Therapeutic Uses

	THERAPEUTIC USES	DOSAGE FORMS	MECHANISM OF ACTION	ELIMINATION	TOXIC EFFECTS/SIDE EFFECTS	OTHER INFORMATION
Amphotericin B	Aspergillosis, Cryptococcosis (meningial)	Suspension in deoxycholate, lipid complex, chlesteryl sulfate complex, liposomal, topical	Binds to ergosterol on the fungal membrane and disrupts the fungal membrane to form channels/leaks (especially with K+) and is fungistatic at low doses and fungicidal at high doses	Renal	Acute anaphylactic reaction, nephrotoxicity	90% protein bound
Nystatin	Candidiasis, vulvovaginal candidiasis, oropharyngeal candidiasis	Topical, lozenges, oral suspension, tablets	Binds to ergosterol on the fungal membrane and disrupts the fungal membrane to form channels/leaks (especially with K+) and is fungistatic at low doses and fungicidal at high doses	Renal
Flucytosine	Disseminated Candidiasis, Chromonycosis, Cryptococcosis	Capsules	Flucytosine is taken up into fungal cells and inhibits Thymidylate Synthase and prevents the production of dTMP, which is the rate limiting step to DNA synthesis	Renal (Reduce dose in renal impairment)	Bone marrow depression (Anemia, leukopenia, thrombocytopenia)	2 - 4% protein bound

Ketoconazole	2nd line therapy for blastomycosis, candidiasis, coccidomycosis, histoplasmosis, paracoccidioidomycosis, psuedallescheriasis	Oral tablets, cream, shampoo	Inhibits 14-Alpha Demethylase enzyme and inhibits the demethylation of lanosterol. This inhibits the formation of ergosterol and causes leaky membranes of the fungal cells	Biliary	Hepatitis, liver toxicity, GI disturbances. Rare, dose dependent supression of steroid synthesis leading to gynecomastia and impotence in males and menstrual irregularities in females	Inhibits CYP3A4, Extensive hepatic metabolism, 99% protein bound. Sometimes used in Prostate Cancer since inhibits testosterone synthesis at high doses.
Itraconazole	Histoplasmosis, blastomycosis, pseudallesheriasis, sporotrichosis	Capsules	Same As Ketoconazole	Biliary	Less inhibition of normal sterol biosynthesis and the related side-effects. Nausea, GI cramps, allergic rash, edema, hepatitis, hypokalemia, HTN	Better selection for 14-Alpha demethylase than ketoconazole. Extensive metabolism (oxidation at triazole ring and subsequent ring opening). Can use pulse therapy to treat onychomycosis. Potent inhibitor of CYP3A4
Fluconazole	Oropharyngeal candida, invasive candida, meningial cryptococcosis, vulvovaginal candida	IV solution, tablets	Same As Ketoconazole	Renal	GI disturbances, HA, occasional hepatotoxicity, Stevens-Johnson syndrome, thrombocytopenia	Less inhibition of CYP3A4
Voriconazole	Fluconazole-resistant candida	NOT YET APPROVED	Same as ketoconazole		Blurred vision, raised liver function enzymes	Undergoes hepatic metabolism
SCH-56592 (Posoconazole)	Aspergillus and resistant strains of candida	NOT YET APPROVED	Same as ketoconazole			Excellent pharmacokinetic profile and undergoing Phase II trials