Pharm_Protozoan Flashcards
Antifungal therapy: Amphotericin B
Mechanism: Binds ergosterol (unique to fungi); forms membrane pores that allow leakage of electrolytes Clinical use: Serious, systemic mycoses. Cryptococcus, Blastomyces, Coccidioides, Aspergillus, Histoplasma, Candida, Mucor (systemic mycoses). Intrathecally for fungal meningitis; does not cross blood-brain barrier. Toxicity: Fever/chills (“shake and bake”), hypotension, nephrotoxicity, arrhythmias, anemia, IV phlebitis (“amphoterrible”). Hydration reduces nephrotoxicity. Liposomal amphotericin reduces toxicity.
Antifungal therapy: Azoles (Fluconazole, ketoconazole, clotrimazole, miconazole, itraconazole, voriconazole)
Mechanism: Inhibit fungal sterol (egosterol) synthesis, by inhibiting the P-450 enzyme that converts lanosterol to egosterol. Clinical use: Systemic mycoses. Fluconazole for cryptococcal meningitis in AIDS patients (because it can cross blood-brain barrier) and candidal infections of all types. Ketoconazole for Blastomyces, Coccidioides, Histoplasma, Candida albicans; hypercortisolism. Clotrimazole and micronazole for topical fungal infections. Toxicity: Hormone synthesis inhibition (gynecomastia), liver dysfunction (inhibits cytochrome P-450), fever, chills.
Antifungal therapy: Caspofungin
Mechanism: Inhibits cell wall synthesis by inhibiting synthesis of β-glucan Clincal use: Invasive aspergillosis Toxicity: GI upset, flushing
Antifungal therapy: Flucytosine
Mechanism: Inhibits DNA synthesis by conversion to 5-fluorouracil Clinical use: Used in systemic fungal infections (e.g., Candida, Cryptococcus) in combination with amphotericin B Toxicity: Nausea, vomiting, diarrhea, bone marrow suppression
Antifungal therapy: Griseofulvin
Mechanism: Interferes with microtubule function; disrupts mitosis. Deposits in keratin-containing tissues (e.g., nails) Clinical use: Oral treatment of superficial infections; inhibits growth of dermatophytes (tinea, ringworm) Toxicity: Teratogenic, carcinogenic, confusion, headaches, ↑P-450 and warfarin metabolism
Antifungal therapy: Nystatin
Mechanism: Binds ergosterol (unique to fungi); forms membrane pores that allow leakage of electrolytes. Topical form because too toxic for systemic use. Clinical use: “Swish and swallow” for oral candidiasis (thrush); topical for diaper rash or vaginal candidiasis
Antifungal therapy: Terbinafine
Mechanism: Inhibits the fungal enzyme squalene epoxidase Clinical use: Used to treat dermatophytoses (especially onychomycosis - fungal infection of finger or toe nails)
Antihelminthic therapy mechanism: Diethylcarbamazine
Unknown
Antihelminthic therapy mechanism: Ivermectin
Intensifies GABA-mediated neurotransmission and causes immobilization. Does not cross the blood-brain barrier; therefore, no effect of humans.
Antihelminthic therapy mechanism: Mebendazole
Inhibits glucose uptake and microtubule synthesis
Antihelminthic therapy mechanism: Praziquantel
Increases membrane permeability to calcium, causing contraction and paralysis of tapeworms and flukes
Antihelminthic therapy mechanism: Pyrantel pamoate
Stimulates nicotinic receptors at neuromuscular junctions. Contraction occurs, followed by depolarization-induced paralysis. No effect on tapeworms or flukes.
Antiprotozoan therapy mechanism: Chloroquine
Blocks plasmodium heme polymerase, leading to accumulation of toxic hemoglobin breakdown products that destroy the organism
Antiprotozoan therapy mechanism: Mefloquine
Unknown
Antiprotozoan therapy mechanism: Melarsoprol
Inhibits sulfhydryl groups in parasite enzymes. CNS involvement.
Antiprotozoan therapy mechanism: Nifurtimox
Forms intracellular oxygen radicals, which are toxic to the organism
Antiprotozoan therapy mechanism: Pyrimethamine
Selectively inhibits plasmodial dihydrofolate reductase (best for P. falciparum). Drug of choice for toxoplasmosis when combined with sulfadiazine.
Antiprotozoan therapy mechanism: Quinine
For chloroquine-resistant species when used in combination with pyrimethamine / sulfonamide
