Antifungals Flashcards
Moa of amphotericin B
Amphotericin B binds to ergosterol in the plasma membranes of sensitive fungal cells -form pores - pores disrupt membrane function, allowing electrolytes (particularly potassium) and small molecules to leak from the cell, resulting in cell death
Antifungal spectrum of amphotericin B
effective against a wide range of fungi: Candida albicans Histoplasma capsulatum Cryptococcus neoformans Coccidioides immitis Blastomyces dermatitidis and many strains of Aspergillus protozoal infection leishmaniasis
Elimination of amphotericinB
Some via bile
Some in urine
Csf penetration of amphotericin B
Minimal penetration in CSF
Method of administration of amphotericin
topical
IV-
conventional( soadium deoxycholate)
Liposomal preparation( less infusion and renal toxicity)
adverse effects of amphotericin
ACUTE
Fever and chills
Thrombophlebitis
CHRONIC
Renal impairment: more if given with other nephrotoxic drugs
Hypokalemia: caution in digoxin
Anemia: BM depression
Moa of flucytosine
Combined with amphotericjn which increases its entry into cell by making it more permeable.
Flucyosine- 5 florouracil - 5 FdUMP which inhibits thymidylate synthase depriving the cell of nucleotide
Adr of flucytosine
BM depression
Hepatic dysfxn
Git: n/v/d
Excretion of 5FC
Urine
2 different classes of azole antifungals
Imidazoles : cutaneous ds
Troazoles : cutaneous and systemic ds
Moa of azoles
block the demethylation of lanosterol to ergosterol, the principal sterol of fungal membranes disrupting membrane structure and function.
All azoles _____ hepatic CYP450 3A4 isoenzymes to varying degrees
INHIBIT
CI of azoles
Pregnancy: teratogenic
Fluconazole use
CRYPTOCOCCUS NEOFORMANS
CANDIDA
Adr of fluconazole
n/v ,headache, and skin rashes Hepatotoxicity
Adr of itraconazole
n/v, rash hypokalemia hypertension edema, headache Hepatotoxicity Itraconazole has a negative inotropic effect and should be avoided in patients with evidence of ventricular dysfunction, such as heart failure.
Itraconazole use
Broad spectrum drug of choice for the treatment of blastomycosis sporotrichosis paracoccidioidomycosis histoplasmosis
Hepatoxicity os common to which class of antifungals
Azoles
Posaconazole use
Candida
Aspergillus
Zygomycetes
Voriconazole use
Broad spectrum
Doc for invasive Aspergillosis
All azole inhibit CYP 450 isoenzymes
All azole are hepatotoxic
Yes
Yes
Primary route of elimination of Flu Itra Vori Posa
Renal
Rest Hepatic
Echinocandins
Moa: interfere with synthesis of fungal cell wall leading to lysis of cell
Use: candida , aspergillus (little against others)
Eg: caspofungin , micafungin , anidulafungin
Antifungal for Tinea capitis and unguim
Oral / topical
Oral
Moa of squalene oxidase inhibitors
These agents act by inhibiting squalene epoxidase, thereby blocking the biosynthesis of ergosterol, an essential component of the fungal cell membrane
Squalene oxidase inhibitors eg
Terbrnafine
Naftifine
Butenafine
Kinetics of terbenafine
Oral terbinafine is extensively metabolized by several CYP450 isoenzymes and is excreted mainly via the urine . The drug should be avoided in patients with moderate to severe renal impairment or hepatic dysfunction.
Adberse effects of terbenafine
gastrointestinal disturbances (diarrhea, dyspepsia, and nausea), headache, and rash.
Taste and visual disturbances
transient elevations in serum hepatic transaminases.
Terbinafine is an inhibitor of the CYP450 2D6 isoenzyme, and concomitant use with substrates of that isoenzyme may result in an increased risk of adverse effects with those agents.
Moa of griseofulvin
causes disruption of the mitotic spindle and inhibition of fungal mitosis
Polyene antifungals
Amphotericin B
Nystatin
Use of nystatin
cutaneous and oral Candida infections.
The drug is negligibly absorbed from the gastrointestinal tract, and it is not used parenterally.
It is administered as an oral agent for the treatment of oropharyngeal candidiasis (thrush), intravaginally for vulvovaginal candidiasis, or topically for cutaneous candidiasis.
Imidazoles
butoconazole clotrimazole econazole ketoconazole miconazole oxiconazole sertaconazole sulconazole
Moa of various antifungals
Echinocandins: inhibit cell wall
Azoles : inhibit cell membrane
Polyenes : inhibit cell membrane
Griseofulvin : mitotic spindle hence mitosos
Flucytosine: DNA synthsis
