M’HAMBATSINTESA
AS.NUKLEAT
MENGGANGGUFUNGSI
MIKROTUBULI
AZOLE POLYENE TERBINAFIN FLUCYTOSIN GRISEOFULVIN
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OBAT UNT. INFEKSI JAMUR OBAT UNT. INFEKSI JAMUR SISTEMIKSISTEMIK
AMFOTERISIN BAMFOTERISIN B STREPTOMYCESNODOSUSSTREPTOMYCESNODOSUS
MEKANISME KERJA :MEKANISME KERJA :POLYENE MEMP. SIFAT HIDROFILIK & POLYENE MEMP. SIFAT HIDROFILIK &
LIPOFILIK (AMPHIPATIC)LIPOFILIK (AMPHIPATIC)B’IKATAN DG ERGOSTEROL (STEROL YG B’IKATAN DG ERGOSTEROL (STEROL YG
TDP PD MEMBR SEL JAMUR)TDP PD MEMBR SEL JAMUR)P’BTKAN P’BTKAN PORI (LUBANG)PORI (LUBANG) K K+ + & MOLEKUL << & MOLEKUL << KELUAR DR SEL KELUAR DR SEL MATI MATI
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FARMAKOKINETIK:FARMAKOKINETIK: ABS : P.O JELEK → IV INFUS PERLAHANABS : P.O JELEK → IV INFUS PERLAHAN DIST: SEMUA JAR KECUALI SSPDIST: SEMUA JAR KECUALI SSP MET : HEPAR LAMBAT T½ :2mingguMET : HEPAR LAMBAT T½ :2minggu EKS : GINJALEKS : GINJAL
PENGGUNAAN KLINIS :PENGGUNAAN KLINIS : 1.MIKOSIS SISTEMIK YG DISEBABKAN :1.MIKOSIS SISTEMIK YG DISEBABKAN :
ASPERGILLUSASPERGILLUSBLASTOMYCESBLASTOMYCESCANDIDA ALBICANSCANDIDA ALBICANSCRYPTOCOCCUSCRYPTOCOCCUSHISTOPLASMAHISTOPLASMAMUCORMUCOR
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2.MENINGITIS OK JAMUR → INTRATEKAL2.MENINGITIS OK JAMUR → INTRATEKAL3.TOPIKAL U/ - ULKUS KORNEA & KERATITIS3.TOPIKAL U/ - ULKUS KORNEA & KERATITIS
TOKSISITAS:TOKSISITAS:-PEMBERIAN IV → DEMAM,MENGGIGIL,SPASME OTOT, MUNTAH, -PEMBERIAN IV → DEMAM,MENGGIGIL,SPASME OTOT, MUNTAH,
SYOKSYOK→→U/ MENGURANGI EFEK TSB DIBERIKAN PREMEDIKASI : U/ MENGURANGI EFEK TSB DIBERIKAN PREMEDIKASI : ANTIHISTAMIN,ANTIPIRETIK, MEPERIDIN DAN ANTIHISTAMIN,ANTIPIRETIK, MEPERIDIN DAN GLUKOKORTIKOID.GLUKOKORTIKOID.
-AMFOTERISIN B ME ↓ KECEPATAN FILTRASI GLOMERULUS -AMFOTERISIN B ME ↓ KECEPATAN FILTRASI GLOMERULUS →ASIDOSIS TUBULI GINJAL DG PENGELUARAN MAGNESIUM & →ASIDOSIS TUBULI GINJAL DG PENGELUARAN MAGNESIUM & KALIUM >>KALIUM >>
-ANEMIA OK PE ↓ PEMBTKAN ERYTROPOETIN DI GINJAL-ANEMIA OK PE ↓ PEMBTKAN ERYTROPOETIN DI GINJAL
→→PEMBERIAN INFUS SALIN DPT MENGURANGI KERUSAKAN PEMBERIAN INFUS SALIN DPT MENGURANGI KERUSAKAN GINJAL.GINJAL.
