CPI Pharmacology & Medication Management 2

Question 1

In a clinical trial, a participant develops QT prolongation after starting a study drug. Which pharmacological mechanism most commonly causes this adverse effect?

Accepted Answer

Inhibition of hERG potassium channels

Answer

hERG (IKr) potassium channel inhibition delays cardiac repolarization, prolonging the QT interval and increasing arrhythmia risk.

Question 2

A Phase I trial is assessing drug X metabolism. CYP2D6 poor metabolizers show 4-fold higher AUC compared to extensive metabolizers. What is the most appropriate dose adjustment strategy?

Accepted Answer

Reduce dose by 75% in poor metabolizers

Answer

A 4-fold AUC increase in poor metabolizers indicates significantly reduced clearance, requiring dose reduction to avoid toxicity.

Question 3

During a trial of an oral anticoagulant, a participant's renal function declines (CrCl drops from 65 to 28 mL/min). What pharmacokinetic parameter is most directly affected?

Accepted Answer

Renal clearance and elimination half-life

Answer

Renal clearance decreases proportionally with GFR decline, prolonging elimination half-life for renally eliminated drugs.

Question 4

A study drug is a potent inhibitor of P-glycoprotein (P-gp). A participant is concurrently taking digoxin. What is the expected drug-drug interaction?

Accepted Answer

Increased digoxin plasma concentrations

Answer

P-gp normally effluxes digoxin from enterocytes and renal tubular cells; P-gp inhibition increases digoxin absorption and reduces its secretion, raising plasma levels.

Question 5

A participant in an analgesic trial develops respiratory depression 6 hours after the last dose of the study opioid. The drug's half-life is 18 hours. What principle best explains this delayed toxicity?

Accepted Answer

Drug accumulation over multiple half-lives

Answer

Drugs with long half-lives accumulate with repeated dosing, reaching toxic concentrations only after several half-lives of administration.

(CPI) Certified Physician Investigator Practice Test

(CPI) Certified Physician Investigator Practice Test

CPI Pharmacology & Medication Management 2