, Question 1
A patient with HIV and latent tuberculosis is being started on a two-drug
short-course regimen. Which statement best explains why the regimen achieves
efficacy comparable to longer isoniazid monotherapy despite a shorter
duration?
A. Rifapentine's long half-life permits weekly dosing that maintains
bactericidal concentrations sufficient to sterilize dormant bacilli.
B. Isoniazid and rifapentine are both prodrugs activated by mycobacterial
catalase-peroxidase, producing synergistic killing of persisters.
C. Rifapentine is a rifamycin that inhibits RNA polymerase, and its
combination with isoniazid targets both actively replicating and
intermittent-metabolism bacilli.
D. The combination induces efflux pump inhibition, preventing
emergence of isoniazid monoresistance.
Correct Answer: C - Rifapentine is a rifamycin that inhibits RNA
polymerase, and its combination with isoniazid targets both
actively replicating and intermittent-metabolism bacilli.
RATIONALE
The 3HP regimen (isoniazid plus rifapentine weekly) is effective
because rifapentine's RNA polymerase inhibition complements
isoniazid's inhibition of mycolic acid synthesis, targeting both actively
replicating and intermittently metabolizing bacilli. Option A is
incorrect because rifapentine's long half-life alone does not fully
explain sterilization of dormant organisms. Option B is wrong because
rifapentine is not a prodrug. Option D describes a mechanism not
responsible for the regimen's efficacy.
Question 2
A patient with multidrug-resistant tuberculosis is prescribed bedaquiline.
Which ECG finding would most strongly warrant discontinuation or
modification of therapy?
Page 2
, A. QTc prolongation to 480 ms with a prior history of syncope
B. QTc prolongation to 450 ms without symptoms
C. New-onset atrial fibrillation with rapid ventricular response
D. Sinus bradycardia with heart rate of 52 beats/min
Correct Answer: A - QTc prolongation to 480 ms with a prior
history of syncope
RATIONALE
Bedaquiline prolongs the QT interval, and a QTc exceeding 480 ms
(or 500 ms in some guidelines) with a history of syncope or
arrhythmia significantly increases the risk of torsades de pointes,
warranting discontinuation or regimen change. Option B is less
concerning as 450 ms is below the threshold for high risk. Options C
and D are not the primary ECG toxicity associated with bedaquiline.
Question 3
A patient on rifampin for tuberculosis develops reduced efficacy of their
antiretroviral therapy. Which mechanism best explains this interaction?
A. Rifampin inhibits CYP3A4, increasing antiretroviral levels and
toxicity.
B. Rifampin induces CYP3A4 and P-glycoprotein, accelerating
metabolism and efflux of protease inhibitors and some integrase
inhibitors.
C. Rifampin chelates antiretrovirals in the gut, reducing absorption.
D. Rifampin displaces antiretrovirals from plasma protein binding sites,
increasing clearance.
Correct Answer: B - Rifampin induces CYP3A4 and
P-glycoprotein, accelerating metabolism and efflux of protease
inhibitors and some integrase inhibitors.
Page 3
, RATIONALE
Rifampin is a potent inducer of CYP3A4 and P-glycoprotein, which
increases the metabolism and efflux of many antiretrovirals (e.g.,
protease inhibitors, some integrase inhibitors), reducing their plasma
concentrations and efficacy. Option A is incorrect because rifampin
induces, not inhibits, CYP3A4. Option C is not a recognized
mechanism. Option D is not the primary mechanism for this
interaction.
Question 4
A patient receiving isoniazid for latent tuberculosis develops peripheral
neuropathy. Which intervention is most appropriate?
A. Discontinue isoniazid immediately and switch to rifampin
monotherapy.
B. Add pyridoxine (vitamin B6) 25-50 mg daily and continue isoniazid.
C. Reduce isoniazid dose by 50% and monitor symptoms.
D. Add pyridoxine 100 mg daily and increase isoniazid dose to
compensate.
Correct Answer: B - Add pyridoxine (vitamin B6) 25-50 mg daily
and continue isoniazid.
RATIONALE
Isoniazid-induced peripheral neuropathy results from pyridoxine
deficiency due to increased excretion of vitamin B6. The standard
management is to add pyridoxine 25-50 mg daily while continuing
isoniazid. Option A is too drastic and unnecessary. Option C is not
standard; dose reduction does not address the deficiency. Option D is
incorrect because increasing isoniazid dose would worsen the
neuropathy.
Question 5
Which statement best describes the role of therapeutic drug monitoring (TDM)
for first-line antitubercular drugs in contemporary practice?
