Which first-line tuberculosis drug is a prodrug that must be activated by the mycobacterial enzyme KatG?
Rifampin
Isoniazid
Ethambutol
Pyrazinamide
Show answer
Answer: B. Isoniazid
Isoniazid requires activation by the mycobacterial catalase-peroxidase KatG before it can inhibit mycolic acid synthesis; mutations in KatG are a major cause of isoniazid resistance.
Which first-line drug's own FDA label states that its mechanism of action is unknown?
Ethambutol
Rifampin
Pyrazinamide
Isoniazid
Show answer
Answer: C. Pyrazinamide
Pyrazinamide's label states the mechanism is unknown, while noting the drug requires an acidic environment and depends on conversion to pyrazinoic acid for activity.
A patient on rifampin reports orange-tinted urine and tears. What is the appropriate response?
Stop rifampin immediately for suspected hepatotoxicity
Reassure the patient this is an expected, harmless effect of the drug
Order an urgent renal function panel
Switch to isoniazid alone
Show answer
Answer: B. Reassure the patient this is an expected, harmless effect of the drug
Rifampin's label describes discoloration of urine, sweat, sputum and tears as an expected effect, not a sign of toxicity, though patients should be counselled about it in advance, including the risk of permanently staining soft contact lenses.
Which toxicity is most specifically associated with ethambutol among the first-line tuberculosis drugs?
Peripheral neuropathy
Hyperuricemia
Optic neuritis
QTc prolongation
Show answer
Answer: C. Optic neuritis
Ethambutol's defining, dose-related toxicity is optic neuritis with decreased visual acuity and color-vision changes, monitored with baseline and periodic visual testing.
What is the standard WHO multidrug therapy combination for leprosy?
Rifampin, isoniazid, pyrazinamide
Dapsone, rifampin, clofazimine
Bedaquiline, linezolid, moxifloxacin
Ethambutol, dapsone, isoniazid
Show answer
Answer: B. Dapsone, rifampin, clofazimine
Leprosy (Hansen disease) is treated with a WHO multidrug regimen of dapsone, rifampin and clofazimine, a combination distinct from the RIPE regimen used for tuberculosis.
Why is bedaquiline never given as a single added drug to a failing regimen?
It has no antimycobacterial activity of its own
Its label requires it be used with at least three other active drugs, partly to avoid amplifying resistance while managing its QTc-prolongation risk
It is only approved for latent tuberculosis
It cannot be taken orally
Show answer
Answer: B. Its label requires it be used with at least three other active drugs, partly to avoid amplifying resistance while managing its QTc-prolongation risk
Bedaquiline's prescribing information restricts its use to combination therapy with at least three other drugs the isolate is susceptible to, both to prevent resistance amplification and because of its own cardiac safety profile requiring ECG monitoring.
Which mechanism is shared by albendazole and mebendazole?
Glutamate-gated chloride channel opening
Inhibition of tubulin polymerization (microtubule synthesis)
Increased calcium permeability of the tegument
Inhibition of heme polymerase
Show answer
Answer: B. Inhibition of tubulin polymerization (microtubule synthesis)
Both are benzimidazoles that inhibit microtubule synthesis by preventing tubulin polymerization, blocking the helminth's glucose uptake and leading to its death.
Ivermectin's mechanism of action is best described as:
Blockade of folate synthesis in the parasite
Binding glutamate-gated chloride channels in invertebrate nerve/muscle, causing paralysis
Inhibition of parasite RNA polymerase
Disruption of the parasite cell wall
Show answer
Answer: B. Binding glutamate-gated chloride channels in invertebrate nerve/muscle, causing paralysis
Ivermectin binds selectively to glutamate-gated chloride channels found in invertebrate nerve and muscle cells, increasing chloride permeability and causing hyperpolarization and paralysis.
Which drug is specifically associated with worsening neurologic disease when used to treat neurocysticercosis?
