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Fungi, malaria parasites, and worms are eukaryotes, like human cells, so selective toxicity is harder to achieve than with bacteria. Each drug group exploits a structure the human cell lacks or uses differently.
| Group | Mechanism |
|---|---|
| Polyenes — amphotericin B (prototype), nystatin | Bind ergosterol in the fungal membrane and form pores → leakage and cell death. Some binding to human cholesterol explains toxicity |
| Azoles — fluconazole, itraconazole, voriconazole, posaconazole; topical clotrimazole, miconazole | Inhibit fungal CYP450 (lanosterol 14-alpha-demethylase) → no ergosterol synthesis. They also inhibit human CYP enzymes → many interactions |
| Echinocandins — caspofungin, micafungin, anidulafungin | Block beta-glucan synthesis in the fungal cell wall (absent in human cells) |
| Allylamines — terbinafine | Inhibit squalene epoxidase in ergosterol synthesis; concentrate in skin and nails |
| Artemisinins — artemether, artesunate | Activated by iron in the parasite → free radicals; very rapid reduction of parasite load |
| 4-aminoquinolines — chloroquine, hydroxychloroquine | Block heme detoxification in the parasite food vacuole |
| 8-aminoquinolines — primaquine, tafenoquine | Kill liver dormant forms (hypnozoites) of P. vivax and P. ovale and mature gametocytes (block transmission); oxidant stress causes hemolysis in G6PD deficiency |
| Benzimidazoles — albendazole, mebendazole | Bind worm tubulin → impaired glucose uptake and death |
| Pyrantel pamoate | Depolarizing neuromuscular blocker in worms → spastic paralysis and expulsion |
| Praziquantel | Increases calcium permeability of fluke and tapeworm membranes → paralysis |
| Ivermectin | Opens glutamate-gated chloride channels in nematodes → paralysis |
| Drug | Key use | Key point |
|---|---|---|
| Amphotericin B (conventional or lipid/liposomal) | Severe systemic fungal infection (cryptococcal meningitis, invasive mold, histoplasmosis) | IV only; nephrotoxicity; formulations are not interchangeable |
| Fluconazole | Candida (oral, esophageal, vaginal, bloodstream), cryptococcal maintenance | Oral or IV; QT and interactions |
| Voriconazole, posaconazole, isavuconazole | Invasive aspergillosis, prophylaxis in leukemia/transplant | Therapeutic drug monitoring for voriconazole |
| Itraconazole | Endemic mycoses, nail fungus | Heart failure (boxed warning) |
| Echinocandins | Candidemia, invasive candidiasis | IV once daily; few interactions |
| Nystatin | Oral thrush, intestinal or skin candidiasis | Not absorbed; swish and swallow |
| Terbinafine | Onychomycosis, tinea capitis | Liver tests |
| Griseofulvin | Tinea capitis (children) | Take with a fatty meal; photosensitivity, hepatotoxicity; reduces oral contraceptive effect; teratogenic |
| Drug | Key use | Key point |
|---|---|---|
| Artemether–lumefantrine | First-line for uncomplicated P. falciparum | 6 doses over 3 days; take with fatty food or milk |
| IV artesunate | Severe malaria (first-line) | Monitor for delayed hemolysis 1–4 weeks later |
| Chloroquine | P. vivax, P. ovale, P. malariae where sensitive; prophylaxis where sensitive | Resistance is widespread in P. falciparum |
| Primaquine, tafenoquine | Radical cure of P. vivax/ovale (prevent relapse); single low dose (0.25 mg/kg) to block falciparum transmission | Test G6PD before the 14-day course; the single low dose needs no G6PD test (WHO 2025) |
| Atovaquone–proguanil | Treatment and travel prophylaxis | Daily; start 1–2 days before travel, continue 7 days after |
| Doxycycline | Travel prophylaxis; adjunct treatment | Start 1–2 days before, continue 4 weeks after; photosensitivity |
| Mefloquine | Travel prophylaxis (weekly) | Neuropsychiatric boxed warning |
| Quinine | Alternative for severe or resistant malaria | Hypoglycemia, cinchonism, QT; boxed warning — not for leg cramps |
| Drug | Key use |
|---|---|
| Albendazole / mebendazole | Soil-transmitted helminths (roundworm, whipworm, hookworm), pinworm; albendazole for neurocysticercosis and hydatid disease (longer courses) |
| Pyrantel pamoate | Pinworm, roundworm (over the counter in the US) |
| Praziquantel | Schistosomiasis, tapeworms, liver flukes |
| Ivermectin | Strongyloidiasis, scabies, head lice, onchocerciasis |
| Diethylcarbamazine (DEC) | Lymphatic filariasis (with albendazole in mass drug administration) |
Single-dose albendazole 400 mg (200 mg for children 12–23 months) or mebendazole 500 mg is the usual regimen for soil-transmitted helminths; pinworm doses are repeated in 2 weeks, and the whole household is treated.
| Drug | Key adverse effects |
|---|---|
| Amphotericin B | Infusion reactions (fever, chills, rigors, hypotension); nephrotoxicity; hypokalemia and hypomagnesemia (tubular wasting); anemia; phlebitis. Lipid formulations have less kidney toxicity |
| Azoles | Hepatotoxicity, QT prolongation, GI upset, rash. Voriconazole: visual disturbances, hallucinations, photosensitivity and skin cancer with long use. Itraconazole: heart failure |
| Echinocandins | Histamine-type infusion reaction, liver enzyme elevation |
| Terbinafine | Hepatotoxicity (rare liver failure), taste and smell disturbance |
| Chloroquine / hydroxychloroquine | GI upset, pruritus (common in dark-skinned clients), QT prolongation, retinal toxicity with long-term use, hypoglycemia |
| Primaquine / tafenoquine | Hemolytic anemia in G6PD deficiency; methemoglobinemia; GI upset |
| Artemether–lumefantrine | Headache, dizziness, GI upset; QT prolongation (lumefantrine) |
| Artesunate | Post-artesunate delayed hemolysis |
| Mefloquine | Anxiety, depression, psychosis, vivid dreams, dizziness and vertigo that may persist |
| Quinine | Cinchonism (tinnitus, headache, nausea, blurred vision), hypoglycemia, QT prolongation; boxed warning: serious hematologic reactions (thrombocytopenia, HUS/TTP) |
| Albendazole / mebendazole | Mild abdominal pain; with long courses — liver enzyme elevation, bone marrow suppression, hair loss |
| Praziquantel | Dizziness, drowsiness, headache, abdominal pain, bitter taste; inflammatory reactions as parasites die |
| Ivermectin | Usually mild; pruritus and rash from dying microfilariae |
| DEC | Fever, headache, and body aches from dying microfilariae |
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