AntiFungal Flashcards
Who is most suspeptible to fungal infections?
- immunocompromised patients
- transplant
- HIV/AIDS
- autominnue condition
- corticosteriod use and antibiotic use
- can happen in immunocompent patients as well
Terbinafine
MOA- inhibition of squalene epoxidase- reducing fungal cell membrance ergosterol synthesis
Indication- Tinea cosporis (ring worm), tinea pedis (athletes foot), tinea cruris (jock itch), onchomycosis (nail fungus)
Renal elimination but hepatic impairment
Oral formuation
Monitor- SCr, LFT, CBC if >6 weeks to treat immunodifficient patients
Butenafine
MOA- inhibition of squalene epoxidase- reducing fungal cell membrance ergosterol synthesis
Indication- Tinea cosporis (ring worm), tinea pedis (athletes foot), tinea cruris (jock itch), onchomycosis (nail fungus)
Naftifine
MOA- inhibition of squalene epoxidase- reducing fungal cell membrance ergosterol synthesis
Indication- Tinea cosporis (ring worm), tinea pedis (athletes foot), tinea cruris (jock itch), onchomycosis (nail fungus)
Amorolfine
MOA- inhibition of squalene epoxidase- reducing fungal cell membrance ergosterol synthesis
Indication- Tinea cosporis (ring worm), tinea pedis (athletes foot), tinea cruris (jock itch), onchomycosis (nail fungus)
Ketoconazole
Azoles- imizaoles
MOA- inhibition of 14 alpha-demethylase whihc converts lonosterol to erogosterol= disruption in cell membrane synthesis; block steriod synthesis in humans
Indication- candida spp, blastomycosis, histoplasmosis NOT aspergillius
Topical formulation
Need gastic pH for absoprtion- DDI H2RA, PPI, antacids
Contraindicated with patients with hepatic impairment
BBB warning- QTc prolongation (do not use in cardiac patients)
INTERACTION WITH CYP INHIBITORS
Alopecia, mentral irregularities
Inhibits the synthesis of aldosterone, cortisol and testosterone (can be used for advanced prostate cancer)
Clotrimazole
Azoles- imizaoles
MOA- inhibition of 14 alpha-demethylase whihc converts lonosterol to erogosterol= disruption in cell membrane synthesis; block steriod synthesis in humans
Indication- Tinea cosporis, tinea pedis, tinea cruris, oropharyngeal candidiasis, vovluvaginal candidiasis
Topical Forumulation
Miconazole
Azoles- imizaoles
MOA- inhibition of 14 alpha-demethylase whihc converts lonosterol to erogosterol= disruption in cell membrane synthesis; block steriod synthesis in humans
Indication- Tinea cosporis, tinea pedis, tinea cruris, oropharyngeal candidiasis, vovluvaginal candidiasis
Topical Forumulation
Econazole
Azoles- imizaoles
MOA- inhibition of 14 alpha-demethylase whihc converts lonosterol to erogosterol= disruption in cell membrane synthesis; block steriod synthesis in humans
Indication- Tinea cosporis, tinea pedis, tinea cruris, oropharyngeal candidiasis, vovluvaginal candidiasis
Topical Forumulation
Mebendazole
Azoles- imizaoles
MOA- inhibition of 14 alpha-demethylase whihc converts lonosterol to erogosterol= disruption in cell membrane synthesis; block steriod synthesis in humans
Indication- Tinea cosporis, tinea pedis, tinea cruris, oropharyngeal candidiasis, vovluvaginal candidiasis
Topical Forumulation
Oxiconazole
Azoles- imizaoles
MOA- inhibition of 14 alpha-demethylase whihc converts lonosterol to erogosterol= disruption in cell membrane synthesis; block steriod synthesis in humans
Indication- Tinea cosporis, tinea pedis, tinea cruris, oropharyngeal candidiasis, vovluvaginal candidiasis
Topical Forumulation
Sertaconazole
Azoles- imizaoles
