Paper I — 2025 March (Supplementary (SAY)) (2019 Scheme) — Q4
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Paper I
2025 March (Supplementary (SAY)) (2019 Scheme) · 100 marks · 180 min
Question
Discuss in detail about FOUR pharmacokinetic drug interactions with suitable examples.
Q46 marksShort Essays
Answer
Pharmacokinetic drug interactions occur when one drug alters the absorption, distribution, metabolism, or excretion of another, changing its plasma concentration without necessarily altering its intrinsic pharmacodynamic action.
Absorption interactions — antacids (Al³⁺/Mg²⁺) chelate tetracyclines and fluoroquinolones in the gut, forming insoluble complexes that reduce their oral absorption; cholestyramine binds and reduces absorption of warfarin and thyroxine if co-administered.
Distribution interactions (protein-binding displacement) — a highly protein-bound drug can be displaced from albumin by another highly bound drug, transiently raising the free (active) fraction of the displaced drug — e.g. aspirin displacing warfarin, increasing bleeding risk, especially significant for drugs with a narrow therapeutic index.
Metabolism interactions — enzyme induction (rifampicin, phenytoin, carbamazepine induce CYP450 enzymes) accelerates metabolism of co-administered drugs, reducing their efficacy (e.g. rifampicin reducing oral contraceptive efficacy); enzyme inhibition (ketoconazole, ritonavir inhibit CYP450) slows metabolism of co-administered drugs, raising their plasma levels and toxicity risk.
Excretion interactions — probenecid competes with penicillin for the same renal tubular organic anion transporter, reducing penicillin’s renal excretion and prolonging its action; NSAIDs reduce renal blood flow and can reduce lithium clearance, raising lithium toxicity risk.
