Drug Interactions
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Direct answer
Drug interactions are either pharmacokinetic — one drug alters the absorption, metabolism or elimination of another, most commonly through cytochrome P450 enzymes — or pharmacodynamic, where effects summate or oppose at receptors or physiological systems. The exam hinges on enzyme inducers (rifampicin, phenytoin, carbamazepine, phenobarbitone, chronic alcohol, smoking, St John's wort) that lose partner-drug effect, and inhibitors (ketoconazole and other azoles, erythromycin and clarithromycin, ciprofloxacin, cimetidine, isoniazid, grapefruit juice, diltiazem and verapamil) that potentiate toxicity. Classic pairs include warfarin with antibiotics or rifampicin, digoxin with amiodarone, statins with clarithromycin, lithium with NSAIDs and thiazides, methotrexate with trimethoprim, and clopidogrel with omeprazole.
What you must remember
- Enzyme inducers: rifampicin, phenytoin, carbamazepine, phenobarbitone, chronic alcohol, cigarette smoking and St John's wort — they lower levels of warfarin, oral contraceptives, antiretrovirals and many antiepileptics, causing treatment failure; induction takes days to weeks.
- Enzyme inhibitors: azoles, macrolides, ciprofloxacin, cimetidine, metronidazole, isoniazid, grapefruit juice, diltiazem and verapamil — they raise levels of statins, warfarin, phenytoin and carbamazepine; inhibition can occur within a day.
- Warfarin interactions: co-trimoxazole, metronidazole, fluconazole and macrolides increase INR (bleeding); rifampicin and carbamazepine reduce it (thrombosis).
- Digoxin interactions: amiodarone, verapamil, quinidine and clarithromycin raise digoxin levels (nausea, xanthopsia, arrhythmia); hypokalaemia from diuretics potentiates toxicity.
- Narrow-index drugs needing vigilance: lithium (NSAIDs, thiazides, ACE inhibitors retain lithium), theophylline (ciprofloxacin, erythromycin raise it), methotrexate (NSAIDs and trimethoprim reduce renal clearance), phenytoin (isoniazid raises it).
- Clopidogrel and omeprazole: omeprazole inhibits CYP2C19, which activates clopidogrel — use pantoprazole instead; proton pump inhibitors remain otherwise compatible partners.
- Pharmacodynamic summation: QT-prolonging combinations (macrolides, fluoroquinolones, ondansetron, antipsychotics, sotalol, methadone) risk torsades; MAO inhibitors with SSRIs, tramadol or pethidine risk serotonin syndrome; NSAIDs with ACE inhibitors or diuretics ("triple whammy" with a diuretic) precipitate renal failure; allopurinol with azathioprine causes marrow suppression.
Common confusion
Inducers and inhibitors are transposed under exam pressure — anchor them by clinical outcome: tuberculosis treatment with rifampicin failing an oral contraceptive or losing warfarin effect is induction; a ketoconazole course causing rhabdomyolysis in a patient on simvastatin is inhibition. The second confusion is blaming interactions only on metabolism: summing QT effect or NSAID-plus-diuretic renal stress are pharmacodynamic and occur without any level change.
Exam-focused takeaway
Stems give the added drug and ask the consequence: amiodarone added to digoxin (toxicity), rifampicin added to warfarin (INR falls), clarithromycin added to simvastatin (rhabdomyolysis), thiazide added to lithium (lithium rises), trimethoprim with methotrexate (marrow suppression), pethidine in a patient on phenelzine (serotonin syndrome). One-liners list inducers or inhibitors as a set. Management questions expect the practical responses — monitor INR or levels, substitute the offending drug (pantoprazole for omeprazole), or space doses.
Frequently asked questions
What is the difference between pharmacokinetic and pharmacodynamic interactions?
Pharmacokinetic interactions change a drug's absorption, metabolism or elimination levels; pharmacodynamic interactions change its effect at receptors or systems without altering levels.
Name the key cytochrome P450 inducers.
Rifampicin, phenytoin, carbamazepine, phenobarbitone, chronic alcohol use, smoking and St John's wort — each lowers levels of co-administered substrates over days to weeks.
Why does omeprazole interact with clopidogrel?
Clopidogrel needs CYP2C19 for activation, and omeprazole inhibits this enzyme, reducing active metabolite and antiplatelet effect; pantoprazole is preferred.
Which drugs raise lithium levels?
NSAIDs, thiazide diuretics and ACE inhibitors, all reducing lithium clearance — combine them only with level monitoring.
Which combined drugs cause serotonin syndrome?
MAO inhibitors with SSRIs, SNRIs, tramadol, linezolid or pethidine — clonus, hyperthermia and agitation are treated with cyproheptadine after stopping the drugs.