MOA- inhibition of 14 alpha-demethylase whihc converts lonosterol to erogosterol= disruption in cell membrane synthesis; block steriod synthesis in humans
Indication- Tinea cosporis, tinea pedis, tinea cruris, oropharyngeal candidiasis, vovluvaginal candidiasis
Topical Forumulation
Sulconazole
Azoles- imizaoles
MOA- inhibition of 14 alpha-demethylase whihc converts lonosterol to erogosterol= disruption in cell membrane synthesis; block steriod synthesis in humans
Indication- Tinea cosporis, tinea pedis, tinea cruris, oropharyngeal candidiasis, vovluvaginal candidiasis
Topical Forumulation
Thiabendazole
Azoles- imizaoles
MOA- inhibition of 14 alpha-demethylase whihc converts lonosterol to erogosterol= disruption in cell membrane synthesis; block steriod synthesis in humans
Indication- Tinea cosporis, tinea pedis, tinea cruris, oropharyngeal candidiasis, vovluvaginal candidiasis
Topical Forumulation
Fluconazole
Azoles- triazole
MOA- inhibition of 14 alpha-demethylase whihc converts lonosterol to erogosterol= disruption in cell membrane synthesis; block steriod synthesis in humans
systemic invasive fungal infections
CYP INTERACTIONS 3A4 (Itra & Posa> Fluc, Vori & Isovuconazole)
Indication Candidasis (oroesophageal/ urogenital/ vulvovigial), prohylaxis in BMT or solid organ translany Cryptococcus NO aspergillius,
Newer- less hormonal inhibitoon, broader spectrum, less toxic, better tissue distribution
CNS Penetration
Renal adjustments for renal failure
ADR- alopecia
Itraconazole
Azoles- triazole
MOA- inhibition of 14 alpha-demethylase whihc converts lonosterol to erogosterol= disruption in cell membrane synthesis; block steriod synthesis in humans
systemic invasive fungal infections
CYP INTERACTIONS 3A4 (Itra & Posa> Fluc, Vori & Isovuconazole)
Indication Candidasis (oropharengeal and esophageal), step down therapy for Aspergillius
Newer- less hormonal inhibitoon, broader spectrum, less toxic, better tissue distribution
Capsule given with meal
Solution should be given on empty stomach (preferred)
ADR- Hypertension, Hypokalemia, Edema
Contraindiated in cardiac patients (QTc prolongation)
Voriconazole
Azoles- triazole
MOA- inhibition of 14 alpha-demethylase whihc converts lonosterol to erogosterol= disruption in cell membrane synthesis; block steriod synthesis in humans
systemic invasive fungal infections
CYP INTERACTIONS 3A4, CYP2C9, CYP2C19 (Itra & Posa> Fluc, Vori & Isovuconazole)
Indication- resistant candida, aspergillius
Newer- less hormonal inhibitoon, broader spectrum, less toxic, better tissue distribution
Larg Vd and good CNS penetration
Take with no food
Monitor- level >5mg/L = CNS toxicity, SCr, electrolytes, LFT, ophthalmic exam
ADR- N/V/D, liver dysfunction, visual abnormalities, hepatotoxicity, SJS, and auditiory disturbance
Posaconazole
zoles- triazole
MOA- inhibition of 14 alpha-demethylase whihc converts lonosterol to erogosterol= disruption in cell membrane synthesis; block steriod synthesis in humans
systemic invasive fungal infections
Oral administration- slow onset
CYP INTERACTIONS 3A4, (Itra & Posa> Fluc, Vori & Isovuconazole)
Indication- resistant candida, aspergillius
Newer- less hormonal inhibitoon, broader spectrum, less toxic, better tissue distribution
Monitor- SCr, electrolytes, LFT
ADR- GI, HA, rare hepatoxicity , QTc prolongation, hemolytic uremic syndrome
Isavuconazole
zoles- triazole
MOA- inhibition of 14 alpha-demethylase whihc converts lonosterol to erogosterol= disruption in cell membrane synthesis; block steriod synthesis in humans
