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[Section 1: Pharmacokinetics, Pharmacodynamics & Pharmacogenomics (Q1-35)]
Q1. A 55-year-old patient on warfarin starts fluconazole for a fungal infection. Which
CYP450 enzyme interaction explains the increased INR?
A. Fluconazole induces CYP2C9, increasing warfarin metabolism
B. Fluconazole inhibits CYP2C9, decreasing warfarin metabolism
C. Fluconazole induces CYP3A4, increasing warfarin metabolism
D. Fluconazole inhibits CYP1A2, decreasing warfarin metabolism
B. Fluconazole inhibits CYP2C9, decreasing warfarin metabolism [CORRECT]
Rationale: Warfarin (S-warfarin) is metabolized by CYP2C9. Fluconazole is a potent
CYP2C9 inhibitor, reducing warfarin clearance and increasing INR/bleeding risk. Options
A and C incorrectly describe induction. Option D identifies the wrong enzyme.
Correct Answer: B
Q2. A patient with HIV is prescribed abacavir. Which pharmacogenomic test must be
performed before initiation?
A. HLA-B5701
B. CYP2D6
C. TPMT
D. HLA-B1502
A. HLA-B5701 [CORRECT]
,Rationale: HLA-B5701 screening is mandatory before abacavir to prevent
hypersensitivity reaction, which can be fatal. Option B is for codeine/tramadol
metabolism. Option C is for thiopurines. Option D is for carbamazepine-induced
Stevens-Johnson syndrome in Asian populations.
Correct Answer: A
Q3. A patient on clopidogrel 75 mg daily after PCI has recurrent stent thrombosis.
Genetic testing shows CYP2C19*2/*2 genotype. Which is the most appropriate action?
A. Increase clopidogrel to 150 mg daily
B. Switch to prasugrel or ticagrelor
C. Add aspirin 325 mg daily
D. Continue current therapy; genotype does not affect clopidogrel
B. Switch to prasugrel or ticagrelor [CORRECT]
Rationale: CYP2C19 poor metabolizers cannot effectively convert clopidogrel to its
active metabolite. Prasugrel and ticagrelor do not require CYP2C19 activation. Option A
is ineffective in poor metabolizers. Option C increases bleeding without addressing
clopidogrel resistance. Option D is incorrect.
Correct Answer: B
Q4. A patient on azathioprine for Crohn's disease develops severe myelosuppression.
Which enzyme deficiency should be tested for?
A. CYP2D6
B. TPMT (thiopurine S-methyltransferase)
C. DPD (dihydropyrimidine dehydrogenase)
D. G6PD
B. TPMT (thiopurine S-methyltransferase) [CORRECT]
Rationale: TPMT deficiency causes accumulation of toxic thiopurine metabolites
(6-TGN), leading to life-threatening myelosuppression. Pretreatment testing is
,recommended. Option A is for codeine metabolism. Option C is for 5-FU/capecitabine.
Option D is for oxidative stress hemolysis.
Correct Answer: B
Q5. A drug with high first-pass metabolism is administered orally. Which route would
bypass hepatic first-pass effect and increase bioavailability?
A. Oral
B. Sublingual
C. Intramuscular
D. Both B and C
D. Both B and C [CORRECT]
Rationale: Sublingual administration bypasses the portal circulation, avoiding first-pass
metabolism. Intramuscular injection also bypasses the liver initially. Oral administration
(Option A) is subject to first-pass metabolism.
Correct Answer: D
Q6. A patient with renal impairment (CrCl 25 mL/min) is prescribed a drug that is 80%
renally excreted unchanged. Which adjustment is most appropriate?
A. No adjustment needed; hepatic metabolism compensates
B. Reduce dose by 50% or extend dosing interval
C. Increase dose to compensate for reduced clearance
D. Switch to a hepatically metabolized alternative only
B. Reduce dose by 50% or extend dosing interval [CORRECT]
Rationale: For drugs primarily renally eliminated, dose reduction or interval extension is
required in renal impairment to prevent accumulation and toxicity. Option A is
dangerous. Option C would worsen toxicity. Option D may be considered but is not the
primary adjustment.
, Correct Answer: B
Q7. A patient on phenytoin has subtherapeutic levels despite appropriate dosing. Which
factor most likely increases phenytoin metabolism?
A. CYP2C9 inhibition by fluconazole
B. CYP450 enzyme induction by carbamazepine co-administration
C. Albumin binding displacement by valproic acid
D. Reduced hepatic blood flow from heart failure
B. CYP450 enzyme induction by carbamazepine co-administration [CORRECT]
Rationale: Carbamazepine is a potent CYP450 inducer that accelerates phenytoin
metabolism, lowering levels. Option A would increase phenytoin levels. Option C
increases free phenytoin but not total levels. Option D reduces hepatic clearance but is
less significant than enzyme induction.
Correct Answer: B
Q8. A patient with a UTI is prescribed ciprofloxacin. Which drug interaction is most
concerning?
A. Reduced absorption with calcium supplements
B. Increased warfarin effect via CYP1A2 inhibition
C. QT prolongation with amiodarone
D. All of the above are clinically significant
D. All of the above are clinically significant [CORRECT]
Rationale: Ciprofloxacin chelates divalent cations (calcium, reducing absorption),
inhibits CYP1A2 (increasing warfarin effect), and prolongs QT interval (additive with
amiodarone). All interactions require monitoring or avoidance.
Correct Answer: D