Antifungal pharmacology and mechanisms MCQs With Answer

Antifungal pharmacology and mechanisms MCQs With Answer is a focused revision resource designed for M.Pharm students preparing for advanced pharmacology exams. This set emphasizes fundamental and mechanistic concepts—ergosterol biosynthesis, cell wall synthesis, nucleic acid inhibitors, and drug resistance—while integrating pharmacokinetics, toxicity, formulations, and clinical use. Each question probes deeper than rote facts, testing understanding of enzymatic targets (e.g., 14α-demethylase, squalene epoxidase, β-(1,3)-D-glucan synthase), resistance mechanisms, therapeutic monitoring, and drug–drug interactions relevant to antifungal therapy. Answers are provided immediately for self-assessment to reinforce learning and guide further study in antifungal drug design and clinical application.

Q1. Which of the following best describes the primary antifungal mechanism of amphotericin B?

• Inhibition of lanosterol 14α-demethylase, blocking ergosterol synthesis
• Binding to ergosterol and forming transmembrane pores that increase membrane permeability
• Inhibition of β-(1,3)-D-glucan synthase, disrupting cell wall synthesis
• Conversion to 5-fluorouracil inside fungal cells, inhibiting nucleic acid synthesis

Correct Answer: Binding to ergosterol and forming transmembrane pores that increase membrane permeability

Q2. The major clinically relevant toxicity associated with conventional amphotericin B is primarily due to which mechanism?

• Hepatocellular enzyme induction leading to cholestasis
• Direct tubular epithelial cell damage and renal vasoconstriction causing nephrotoxicity
• Suppression of bone marrow causing severe neutropenia
• Peripheral neuropathy from microtubule inhibition

Correct Answer: Direct tubular epithelial cell damage and renal vasoconstriction causing nephrotoxicity

Q3. Liposomal formulations of amphotericin B are clinically preferred over conventional deoxycholate formulation mainly because:

• They entirely eliminate all adverse effects without efficacy loss
• They reduce nephrotoxicity and alter tissue distribution, improving therapeutic index
• They increase systemic half-life but substantially reduce antifungal potency
• They change the drug’s mechanism to inhibit ergosterol synthesis

Correct Answer: They reduce nephrotoxicity and alter tissue distribution, improving therapeutic index

Q4. Azole antifungals exert their antifungal effect primarily by inhibiting which enzyme?

• Squalene epoxidase, preventing conversion of squalene to squalene epoxide
• Lanosterol 14α-demethylase (fungal cytochrome P450 51), blocking ergosterol biosynthesis
• β-(1,3)-D-glucan synthase, preventing cell wall β-glucan synthesis
• Thymidylate synthase, preventing DNA synthesis

Correct Answer: Lanosterol 14α-demethylase (fungal cytochrome P450 51), blocking ergosterol biosynthesis

Q5. Compared to older imidazoles, triazole antifungals (e.g., fluconazole, voriconazole) are characterized pharmacologically by which property?

• Greater general inhibition of human CYP enzymes and therefore more drug–drug interactions
• Poor oral bioavailability requiring intravenous administration only
• Improved systemic safety profile with reduced inhibition of human CYPs and broader systemic use
• Primary fungicidal activity through pore formation in fungal membranes

Correct Answer: Improved systemic safety profile with reduced inhibition of human CYPs and broader systemic use

Q6. Echinocandins (caspofungin, micafungin, anidulafungin) act by targeting which fungal process?

• Ergosterol binding and membrane pore formation
• Synthesis of β-(1,3)-D-glucan in the fungal cell wall via inhibition of glucan synthase
• Lanosterol 14α-demethylase inhibition in the ergosterol pathway
• Mitosis inhibition via tubulin binding

Correct Answer: Synthesis of β-(1,3)-D-glucan in the fungal cell wall via inhibition of glucan synthase

Q7. Terbinafine’s antifungal effect is primarily due to inhibition of which enzyme?

• Lanosterol 14α-demethylase leading to decreased ergosterol synthesis
• Squalene epoxidase leading to accumulation of squalene and ergosterol depletion
• β-(1,3)-D-glucan synthase destabilizing the cell wall
• Thymidylate synthase impairing DNA synthesis

Correct Answer: Squalene epoxidase leading to accumulation of squalene and ergosterol depletion

Q8. Flucytosine (5-FC) exerts antifungal activity by which intracellular transformation and subsequent mechanism?

