Drug Interactions: Types & Factors

Drug Interactions: Predisposing Factors

• Factors increasing the risk of drug interactions include advanced age, polypharmacy (taking multiple medications), and concurrent illnesses.
• Elderly individuals frequently take multiple drugs for chronic conditions (e.g., hypertension, heart failure, arthritis, osteoporosis).
• Polypharmacy significantly increases the potential for drug interactions.

Types of Drug Interactions

• A drug interaction occurs when one substance (drug) modifies the action of another.
• Synergistic: One drug enhances the effect of another.
• Antagonistic: One drug reduces the effect of another.

Pharmacodynamic Interactions: Examples

• Beta-blockers reduce the effectiveness of beta-adrenoceptor agonists (e.g., salbutamol).
• Glucocorticoids are often coadministered to enhance the action of other drugs.
• Monoamine oxidase inhibitors (MAOIs) increase catecholamine levels, potentially leading to a "cheese reaction" (hypertensive crisis) if tyramine-rich foods are consumed.
• Patients on MAOIs must avoid tyramine-rich foods.
• Warfarin antagonizes vitamin K, affecting coagulation factor synthesis. Vitamin K supplements decrease warfarin's effectiveness.
• Warfarin's anticoagulant effect can be augmented by drugs that contribute to bleeding through different mechanisms (e.g., aspirin).
• Benzodiazepines, barbiturates, and alcohol can produce a synergistic effect, potentially leading to respiratory depression.

Pharmacokinetic Interactions: Absorption

• Proton pump inhibitors (PPIs) and antacids increase gastric pH.
• This can reduce the absorption of acid-sensitive drugs (e.g., aspirin).
• Tetracycline absorption is diminished by divalent cations (especially calcium and magnesium), present in antacids.
• Adrenaline, when co-administered with local anesthetics, can narrow blood vessels, slowing anesthetic absorption and prolonging its local effect.

Pharmacokinetic Interactions: Distribution

• One drug may alter the distribution of another by competing for binding sites on plasma albumin or tissue proteins.
• Displacement from binding sites leads to increased free drug concentration, potentially causing toxicity.
• Warfarin, a protein-bound anticoagulant is displaced by aspirin, increasing free warfarin and the risk of bleeding.

Pharmacokinetic Interactions: Metabolism

• Cytochrome P450 (CYP450) enzymes metabolize numerous drugs.
• CYP450 inducers decrease drug plasma concentrations, potentially reducing therapeutic effectiveness (e.g., barbiturates, rifampicin, phenytoin, carbamazepine, smoking).
• CYP450 inhibitors increase drug plasma concentrations; high concentrations may lead to harm (e.g., cimetidine, macrolides, ketoconazole, grapefruit juice).

Explore predisposing factors such as age and polypharmacy that increase drug interaction risks. Learn about synergistic and antagonistic interactions when drugs modify each other's effects. Understand pharmacodynamic interactions like beta-blockers reducing agonist effectiveness.