antifungals Flashcards
Amphotericin B
IV injection only, broad spectrum standard treatment for life threatening mycoses. associated with significant adverse effects. Only anti fungal for pregnant women
MOA amphotericin
Ampho B binds to ergosterol in fungal membrane, forming pore
What is ampho B not active against?
Pseudallescheria boydii and C lusitaniae
Flucytosine
Treats cryptococcal meningitis, good oral absorption, used with other drugs
MOA flucytosine
Inhibits thymidylate synthase (dna synthesis) and 5-FUTP (RNA synthesis)
What is the spectrum of activity for the azoles?
Fluconazole «_space;itraconazole < voriconazole< posaconazole
How do azoles work?
inhibit 14a sterol demthylase involved int he biosynthesis of ergosterol, increasing membrane permeability and decreasing membrane function
Azole drug interactions
CYP450. most drug interactions with itraconazole and voriconazole. NEVER give itraconazole and voriconazole with statins due to rhabdo. inducers of cyp450 reduce levels of drug
Ketonazole
Not used frequently. issues with cortisol and testoerone. requires acidic environment for absoprtion
fluconazole
narrowest spectrum of activity, but good oral bioavailability and excellent CSF penetrasion. used for cyrptococcal meningitis and against mucocutaneous candida. associated with alopecia and mild ae
Itraconazole
used for oral treatment of dermatophyte infections, preferred for non meningeal endemic dimophroic infections
Itraconazole AE
hypertension, hypokalemia, and peripheral edema. Should not be used with ventricular dysfunction or CHF
Voriconazole
good absorption into CSF but inhibited by fatty meals. Non linear metabolism. good activity against everything, treatment of choice for invasive aspergillus
Voriconazole AE
Periostitis, transient vision changes, photosensititvyt and stevens johnson
Posaconazole
poor penetration of CSF and urine, broadest spectrum, good safety profile. Used for invasive fungal infections and antifungal prophylazis in patients with prolonged neutropenia and severe graft vs host disease
Echinocandins
Caspofungin, micafungin, anidulafungin. Directly target the fungal cell wall, not significant interactions with CYP45 no significant activity. good activity against aspergillus. towards Crypto or dimorphic fungihistimaine like effect. must be administered IV
Echinocandin MOA
inhibits B(1-3)-D glucan synthase complex. impair structural integrity of fungal cell well and increases osmotic instability leading to cell death
What drugs are used for cutaneous fungal infections?
Griseofulvin and terbinafine
Griseofulvin
only effective against dermatophytes-microsporum, epidermophyton, and trichophyton. Many adverse effects and drug interactions.
MOA griseofulvin
binds to fungal microtubules, preventing the formation of the mitotic spindle and inhibiting fungal mitosis. Infected cells are exfoliated and replaced by new uninfected cells because it accumulates in newly differentied keratin producing precursor cells.
Terbinafine
activity limited to dermatophytes and candida albicans. Much more effective than other meds for these. well tolerated
Terbafine MOA
inhibiton of fungal squalene epoxidase leading to impaired membrane function and increased toxic products
Topical antifungals for cutaneous fungal infections
nyastatin, clotrimazole, miconazole, terconazole, terbinafine, naftifine, butenafine
Nyastatin
binds to ergosterol and forms pores, but too toxic for IV administration and not active against dermatophytes. used for oral candidiasis (swish and swallow)
