K-31 Efek Non Terapi2010.ppt
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Transcript of K-31 Efek Non Terapi2010.ppt
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Efek Non Terapi
(Adverse Drug Reaction)
School of Medicine
Universitas Sumatera Utara
2010
Hasanul Arifin, Tri Widyawati
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All substances are poisons; there is
none which is not a poison; the right
dose differentiates a poison and aremedy.
Key Principle of Pharmacology
Paracelsus (1493-1541)
No drug has a single action.
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1956 Talidomid obat yang sangat aman
5 tahun kemudian
8000 bayi di 46 negara cacat
Medicines Control Agency (MCA) : Inggris
Food and Drug Administration (FDA) : AS
Badan Pengawas Obat dan Makanan (Badan POM) : Indonesia
Mengevaluasi obat baru yang belum / sudah beredar di masyarakat
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Drugs removed from or restricted
in Europe an USA
Terfenadine (1998)
Mibefradil (1998)
Astemizole (1999)
Grepafloxacin (1999)
Cisapride (2000)
Cerivastatin (2001)
Troglitazone (Rezulin) (2000)
Rofecoxib (Vioxx) (2004)
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ADRs are important
USA :
- Over 2 million serious ADRs/year
- 100.000 deaths/year from ADRs
- ADRs are fourth leading cause of death
more than lung disease, Diabetes, AIDS, and accidents
- 3-5% are preventable in-hospital ADRs due to drug interactions(Lazarou J et al.JAMA.1998; 279(15):1200-1205. Gurwitz JH et al.Am.J.Med.2000;109(2):87-94.)
Only heart disease, cancer, and stroke kill more Americans than
ADRs
The number of deaths from ADRs is three times the number of
deaths from people killed by automobile accidents
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Adverse drug reactions may lead to
complications:
Prevents optimal drug use in some patients
Necessitates supportive care
Significantly complicates treatment
Decreases patients quality of life
Results in temporary or permanent harm,
disability, or death
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What is an
Adverse Drug Reaction (ADR)?
an unwanted or harmful reaction
experienced following the administration of
a drug or combination of drugs under
normal conditions of use and suspected to
be related to the drug
Ref. MCA/CSM Suspected adverse drug reaction (ADR) reporting and the Yellow Card Scheme, Guidance notes
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Who might get an ADR?
Anyone who takes a medicine
Differential diagnosis should include the
possibility of an ADR if the patient is takingany form of medication
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Examples of ADRs
Common ADRs
Constipation with opioids
Sedation with antihistamines
Nausea when starting fluoxetine Gastrointestinal upset with non steroidal anti-
inflammatory drugs
Uncommon but well recognised ADRs
Achilles tendonitis caused by quinolone antibiotics
Visual field defects with vigabatrin
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What should raise
our suspicion of an ADR?
A symptom :
appears soon after a new drug is started
appears after a dosage increase
disappears when the drug is stopped
reappears when a drug is restarted (do notdeliberately rechallenge!)
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Classification
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ADR
PREDICTABLE
Perpanjangan respons
farmakologik
UNPREDICTABLE
Penyebab
imunologik
(alergi dan
hipersensitifitas)
Cytotoksisitas Defek genetik
Tipe I Tipe II Tipe III Tipe IV
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Type I reaction (IgE-mediated) Anaphylaxis from lactam antibiotic
Type II reaction (cytotoxic) Hemolytic anemia from penicillin
Type III reaction (immune complex) Serum sickness from anti-thymocyte
globulin
Type IV reaction (delayed, cell-mediated) Contact dermatitis from topical
antihistamine
Specific T-cell activation Morbilliform rash from sulfonamides
Immunologic and Nonimmunologic
Drug Reactions
Immunologic
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Pharmacologic side effect Dry mouth from antihistamines
Secondary pharmacologic side effect Thrush while taking antibiotics
Drug toxicity Hepatotoxicity from methotrexate
Drug-drug interactions Seizure from theophylline while taking erythromycin
Drug overdose Seizure from excessive lidocaine (Xylocaine)
Immunologic and Nonimmunologic
Drug Reactions
Non Immunologic Predictable
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Pseudoallergic Anaphylactoid reaction after radiocontrast media
Idiosyncratic Hemolytic anemia in a patient with G6PD deficiencyafter primaquine therapy
Intolerance Tinnitus after a single, small dose of aspirin
Immunologic and Nonimmunologic