→→PEMBERIAN BERSAMA FLUCITOSIN DAPAT MENURUNKAN PEMBERIAN BERSAMA FLUCITOSIN DAPAT MENURUNKAN TOKSISITASNYATOKSISITASNYA
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FLUCYTOSINFLUCYTOSIN
MRP ANTIMETABOLIT SINTETIK MRP ANTIMETABOLIT SINTETIK PRIMIDINPRIMIDIN
MEKANISME KERJA:MEKANISME KERJA:→→OBAT MASUK MELL ENZ. PERMEASE OBAT MASUK MELL ENZ. PERMEASE SITOSIN SPES (PD.JAMUR)→5FLUORO SITOSIN SPES (PD.JAMUR)→5FLUORO DEOKSIURIDILAT→M’HAMB TIMIDILAT DEOKSIURIDILAT→M’HAMB TIMIDILAT SINTETASE→M’HAMB SINTESA ASAM SINTETASE→M’HAMB SINTESA ASAM NUKLEAT & PROTEIN JAMURNUKLEAT & PROTEIN JAMUR
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FARMAKOKINETIK:FARMAKOKINETIK:-ABS : P.O BAIK-ABS : P.O BAIK-DIST: KESELURUH JARINGAN TERMASUK -DIST: KESELURUH JARINGAN TERMASUK SSPSSP-EKS : GINJAL (URIN)-EKS : GINJAL (URIN)
PENGGUNAAN KLINIK:PENGGUNAAN KLINIK: Tx KOMBINASI DG AMFOTERISIN B U/ :Tx KOMBINASI DG AMFOTERISIN B U/ :INFEKSI JAMUR :INFEKSI JAMUR :
-CRYPTOCOCCUS NEOFORMANS-CRYPTOCOCCUS NEOFORMANS-CANDIDA -CANDIDA
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TOKSISITAS :TOKSISITAS : DEPRESI SUMSUM TLGDEPRESI SUMSUM TLG ALOPESIAALOPESIA GANGGUAN FUNGSI HATIGANGGUAN FUNGSI HATI
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AZOLEAZOLE
KETOCONAZOLEKETOCONAZOLE FLUCONAZOLEFLUCONAZOLE ITRACONAZOLEITRACONAZOLE VORICONAZOLEVORICONAZOLE
MEKANISME KERJA :MEKANISME KERJA :
→→MENGUBAH PERMEABILITAS SEL MEMBRAN MENGUBAH PERMEABILITAS SEL MEMBRAN JAMUR DG M’HAMBAT SINTESIS JAMUR DG M’HAMBAT SINTESIS ERGOSTEROLERGOSTEROL
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FARMAKOKINETIK :FARMAKOKINETIK :
● ● ABS : P.O FLUCONAZOL& VORICONAZOL ABS : P.O FLUCONAZOL& VORICONAZOL > BAIK DR YG LAIN> BAIK DR YG LAIN
● ● DIST : KESELURUH TUBUH, KECUALI DIST : KESELURUH TUBUH, KECUALI FLUCONAZOL→ KDR DLM SSP <<<FLUCONAZOL→ KDR DLM SSP <<<
● ● MET : HEPAR ( KETO,ITRA & MET : HEPAR ( KETO,ITRA & VORICONAZOL)VORICONAZOL)
● ● EKS : GINJAL DLM BTK METABOLIT,KECEKS : GINJAL DLM BTK METABOLIT,KEC
→ → FLUCONAZOL >> DLM BTK UTUHFLUCONAZOL >> DLM BTK UTUH
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PENGGUNAAN KLINIKPENGGUNAAN KLINIK
KETOKONAZOL :KETOKONAZOL :→ → SPEKTRUM SEMPIT ,EFEK SAMPING >>→ SPEKTRUM SEMPIT ,EFEK SAMPING >>→ JARANG DIGUNAKAN U/ MIKOSIS SISTEMIKJARANG DIGUNAKAN U/ MIKOSIS SISTEMIKKETOKONAZOL + FLUCYTOSIN : ADITIF KETOKONAZOL + FLUCYTOSIN : ADITIF THD KANDIDATHD KANDIDAKETOKONAZOL M’ANTAGONIS AKTIFITAS KETOKONAZOL M’ANTAGONIS AKTIFITAS AMFOTERISIN B AMFOTERISIN B →→U/:-MUCOCUTANEOUS CANDIDIASIS U/:-MUCOCUTANEOUS CANDIDIASIS
KRONIK.KRONIK. -DERMATOFIT-DERMATOFIT
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FLUKONAZOLE:FLUKONAZOLE:
-”-”DRUG OF CHOIICEDRUG OF CHOIICE “ : “ :
1.CANDIDIASIS ESOFAGUS & OROFARING1.CANDIDIASIS ESOFAGUS & OROFARING
2.PROFILAKSIS CRYPTOCOCCAL MENINGITIS2.PROFILAKSIS CRYPTOCOCCAL MENINGITIS
3.INFEKSI O/ COCCIDIODES.3.INFEKSI O/ COCCIDIODES.
