Pharmacology III: Drug Interactions

Comprehensive vocabulary flashcards detailing the mechanisms, classifications, and examples of pharmacodynamic and pharmacokinetic drug-drug interactions from Pharmacology III.

Polypharmacy

The clinical practice of administering several drugs concurrently to a patient, either to treat multiple medical conditions or to employ multiple approaches in treating a single disease.

Drug Interaction

A situation in which the pharmacological action of one drug is altered by the concurrent use of another drug, food, or herb.

Pharmacodynamic Interactions

Drug interactions that develop when one drug increases or decreases the pharmacological effect of another, resulting in addition, potentiation, or antagonism.

Addition (Summation)

The most common type of pharmacodynamic interaction, occurring when two drugs act on the same receptor or effector system to give an additive combined effect ($2 + 2 = 4$).

Potentiation

A pharmacodynamic interaction where the combined effect of two drugs exceeds the sum of their individual effects ($2 + 2 = 5$), or where a drug lacking a specific action enhances the action of another ($0 + 2 = 5$).

Antagonism (Inhibition)

A pharmacodynamic interaction occurring when one drug (the antagonist or inhibitor) diminishes, opposes, or prevents the action of another (the agonist or substrate).

Naloxone

A pure opioid antagonist that acts as a competitive inhibitor of morphine by competing for and displacing opioids at opioid receptor sites to reverse opioid overdose.

Pharmacokinetic Interactions

Interactions arising when one drug alters the absorption, distribution, metabolism, or excretion (ADME) behavior of another co-administered drug.

Chelating Agents

Compounds that bind to multivalent metal ions (such as $\text{Ca}^{2+}$, $\text{Mg}^{2+}$, $\text{Al}^{3+}$, and $\text{Fe}^{2+}$) to form poorly absorbed complexes or salts; this interaction can be minimized by separating administration by at least $2\,\text{hours}$.

Adsorption Interactions

Absorption interactions occurring when drug molecules physically bind to the surface of a solid adsorbent (such as activated charcoal, antacids, or cholestyramine), reducing the concentration available for systemic absorption.

Gastric pH Alteration

An absorption-altering mechanism where drugs that raise stomach $\text{pH}$ (such as antacids, $\text{H}_2$ blockers, or PPIs) modify the ionization ratio of weak acids and weak bases, altering their dissolution, rate of absorption, and bioavailability.

GI Motility Alteration

A pharmacokinetic mechanism where changes in gastrointestinal transit speed (such as increased motility from laxatives) reduce residence time in the small intestine, decreasing the extent and rate of drug absorption.

Intestinal Flora Alteration

An interaction where oral antibiotics destroy normal intestinal bacteria, such as macrolides inhibiting Eubacterium lentum in the gut, which prevents digoxin breakdown and precipitates digoxin toxicity.

Plasma Protein Displacement

A distribution interaction where a drug with a higher affinity displaces another drug from plasma proteins (primarily albumin), temporarily raising the free/unbound concentration and pharmacological effect of the displaced drug.

Unbound Drug Fraction

The free, biologically active fraction of a drug that can diffuse into interstitial fluid, tissues, and cells to exert a therapeutic effect, while the protein-bound fraction acts as a reservoir depot.

Enzyme Induction

A metabolic interaction where a substance increases the cellular biosynthesis of drug-metabolizing enzymes (such as CYP3A4), leading to increased drug metabolism, decreased plasma concentration, and shorter duration of action.

Autoinduction

The metabolic phenomenon in which a drug induces the specific hepatic microsomal enzymes that metabolize itself, triggering increased clearance and lowered plasma levels (e.g., carbamazepine).

NAPQI (N-acetyl-p-benzoquinoneimine)

A toxic reactive metabolite produced from paracetamol biotransformation by CYP450 enzymes; the risk of liver failure from NAPQI rises if CYP450 has been induced by chronic alcohol use.

Enzyme Inhibition

The mechanism most frequently responsible for life-threatening drug interactions, wherein drug biotransformation is halted or reduced, leading to elevated blood concentrations and potential toxicity.

Urinary pH Alteration

An excretion interaction where changing urine $\text{pH}$ influences drug clearance; urine acidifiers (e.g., ammonium chloride) accelerate basic drug excretion, whereas alkalinizers (e.g., sodium bicarbonate) enhance acidic drug excretion.

Renal Active Transport Inhibition

An excretion interaction where a drug inhibits renal tubular active transporters (such as P-glycoprotein or anion transporters), decreasing substrate clearance; for example, probenecid inhibiting penicillin excretion to prolong its action.