Drug-drug interactions

Vivian Imbriotis | Jan. 5, 2026

Drug-drug interactions can be pharmacokinetic or pharmacodynamic.

Pharmacokinetic interactions involve absorption, distribution, metabolism and elimination.

Pharmacodynamic interactions can produce synergism or antagonism.

Pharmacodynamic interactions involve

  1. Binding to the same site
  2. Binding to different sites on the same receptor
  3. Binding to different receptors, but affecting the same messenger system
  4. Affecting different messenger systems, but the same physiological process

Absorption interactions

Insoluble complexes: bisphosphinates and calcium

Inhibition of efflux pumps: verapamil inhibits p-glycoprotein, increases digoxin absorption.


Distribution interactions

Competition for protein bindings sites: phenytoin and valproate


Metabolism interactions

Competition for enzyme: warfarin and phenytoin both metabolized by CYP2C9

Induction or inhibition of enzyme: carbemazepine increases CYP2C9, removing warfarin


Excretion interactions

Competition for transporters: metformin and trimethoprim at the OCT

Ion trapping: acetezolimide ion traps salicylates in urine

Binding to the same site: Antagonism between opioids and naloxone

Binding to different sites on the same receptor: synergism between benzodiazepines and alcohol on the GABAa receptor

Binding to different receptors, but affecting the same messenger system: e.g. high-dose insulin increases intracellular calcium in beta-blocker overdose

Affecting different messenger systems, but the same physiological process: e.g. administration of noradrenaline in dihydropyradine overdose.