-- ALTERNATIF ALTERNATIF → KOMBINASI DG AMF.B→ KOMBINASI DG AMF.B
U/ : - CRYPTOCOCCUS NEOFORMANSU/ : - CRYPTOCOCCUS NEOFORMANS
- CANDIDEMIA- CANDIDEMIA
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ITRACONAZOLEITRACONAZOLE -CANDIDIASIS ESOFAGUS YG RESISTEN -CANDIDIASIS ESOFAGUS YG RESISTEN
FLUCONAZOLFLUCONAZOL
-”-”DRUG OF CHOICE” :DRUG OF CHOICE” :1.BLASTOMYCES1.BLASTOMYCES2.SUBKUTAN CHROMOBLASTOMYCOSIS.2.SUBKUTAN CHROMOBLASTOMYCOSIS.
-ALTERNATIF U/ :-ALTERNATIF U/ :1.ASPERGILUS1.ASPERGILUS2.COCCIDIODES2.COCCIDIODES3.CRYPTOCOCCUS3.CRYPTOCOCCUS4.HISTOPLASMA4.HISTOPLASMA
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VORICONAZOLEVORICONAZOLE- SPEKTRUM > LUAS- SPEKTRUM > LUAS-”DRUG OF CHOICE” U/ INVASIVE ASPERGILOSIS -”DRUG OF CHOICE” U/ INVASIVE ASPERGILOSIS > EFEKTIF DP AMF B> EFEKTIF DP AMF B-ALTERNATIF : CANDIDEMIA -ALTERNATIF : CANDIDEMIA -Px. AID -Px. AID → CANDIDAL ESOFAGOSITIS & → CANDIDAL ESOFAGOSITIS & STOMATITISSTOMATITIS
● ● TOKSISITAS :TOKSISITAS :- MUNTAH, DIARE ,RASH- MUNTAH, DIARE ,RASH- HEPATOTOKSIK TU Px DG GG-AN FGS HATI- HEPATOTOKSIK TU Px DG GG-AN FGS HATI
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INTERAKSI OBATINTERAKSI OBAT TERUTAMA OLEH KETOCONAZOLETERUTAMA OLEH KETOCONAZOLE
→ → M’HAMBAT CYT P 450 SHG ME ↑↑ KDR M’HAMBAT CYT P 450 SHG ME ↑↑ KDR PLASMA OBAT, SPT :PLASMA OBAT, SPT :
CYCLOSPORIN, OAD, FENITOIN, WARFARIN.CYCLOSPORIN, OAD, FENITOIN, WARFARIN.
→→M’GG SINT.ADRENAL & GONADAL M’GG SINT.ADRENAL & GONADAL STEROID SHG MENYEB :STEROID SHG MENYEB :
-GYNECOMASTI-GYNECOMASTI-GG-AN MENSTRUASI-GG-AN MENSTRUASI- INFERTIL - INFERTIL
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CASPOFUNGINCASPOFUNGIN
ECHINOCANDIN ECHINOCANDIN → ANTIFUNGI BARU→ ANTIFUNGI BARU
MEKANISME KERJA :MEKANISME KERJA :→ → M’HAMB SINTESA GLYCAN PD DINDING M’HAMB SINTESA GLYCAN PD DINDING SEL FUNGISEL FUNGI
PENGGUNAAN KLINIS :PENGGUNAAN KLINIS :-CANDIDA-CANDIDA-INVASIVE ASPERGILOSIS-INVASIVE ASPERGILOSIS
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ANTIFUNGI SISTEMIK UNTUK ANTIFUNGI SISTEMIK UNTUK INFEKSI SUPERFISIALINFEKSI SUPERFISIAL
GRISEOFULVINGRISEOFULVIN
MEKANISME KERJAMEKANISME KERJA : :
M’GG FUNGSI MIKROTUBULI DAN M’GG FUNGSI MIKROTUBULI DAN M’HAMBAT SINTESISIS & POLIMERISASI AS. M’HAMBAT SINTESISIS & POLIMERISASI AS. NUKLEAT.NUKLEAT.