Page 4
A patient with HIV and latent tuberculosis is being started on a two-drug
short-course regimen. Which statement best explains why the regimen achieves
efficacy comparable to longer isoniazid monotherapy despite a shorter
duration?
A. Rifapentine's long half-life permits weekly dosing that maintains
bactericidal concentrations sufficient to sterilize dormant bacilli.
B. Isoniazid and rifapentine are both prodrugs activated by mycobacterial
catalase-peroxidase, producing synergistic killing of persisters.
C. Rifapentine is a rifamycin that inhibits RNA polymerase, and its
combination with isoniazid targets both actively replicating and
intermittent-metabolism bacilli.
D. The combination induces efflux pump inhibition, preventing
emergence of isoniazid monoresistance.
Correct Answer: C - Rifapentine is a rifamycin that inhibits RNA
polymerase, and its combination with isoniazid targets both
actively replicating and intermittent-metabolism bacilli.
RATIONALE
The 3HP regimen (isoniazid plus rifapentine weekly) is effective
because rifapentine's RNA polymerase inhibition complements
isoniazid's inhibition of mycolic acid synthesis, targeting both actively
replicating and intermittently metabolizing bacilli. Option A is
incorrect because rifapentine's long half-life alone does not fully
explain sterilization of dormant organisms. Option B is wrong because
rifapentine is not a prodrug. Option D describes a mechanism not
responsible for the regimen's efficacy.
Question 2
A patient with multidrug-resistant tuberculosis is prescribed bedaquiline.
Which ECG finding would most strongly warrant discontinuation or
modification of therapy?
Page 2
, A. QTc prolongation to 480 ms with a prior history of syncope
B. QTc prolongation to 450 ms without symptoms
C. New-onset atrial fibrillation with rapid ventricular response
D. Sinus bradycardia with heart rate of 52 beats/min
Correct Answer: A - QTc prolongation to 480 ms with a prior
history of syncope
RATIONALE
Bedaquiline prolongs the QT interval, and a QTc exceeding 480 ms
(or 500 ms in some guidelines) with a history of syncope or
arrhythmia significantly increases the risk of torsades de pointes,
warranting discontinuation or regimen change. Option B is less
concerning as 450 ms is below the threshold for high risk. Options C
and D are not the primary ECG toxicity associated with bedaquiline.
Question 3
A patient on rifampin for tuberculosis develops reduced efficacy of their
antiretroviral therapy. Which mechanism best explains this interaction?
A. Rifampin inhibits CYP3A4, increasing antiretroviral levels and
toxicity.
B. Rifampin induces CYP3A4 and P-glycoprotein, accelerating
metabolism and efflux of protease inhibitors and some integrase
inhibitors.
C. Rifampin chelates antiretrovirals in the gut, reducing absorption.
D. Rifampin displaces antiretrovirals from plasma protein binding sites,
increasing clearance.
Correct Answer: B - Rifampin induces CYP3A4 and
P-glycoprotein, accelerating metabolism and efflux of protease
inhibitors and some integrase inhibitors.
Page 3
, RATIONALE
Rifampin is a potent inducer of CYP3A4 and P-glycoprotein, which
increases the metabolism and efflux of many antiretrovirals (e.g.,
protease inhibitors, some integrase inhibitors), reducing their plasma
concentrations and efficacy. Option A is incorrect because rifampin
induces, not inhibits, CYP3A4. Option C is not a recognized
mechanism. Option D is not the primary mechanism for this
interaction.
Question 4
A patient receiving isoniazid for latent tuberculosis develops peripheral
neuropathy. Which intervention is most appropriate?
A. Discontinue isoniazid immediately and switch to rifampin
monotherapy.
B. Add pyridoxine (vitamin B6) 25-50 mg daily and continue isoniazid.
C. Reduce isoniazid dose by 50% and monitor symptoms.
D. Add pyridoxine 100 mg daily and increase isoniazid dose to
compensate.
Correct Answer: B - Add pyridoxine (vitamin B6) 25-50 mg daily
and continue isoniazid.
RATIONALE
Isoniazid-induced peripheral neuropathy results from pyridoxine
deficiency due to increased excretion of vitamin B6. The standard
management is to add pyridoxine 25-50 mg daily while continuing
isoniazid. Option A is too drastic and unnecessary. Option C is not
standard; dose reduction does not address the deficiency. Option D is
incorrect because increasing isoniazid dose would worsen the
neuropathy.
Question 5
Which statement best describes the role of therapeutic drug monitoring (TDM)
for first-line antitubercular drugs in contemporary practice?
Page 4
