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UNIT 1: PHARMACOKINETICS & PHARMACODYNAMICS (15 Questions)
Q1: A 68-year-old male with chronic kidney disease (eGFR 35 mL/min/1.73m²) is
prescribed gentamicin 5 mg/kg IV q8h for sepsis. On day 3, his serum creatinine
increases from 1.8 to 3.2 mg/dL. Which pharmacokinetic principle best explains this
adverse effect?
A. Decreased absorption due to reduced GI blood flow
B. Reduced hepatic metabolism causing drug accumulation
C. Decreased renal elimination leading to nephrotoxicity [CORRECT]
D. Increased volume of distribution in elderly patients
Correct Answer: C
Rationale: Gentamicin is primarily eliminated unchanged by glomerular filtration. In CKD
(eGFR 35), renal clearance is significantly impaired, causing drug accumulation.
Aminoglycosides concentrate in the renal cortex, causing dose-dependent
nephrotoxicity through lysosomal phospholipidosis and mitochondrial damage.
, ● A is incorrect: Gentamicin is administered IV; absorption is not relevant.
● B is incorrect: Gentamicin undergoes minimal hepatic metabolism (<10%).
● D is incorrect: While elderly patients may have altered Vd, this does not explain
the acute nephrotoxicity observed.
Q2: A 45-year-old female with atrial fibrillation is started on warfarin 5 mg daily. The
prescriber explains that steady state will be reached in approximately 5 days. This
timeframe is based on which pharmacokinetic parameter?
A. Time to peak concentration
B. Five half-lives of the drug [CORRECT]
C. First-pass metabolism completion
D. Duration of distribution phase
Correct Answer: B
Rationale: Steady state is achieved when drug elimination equals drug administration,
theoretically occurring after 5 half-lives when approximately 97% of steady-state
concentration is reached. Warfarin has a half-life of 20-60 hours (mean 40 hours); 5 × 40
hours = ~8 days, though clinical steady state is often observed earlier.
● A is incorrect: Time to peak relates to absorption, not steady-state achievement.
● C is incorrect: First-pass metabolism occurs with initial dosing, not steady-state
establishment.
● D is incorrect: Distribution phase (alpha) is brief compared to elimination phase
(beta).
,Q3: A 28-year-old male receives morphine 10 mg IV for post-operative pain. He
experiences significant respiratory depression. Genetic testing reveals he is a CYP2D6
ultra-rapid metabolizer. Which pharmacodynamic concept explains this exaggerated
response?
A. Increased active metabolite production [CORRECT]
B. Decreased protein binding
C. Enhanced renal tubular secretion
D. Reduced first-pass effect
Correct Answer: A
Rationale: CYP2D6 metabolizes morphine to active metabolites
(morphine-6-glucuronide and morphine-3-glucuronide). Ultra-rapid metabolizers (UM)
have multiple copies of functional CYP2D6 genes, producing excessive active
metabolites that potentiate mu-opioid receptor agonism, causing exaggerated
respiratory depression.
● B is incorrect: Protein binding alterations would affect free drug concentration
but not specifically metabolite production.
● C is incorrect: Renal secretion affects elimination, not the metabolic conversion
causing toxicity.
● D is incorrect: IV administration bypasses first-pass metabolism entirely.
Q4: A 55-year-old patient with hypertension is prescribed propranolol 40 mg twice daily.
After 2 weeks, blood pressure remains elevated. The nurse practitioner considers that
the patient smokes 1 pack/day. Which pharmacokinetic interaction is most likely?
, A. Smoking induces CYP1A2, increasing propranolol metabolism [CORRECT]
B. Nicotine inhibits hepatic blood flow, reducing clearance
C. Carbon monoxide increases propranolol protein binding
D. Smoking decreases gastric pH, reducing absorption
Correct Answer: A
Rationale: Polycyclic aromatic hydrocarbons in cigarette smoke induce CYP1A2, which
metabolizes propranolol. This increases hepatic clearance, reduces bioavailability, and
necessitates higher doses. Smoking cessation requires dose reduction to prevent
bradycardia/hypotension.
● B is incorrect: Nicotine does not significantly inhibit hepatic blood flow.
● C is incorrect: Carbon monoxide binds hemoglobin, not plasma proteins affecting
drug binding.
● D is incorrect: Propranolol is lipophilic with high bioavailability; gastric pH
changes minimally affect absorption.
Q5: A 72-year-old female with CHF (EF 30%) receives digoxin 0.25 mg daily. Her serum
digoxin level is 3.2 ng/mL (therapeutic 0.5-0.9 ng/mL). She reports nausea, visual
disturbances, and bradycardia. Which factor most contributed to toxicity?
A. Increased cardiac output enhancing distribution
B. Reduced renal clearance and decreased Vd [CORRECT]
C. Enhanced hepatic metabolism in elderly
D. Increased P-glycoprotein activity