Pharmacokinetics and Pharmacodynamics Flashcards

A patient requires a loading dose of gentamicin. The target plasma concentration is 8 mg/L and the volume of distribution is 0.25 L/kg. For a 60 kg patient, what is the loading dose?

Answer: 120 mg

Loading dose = Vd × target concentration = (0.25 × 60) × 8 = 15 × 8 = 120 mg.

Phenytoin exhibits zero-order (saturation) kinetics at therapeutic doses. What clinical implication does this have?

Answer: Small dose increases can cause disproportionately large rises in plasma concentration

At saturation kinetics, elimination capacity is at maximum; small dose increases cannot be metabolized faster, causing disproportionate plasma level rises and toxicity risk.

A drug is 95% bound to plasma proteins. Which statement best describes the pharmacokinetic consequence?

Answer: Only the 5% unbound fraction is pharmacologically active

Only the unbound (free) fraction can interact with receptors, cross membranes, and be eliminated; the protein-bound portion acts as an inactive reservoir.

Creatinine clearance (CrCl) is used in clinical practice primarily to:

Answer: Adjust doses of renally eliminated drugs

CrCl estimates glomerular filtration rate (GFR) and is used to adjust doses of drugs that are primarily eliminated unchanged by the kidneys.

CYP3A4 is the most abundant hepatic CYP450 enzyme. A drug that strongly inhibits CYP3A4 (e.g., ketoconazole) will most likely:

Answer: Increase plasma levels of CYP3A4 substrates

Inhibiting CYP3A4 reduces metabolism of its substrates, causing drug accumulation and increased plasma concentrations, which may lead to toxicity.

In therapeutic drug monitoring (TDM), which of the following drugs has a narrow therapeutic index making TDM essential?

Answer: Lithium

Lithium has a narrow therapeutic index (0.6–1.2 mEq/L); levels above 1.5 mEq/L cause significant toxicity, making regular TDM mandatory.

Which pharmacokinetic change is most commonly observed in elderly patients that necessitates dose adjustments?

Answer: Decreased renal clearance

Renal function declines progressively with age (GFR decreases ~1%/year after age 40), reducing clearance of renally eliminated drugs and increasing toxicity risk.