systemic invasive fungal infections
Prodrug- isavuconazonium (372 mg= 200 of isavuconazole)
CYP INTERACTIONS 3A4 CONTRAINDICATED in inhibition and inducer
Indication- invasive aspergillius, mucormycosis NO Candidis
Newer- less hormonal inhibitoon, broader spectrum, less toxic, better tissue distribution
HALF LIFE- 130 hours
ADR- GI, Hypokalemia, elevated LFTs, HA
Monitor- LFT
Nystatin
Polyenes
MOA- Bind with sterols in the fungal cell memebrane (prinically ergosterol. leads to cell contents to leak out and ultimately cell death
Indication- Candidia
Minimal systemic absorption- almost entirely excreted in feces unchanged
Too toxic for systemic administration
Oropharyngeal candidiasis- retaini mouth for as long as possible
Intestinal candidiasis
also administed topically
Amphotericin deoxycholate- AmB-d
Polyenes
MOA- Bind with sterols in the fungal cell memebrane (prinically ergosterol. leads to cell contents to leak out and ultimately cell death
Indication- most candida spp and aspergiluss, most fungus except fusarium spp. and A. terreus LIFE THREATENING INFECTIONS
Amphoteric- soluable both basic and acid environment and insoluable in water
more then 90% protein bound
ADR- neprotoxic, infusion-replated reactions (premedicated with APAP or IBU, diphenhydramine w/wo steroid. Rigors- meperidine
Side effects- thromphlebitis (add Heparin), cadiac arrhythmia rash, decrease erthropoietin production and electrolyte derangement
Monitor- SCr, BUN, electrolyte, CBC, LFT
Amphotericin B lipid compex
Polyenes
MOA- Bind with sterols in the fungal cell memebrane (prinically ergosterol. leads to cell contents to leak out and ultimately cell death
Indication- most candida spp and aspergiluss, most fungus except fusarium spp. and A. terreus LIFE THREATENING INFECTIONS
Less nephrotoxic, less infusion related reactions
High Cmax and larger AUC
Higher tissue concentration
Hepatoxicity- increased alk phos and conjugated bili
Liposomal ampotericin
Caspofugins
Echinocandins
MOA- inhibit beta 1,3 synthase so beta 1,3 glucan in cell wall cannot be made
Indication- Invasive candidiasis, Empiric coverage for neutropenic fever, (fungicidal against most Candida spp, fungistatic against aspergillus
IV formulation only
Minumum CSF penetration
No renal adjustments
Well tolerated-low adverse eventd rates
CYP inducers reduce dose (increase dose)
Cycoporine may incrase AUC by 35%
Reduce tacrolimus levels by 20%
Micafungin
Echinocandins
MOA- inhibit beta 1,3 synthase so beta 1,3 glucan in cell wall cannot be made
Indication- Invasive candidiasis, Empiric coverage for neutropenic fever, (fungicidal against most Candida spp, fungistatic against aspergillus
IV formulation only
Increases concentration of sirolimus
Increases AUC and Cmas of nifedipine
Anidulafungin
Echinocandins
MOA- inhibit beta 1,3 synthase so beta 1,3 glucan in cell wall cannot be made
Indication- Invasive candidiasis, Empiric coverage for neutropenic fever, (fungicidal against most Candida spp, fungistatic against aspergillus
IV formulation only
Flucytosine
MOA- converted to 5- florouracil by suspectible fungi
Indication- candida spp (except krusei), cryptococcus neoformans, aspergillus
NOT USED AS MONOTHERAPY
Synergistic effecr AmB
administer with food to limit n/v
toxicity- n/v/d, bone marrow supression, enterocolitis, hepatotoxicity
monitor- CBC, SCr, LFT
DDI- avoid with other nephortoxic and bone marrow supressive drugs
