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Predisposing factors
• Multiple drug therapy
• Age
== Elderly
== Neonates- chloramphenicol, morphine, Reye’s syndrome - ?
Hepatotoxicity – Aspirin
Predisposing factors
• Gender
- Females have 1.5-1.7 folds of developing ADR than males
- Women are prone to develop blood dyscrasias with phenylbutazone & chloramphenicol
• Presence of disease
- HIV –skin reactions with co-trimoxazole
Predisposing factors
• Race and genetic polymorphism
- Drug-metabolizing enzymes (poor, extensive & ultra-rapid metabolizers)
- Drug receptors
- Drug transporters (P-glycoproteins, P-gp )
Mechanism of dose related (Type A) reactions
• Pharmaceutical cause
-pharmaceutical aspects of a dosage form Indomethacin – GI bleeding
Mechanism of dose related (Type A) reactions
• Pharmacokinetic causes 1. Absorption
GI motility, gastric contents, disease, absorption in the GI tract, first-pass metabolism in liver & gut wall, concomitant drugs
2. Distribution
Plasma-protein and tissue binding
Mechanism of dose related (Type A) reactions
• Pharmacokinetic causes
3. Metabolism
Enzyme induction or inhibition – efficacy??
Genetic variants – oxidation, hydrolysis, acetylation
Drugs competing for glucuronidation 4. Elimination
-digoxin
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* Anesthetics e.g. Halothane and succinylcholine cause Malignant hyperthermia treated with dantrolene
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