Question
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- (a) Classify Antiretroviral drugs used in HIV. Describe the mechanism of action, uses and adverse effects of Zidovudine. Add a note on Post exposure prophylaxis. ( 5 mark(s)
- (b) Azole Antifungals 3 mark(s)
Answer
a) Classification of antiretroviral drugs
| Class | Examples |
|---|---|
| NRTIs | Zidovudine, Lamivudine, Tenofovir |
| NNRTIs | Efavirenz, Nevirapine |
| Protease inhibitors | Ritonavir, Atazanavir |
| Integrase strand transfer inhibitors | Dolutegravir, Raltegravir |
| Entry/fusion inhibitors | Maraviroc, Enfuvirtide |
Zidovudine — mechanism, uses, adverse effects Mechanism: a nucleoside analogue that, after intracellular phosphorylation to its active triphosphate form, is incorporated into the growing proviral DNA chain by HIV reverse transcriptase, acting as a chain terminator (lacking the 3’-OH group). Uses: combination antiretroviral therapy (as part of an NRTI “backbone”), prevention of mother-to-child transmission. Adverse effects: bone marrow suppression (anemia, neutropenia — from off-target inhibition of human mitochondrial DNA polymerase gamma), headache, myopathy with prolonged use.
Note on post-exposure prophylaxis Started after significant HIV exposure (needlestick, mucosal, or sexual), ideally within hours and no later than 72 hours, continued for 28 days. A standard regimen combines three antiretroviral drugs, commonly two NRTIs plus an integrase inhibitor (e.g. Tenofovir + Emtricitabine + Dolutegravir) — the same combination-therapy resistance-prevention logic as standard HIV treatment, never a single agent.
b) Azole Antifungals Inhibit fungal cytochrome P450 14-alpha-demethylase, blocking conversion of lanosterol to ergosterol, depleting the fungal membrane’s essential sterol component — fungistatic. Examples: Fluconazole, Itraconazole, Voriconazole (triazoles, systemic use); Ketoconazole, Clotrimazole (imidazoles, mostly topical now). Uses: candidiasis, cryptococcal meningitis (fluconazole), dermatophyte/dimorphic fungal infections (itraconazole), invasive aspergillosis (voriconazole). Adverse effects: hepatotoxicity, CYP450 inhibition (numerous drug interactions); ketoconazole specifically — endocrine effects (gynecomastia, adrenal suppression) from poor fungal-versus-human CYP450 selectivity.