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15 Cards in this Set

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what antifungals are cell membrane inhibitors?
amphotericin B

nystatin

fluconazole (azoles)

allylamine drugs (terbinafine)

ciclopirox
what antifungals inhibit RNA?
flucytosine
what antifungals inhibit mitosis?
griseofulvin
polyene antibiotic -

Amphotericin B
Amphotericin B

Class: polyene antibiotic

MOA: bind to ergosterol and form a pore (increase cell membrane permeability)

Use: severe systemic, subQ mycoses.. cryptococcal meningitis, histo, blasto, coccidio

AE: renal toxicity 90% {decreased GFR -> azotemia, hypokal, hypomg... chills, fever, headache (shake and bake)... liver, heart, hematopoietic toxicity (suppress EPO, anemia)... anaphylaxis, convulsions.. decrease dosage when electrolytes get bad

Contra: pregnancy, crosses placenta

Interaction: nephrotoxicity exacerbated by aminoglycoside, cyclosporine, pentamidine... hypokal careful in digitalis pt... increase anemia in zidovudine pt

Admin: IV - lipid formulations sequestered and slowly released from reticuloendothelial system - has decreased renal drug [] / toxicity
Azole Derivatives-

Clotrimazole
Clotrimazole

Class: azole derivative

MOA: inhibit 14-alpha-demethylase (cyto P450 enzyme) that converts lanosterol to ergosterol

Use: superficial mycoses - cadidiasis, tinea
MALASSEZIA FURFUR - HYPO/HYPERPIGMENTED LESIONS

AE: contact dermatitis, vulvar irritation, edema... typical azole effect: well tolerated, rash, liver, hematologic, GI

Contra:

Interaction: inhibit P450 enzymes - increase levels of warfarin, lovastatin, benzodiazepines, carbamazepine LIKE ERYTHRO & CLARITHRO MACROLIDES... rifampin decreases azole duration of axn

Admin: topical
Azole Derivatives

Fluconazole
Fluconazole

Class: azole

MOA: inhibit 14 alpha demethylase, enzyme that converts lanosterol to ergosterol

Use: fungal (cryptococcal) meningitis prophy and rx - penetrates CNS... candidasis (single oral dose for vaginal infection)
DOC crypto, candida, coccidio

AE: N/V/rashes/hepatitis

Contra: preg

Interaction: inhibit P450 enzymes

Admin: oral, IV (penetrates CNS).. good absorption, bad metabolism
Azole Derivative

Itraconazole
Itraconazole

Class: azole

MOA: inhibit 14 alpha demethylase, P450 enzyme that converts lanosterol to ergosterol

Use: blasto, histo (+AIDS histo), coccidio
onychomycosis, sporotrichosis (give K Iodide for cutaneous lesions)

AE: N/V/rash, hypokal, HTN, edema, headache

Contra: preg

Interaction: oral anticoag, statin, quinidine... inducers of P450 increase intraconazole metab

Admin: oral - need gastric acid for dissolution.. active metabolite
Azole Derivative

Ketoconazole
Ketoconazole

Class: azole

MOA: inhibit 14 alpha demethylase, a P450 enzyme that converts lanosterol to ergosterol

Use: NOT aspergillosus, shampoo for seborrheic dermatitis...

AE: inhibit human gonadal (testosterone) synth... inhibit adrenal steroid (cortisol synth)... N/V/anorexia, allergies, transient elevated serum transaminases

Contra: preg

Interaction: require gastric acid for breakdown and absorbed in gastric mucosa.. PPI, H2 inhibitor, sucralfate, antacids impair absorption... acidifying agents improve absorption in pt with achlorhydria

Admin: oral
Azole Derivative

Voriconazole
Voriconazole

Class: azole

MOA: inhibit 14 alpha demethylase, P450 enzyme that converts lanosterol to ergosterol

Use: invasive aspergillosis, DRUG RESISTANT CANDIDA, DRUGS RESISTANT TO FLUCONAZOLE, additive effects with caspofungin

AE: normal azole (N/V/rash, hematologic) + transient visual disturbance after dose

Contra: preg

Interaction: inhibit P450

Admin: oral, penetrates tissues/CNS well
Echinocandin

Caspofungin
Caspofungin

Class: echinocandin

MOA: inhibit cell wall glucan synthesis

Use: aspergillus, resistant candida, alternative use for allergic amphotericin B/ itraconazole

AE: fever, rash, nausea, phlebitis, flushing

Contra: it pt taking cyclosporine

Interaction: slowly metab by hydrolysis/ acetylation

Admin:
Allylamine drugs -

Terbinafine
Terbinafine

Class: allylamine

MOA: inhibit squaline epoxidase, enzyme for ergosterol synthesis

Use: superficial infections, onychomycosis, dermatophytoses, candida

AE: GI, headache, rash, taste/visual disturbance

Contra: nursing mom

Interaction: rifampin decreases serum terbinafine level... Cimetidine increases serum terbinafine level

Admin: topical, oral
Flucytosine
Flucytosine

Class:

MOA: inhibits thymidilate synthase (RNA synth)

Use: crypto meningitis, systemic candidiasis (used with amphotericin B)... systemic/ subQ mycoses

AE: reversible neutropenia, thrombocytopenia, bone marrow depression, reversible hepatic dysfxn, N/V/D, enterocolitis

Contra:

Interaction: dose must be adjusted in renal compromise pt

Admin: oral, penetrates CSF
Griseofulvin
Griseofulvin

Class:

MOA: inhibits microtubule fxn, mitosis - concentrates in keratin precursor cells of dermis (works from inside out)

Use: superficial mycoses

AE:

Contra: alcohol - potentiates alcohol effects

Interaction: induces P450

Admin: oral - bioavailability increased by micronized drug particle + fatty meals
what are drugs used for systemic and subQ mycoses
amphotericin B

itraconazole, fluconazole

voriconazole, caspofungin (drug resistant and invasive candidiasis and aspergillosus)

flucytosine
what drugs are used for superficial mycoses
clotrimazole

terbinafine

friseofulvin

nystatin - (binds ergocholesterol), for oral candida "swish and swallow"

ciclopirox (membrane structure), nail lacquer formation for onychomycosis

tolnaftate