STEPTRACKERPHARMACOLOGY + MICROBIOLOGY | ANTIMICROBIALS | HIGH-YIELD REVIEW

Antifungal & Antiparasitic Drugs

Fungal drugs exploit ergosterol (instead of cholesterol) and the β-glucan wall; antiparasitic drugs are matched to protozoa, worms or ectoparasites.

FOCUS ON
Amphotericin B: binds ergosterol → pores; severe systemic mycoses, cryptococcal meningitis (+ flucytosine), mucormycosis; toxicity — nephrotoxicity, ↓ K⁺, ↓ Mg²⁺, fevers/rigors, anemia, arrhythmia (liposomal less toxic; hydrate). Nystatin: topical/oral (thrush). Azoles (fluconazole, itraconazole, voriconazole, posaconazole, isavuconazole): block 14α-demethylase (lanosterol → ergosterol); CYP inhibitors, hepatotoxicity, QT; ketoconazole antiandrogen; voriconazole visual changes, photosensitivity — invasive aspergillosis first-line. Echinocandins (caspofungin, micafungin): block β-1,3-glucan synthase; invasive candidiasis, aspergillosis salvage. Flucytosine: → 5-FU; marrow toxicity. Terbinafine: squalene epoxidase; onychomycosis; hepatotoxic, taste loss. Griseofulvin: microtubules; tinea capitis; teratogen, CYP inducer. Antiparasitic: metronidazole, tinidazole; nitazoxanide; chloroquine/hydroxychloroquine, mefloquine, atovaquone-proguanil, artemisinins, primaquine (malaria); pyrimethamine-sulfadiazine + leucovorin (toxo); albendazole/mebendazole (microtubules), ivermectin (Cl⁻ channels), praziquantel (Ca²⁺ permeability; trematodes, cestodes), pyrantel; permethrin.
DRUG
MECHANISM
USE
ADVERSE · NOTES
Amphotericin B
Binds ergosterol → membrane pores
Cryptococcal meningitis (+ 5-FC), mucormycosis, severe endemic mycoses
Nephrotoxicity, ↓ K⁺, ↓ Mg²⁺, infusion fever/rigors, anemia (↓ EPO)
Nystatin · clotrimazole
Ergosterol binding · azole (topical)
Oral thrush, cutaneous candidiasis
Too toxic for IV (nystatin)
Fluconazole
14α-demethylase inhibitor
Candidiasis (not C. krusei/glabrata), cryptococcal maintenance, coccidioidal meningitis
Hepatotoxicity, QT, CYP inhibition
Itraconazole
Azole
Histoplasmosis, blastomycosis, sporotrichosis, onychomycosis
Negative inotrope (HF)
Voriconazole · posaconazole · isavuconazole
Broad azoles
Invasive aspergillosis (vori), mold prophylaxis (posa), mucor (posa, isavu)
Vori: visual disturbance, photosensitivity, skin cancer, periostitis
Ketoconazole
Azole + ↓ steroid synthesis
Topical tinea, seborrheic dermatitis; Cushing (oral, rarely)
Gynecomastia, hepatotoxicity
Caspofungin · micafungin · anidulafungin
β-1,3-glucan synthase inhibitors (cell wall)
Invasive candidiasis (first-line), refractory aspergillosis
Histamine flushing; no cryptococcus coverage
Flucytosine
Converted to 5-FU in fungi → DNA/RNA
Cryptococcal meningitis (with amphotericin)
Marrow suppression; resistance alone
Terbinafine · griseofulvin
Squalene epoxidase · binds microtubules (dermatophytes)
Onychomycosis · tinea capitis
Terbinafine hepatotoxicity, taste loss · griseofulvin teratogen, CYP inducer
Antimalarials
Chloroquine (heme polymerization), mefloquine, atovaquone-proguanil, artemether-lumefantrine, quinine/artesunate (severe)
Malaria treatment and prophylaxis
Chloroquine retinopathy; mefloquine neuropsychiatric; quinine cinchonism
Primaquine · tafenoquine
Kill liver hypnozoites
P. vivax / ovale radical cure
Hemolysis in G6PD deficiency — test first
Albendazole · mebendazole
Bind β-tubulin → ↓ glucose uptake in worms
Pinworm, ascaris, hookworm, neurocysticercosis, hydatid
Teratogen, hepatotoxicity, marrow (prolonged)
Ivermectin · praziquantel · pyrantel
Glutamate-gated Cl⁻ channels · ↑ Ca²⁺ permeability · depolarizing NM block
Strongyloides, onchocerciasis, scabies · schistosomes, flukes, tapeworms · pinworm
Mazzotti reaction (ivermectin in heavy microfilaria)
Nifurtimox · benznidazole · miltefosine · pentamidine
Antiprotozoal agents
Chagas · leishmaniasis · African sleeping sickness, PJP alternative
Pentamidine hypoglycemia, pancreatitis

Mechanism — ergosterol pathway

Squalene
→
Squalene epoxidaseTerbinafine blocks
→
Lanosterol → ergosterolAzoles block 14α-demethylase
→
Ergosterol in membraneAmphotericin, nystatin bind it

Echinocandins skip the membrane entirely and target the β-glucan wall.

Worm → drug

WORM TYPE
DRUG
EXAMPLE
Nematodes (gut)
Albendazole, mebendazole
Ascaris, hookworm
Strongyloides, filaria
Ivermectin
Onchocerca
Trematodes
Praziquantel
Schistosoma
Cestodes
Praziquantel / albendazole
Taenia, cysticercosis

How it's tested

COMMON CONFUSIONAmphotericin's toxicity comes from also binding cholesterol in human membranes (kidney tubules) — salt loading and liposomal forms reduce it.
THE TRAPPrimaquine for vivax malaria in a G6PD-deficient patient → severe hemolysis; always test before giving.
YOUR APPROACHFungus (yeast, mold, endemic, mucor, dermatophyte) → drug class → toxicity and CYP interactions. Parasite group → drug.

If you see… think…

Fever, rigors, hypokalemia, rising creatinine on IV antifungal → amphotericin B
Visual disturbances and photosensitivity → voriconazole
Gynecomastia on antifungal → ketoconazole
Antifungal targeting the cell wall → echinocandin
Tinea capitis in a child → griseofulvin or terbinafine
Toenail onychomycosis → terbinafine
Hemolysis after malaria radical cure → primaquine + G6PD deficiency
Schistosomiasis → praziquantel
Strongyloides hyperinfection in steroid user → ivermectin
Hypoglycemia on PJP alternative → pentamidine