19 - Drug Metabolism and Excretion (ADME) - Vocabulary Flashcards

Vocabulary flashcards covering key terms and definitions from the lecture notes on drug metabolism, excretion, and pharmacokinetics.

Drug Elimination

Irreversible removal of a drug from the body; includes metabolism and excretion.

Metabolism (biotransformation)

Enzymatic modification of drugs, primarily in the liver, in a two-phase process (Phase 1: modification; Phase 2: conjugation).

Phase 1 (Modification)

Oxidation, reduction, or hydrolysis (often by CYP450 enzymes) that creates reactive metabolites.

Phase 2 (Conjugation)

Conjugation of Phase 1 products with polar groups (e.g., GSH, sulfate, glycine, glucuronic acid) to aid excretion.

Cytochrome P450 (CYP)

Family of haem-containing enzymes that catalyse many Phase 1 reactions; common site of drug interactions (inhibition/induction).

Mixed-function oxidase

Phase 1 enzyme systems (including CYPs) that perform oxidation, reduction, or hydrolysis.

Glucuronidation

A Phase 2 conjugation using glucuronic acid to form glucuronides for enhanced excretion.

Glutathione (GSH)

A conjugating molecule used in Phase 2 to detoxify reactive metabolites.

Induction

Drugs that increase enzyme activity, leading to faster metabolism of substrates (e.g., barbiturates, rifampicin, phenytoin).

Substrate inhibition

Inhibition of a CYP enzyme when a substrate competes with another substrate (e.g., amiodarone slowing caffeine metabolism via CYP1A2).

Non-substrate inhibition

Inhibition of metabolism by a compound that is not itself a substrate (e.g., quinidine).

Active metabolites

Metabolites that retain pharmacological activity; can be therapeutic or toxic; examples include morphine-6-glucuronide and norpethidine.

Prodrug

An inactive compound that is converted into an active drug after metabolism.

NAPQI

Reactive toxic metabolite formed from paracetamol via CYP enzymes; detoxified by glutathione; accumulates in overdose.

N-hydroxylation

Phase 1 oxidation step forming N-hydroxyl metabolites (e.g., paracetamol to NAPQI).

Excretion routes

Renal (kidneys), hepatic/biliary (faecal), and other routes such as sweat, milk, and breath.

Renal elimination

Filtration in the glomerulus and secretion in the proximal tubule; charged/polar drugs may be trapped in urine; urine pH can cause ion trapping.

Organic acid/base transporters

Transporters mediating renal secretion: acid transporters for penicillin/uric acid and organic base transporters for drugs like pethidine/quinine.

Volume of distribution (Vd)

Hypothetical compartment volume that relates drug amount to plasma concentration; used in one-compartment models.

Single-compartment model

Body viewed as a single homogeneous compartment; IV bolus yields monoexponential decline in concentration.

First-order kinetics

Elimination rate proportional to concentration (dC/dt = -kC); concentration decays exponentially (C = C0 e^{-kt}).

Zero-order kinetics

Elimination rate is constant and independent of concentration due to enzyme saturation (e.g., ethanol at high levels).

Half-life (t1/2)

Time required for drug concentration to fall to 50% of its initial value; most intuitive for first-order processes.

Infusion and steady state

Continuous IV infusion delivers drug at rate r; concentration approaches r/k; target concentration can be achieved by choosing r.

Therapeutic window

Plasma concentration range in which a drug is effective without unacceptable toxicity.

Enterohepatic circulation

Drug/metabolite excreted into bile and reabsorbed from the intestine, prolonging exposure.

Ethanol kinetics (zeroth order)

At high concentrations, alcohol is metabolized at a constant rate (about 10 g/hour) due to enzyme saturation.