Summary Summary This document outlines various antimicrobial agents, including antifungals, antivirals, antihelminthics, and antiprotozoals, detailing their mec
Summary Summary This document outlines various antimicrobial agents, including antifungals, antivirals, antihelminthics, and antiprotozoals, detailing their mechanisms of action, uses, and key side effects. It also provides comprehensive notes on HIV management, covering antiretroviral therapy (ART) classes, when to start treatment, monitoring parameters, opportunistic infection (OI) prophylaxis, and management of common HIV co-infections like TB, cryptococcal meningitis, PCP, toxoplasmosis, and CMV. Special considerations for HIV in pregnancy, PrEP, PEP, drug interactions, and key clinical numbers are also highlighted. Key Points - Summary This document outlines various antimicrobial agents, including antifungals, antivirals, antihelminthics, and antiprotozoals, detailing their mechanisms of action, uses, and key side effects. - It also provides comprehensive notes on HIV management, covering antiretroviral therapy (ART) classes, when to start treatment, monitoring parameters, opportunistic infection (OI) prophylaxis, and management of common HIV co-infections like TB, cryptococcal meningitis, PCP, toxoplasmosis, and CMV. - Special considerations for HIV in pregnancy, PrEP, PEP, drug interactions, and key clinical numbers are also highlighted. - Key Points - Antifungals target ergosterol or fungal cell walls, with polyenes, azoles, echinocandins, and allylamines representing major classes. - - Antivirals are often virostatic and target specific viral enzymes or processes, with examples including anti-herpes drugs, anti-influenza agents, and anti-hepatitis treatments. - - Antihelminthics target neuromuscular function or metabolic pathways of parasitic worms, with drugs like albendazole, mebendazole, and ivermectin being crucial. - - Antiprotozoals cover a range of parasitic protozoa, with specific drugs for malaria, amoeba, leishmania, trypanosoma, and toxoplasma. - - Antiretroviral therapy (ART) for HIV aims to suppress viral load to undetectable levels, preserve CD4 counts, prevent transmission, and reduce morbidity/mortality. Detailed Notes Key Points - Antifungals target ergosterol or fungal cell walls, with polyenes, azoles, echinocandins, and allylamines representing major classes. - Antivirals are often virostatic and target specific viral enzymes or processes, with examples including anti-herpes drugs, anti-influenza agents, and anti-hepatitis treatments. - Antihelminthics target neuromuscular function or metabolic pathways of parasitic worms, with drugs like albendazole, mebendazole, and ivermectin being crucial. - Antiprotozoals cover a range of parasitic protozoa, with specific drugs for malaria, amoeba, leishmania, trypanosoma, and toxoplasma. - Antiretroviral therapy (ART) for HIV aims to suppress viral load to undetectable levels, preserve CD4 counts, prevent transmission, and reduce morbidity/mortality. - ART is recommended for all HIV-positive individuals regardless of CD4 count, with preferred regimens typically consisting of two NRTIs plus an INSTI. - Opportunistic infections in HIV are managed with prophylaxis based on CD4 count thresholds, with common examples including PCP, toxoplasmosis, and MAC. - Managing HIV co-infections requires careful consideration of drug interactions, especially with rifampicin and TB treatment, and the risk of Immune Reconstitution Inflammatory Syndrome (IRIS). - Antiretroviral drugs have significant drug interactions, particularly with CYP450 enzyme inducers/inhibitors, and require careful monitoring. - Pre-Exposure Prophylaxis (PrEP) and Post-Exposure Prophylaxis (PEP) are vital tools for HIV prevention. Detailed Notes WEEK 8 — Antifungals, Antivirals, Antihelminthics & Antiprotozoals --- ANTIFUNGALS Key Concept Fungi are eukaryotes — harder to kill without harming host. Target: ergosterol (fungal cell membrane equivalent of cholesterol). --- 1. Polyenes — Amphotericin B, Nystatin MOA: Binds