antifungals Flashcards
potential antifungal targets
membranes (ergosterol), nucleic acids, cell wall
drugs used for systemic fungal infections (full list)
amphotericin B, flucytosine, fluconazole, itraconazole, voriconazole, caspofungin
effective (brad-spectrum agent) for most serious systemic mycoses, esp life-threatening ones. ONLY use for proven or highly suspected systemic infections
amphotericin B
amphotericin B mechanism of action
very lipophilic, inserts into fungal membrane, binds ergosterol, increases pores/leakiness
amphotericin side effects
fever, N/V, HA, chills, hypotension, hypokalemia, tachypnea. 90% get nonpermanent nephrotoxicity. total cumulative dose important for reasons of permanent renal toxicity. reversible hypochromic, normocytic anemia
used for serious infections (candida, cryptococcus), synergistic with amphotericin B (permits reduction of dose), fungistatic
flucytosine
flucytosine mechanism of action
acts on cytosine permease
flucytosine side effects
N/V, diarrhea, enterocolitis, leukopenia, thrombocytopenia, reversible elevated hepatic enzymes. use caution with renal insufficiency or bone marrow depression. monitor closely
relative to amphotericin, other drugs for serious fungal infections…:
have narrower spectrum of action, not for immediately life-threatening infections, have fewer/less serious side effects
triazoles for serious fungal infections (imidazoles also used)
fluconazole, itraconazole, voriconazole
MOA for imidazoles and triazoles
inhibit 14-a-sterol demethylase, a fungal cytochrome P450 that converts lanosterol to ergosterol. inhibits ergosterol synthesis –> membrane instability
used for cryptococcus (esp after amphotericin therapy), candida at many sites including CNS and urinary, some albicans and galbrata, NOT krusei
fluconazole
used for blastomyces, histoplasma, candida (not CNS & urinary), more c. albicans and galbrata
itraconazole
used for aspergillus, fusarium, scedosporium, candida (not urinary), covers many candida spp including galbrata and krusei
voriconazole
which azole has CNS penetration and has active drug in urine?
fluconazole
azole side effects
N/V, rash, diarrhea, headache, mild hepatotoxicity (discontinue with onset of liver dysfunction), inhibit metabolism of several other drugs (CYP 3A and 2C family inhibitors)
itraconazole contraindications
DO NOT GIVE with other drugs that are metabolized by CYP 3A4. potential for serious CV events including death
which azole has lowest incidence of hepatotoxicity?
fluconazole
voriconazole side effects
visual disturbances (30%), rash with photosensitive component
antifungal that targets cell wall
caspofungin
uses of caspofungin
invasive aspergillus, candida (esophageal and systemic)
caspofungin MOA
inhibits fungal cell wall synthesis by noncompetitively blocking synthesis of B(1,3)-D-glucan in filamentous fungi. no cross resistance with azoles
caspofungin side effects (based on limited experience)
generally well-tolerated, but fever, N/V, flushing, phlebitis at injection site
drugs for treatment of superficial mycoses
nystatin, fluconazole, miconazole, ketoconazole, clotrimazole, itraconazole, natamycin
treatment for superficial candidiasis (vaginal, urinary tract, oropharynx)
fluconazole
cream/suppository for vaginal candida, causes itching/burning
miconazole
topical or oral troche use for candida, not opthalmic. allergic/irritation reactions. oral troches cause?
clotrimazole.
oral troches cause abnormal liver function tests
used for oropharyngeal and esophageal candida
itraconazole
effective against azole-resistant strains, topical use for candida (not opthalmic), oral for GI candida (can cause GI distress)
nystatin
treatment of opthalmic fungal infections
natamycin
natamycin toxicity
conjunctival chemosis and hyperemia
causative agents for dermatophytic infections
trichyphyton, epidermophyton, microsporum
topical treatments for dermatophytes
miconazole, clotrimazole, tolnaftate, terbinafine, ciclopirox
only FDA-approved topical rx for mild-to-moderate fungal nail infections
ciclopirox
dermatophyte therapy– oral preparations use
sever dermatophyte infections, those that are refractory to topical therapy
12-week therapy for nail infections, shorter for other dermatophytic infections
terbinafine
terbinafine mechanism of action
blocks squalene epoxidase so squalene (toxic) builds up. fungicidal.
terbinafine side effects
diarrhea, dyspepsia, abdominal pain
for recalcitrant dermatophytic infections of skin, hair, nails. therapy for kids esp tinea capitis
griseofulvin
griseofulvin mechanism
interferes with microtubule function/mitotic spindle/mitosis
griseofulvin side effects
low incidence. contraindicated in those with porphyria and advanced liver disease. increased metabolism of several drugs (CYP inducer). use with caution if penicillin allergy.
oral 3-month therapy for fungal toenail infections
itraconazole
side effects of itraconazole
N/V, rash, diarrhea, headache, edema, inhibits metabolism of many drugs, discontinue with signs of liver dysfunction