Ivermectin
Mebendazole
Praziquantel
Atovaquone/proguanil
Show answer
Answer: C. Praziquantel
Praziquantel's label warns it can exacerbate CNS pathology due to neurocysticercosis, since killing the cysts provokes an inflammatory response.
Why is artemether never used as monotherapy for malaria?
It has no antimalarial activity alone
Monotherapy risks recrudescence and encourages the emergence of artemisinin partial resistance, so it is paired with a longer-acting partner drug like lumefantrine
It is too toxic to give without a second drug
It only works against Plasmodium vivax
Show answer
Answer: B. Monotherapy risks recrudescence and encourages the emergence of artemisinin partial resistance, so it is paired with a longer-acting partner drug like lumefantrine
Artemisinin-class drugs act quickly but clear rapidly from the body, so pairing them with a longer-acting partner drug like lumefantrine prevents recrudescence and slows the development of artemisinin resistance.
What is the principal serious adverse effect that drives blood-count monitoring during prolonged albendazole therapy?
QT prolongation
Bone marrow suppression
Optic neuritis
Hepatic cytochrome induction
Show answer
Answer: B. Bone marrow suppression
Albendazole's label describes fatalities from bone marrow suppression with prolonged or repeated dosing, which is why complete blood counts are checked at the start of and during each treatment cycle.
Between artemether-lumefantrine and atovaquone-proguanil for uncomplicated P. falciparum malaria, what is the main reason CDC prefers the former as first-line?
Atovaquone-proguanil is not FDA-approved for treatment
Artemether-lumefantrine achieves faster parasite clearance because of its artemisinin component
Atovaquone-proguanil cannot be used in adults
Artemether-lumefantrine has no food interaction
Show answer
Answer: B. Artemether-lumefantrine achieves faster parasite clearance because of its artemisinin component
CDC guidance identifies artemether-lumefantrine as preferred because the artemisinin component rapidly reduces parasite load, while atovaquone-proguanil, though generally better tolerated, has slower parasite clearance and a higher treatment-failure risk.
Why is HIV treated with combination antiretroviral therapy rather than a single drug?
Because no single antiretroviral is potent enough to suppress viral load
Because HIV's error-prone reverse transcriptase generates resistance mutations quickly, and combining classes closes off more resistance pathways than any one class can alone
Because combination pills are easier to manufacture
Because single-drug regimens are more expensive
Show answer
Answer: B. Because HIV's error-prone reverse transcriptase generates resistance mutations quickly, and combining classes closes off more resistance pathways than any one class can alone
HIV's high mutation rate under drug pressure means a single agent is quickly overcome by resistant variants; combining agents from different classes with different resistance pathways is what keeps suppression durable.
What distinguishes the mechanism of NNRTIs from NRTIs?
NNRTIs terminate the DNA chain like NRTIs but at a different nucleotide
NNRTIs bind an allosteric pocket on reverse transcriptase and block its conformational change, without being incorporated into the DNA chain
NNRTIs act on integrase rather than reverse transcriptase
NNRTIs and NRTIs have an identical mechanism
Show answer
Answer: B. NNRTIs bind an allosteric pocket on reverse transcriptase and block its conformational change, without being incorporated into the DNA chain
NRTIs are incorporated into viral DNA and terminate the chain because they lack a 3'-hydroxyl group; NNRTIs instead bind an allosteric site and block the enzyme's necessary movement without becoming part of the DNA.
Before starting abacavir, which test is specifically required by the drug's labelling?
CD4 count only
HLA-B*5701 genetic testing
Liver biopsy
Tropism testing
Show answer
Answer: B. HLA-B*5701 genetic testing
Abacavir carries a labelled requirement for HLA-B*5701 screening because patients who carry the allele are at markedly higher risk of a serious multi-organ hypersensitivity reaction.
Why must darunavir be co-administered with ritonavir or cobicistat?
To improve its taste
To boost darunavir's plasma exposure via CYP3A4 inhibition, which is required to achieve the intended antiviral effect
Because darunavir has no antiviral activity alone
To reduce pill burden
Show answer
Answer: B. To boost darunavir's plasma exposure via CYP3A4 inhibition, which is required to achieve the intended antiviral effect
The PREZISTA label states darunavir must be co-administered with ritonavir (or cobicistat) and food to achieve the desired antiviral effect; boosting is required, not optional.