• Direct binding to ergosterol and membrane disruption
• Conversion to 5-fluorouracil in fungal cells, interfering with DNA and RNA synthesis
• Inhibition of squalene epoxidase causing cell membrane instability
• Irreversible inhibition of fungal ribosomes preventing protein synthesis

Correct Answer: Conversion to 5-fluorouracil in fungal cells, interfering with DNA and RNA synthesis

Q9. Griseofulvin’s antifungal mechanism is best described as:

• Binding to ergosterol and creating membrane pores
• Inhibiting fungal cytochrome P450 enzymes
• Binding to tubulin and disrupting mitotic spindle formation, inhibiting fungal mitosis
• Inhibiting β-(1,3)-D-glucan synthase in the cell wall

Correct Answer: Binding to tubulin and disrupting mitotic spindle formation, inhibiting fungal mitosis

Q10. A common molecular mechanism of resistance to azole antifungals in Candida species is:

• Mutations in ERG11 (encoding 14α-demethylase) and overexpression of drug efflux pumps
• Increased incorporation of ergosterol into the fungal membrane making the azoles more effective
• Mutation in human CYP enzymes reducing azole metabolism
• Inhibition of fungal cell wall synthesis by upregulating β-glucan production

Correct Answer: Mutations in ERG11 (encoding 14α-demethylase) and overexpression of drug efflux pumps

Q11. Which antifungal agent’s mechanism and toxicity profile most closely explain its role as fungistatic for dermatophytes and need for prolonged oral therapy due to accumulation in keratinized tissues?

• Amphotericin B
• Griseofulvin
• Terbinafine
• Flucytosine

Correct Answer: Griseofulvin

Q12. For prophylaxis of invasive fungal infections in high-risk neutropenic patients, which triazole is commonly recommended because of its broad-spectrum activity including Aspergillus coverage?

• Fluconazole
• Ketoconazole
• Posaconazole
• Nystatin

Correct Answer: Posaconazole

Q13. Clinically important drug–drug interactions with azole antifungals are primarily due to which pharmacokinetic effect?

• Induction of P-glycoprotein leading to rapid drug clearance
• Direct chemical inactivation of co-administered drugs in plasma
• Inhibition of hepatic cytochrome P450 enzymes altering metabolism of many drugs
• Increasing renal excretion of co-administered drugs by competing for tubular secretion

Correct Answer: Inhibition of hepatic cytochrome P450 enzymes altering metabolism of many drugs

Q14. Therapeutic drug monitoring (TDM) is routinely recommended for which antifungal to optimize dosing and minimize toxicity due to variable pharmacokinetics?

• Flucytosine
• Fluconazole
• Voriconazole
• Nystatin

Correct Answer: Voriconazole

Q15. Which class of antifungal drugs targets a fungal structure absent in mammalian cells, making them selectively toxic to fungi?

• Polyenes targeting ergosterol
• Azoles targeting fungal CYP51
• Echinocandins targeting β-(1,3)-D-glucan in the fungal cell wall
• Allylamines targeting squalene epoxidase

Correct Answer: Echinocandins targeting β-(1,3)-D-glucan in the fungal cell wall

Q16. Terbinafine is especially effective for onychomycosis because:

• It is fungistatic for dermatophytes and poorly absorbed into keratin
• It accumulates in keratinized tissues (skin, hair, nails) achieving high local concentrations
• It inhibits β-(1,3)-D-glucan synthesis in nail plate cells
• It is only administered topically and therefore concentrates in the nail bed

Correct Answer: It accumulates in keratinized tissues (skin, hair, nails) achieving high local concentrations

Q17. Which statement about echinocandins is correct regarding their route of administration and spectrum?

• They are available orally and are first-line for mucosal candidiasis
• They are administered intravenously and are active against Candida species and have variable activity against Aspergillus
• They are topical agents used for dermatophytoses due to poor systemic absorption
• They are primarily used as single-dose oral therapy for cryptococcal meningitis

Correct Answer: They are administered intravenously and are active against Candida species and have variable activity against Aspergillus

Q18. Which antifungal has excellent cerebrospinal fluid penetration and is routinely used in combination with amphotericin B for induction therapy of cryptococcal meningitis?

• Fluconazole
• Flucytosine
• Voriconazole
• Terbinafine

Correct Answer: Flucytosine

Q19. A major biochemical basis for acquired resistance to amphotericin B in some fungal strains involves:

• Increased expression of β-(1,3)-D-glucan making amphotericin ineffective
• Decreased ergosterol content or altered ergosterol structure in the fungal membrane
• Enhanced conversion of amphotericin to inactive metabolites by fungal enzymes
• Overexpression of human CYP enzymes that metabolize amphotericin B

Correct Answer: Decreased ergosterol content or altered ergosterol structure in the fungal membrane

Q20. Which antifungal is notably associated with visual disturbances (photopsia, color vision changes) and requires dose adjustments in hepatic impairment?

• Fluconazole
• Voriconazole
• Amphotericin B
• Nystatin

Correct Answer: Voriconazole

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