ergosterol → pokes holes in fungal membrane → leakage → cell death Drug Use Key SE --- --- --- Amphotericin B Serious systemic fungal infections (Cryptococcus, Aspergillus, Candida) Nephrotoxicity (big one!), fever/rigors, hypoK, anaemia Nystatin Oral/vaginal candidiasis (topical only) GI upset — too toxic for systemic use Medic tip: Pre-hydrate before Ampho B IV. Monitor K⁺, creatinine daily. Liposomal form = less nephrotoxic. --- 2. Azoles — Fluconazole, Itraconazole, Voriconazole, Clotrimazole MOA: Inhibit 14α-demethylase (CYP450) → blocks ergosterol synthesis → membrane instability Drug Use Key SE --- --- --- Fluconazole Candida, Cryptococcal meningitis (maintenance) Hepatotoxicity, lots of drug interactions Voriconazole Aspergillosis (1st line) Visual disturbances, photosensitivity Itraconazole Histoplasma, dermatophytes Negative inotrope — avoid in heart failure Clotrimazole Topical skin/vaginal Local irritation only Azoles inhibit CYP3A4 — watch with warfarin, statins, immunosuppressants --- 3. Echinocandins — Caspofungin, Micafungin MOA: Inhibit β-1,3-glucan synthase → disrupts fungal cell wall (no human equivalent!) - Use: Invasive Candida, Aspergillus (when azoles fail) - SE: Well tolerated — mild LFT elevation, histamine reaction - Route: IV only --- 4. Allylamines — Terbinafine MOA: Inhibit squalene epoxidase → blocks ergosterol synthesis - Use: Dermatophytes (tinea, onychomycosis) - SE: GI upset, hepatotoxicity (rare), taste disturbance --- ANTIVIRALS Key Concept Viruses use host machinery — targets must be virus-specific. Most antivirals are virostatic (suppress replication, don't cure). --- 1. Anti-Herpes Drugs — Aciclovir, Valaciclovir, Ganciclovir MOA: Nucleoside analogues → activated by viral thymidine kinase → inhibit viral DNA polymerase → chain termination Drug Use Key SE --- --- --- Aciclovir HSV, VZV (shingles, chickenpox, encephalitis) Nephrotoxicity (crystalluria — hydrate well!), neuro SE at high doses Valaciclovir Prodrug of aciclovir — better oral bioavailability Same as aciclovir Ganciclovir CMV (retinitis, colitis in immunocompromised) Bone marrow suppression (neutropenia, thrombocytopenia) Medic tip: HSV encephalitis = IV Aciclovir immediately (don't wait for PCR). Ganciclovir — check FBC weekly. --- 2. Anti-Influenza — Oseltamivir (Tamiflu), Zanamivir MOA: Neuraminidase inhibitors → block viral release from host cells - Use: Influenza A & B — must start within 48hrs of symptoms - SE: Nausea, vomiting (oseltamivir); bronchospasm (zanamivir — avoid in asthma) - Who gets it: Elderly, immunocompromised, pregnant, severe disease --- 3. Anti-Hepatitis Drug Target Use Key SE --- --- --- --- Tenofovir / Entecavir DNA polymerase Hepatitis B (chronic) Nephrotoxicity (tenofovir), lactic acidosis Sofosbuvir + Daclatasvir NS5B/NS5A Hepatitis C (DAAs — cure 95%) Well tolerated; fatigue, headache Pegylated IFN-α + Ribavirin Immune modulation + viral RNA HBV/HCV (older regimen) Depression, flu-like, haemolytic anaemia (ribavirin), cytopenias Medic tip: DAAs (Direct Acting Antivirals) have essentially replaced interferon-based HCV treatment. Check drug interactions — many via CYP enzymes. --- ANTIHELMINTHICS Key Concept Worms (helminths) are multicellular eukaryotes — drugs target neuromuscular function or metabolic pathways specific to parasites. --- Drug MOA Use Key SE --- --- --- --- Albendazole Inhibits tubulin polymerisation → disrupts microtubules → worm paralysis/death Roundworm, hookworm, tapeworm, neurocysticercosis , hydatid disease GI upset, hepatotoxicity, teratogenic Mebendazole Same as albendazole Threadworm (1st line), roundworm, whipworm Minimal systemic SE (poorly absorbed) Ivermectin Hyperpolarises GABA-gated Cl⁻ channels → paralysis of worm Strongyloides , onchocerciasis, scabies, head lice Mazzotti reaction (if onchocerciasis — fever, rash from dying worms) Praziquantel Increases Ca²⁺ permeability → spastic paralysis → worm detaches Schistosomiasis , tapeworms, flukes GI upset, headache, dizziness Diethylcarbamazine (DEC) Immobilises microfilariae Lymphatic filariasis, loiasis