Which class does dolutegravir belong to, and what is a key drug-interaction concern with it?
Protease inhibitor; interacts with grapefruit juice
Integrase strand transfer inhibitor; polyvalent cation-containing products (antacids, iron, calcium) reduce its absorption
NNRTI; interacts with St John's wort only
Fusion inhibitor; no significant interactions
Show answer
Answer: B. Integrase strand transfer inhibitor; polyvalent cation-containing products (antacids, iron, calcium) reduce its absorption
Dolutegravir is an INSTI, and its label specifies separating dosing from cation-containing antacids, supplements or laxatives by two hours before or six hours after to avoid reduced absorption.
What can happen if a patient coinfected with HIV and hepatitis B stops a tenofovir- or emtricitabine-containing regimen?
Nothing of clinical significance
A severe, sometimes fatal, acute exacerbation of hepatitis B
Immediate HIV cure
Improved renal function only
Show answer
Answer: B. A severe, sometimes fatal, acute exacerbation of hepatitis B
Both drugs are active against HBV as well as HIV; stopping them removes HBV suppression and can trigger a severe hepatic flare, so hepatic function is monitored closely for months afterward.
Answer: C. Lanosterol 14-alpha-demethylase (CYP51)
Every azole is a non-competitive inhibitor of fungal lanosterol 14-alpha-demethylase, the enzyme that converts lanosterol toward ergosterol in the fungal membrane synthesis pathway.
Which Candida species is intrinsically considered resistant to fluconazole?
Candida albicans
Candida krusei
Candida parapsilosis
Candida tropicalis
Show answer
Answer: B. Candida krusei
Fluconazole's own prescribing information states that Candida krusei should be considered resistant to fluconazole.
Which azole is distinguished from the others by causing QT interval SHORTENING rather than prolongation?
Fluconazole
Voriconazole
Posaconazole
Isavuconazole
Show answer
Answer: D. Isavuconazole
Isavuconazole's label describes concentration-related QT interval shortening, the opposite cardiac effect from fluconazole, voriconazole and posaconazole, and it is contraindicated in familial short QT syndrome for this reason.
Approximately what proportion of voriconazole-treated patients experienced visual disturbance in labelled trial data?
About 1%
About 21%
About 50%
Visual disturbance was not reported
Show answer
Answer: B. About 21%
Voriconazole's label states approximately 21% of patients experienced abnormal vision, colour vision change and/or photophobia.
Which drug interaction is specifically contraindicated with posaconazole because of an approximately nine-fold rise in the other drug's concentration?
Warfarin
Sirolimus
Metformin
Amoxicillin
Show answer
Answer: B. Sirolimus
Posaconazole increases sirolimus concentrations by approximately nine-fold, and coadministration is contraindicated.
Which two organisms does voriconazole cover that fluconazole does not, according to its own labelled indications?
Cryptococcus neoformans and Candida albicans
Scedosporium apiospermum and Fusarium species
Trichophyton and Microsporum
Malassezia and Pityrosporum
Show answer
Answer: B. Scedosporium apiospermum and Fusarium species
Voriconazole is labelled for serious infections caused by Scedosporium apiospermum and Fusarium species, in addition to invasive aspergillosis and candidiasis, none of which fluconazole reliably covers.
What does sustained virologic response (SVR) mean for hepatitis C treatment?
A temporary drop in viral load during treatment
Continued absence of detectable HCV RNA 12 or more weeks after completing therapy, considered a virologic cure
A measure of liver fibrosis only
The point at which treatment must be extended
Show answer
Answer: B. Continued absence of detectable HCV RNA 12 or more weeks after completing therapy, considered a virologic cure
SVR12 — undetectable HCV RNA 12 or more weeks after finishing therapy — is treated by AASLD-IDSA guidance as equivalent to virologic cure.
