antifungals Flashcards
Amphotericin B mechanism
binds ergosterol in the fungal membrane
forms membrane pores that allow leakage of electrolytes leading to cell death
side effect profile is intense, including nephrotoxicity
use for serious, severe, systemic infections such as cryptococcosis blastomycosis coccidiomycosis aspergillosis histoplasmosis mucormycosis
give IV, occasionally infuse intrathecally. does not cross BBB
amphotericin B
fever and chills hypotension hypokalemia anemia phlebitis arrhythmias nephrotoxicity!!
Nystatin
binds polyene ergosterol, forming pores
too toxic for systemic use; only use for topical use
cutaneous candidiasis
- diaper rash
- vulvovaginitis
oropharyngeal candidiasis
“swish and swallow”
side effects: occasional GI complaints
Azoles
fluconazole ketoconazole voriconazole clotrimazole miconazole posaconazole
inhibit ergosterol synthesis by inhibiting the p450 enzyme that converts lanosterol to ergosterol
use topically, orally, IV
crosses BBB
Fluconazole
cryptococcal meningitis (crosses BBB) candidal infections
Ketoconazole
blastomyces
coccidioides
histoplasma
candida
not firstline
Itraconazole
first line for many infections blastomyces caccidioides pacacoccidioides histoplasma sporothrix
Voriconazole
active against aspergillus!
Posaconazole
active against many fungi that are refractory to other treatments:
mucor
Clotrimazole and miconazole
topical fungal infections (OTC)
azole side effects
decreased production of cortisol and testosterone
gynecomastia
impotence
also blocks CYP450, which affects drug- drug interactions, increased hepatic enzymes
Flucytosine
converted to 5FU
systemic fungal infections (especially cryptococcal meningitis), and for systemic candidal infections
USE IN COMBINATION with amphotericin B
tox: bone marrow suppression
GI symptoms
Disrupts DNA and RNA synthesis
cASPofungin- echinocandin
Inhibits cell wall synthesis by inhibiting synthesis of beta-(1,3)-D-glucan, leading to cell lysis and cell death
clinical uses: invasive aspergillosis
candida infection
Toxicity: GI upset, flushing
Terbinafine
inhibits the fungal enzyme squalene epoxidase
This decreases ergosterol synthesis
use for topical treatment: -tinea pedis -tinea corporis use PO: -onchomycosis -tinea capitis
dermatophytoses (especially onchomycosis- fungal infection of finger or toe nails)
tox: GI upset, HEPATOTOXICITY, HA, hepatotoxicity, taste disturbance
Griseofulvin
targets microtubule function- inhibits mitosis
deposits in keratin- containing tissues (like the nails)
oral treatment of superficial infections, inhibits growth of dermatophytes (tinea corporis, ringworms- tinea capitis, onchomycosis)
toxicity: teratogenicity HA GI symptoms confusion CYP450 inducer
