Antifungals Flashcards
clotrimazole
topical OTC for tinea and candida
miconazole
topical OTC for tinea and candida
ketoconazole
for systemic infection; relies on gastric acidity for absorption
used for superficial dermatophytes, Cushing’s syndrome (dec cort synth), prostate cancer (dec test synth), hypercalcemia in sarcoidosis (inh form active vit D)
ADR ketoconazole
less specific affinity for fungal P450 -> GI, rash, inhibits adrenal steroid synthesis (gynecomastira, dec libido), hepatotoxic potential
potent CYP 3A4 inhibitor
MOA azoles
inhibit lanosterol -> ergosterol by inhibiting P450-dependent lanosterol C14-demethylase
ADR of azoles
drugs intx, cholesterol synthesis, cell toxicity pregnancy cat C (vori is D) liver failure (monitor LFTs)
fluconazole
oral and IV for candida prophylaxis and tx
*renal elimination
best tolerated of all azoles
ADR: GI, rash, HA, alopecia (high dose); strong CYP 2C9 and 2C19 inhibitor, 3A4 in high doses
itraconazole
greater spectrum than flu, includes Aspergillus
used for onychomycosis
ADR: GI, diarrhea, taste disturbances, elevated LFTs, rare HF with long therapy (neg inotrope)
strong CYP 3A4 and P-glycoprotein inhibitor
voriconazole
better against Aspergillus than itra
for invasive candidiasis and aspergillosis, penetrates CNS but not urine
ADR: transient visual disturbances, rash, photosensitivity, hallucinations, prolonged QT
inhibits CYP 2C9, 2C19, 3A4; preg cat D
posaconazole
better for mucor than vori
oral suspension taken with high-fat meal or liquid supplement, reserved for mod fungal infxn res to itra
poor penetration to CSF and urine
ADR: like flu, strong CYP 3A4 inhibitor
terbinafine MOA
inhibits squalene -> squalene epoxide = toxic, suicidal mechanism
uses and ADR terbinafine
onychomycosis (> itra)
ADR: GI complaints, HA, rash; less common: hepatotoxicity, SJS, blood dycrasias, taste disturbances
strong CYP 2D6 inhibitor, preg cat B
polyenes MOA
bind ergosterol in cell membrane
uses amphotericin B
slow IV infusion for systemic infections and in pregnancy
lipid formulation of ampho B
fewer acute reactions but more expensive
ADR ampho B
infusion-related (fever, chills, n/v, HA, myalgias - prophy with NSAID, hydrocortisone, diphenhydramine), nephrotoxicity d/t aff arteriole constriction (prophy with saline), hypokalemia d/t renal tubule toxicity
nystatin
polyene; topical cream or ointment, sometimes oral suspension for oral thrush
can be used for recurrent gut infections in AIDS patients
echinocandin MOA
inhibits B-glucan synthase, disrupting glucan polymers in cell wall
caspofungin, micafungin, anidulafungin
echinocandin antifungals
uses of echinocandins
DOC for invasive candidiasis (minimal CSF or urine penetration), alternative to azole antifungals for candida and aspergillus infections
echinocandin ADRs
fever, phlebitis at IV site, elevated LFTs, minimal drug interactions
griseofulvin
for dermatophyte infections
poor tolerance d/t allergic reactions, photosensitivity, GI distress, neurologic effects
take with high-fat meal for best absorption
enzyme inducer
flucytosine
anti-cancer drug not used anymore d/t BM toxicity
inhibits DNA/RNA synthesis when converted to 5-FU intracellularly (toxic antimetabolite)
was used for severe systemic infections with ampho B