Which of the following best describes the treatment endpoint for chronic hepatitis B with entecavir or tenofovir?
Cure, equivalent to HCV DAA therapy
Ongoing viral suppression, not a cure, with relapse expected if therapy is stopped
Complete clearance of cccDNA from hepatocytes
No monitoring required once started
Show answer
Answer: B. Ongoing viral suppression, not a cure, with relapse expected if therapy is stopped
Current oral HBV nucleos(t)ide analogues suppress replication but do not eliminate the intranuclear cccDNA reservoir, so withdrawal of therapy usually results in relapse.
Why must patients be tested for HBsAg and anti-HBc before starting a hepatitis C DAA regimen?
To determine HCV genotype
Because HBV reactivation, in some cases fulminant, has occurred in coinfected patients treated with a DAA without concurrent HBV-active therapy
It is not actually required
To rule out hepatitis A
Show answer
Answer: B. Because HBV reactivation, in some cases fulminant, has occurred in coinfected patients treated with a DAA without concurrent HBV-active therapy
Both EPCLUSA and MAVYRET labelling warn of HBV reactivation in HCV/HBV-coinfected patients not receiving HBV-active antiviral therapy, so HBV status is checked before starting.
What distinguishes a pangenotypic HCV regimen such as glecaprevir/pibrentasvir?
It only treats genotype 1
It covers HCV genotypes 1 through 6, removing the need for genotype-specific drug selection
It requires interferon co-administration
It is used only for hepatitis B
Show answer
Answer: B. It covers HCV genotypes 1 through 6, removing the need for genotype-specific drug selection
MAVYRET (glecaprevir/pibrentasvir) and EPCLUSA (sofosbuvir/velpatasvir) are both labelled for HCV genotypes 1-6, which is what "pangenotypic" means in this context.
Which three HCV non-structural proteins do direct-acting antivirals target?
NS1, NS2, NS3
NS3/4A protease, NS5A, and NS5B polymerase
Core, E1 and E2 envelope proteins
Only the RNA genome directly
Show answer
Answer: B. NS3/4A protease, NS5A, and NS5B polymerase
The three DAA classes target the NS3/4A protease (polyprotein cleavage), NS5A (replication complex assembly) and NS5B polymerase (RNA synthesis).
What is a key administration difference between entecavir and glecaprevir/pibrentasvir?
Both must be taken with food
Entecavir is taken on an empty stomach, while glecaprevir/pibrentasvir must be taken with food for adequate absorption
Both must be taken on an empty stomach
Neither has a food requirement
Show answer
Answer: B. Entecavir is taken on an empty stomach, while glecaprevir/pibrentasvir must be taken with food for adequate absorption
Entecavir's label specifies dosing at least 2 hours after and before a meal, while MAVYRET's label specifies dosing with food to achieve adequate absorption — opposite requirements.
Other antifungals: polyenes, echinocandins and allylamines
What is the immediate cause of fungal cell death after amphotericin B binds ergosterol in the membrane?
Inhibition of glucan synthase
Formation of transmembrane pores causing leakage of monovalent ions
Inhibition of squalene epoxidase
Blockade of the fungal ribosome
Show answer
Answer: B. Formation of transmembrane pores causing leakage of monovalent ions
Amphotericin B forms transmembrane channels after binding ergosterol, and leakage of ions such as Na+, K+, H+ and Cl- through these channels causes cell death, a direct physical mechanism rather than enzyme inhibition.
Which enzyme do the echinocandins inhibit?
Lanosterol 14-alpha-demethylase
Squalene epoxidase
1,3-beta-D-glucan synthase
Dihydropteroate synthase
Show answer
Answer: C. 1,3-beta-D-glucan synthase
Echinocandins such as caspofungin noncompetitively inhibit beta-(1,3)-D-glucan synthase, blocking synthesis of an essential fungal cell-wall polymer that has no mammalian counterpart.
Which organism is NOT covered by echinocandin therapy?