Drug Reactions
Non ImmunologicUnPredictable
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Obat Efek yang mungkin
Gol ACE inhibitor Gagal ginjal pada janin dan neonatus
Obat antitiroid Hipertirodisme pada janin
Benzodiazepin Ketergantungan obat pada janin
Barbiturat Ketregantungan Obat
AINS Konstriksi pada ductus arterious
Tetrasiklin Pewarnaan gigi, hambatan pertumbuhan tulang
Warfarin Pendarahan dalam otak jantung
Penggunaan Obat bagi yang menyusui juga perlu mendapat perhatian
untuk meminimal ROTD
Obat Efek yang mungkin
Tetrasiklin Resiko perwarnaan gigi
Karbimazol Hipotiroidisme
Benzodiazepin Letargia
Aspirin Resiko sindroma reye
Barbiturat Mengantuk
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PREDICTABLE UNPREDICTABLE
Synonyms Augmented, toxic, quantitative, dose-related Bizarre, allergic, idiosyncratic, or
drug intolerance, qualitative, dose-
independent
Mechanism Predictable, understood Usually poorly understood
Site 1.Same site of primary drug action2.Another site for primary & secondary action
Unrelated to the site of action
Incidence High (70%) Low(30%)
Morbidity Mild Severe
Mortality Low High
Causes
Phseutic availab. at site of absorption : quantity &
release of dosage form
Decomposition products, additives,
excepients, etc
Phkinetic level at site of action due to abnormalities of
ADME
Liberation of an abnormal
metabolite
Phdynamic 1.Enhanced organ or tissue responsiveness
due to enhanced number or sensitivity of
receptors
2.Homeostatic imbalance
3.Disease state
1. Genetic
2. Immunologic
3. Neoplastic
4. Teratologic
Reproducibility Reproducible Not reproducible
Treatment Adjust the dose Stop treatment
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Risk Factors for Developing an
ADR
Multiple drug therapy Over the counter medications
Alcohol
Drugs of abuse
Number of drugs
Age
- Very young Very old
Pregnancy
Risk to fetal development (first trimester, phenytoin) Co-morbidity/chronic diseasescan alter a drugs
absorption, distribution, metabolism or elimination
Hereditary factorsslow acetylators
Have a history of allergy or a previous reaction to drugs
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Are ADRs avoidable?
30-50% are preventable
Obvious interactions
many drugs interact with warfarin
Use of contra-indicated drugs
use of a non-selective beta-blocker in an
asthmaticbronchospasm
Drug use in an inappropriate clinical indication ormedically unnecessary
antibiotics for a viral infection
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Prevention of ADRs
Avoid inappropriate in the context of clinical condition
Use right dose, route, frequency, based on patient variables
Elicit medication history; consider untoward incidents
Elicit history of allergies (in patients with allergic disease)
Rule out drug interactions
Adopt right tehnique, eg. Slow iv injection of Aminophylline
Carry out appropriate monitoring (eg. PT with warfarin, Li level)
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DOKTER
APOTEKER
PERAWAT
PASIEN
Pemantauan pasien
Pengurangan dosis
Pemantauan kadar serum
Pemantauan kerja farmakologi
PENCEGAHAN ROTD
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Evaluation and Management of Drug Reaction
Medical history: symptoms, detailed
medication list, temporal sequence
Physical examination
Clinical laboratory data
Is a drug reaction likely?Yes No
Other etiology likely
Evaluate and treat other
causes of symptoms.
Is there a suspicion of
drug-induced hypersensitivity/
immunologic reaction?
Immune mechanism
IgE-mediated
Cytotoxic
Immune complex
Delayed, cell-mediated
Other immune mechanism
Nonimmune mechanism
Pharmacologic side effect
Drug toxicity
Drug-drug interactions
Drug overdose
Pseudoallergic
Idiosyncratic
Intolerance
Evaluate with appropriateconfirmatory tests.
Are tests supportive of
immune drug reaction?
Diagnosis of drug
hypersensitivity/
immunologicreaction confirmed
Management Consider desensitization (IgE) or
graded challenge (non-IgE) before
administration, as appropriate.*
Anaphylactic reactions require prompt
emergency treatment.
Avoid drug if possible.
Consider prophylactic regimen before
administration (if shown to be effective).
Prudent use of drugs in future Patient education
Does test have high
negative predictive
value?
Yes
NoNo
Yes
Administer drug with observation.
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Remember
All health-care professionals have a
responsibility to inform colleagues
about clinically important adversedrug reactions that they detect, even
if a well-recognised or causal link is
uncertain.
Edwards IR and Aronson JK. Adverse drug reactions: definitions, diagnosis, and
management. Lancet 2000; 356: 1255-59
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