Clinical Pharmacy · Short notes

Drug Interactions: Short Notes & Cheat Sheet

Pharmaceutical, pharmacokinetic and pharmacodynamic interactions, the classic dangerous pairs, and food–drug interactions.

Short notes

Read these before you attempt the topic's MCQs.

Classify the interaction first: that tells you how to manage it (separate doses, change dose, monitor or avoid).

Pharmaceutical: physical or chemical incompatibility before the drug enters the body, e.g. ceftriaxone with calcium, or phenytoin precipitating in dextrose.
Pharmacokinetic: one drug changes the absorption, distribution, metabolism or excretion of another.
Pharmacodynamic: drugs act on the same system with additive, synergistic or opposing effects.
The drugs most likely to cause harm are those with a narrow therapeutic index: warfarin, digoxin, lithium, theophylline, phenytoin, ciclosporin.

Absorption: calcium, magnesium, aluminium and iron chelate tetracyclines and fluoroquinolones; separate the doses by 2–4 hours.
Levothyroxine absorption is reduced by iron, calcium and PPIs. Cholestyramine binds many drugs.
Metabolism: enzyme inhibitors (clarithromycin, fluconazole, metronidazole) raise warfarin's INR; rifampicin lowers it.
Simvastatin with clarithromycin raises the risk of rhabdomyolysis. Ciprofloxacin raises theophylline levels.
Excretion: NSAIDs, thiazides and ACE inhibitors raise lithium levels. Probenecid raises penicillin and methotrexate levels.

Additive CNS depression: alcohol, benzodiazepines, opioids and sedating antihistamines.
Serotonin syndrome: SSRIs with MAOIs, linezolid, tramadol, pethidine or triptans.
QT prolongation adds up: macrolides, fluoroquinolones, antipsychotics, ondansetron, methadone.
Hyperkalaemia: ACE inhibitors or ARBs with spironolactone, amiloride, potassium supplements or trimethoprim.
Bleeding: warfarin with aspirin, NSAIDs or SSRIs.
Opposing effects: NSAIDs blunt antihypertensives; non-selective β-blockers block salbutamol.
Sildenafil with nitrates causes severe hypotension, so the combination is contraindicated.

Grapefruit juice raises levels of simvastatin, felodipine and ciclosporin (gut CYP3A4 inhibition).
Tyramine-rich foods (aged cheese, cured meat) with MAOIs can cause a hypertensive crisis.
Large changes in vitamin K intake (green leafy vegetables) alter warfarin's effect.
Alcohol with metronidazole causes a disulfiram-like reaction. Milk reduces tetracycline absorption.

High-yield facts in one place. Cover the right-hand column and test yourself.

Combination	Result
Warfarin + metronidazole / fluconazole	↑ INR, bleeding
Warfarin + rifampicin	↓ INR, clotting
Simvastatin + clarithromycin	Rhabdomyolysis
Methotrexate + trimethoprim	Bone marrow suppression
Allopurinol + azathioprine	Azathioprine toxicity
Lithium + NSAID / thiazide / ACEi	Lithium toxicity
Digoxin + amiodarone / verapamil	↑ Digoxin
ACEi + spironolactone	Hyperkalaemia
SSRI + MAOI / linezolid	Serotonin syndrome
Sildenafil + nitrate	Severe hypotension
COC + carbamazepine / rifampicin	Contraceptive failure
Clopidogrel + omeprazole	↓ Antiplatelet effect

Type	Example
Pharmaceutical	Ceftriaxone + calcium in IV line
Absorption	Ciprofloxacin + antacid
Metabolism	Theophylline + ciprofloxacin
Excretion	Methotrexate + probenecid
Pharmacodynamic	Benzodiazepine + opioid

Triple whammy: NSAID + ACE inhibitor/ARB + diuretic can cause acute kidney injury.

Protein-binding displacement alone rarely causes a lasting problem, because free drug is also cleared faster.
Azithromycin causes far fewer CYP3A4 interactions than clarithromycin or erythromycin.
Enzyme induction takes 1–2 weeks to reach its peak and to wear off after the inducer is stopped.
Grapefruit affects oral, not IV, doses of affected drugs.

Attempt the Drug Interactions MCQs while the notes are fresh. Anything you get wrong is saved to your incorrect list for the next revision round.