Candida albicans
Candida glabrata
Cryptococcus neoformans
Candida krusei
Show answer
Answer: C. Cryptococcus neoformans
Echinocandins have no meaningful activity against Cryptococcus neoformans, despite being fungicidal against most Candida species including some azole-resistant strains.
What enzyme does terbinafine inhibit, and how does its position in the ergosterol pathway compare with the azoles?
Lanosterol 14-alpha-demethylase, the same target as the azoles
Squalene epoxidase, an earlier step in ergosterol synthesis than the azoles' target
1,3-beta-D-glucan synthase, a cell-wall target unrelated to ergosterol
Dihydrofolate reductase, unrelated to fungal membranes
Show answer
Answer: B. Squalene epoxidase, an earlier step in ergosterol synthesis than the azoles' target
Terbinafine non-competitively inhibits squalene epoxidase, which acts earlier in the ergosterol biosynthesis pathway than the azoles' target, lanosterol 14-alpha-demethylase.
What is required before starting oral terbinafine, given its labelled risk profile?
An ECG for QT monitoring
Baseline liver function testing
A renal biopsy
HIV testing
Show answer
Answer: B. Baseline liver function testing
Oral terbinafine's label requires pre-treatment evaluation of liver function given reported hepatotoxicity, including liver failure, transplant and death, with periodic monitoring during treatment.
Does the liposomal formulation of amphotericin B eliminate its nephrotoxicity risk?
Yes, liposomal amphotericin B carries no renal risk
No, it reduces but does not eliminate nephrotoxicity relative to conventional amphotericin B
No, liposomal amphotericin B is actually more nephrotoxic
Nephrotoxicity is not associated with any amphotericin B formulation
Show answer
Answer: B. No, it reduces but does not eliminate nephrotoxicity relative to conventional amphotericin B
Labelled comparative data show a lower, but still present, incidence of nephrotoxicity and electrolyte disturbance with liposomal amphotericin B compared with the conventional deoxycholate formulation, which is why renal monitoring continues regardless of formulation.
What is the basis of acyclovir's selectivity for HSV/VZV-infected cells?
It only binds receptors present on infected cells
Viral thymidine kinase phosphorylates it far more efficiently than host thymidine kinase does, concentrating the active triphosphate in infected cells
It is inactive in uninfected cells entirely
It requires host RNA polymerase to be activated
Show answer
Answer: B. Viral thymidine kinase phosphorylates it far more efficiently than host thymidine kinase does, concentrating the active triphosphate in infected cells
Viral thymidine kinase converts acyclovir to its monophosphate roughly a million-fold more efficiently than host thymidine kinase, leading to much higher active triphosphate concentrations in infected cells.
What is the most common mechanism of acyclovir resistance in HSV?
Efflux pump overexpression
Mutation or deficiency of viral thymidine kinase
A mutation in host cell DNA polymerase
Increased viral entry receptors
Show answer
Answer: B. Mutation or deficiency of viral thymidine kinase
Loss or mutation of viral thymidine kinase removes the first, most selective activation step acyclovir depends on, making this the most common resistance mechanism.
Why does ganciclovir require a different activating enzyme than acyclovir?
Ganciclovir does not need activation
CMV does not encode a thymidine kinase, so ganciclovir is instead activated by the CMV UL97 phosphotransferase
Ganciclovir is activated by host thymidine kinase only
There is no difference in activation between the two drugs
Show answer
Answer: B. CMV does not encode a thymidine kinase, so ganciclovir is instead activated by the CMV UL97 phosphotransferase
CMV lacks a thymidine kinase gene, so ganciclovir and valganciclovir depend on the viral UL97 kinase for their first phosphorylation step instead.
Which toxicity is dose-limiting for ganciclovir, distinguishing it from acyclovir and foscarnet?
Answer: B. Myelosuppression (neutropenia, anemia, thrombocytopenia)
Ganciclovir's defining, dose-limiting toxicity is hematologic — neutropenia, anemia and thrombocytopenia — monitored with specific blood-count thresholds, unlike the predominantly renal toxicities of acyclovir, foscarnet and cidofovir.
