Flashcards in Pharm antifungal Deck (31):
what are the major categories of pathogenic fungi?
yeast: candida, cryptococcus
mold: aspergillus, fusarium, mucorales
endmic mycoses: histoplasma, coccidioides, blastomyces, pneumocystis jiroveci
what are the categories of antifungal agents?
triazoles, polyenes, echinocandins, flucytosine
what are the triazole antifungals?
fluconazole, itraconazole, posaconazole, voriconazole
impede ergosterol synthesis through direct inhibition of the cytochrome P450 dependent enzyme 14-alpha-sterol demethylase (necessary for biosynthetic pathway or ergosterol)
triazole adverse effects
relatively safe - liver enzyme abnormalities, GI side effects, voriconazole = visual disturbances
what is a specific side effect to voriconazole
visual disturbance (Visual Voriconazole)
triazole drug interactions? which has lowest?
potential inhibitors of CYP450 - fluconazole has lowest
what is fluconazole the treatment of choice for?
susceptible candidiasis; severe thrush/esophageal candidiasis; secondary treatment and prophylaxis of cryptococcal meningitis
what is itrazonazole the treatment of choice for?
secondary treatment and prophylaxis of systemic histoplasmosis
what is voriconazole the treatment of choice for?
what is posaconazole the treatment of choice for?
Prophylaxis of aspergillosis/immunocompromised patients
P = Prophylaxis Posaconazole
amphotericin B MOA
inhibition of ergosterol - generates pores
amphotericin B class
what are the polyene macrolides?
amphotericin B and nystatin
amphotericin B clinical use
life-threatening invasive fungal infections - broad spectrum
what is amphotericin used with in immunocompromised hosts?
amphotericin B side effects
poor tolerability - nephrotoxicity (so common expected); acute infusion related reactions (fever, chills, rigors); electrolyte abnormalities (d/t pores in cell and kidney dysfunction) - hypomagnesemia, hypokalemia
what has been done to amphotericin B to give it better tolerability?
lipid formulations - more renal protective and less infusion-related side effects
what are the echinocandins?
caspofungin, micafungin, anidulafungin
disadvantages to echinocandins
expensive and only available IV
echinocandins (-fungins) mechanism
cell wall synthesis inhibitor - inhibit synthesis of beta (1,3)-D-glucan
echinocandins (-fungins) clinical uses
life-threatening fungal infections unresponsive to older agnets
echinocandins (-fungins) side effects
low side effect profile (some liver toxicity possible)
pyrimidine analogue that inhibits DNA and RNA synthesis - only oral
flucytosine clinical use
ALWAYS used in combination with something else (amphotericin B usually) - only active against cryptococcus and some candida
flucytosine side effects
chemotherapy like - bone marrow toxicity (decreased WBC and anemia), liver disfunction possible, GI intolerances
what are the allylamines?
tolnaftate and terbinafine
tolnaftate and terbinafine (allylamines) MOA
inhibit ergosterol synthesis by inhibiting squalene epoxidase = increase levels of squalene which are toxic to fungi
what are the clinical uses of tolnaftate and terbinafine (allylamines)?
tolnaftate and terbinafine (allylamines) side effects
hepatotoxicity - otherwise low side effect profile