Classification of Antifungal Drugs, Its Pharmacokinetics and Pharmacology and MCQ for GPAT, NEETPG, NORCET, Pharmacy and Nursing exams
Classification of Antifungal Drugs
| Class | Examples | Target/Mechanism |
|---|---|---|
| Polyenes | Amphotericin B, Nystatin | Binds ergosterol → forms pores in fungal membranes |
| Azoles | Ketoconazole, Fluconazole, Itraconazole, Voriconazole, Posaconazole | Inhibit 14-α-demethylase → inhibit ergosterol synthesis |
| Echinocandins | Caspofungin, Micafungin, Anidulafungin | Inhibit β-1,3-glucan synthase → cell wall inhibition |
| Allylamines | Terbinafine | Inhibit squalene epoxidase → ergosterol synthesis ↓ |
| Antimetabolites | Flucytosine | Converted to 5-FU → inhibits DNA & RNA synthesis |
| Others | Griseofulvin | Inhibits microtubule function → interferes mitosis |
📊 Pharmacokinetics of Antifungal Drugs
| Drug/Class | Route | Bioavailability | Distribution | Metabolism | Elimination (T½) |
|---|---|---|---|---|---|
| Amphotericin B | IV | Poor oral | Poor CNS, binds to tissues | Minimal hepatic | Renal (15 days) |
| Nystatin | Topical/Oral | Not absorbed systemically | Local use only | Not systemic | Not applicable |
| Fluconazole | Oral, IV | High | Good CNS penetration | Hepatic (CYP2C9/3A4) | Renal (~30 hrs) |
| Itraconazole | Oral | Variable (↑ with food) | Poor CNS | Hepatic (CYP3A4) | Hepatic (~20 hrs) |
| Voriconazole | Oral, IV | Good | Good CNS | Hepatic (CYP2C19/3A4) | Hepatic (~6 hrs) |
| Posaconazole | Oral, IV | Improved with fatty meal | Variable | Hepatic (glucuronidation) | Fecal (~35 hrs) |
| Caspofungin | IV | N/A | Wide, not CNS | Slow hydrolysis | Hepatic (~9-11 hrs) |
| Terbinafine | Oral, Topical | Good | Concentrates in skin/nails | Hepatic | Renal (~200-400 hrs) |
| Flucytosine | Oral, IV | Good | Good CNS penetration | Minimal | Renal (~3-6 hrs) |
| Griseofulvin | Oral | Variable (↑ with fatty meal) | Deposits in keratin tissues | Hepatic (induces CYP) | Hepatic (~24 hrs) |
📋 Mechanism, Side Effects, Contraindications, Drug Interactions
| Drug/Class | Mechanism of Action | Side Effects | Contraindications | Drug Interactions |
|---|---|---|---|---|
| Amphotericin B | Binds ergosterol → pore formation | Nephrotoxicity, infusion rxns, anemia | Renal impairment (caution) | Additive nephrotoxicity with aminoglycosides |
| Nystatin | Same as amphotericin (topical use) | Local irritation | Systemic use contraindicated | None (topical) |
| Fluconazole | Inhibits ergosterol synthesis (CYP450 inhibition) | Hepatotoxicity, GI upset | Liver disease, pregnancy (relative) | Inhibits CYP2C9 → ↑ warfarin, phenytoin |
| Itraconazole | Same as fluconazole | CHF, hepatotoxicity | Heart failure | CYP3A4 inhibitor → ↑ statins, benzodiazepines |
| Voriconazole | Same class | Visual disturbances, hepatotoxicity | Pregnancy | CYP interactions → monitor drug levels |
| Caspofungin | Inhibits fungal cell wall synthesis | Histamine-like infusion reactions, ↑ LFTs | Hypersensitivity | Cyclosporine ↑ toxicity |
| Terbinafine | Inhibits squalene epoxidase | Hepatotoxicity, taste disturbance | Liver disease | Rifampin ↓ terbinafine levels |
| Flucytosine | Inhibits DNA/RNA synthesis via 5-FU conversion | Bone marrow suppression, GI upset | Renal impairment | Amphotericin B ↑ toxicity synergistically |
| Griseofulvin | Disrupts mitotic spindles | Headache, hepatotoxicity, photosensitivity | Pregnancy | Induces CYP → ↓ warfarin, OCPs |
🧠 MCQs on Antifungal Drugs
1. Which antifungal drug is known for nephrotoxicity as its major side effect?
A. Fluconazole
B. Terbinafine
C. Amphotericin B
D. Caspofungin
✅ Answer: C
2. Which antifungal drug inhibits microtubule formation in fungi?
A. Griseofulvin
B. Flucytosine
C. Voriconazole
D. Nystatin
✅ Answer: A
3. Which antifungal has good CNS penetration and is commonly used for cryptococcal meningitis?
A. Itraconazole
B. Caspofungin
C. Fluconazole
D. Terbinafine
✅ Answer: C
4. What is the mechanism of action of echinocandins like caspofungin?
A. Inhibits ergosterol synthesis
B. Inhibits fungal DNA polymerase
C. Inhibits β-1,3-glucan synthase
D. Binds to microtubules
✅ Answer: C
5. Which of the following is contraindicated in patients with congestive heart failure?
A. Terbinafine
B. Itraconazole
C. Fluconazole
D. Caspofungin
✅ Answer: B