7: Drug Interactions

7: Drug Interactions

Drug interactions occur when the effects of one drug are altered by the concurrent administration of another drug, food, beverage, or substance (e.g., herbal supplements). These interactions can lead to either an increased (potentiated) or decreased (inhibited) therapeutic effect, or an increased risk of adverse reactions. Understanding interactions is critical for safe and effective pharmacotherapy.

Interactions are broadly classified into two main categories:

1. Pharmacokinetic Interactions: These affect the ADME processes (Absorption, Distribution, Metabolism, Excretion) of a drug, altering its concentration at the site of action.

   • Absorption: Drugs altering gastric pH (antacids, PPIs) can affect the solubility and absorption of other drugs (e.g., ketoconazole, iron). Binding agents (cholestyramine) can reduce absorption of drugs like digoxin or warfarin. Food can significantly impact absorption (e.g., tetracyclines with dairy).
   • Distribution: Competition for plasma protein binding sites (e.g., albumin) can displace a drug, increasing its free, active concentration (e.g., warfarin displaced by sulfonamides, leading to bleeding risk).
   • Metabolism (Biotransformation): This is the most common and clinically significant mechanism. It primarily involves hepatic Cytochrome P450 (CYP) enzymes.
     • Enzyme Inhibition: One drug inhibits the enzyme metabolizing another, leading to increased levels and potential toxicity of the inhibited drug (e.g., erythromycin inhibits CYP3A4, increasing levels of simvastatin causing myopathy; fluconazole inhibits CYP2C9, increasing warfarin levels).
     • Enzyme Induction: One drug induces (increases) the activity of enzymes metabolizing another, leading to decreased levels and reduced efficacy of the induced drug (e.g., rifampin induces multiple CYPs, decreasing levels of oral contraceptives causing failure; phenytoin induces metabolism of warfarin, decreasing anticoagulation).
   • Excretion: Altering renal blood flow, urine pH, or active transport systems can affect drug elimination (e.g., probenecid inhibits penicillin excretion; quinidine inhibits digoxin renal secretion).

2. Pharmacodynamic Interactions: These occur when drugs interact at their site of action or affect the same physiological system, altering the pharmacological effect without necessarily changing plasma concentrations.

   • Additive Effects: Combined effect equals the sum of individual effects (e.g., two sedatives like benzodiazepine + alcohol causing excessive CNS depression).
   • Synergistic Effects: Combined effect is greater than the sum of individual effects (e.g., sulfamethoxazole + trimethoprim inhibiting sequential steps in bacterial folate synthesis).
   • Antagonistic Effects: One drug reduces or blocks the effect of another (e.g., naloxone reversing opioid overdose; beta-blockers antagonizing beta-agonists in asthma).

Clinical Significance: Drug interactions can lead to therapeutic failure, toxicity, increased healthcare costs, and hospitalization. Factors increasing risk include polypharmacy (taking multiple drugs), genetic polymorphisms in drug-metabolizing enzymes, and patient-specific factors like age or organ dysfunction. Careful medication review, utilizing interaction databases, therapeutic drug monitoring, and patient education on potential interactions (including OTC/herbals) are essential prevention strategies.