2.6 Drug Interactions
Drug interactions occur when one drug alters the effect of another. Understanding mechanisms is crucial for predicting and managing clinically significant interactions.
Pharmacokinetic Interactions
Absorption
Antacids reduce absorption of tetracyclines (chelation). Metoclopramide speeds gastric emptying.
Distribution
Protein binding displacement. Aspirin displaces warfarin from albumin (transient effect).
Metabolism
CYP450 induction/inhibition. Most clinically important interactions. Ketoconazole + midazolam, rifampin + OCP.
Excretion
Probenecid inhibits penicillin secretion. Lithium toxicity with NSAIDs (reduced renal clearance).
Pharmacodynamic Interactions
Additive
1 + 1 = 2. Two CNS depressants (alcohol + benzodiazepine).
Synergistic
1 + 1 > 2. Trimethoprim + sulfamethoxazole (sequential enzyme block).
Antagonistic
Effect cancelled. Naloxone reverses opioid effects.
Potentiation
0 + 1 = 2. Inactive drug enhances another's effect.
High-Risk Drug Classes
| Drug | Risk | Common Interactions |
|---|---|---|
| Warfarin | Bleeding | NSAIDs, antibiotics, amiodarone |
| Digoxin | Toxicity | Amiodarone, verapamil, quinidine |
| Lithium | Toxicity | NSAIDs, ACE inhibitors, diuretics |
| Theophylline | Toxicity | Ciprofloxacin, erythromycin |
Clinical Management
Identify Risk
Narrow therapeutic index drugs, polypharmacy, elderly, hepatic/renal impairment.
Monitor
Drug levels (when available), clinical response, adverse effects.
Adjust
Dose modification, timing changes, alternative drugs, close follow-up.