Preparatory Mindset
Antivirals target specific viral replication steps: entry, uncoating, reverse transcription (HIV), integration (HIV), protease cleavage (HIV), neuraminidase (influenza). Antifungals target ergosterol synthesis (azoles) or function (amphotericin B). HAART for HIV uses combination therapy targeting multiple steps — this is frequently tested.
Core Concepts
Ch08: Antivirals & Antifungals
Exam Note: Only tested in MCQs (according to examiner)
Part A: Antivirals
Anti-HIV Drugs — High Yield
| Drug Class | Drug(s) | MOA | Key Side Effects |
|-----------|---------|-----|-----------------|
| NRTI | Zidovudine (AZT) | Reverse transcriptase inhibitor (chain terminator) | Bone marrow suppression (anemia, neutropenia) |
| NRTI | Tenofovir | Same | Nephrotoxicity, bone density loss |
| NNRTI | Nevirapine | Non-competitive RT inhibitor | Skin rash, hepatotoxicity |
| Protease Inhibitor (PI) | Ritonavir | HIV protease inhibitor | GI intolerance, dyslipidemia, CYP3A4 interactions |
| Integrase Inhibitor | Raltegravir | Integrase strand transfer inhibitor | Well-tolerated; less interactions |
| Entry Inhibitor | Maraviroc | CCR5 co-receptor antagonist | Only effective against CCR5-tropic HIV |
Key HIV Concept: HAART (Highly Active Antiretroviral Therapy) = combination of ≥3 drugs from ≥2 classes to prevent resistance.
Other Antivirals
| Drug | MOA | Spectrum | Key Use |
|------|-----|---------|---------|
| Acyclovir | Viral DNA polymerase inhibitor (HSV thymidine kinase activates) | HSV, VZV | Herpes (HSV-1, HSV-2), Shingles (VZV) |
| Ribavirin | Guanosine analogue → inhibits viral mRNA | Broad — RNA + DNA viruses | RSV, HCV (with interferon) |
| Amantadine | Blocks M2 ion channel (influenza A) | Influenza A only | Resistance common; also antiparkinsonian |
| Idoxuridine | Thymidine analogue → incorporated into viral DNA | HSV, VZV | Highly toxic → topical use only (ocular/cutaneous) |
| Oseltamivir | Neuraminidase inhibitor | Influenza A+B | Must start within 48h of symptoms |
Part B: Antifungals
| Drug | MOA | Spectrum | Toxicity |
|------|-----|---------|---------|
| Amphotericin B | Binds ergosterol → membrane disruption | Broad — most fungi | Nephrotoxicity (dose-limiting); infusion reactions |
| Nystatin | Same as amphotericin B | Topical candida | Too toxic for IV → topical/oral only |
| Fluconazole | Inhibits 14α-demethylase (ergosterol synthesis) | Candida, Cryptococcus | Well-tolerated; CYP450 interactions |
| Ketoconazole | Same | Topical/systemic | Hepatotoxicity; multiple drug interactions |
| Terbinafine | Inhibits squalene epoxidase | Dermatophytes | Onychomycosis, tinea |
| Griseofulvin | Binds tubulin → disrupts mitotic spindle | Dermatophytes | Tinea capitis (>90% effective); deposits in keratin |
| Flucytosine | Inhibit DNA/RNA synthesis | Candida, Cryptococcus | Used in combination with amphotericin B |
High-Yield Points
- HAART: combination of ≥3 drugs from ≥2 classes — prevents resistance
- NRTIs (tenofovir): nucleoside analogs → chain termination
- NNRTIs (efavirenz): non-nucleoside RT inhibitors
- Protease inhibitors (ritonavir): prevent viral maturation
- Integrase inhibitors (dolutegravir): block HIV integration
- Azoles (fluconazole): inhibit ergosterol synthesis → first-line for most Candida
- Amphotericin B: binds ergosterol → broadest spectrum but nephrotoxic
Topic Summary
HIV treatment requires combination therapy (HAART). Resistance is a major problem with monotherapy. Antifungals: azoles inhibit ergosterol synthesis, amphotericin B binds ergosterol (broadest spectrum but nephrotoxic). Fluconazole is first-line for most Candida infections.