Antifungals Flashcards
Fungicidal
Bind to ergosterol to form holes in the cell membrane leading to cell death (tears fungal cell mem)
Resistance: decreasing the amount if ergosterol
Amp B
Treats all life threatening systemic fungal inf, coccidioidomycosis and aspergillosis
Amp B
DOC for mucomycosis
Amp B
Dose dependent renal impairment
1) reversible damage by decreasing perfusion
2) irreversible damage by tubular injury
Amp B
ADR:
1) shake and bake [tx antipyretic, steroids, antihistamine]
2) nephrotoxicity
3) thrombophlebitis
4) seizure and other CNS effects
Amp B
Type of admin for amp B to treat fungal CNS Effects
Intrathecal
Non colloidal suspension - amp B deoxycholate (C-AMP)
Lipid Amp B (L-AMP) - reduces toxicity
Amp B
Converts flucytosine to 5 flourouracil
Cytosine deaminase
MOR: decrease activity of deaminase
ADR: BM depression [due to conversion of 5FU by gut flora], alpoecia, liver dysfunction
Flucytosine
Never used alone
- used with Amp B tx cryptococcal meningitis
- used with itraconazole tx chromoblastomycosis
Flucytosine
Same MOA as amp B 0 binding ergosterol to form holes in the cell membrane
Active against candida - oral rinse - local effect
Topical tx for mucocutaneous candidiasis (vaginal candidiasis)
Nystatin
fungistatic
depend on CYP450 and inhibit CYP450 - 3A
inhibit 14 alpha demethylase
Azoles
responsible for converting lanosterol to ergosterol
14 alpha demethylase
inhibit CYP450
may cause visual disturbances, blurry vision, flashes of light, color vision changes (blue/green)
treats invasive aspergillosis
voriconizole
only azole to treat mucormycosis - 2nd line
posaconazole
DOC for cryptococcal and coccidioidal meningitis (and prophylaxis) and vaginal candidiasis
Also treats candida stomatitis and esophagitis
fluconazole
only azole with high level CNS penetration
fluconazole
treats systemic infections with dimorphic fungi - blastomycosis and sporothrix
absorption increased with food
itraconazole
treats tinea infections
clotrimazole
miconazole
treats dermatomycosis
inhibits 17, 20 desmolase (1st step of steroid synthesis form cholesterol); production of androgens and estrogens; overproduction of adrenal cortisol; CYP450-3A
ketaconazole
fungistatic
binds fungal cell microtubules polymerization - halting metaphase
activates CYP450
treats dermatophytosis
griseofulvin
1st line therapy for tinea corpis in children, and for nail fungi
needs prolong therapy - 6 months
griseofulvin
toxicity: photosensitivity, disulfiram like rxn, contraceptive failure with OCPs, carcinogenic, liver toxicity
griseofulvin
fungicidal
inhibits fungal squalene epoxidase causing accumulation of squalene
No P450 inhibition
terbanifine
highly lipophilic: [ ] in dermis, epidermis and adipose tissue
Tx: fungal inf of nails 6- 12 weeks
terbanifine
fungicidal
inhibits beta 1-3 glucan of cel wall - no cell wall
avoid combo with cyclosporins
no effect on P450
caspofungin (echinocandins)
activity against candida and aspergillus
caspofungin
treats for aspergillus
1) Amp B
2) voriconazole
3) caspofungin
