DHA Pharmacist Pharmacokinetics and Pharmacodynamics 2 — Questions and Answers
Question 1: 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?
- 30 mg
- 60 mg
- 120 mg (Correct answer)
- 240 mg
Correct answer: 120 mg
Loading dose = Vd × target concentration = (0.25 × 60) × 8 = 15 × 8 = 120 mg.
Question 2: Phenytoin exhibits zero-order (saturation) kinetics at therapeutic doses. What clinical implication does this have?
- Small dose increases produce proportionally small increases in plasma levels
- Half-life is constant regardless of dose
- Small dose increases can cause disproportionately large rises in plasma concentration (Correct answer)
- Steady-state is reached faster than with first-order drugs
Correct 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.
Question 3: A drug is 95% bound to plasma proteins. Which statement best describes the pharmacokinetic consequence?
- A large fraction is available for renal filtration
- Only the 5% unbound fraction is pharmacologically active (Correct answer)
- The drug will have a very large volume of distribution
- The drug cannot be displaced by other highly bound drugs
Correct 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.
Question 4: Creatinine clearance (CrCl) is used in clinical practice primarily to:
- Estimate hepatic metabolic capacity
- Adjust doses of renally eliminated drugs (Correct answer)
- Predict protein binding changes
- Calculate the volume of distribution
Correct 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.
Question 5: CYP3A4 is the most abundant hepatic CYP450 enzyme. A drug that strongly inhibits CYP3A4 (e.g., ketoconazole) will most likely:
- Increase the metabolism of CYP3A4 substrates
- Decrease plasma levels of CYP3A4 substrates
- Increase plasma levels of CYP3A4 substrates (Correct answer)
- Have no effect on drugs administered simultaneously
Correct 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.
Question 6: In therapeutic drug monitoring (TDM), which of the following drugs has a narrow therapeutic index making TDM essential?
- Amoxicillin
- Metformin
- Lithium (Correct answer)
- Ibuprofen
Correct 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.
Question 7: Which pharmacokinetic change is most commonly observed in elderly patients that necessitates dose adjustments?
- Increased hepatic blood flow
- Decreased renal clearance (Correct answer)
- Increased gastric acid secretion
- Increased volume of distribution for water-soluble drugs
Correct 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.
DHA Pharmacist Pharmacokinetics and Pharmacodynamics 2
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?