Antifungal agents Flashcards
fungal infections- Dermatophytes are restricted to what?
restricted to the keratinized layers of the integument
Treatment for fungal infections- Dermatophytes
Treatment is usually conservative with use of topical antifungal agents
- Clotrimazole
- Terbinafine
Nail infection (onychomychosis) TX
This usually requires systemic Tx for weeks to 6 months
- Itraconazole
- Terbinafine
Topical therapy can be ciclopirox
Fungal infections- Candida Tx
Topical Tx: Clotrimazole
can use nystatin for mucocandidiasis
If someone tried using clotrimazole or nystatin for their candida infections what medicine can they try?
Flucanozole via systemic (oral)
Describe the organisms for systemic fungal infections
Causative organism are inherently virulent and cause disease in HEALTHY humans
Tx for systemic fungal infectons?
Amphotericin B infusions
Some with a BLASTOMYCOSIS systemic fungal infection needs to be Tx with what?
Amphotericin B then Itraconazole then fluconazole.
Tx for coccidiodomycosis systemic fungal infection?
Amphotericin B then maintenance with fluconazole or itraconazole
Tx for cryptococcosis systemic fungal Tx
Amphotericin B plus fluconazole
Tx for histoplasmosis systemic fungal infection
Amphotericin B or itraconazole
Tx for disseminated candidiasis
Fluconazole
Tx for aspergillosis opportunistic systemic fungal infection?
Amphotericin B, casopfungin, itraconazole
Tx for pnuemocystis pneumonia?
TMP-SMX (bactrim)
Amphotericin B pharmokinetics
rapidly sequestered in tissues then slowly released
Amphotericin B adverse reactions
Nephrotoxicity-major dose limiting factor
Infusion related toxicities
Anemia
Liposomal preps may reduce renal and infusion toxicities
The lipid vehicle serves as Amphotericin B reservoir reducing non-specific binding to human cell membranes
is Nystatin absorbed by GI tract
no
What limits nystatin use?
Toxicity limits systemic use
What is Nystatin safe and effective for?
Safe and effective for topical tx of candidal infections
MOA of Fluconazole - Itraconazole
selective inhibition of fungal cytochrome P450 (static-Cidal)
Clinical use of Fluconazole?
Vaginal Candidiasis- if topical tx fails taken orally
Oropharyngeal and esophageal Candidiasis- systemic
Pharmacokinetics of fluconazole?
cleared primarily by the kidneys so renal dosing adjustment if impaired- has the least effect on liver compared to other azoles
Readily enters CNS
Pharmacokinetics of itraconazole
Eliminated by the hepatic metabolism
What are the imidazoles?
Ketoconazole
Clotrimazole
Miconazole
MOA of imidazoles?
inhibit P450-dependent enzyme (fungicidal)
Imidazoles clinical uses?
- there is a decline in systemic use of ketoconazole
- Chronic mucocutaneous candidiasis
- ORAL AND VAGINAL CANDIDIASIS (CLOTRIMAZOLE TOPICALLY)
Imidazoles pharmacokinetics
- only ketoconazole has been used systemically (oral and IV)
- Eliminated by hepatic metabolism (CYP450 oxidation)
- Excreted in breast milk
Ketoconazole (can be used systemically) which causes what adverse reactions
Hepatotoxicity- generally avoid if liver dysfunction
Remember this one: CAN INHIBIT MAMMALIAN TESTOSTERONE SYNTHESIS CAUSING DECREASED LIBIDO AND GYNECOMASTIA
Is terbinafine bactericidal or static
Its CIDAL
it inhibits squalene oxidase
What is the agent of choice for toe/finger nail infections caused by onychomycosis?
Terbinafine- its a once daily oral dose
Available TOPICALLY for ATHLETES FOOT
What are the adverse reactions of Terbinafine?
Inhibition of CYP450 drug metabolism