PENGGUNAAN KLINIKPENGGUNAAN KLINIK::
DERMATOFITOSIS PADA KULIT & RAMBUTDERMATOFITOSIS PADA KULIT & RAMBUT
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EFEK SAMPING :EFEK SAMPING :
SAKIT KEPALA, IRITASI LAMBUNG, SAKIT KEPALA, IRITASI LAMBUNG, FOTOSENSITIF DAN M’GG FGS HATI.FOTOSENSITIF DAN M’GG FGS HATI.
KONTRA INDIKASI:KONTRA INDIKASI:
Px. PORPHYRIAPx. PORPHYRIA
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TERBINAFINTERBINAFIN MEKANISME KERJAMEKANISME KERJA::
M’HAMB. SQUALENE EPOKSIDASE M’HAMB. SQUALENE EPOKSIDASE → → PENUMPUKAN SQUALEN→ M’GG SINT. PENUMPUKAN SQUALEN→ M’GG SINT. ERGOSTEROL.ERGOSTEROL.
PENGGUNAAN KLINIK:PENGGUNAAN KLINIK: = GRISEOFULVIN ,TP > EFEKTIF OK = GRISEOFULVIN ,TP > EFEKTIF OK
T’AKUMULASI PD JAR. KERATIN.T’AKUMULASI PD JAR. KERATIN.
EFEK SAMPINGEFEK SAMPING::SAKIT KEPALA, GG’AN GIT, RASH & GG’AN SAKIT KEPALA, GG’AN GIT, RASH & GG’AN RASARASA
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AZOLEAZOLE
SEMUA DERIVAT AZOLE, KECUALI SEMUA DERIVAT AZOLE, KECUALI VORICONAZOLEVORICONAZOLE DAPAT DIBERIKAN DAPAT DIBERIKAN P.O P.O
PENGGUNAAN KLINIK :PENGGUNAAN KLINIK :
Tx. DERMATOPHYTOSISTx. DERMATOPHYTOSIS
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OBAT TOPIKAL UNTUK INFEKSI OBAT TOPIKAL UNTUK INFEKSI SUPERFICIALSUPERFICIAL
NYSTATINNYSTATIN-POLYENE ANTIBIOTIK ~ AMPHOTERICIN B-POLYENE ANTIBIOTIK ~ AMPHOTERICIN B-TOKSIK U/ P.E -TOKSIK U/ P.E TOPIKAL TOPIKAL-BTK : KRIM,OINTMENT,SUPOSITORIA-BTK : KRIM,OINTMENT,SUPOSITORIA U/KULIT & MUKOSAU/KULIT & MUKOSA-SPEKTRUM : SPES.CANDIDA U/:-SPEKTRUM : SPES.CANDIDA U/:
-OROPHARYNGEAL THRUSH-OROPHARYNGEAL THRUSH-VAGINAL CANDIDIASIS-VAGINAL CANDIDIASIS-INTERTRIGINOUS -INTERTRIGINOUS
CANDIDALCANDIDAL
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TOPIKAL AZOLE :TOPIKAL AZOLE :-CLOTRIMAZOL-CLOTRIMAZOL-MICONAZOL-MICONAZOL
-BENTUK KRIM, UNT:-BENTUK KRIM, UNT:-DERMATOPHYTIC INFECTION O.K:-DERMATOPHYTIC INFECTION O.K:
-TINEA CORPORIS-TINEA CORPORIS-TINEA PEDIS-TINEA PEDIS-TINEA CRURIS-TINEA CRURIS
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TOPIKAL ALILAMINTOPIKAL ALILAMIN
-BENTUK KRIM: TERBINAFIN & -BENTUK KRIM: TERBINAFIN & NAFTIDINNAFTIDIN
-EFEKTIF U/ : - TINEA CRURIS-EFEKTIF U/ : - TINEA CRURIS
- TINEA CORPORIS- TINEA CORPORIS