Expansion
Pharmacokinetic interactions alter concentration; pharmacodynamic interactions alter effect
Expansion
Pharmacokinetic (one drug changes the concentration of another)
- Absorption: chelation of tetracyclines and quinolones by calcium, iron and antacids; altered gastric pH with proton pump inhibitors
- Distribution: displacement from protein binding, usually transient and less important than once taught
- Metabolism: cytochrome P450 induction and inhibition, the largest group
- Excretion: competition for renal tubular secretion (probenecid and penicillin), or altered urinary pH
Pharmacodynamic (no change in level, but changed effect)
- Additive or synergistic: alcohol with benzodiazepines causing sedation; multiple QT-prolonging drugs; NSAIDs with anticoagulants increasing bleeding
- Antagonistic: beta blockers reducing the effect of salbutamol; NSAIDs opposing antihypertensives
- Indirect: diuretic-induced hypokalaemia potentiating digoxin toxicity
High risk combinations worth memorising: warfarin with almost anything, the triple whammy of ACE inhibitor plus diuretic plus NSAID, allopurinol with azathioprine, verapamil with a beta blocker (bradycardia and asystole), and methotrexate with trimethoprim.
The patients at greatest risk are those on many drugs with narrow therapeutic indices and impaired renal or hepatic function.