Pharmacology and Toxicology
Pharmacology and Toxicology tests receptor theory, dose–response analysis, pharmacokinetic variability, and mechanisms of toxicity. Questions often require distinguishing potency from efficacy and predicting how antagonists or enzyme induction change effect.
Core rules
- Graded dose–response: EC50 reflects potency; Emax reflects efficacy. A competitive antagonist shifts the curve right with unchanged Emax; a noncompetitive antagonist lowers Emax.
- Therapeutic index = TD50/ED50; it is a population estimate, not a guarantee of safety. Narrow-index drugs include digoxin, warfarin, lithium, and aminoglycosides.
- Toxicology pathways: acetaminophen overdose depletes glutathione and accumulates NAPQI; N-acetylcysteine replenishes cysteine. Warfarin effect is increased by CYP2C9 inhibition and by displacement or vitamin K antagonism.
- Adverse drug reactions are classified by mechanism; type A reactions are dose-related and predictable.
Worked example
A drug's ED50 is 5 mg/kg and TD50 is 50 mg/kg in rats. TI = 50/5 = 10. If a competitive antagonist is added, the ED50 rises but the TD50 may also shift; if the antagonist is noncompetitive, Emax falls. Reasoning: do not infer safety from a single TI; species differences and curve steepness matter. For a narrow-index drug, therapeutic drug monitoring and renal adjustment reduce toxicity.
Traps
Calling a drug with higher EC50 more potent; assuming a right shift always means noncompetitive antagonism; confusing type A and type B reactions; ignoring active metabolites and CYP polymorphisms.