Why does foscarnet remain active against thymidine-kinase-deficient, acyclovir-resistant HSV?
Foscarnet is metabolised by a completely different pathway inside human cells
Foscarnet requires no viral kinase activation at all, acting directly on viral DNA polymerase
Foscarnet targets a different virus entirely
Foscarnet is a prodrug of acyclovir
Show answer
Answer: B. Foscarnet requires no viral kinase activation at all, acting directly on viral DNA polymerase
Foscarnet is a pyrophosphate analogue that inhibits viral DNA polymerase directly without needing any kinase-mediated activation, so thymidine-kinase-deficient resistant strains remain susceptible to it.
What specific supportive measures does cidofovir's label require with every dose?
No special measures are required
Mandatory intravenous prehydration with normal saline and administration of probenecid
Co-administration of a diuretic only
Fasting for 12 hours before infusion
Show answer
Answer: B. Mandatory intravenous prehydration with normal saline and administration of probenecid
Cidofovir's severe, dose-dependent nephrotoxicity means every infusion requires prehydration and probenecid, plus renal function testing within 48 hours beforehand.
What viral enzyme do oseltamivir, zanamivir and peramivir all inhibit?
The PA endonuclease of the viral polymerase
Viral neuraminidase
The M2 ion channel
Viral haemagglutinin
Show answer
Answer: B. Viral neuraminidase
All three are neuraminidase inhibitors: they block the enzyme that cleaves sialic acid to release newly assembled virions from the infected cell surface.
How does baloxavir marboxil's mechanism differ from that of the neuraminidase inhibitors?
It also inhibits neuraminidase but with longer duration
It inhibits the endonuclease activity of the viral polymerase acidic protein, blocking cap-snatching and mRNA transcription
It blocks the M2 ion channel
It has no antiviral mechanism and works only symptomatically
Show answer
Answer: B. It inhibits the endonuclease activity of the viral polymerase acidic protein, blocking cap-snatching and mRNA transcription
Baloxavir inhibits the PA endonuclease, an earlier step in the replication cycle (viral transcription) than the neuraminidase inhibitors' target (viral release).
Which resistance mutation is specifically associated with oseltamivir and became dominant in one historical seasonal influenza lineage?
I38T
M2 S31N
H275Y
PA/E23K
Show answer
Answer: C. H275Y
H275Y in the neuraminidase gene reduces oseltamivir binding and was found in more than 99% of US-circulating 2008 seasonal H1N1 isolates.
Why is zanamivir avoided in patients with asthma or COPD?
It causes hepatotoxicity in these patients
It carries a specific risk of serious bronchospasm because it is delivered by oral inhalation
It is ineffective against influenza in these patients
It requires an IV line that these patients cannot tolerate
Show answer
Answer: B. It carries a specific risk of serious bronchospasm because it is delivered by oral inhalation
Zanamivir's own label carries a specific warning about serious bronchospasm, including in patients without prior airway disease, and it is not recommended for patients with asthma or COPD.
What is the current status of amantadine and rimantadine for influenza?
First-line therapy for influenza A and B
Not recommended for treatment or chemoprophylaxis because of high resistance among circulating influenza A viruses, and never active against influenza B
Reserved for hospitalised patients only
Recommended only in children under 2 weeks of age
Show answer
Answer: B. Not recommended for treatment or chemoprophylaxis because of high resistance among circulating influenza A viruses, and never active against influenza B
The CDC states these adamantanes are not recommended because of high-level resistance in circulating influenza A, and they were never active against influenza B, which has a structurally different M2-equivalent protein.
Within what time frame from symptom onset is treatment with oseltamivir or baloxavir indicated for uncomplicated outpatient influenza?
7 days
48 hours
24 hours only
There is no time limit specified in the label
Show answer
Answer: B. 48 hours
Both labels define the treated population for acute uncomplicated influenza as patients symptomatic for no more than 48 hours, reflecting where the clinical trial benefit was demonstrated.