Exam 2: Anti Fungals Flashcards
- Therapeutic Use: antifungal; Imidazole–>(Clotrimazole and Miconazole)
- MOA: inhibit P450–>impairs ergosterol synthesis–>impairs fungal membrane formation.
- AE: Many (i.e., NV, photophobia, hepatic toxicity and necrosis)
- Drug interactions: inhibits CYP3A4; absorption reduced by drugs that decrease gastric activity.
- Notes: Selective activity due to difference in membrane steroids. Can be used as an antagonist to steroids.
Ketoconazole (nizoral)
- Therapeutic Use: Triazole antifungal against most Candida but not molds.
- MOA: inhibit P450–>impairs ergosterol synthesis–>impaired fungal membrane formation.
- AE: Stevens-Johnson, GI distress, HA
- Drug interactions: Strong inhibitor of CYP2C9 and 2C19. Prolongs QT interval.
- Notes: lowest affinity for mammalian P450. Good water solubility and PENETRATES CSF.
Fluconazole (diflucan)
- Therapeutic Use: Broad triazole antifungal
- MOA: inhibit P450–>impairs ergosterol synthesis–>impaired fungal membrane formation.
- AE: CHF, GI distress, Stevens-Johnson, peripheral neuropathy, hepatotoxicity
- Drug interactions: Inhibits CYP3A4. Absorption reduced by drugs that decrease gastric activity (antacids, PPI’s, H2-receptro antagonists).
- Notes: Don’t give to pt with a heart condition.
Itraconazole (spronox)
- Therapeutic Use: Broad triazole antifungal.
- MOA: inhibit P450–>impairs ergosterol synthesis–>impaired fungal membrane formation.
- AE: visual disturbances, rash, Stevens-Johnson, anaphylaxis
- Drug interactions: inhibits CYP2C19, CYP2C9, and CYP3A4.
- Notes: Superior to amphotericin for invasive asperigillos.
Voriconazole (Vfend)
- Therapeutic Use: Broad triazole antifungal. Increased with Absidia spp.
- MOA: inhibit P450–>impairs ergosterol synthesis–>impaired fungal membrane formation.
- AE: HA, hepatotoxicity, GI distress, arrhythmias, anaphylaxis
- Drug interactions: Inhibits CYP3A4, prolongs QT interval. Absorption reduced with drugs that decrease gastric acidity.
- Notes: 2X activity to itraconazole. Oral admin taken with meals.
Posoconazole (Noxafil)
• Therapeutic Use: Broad spectrum systemic fungicidal (life-threatening infections)
• MOA: binds to ergosterol to disrupt membrane integrity (No effect on synthesis)
• AE:
o Deoxycholate: cytokine release, nephrotoxicity is dose limiting. Premedicate with other drugs.
o Lipid formulations: less severe reactions, reduces nephrotoxicity.
Ampho B lipid complex: ribbon-like sheets, less nephrotoxic
Ampho B cholesteryl complex: disk chaped colloid dispersion, nephrotoxicity is dose limiting.
Liposomal ampho B: Unilammellar vesicle (infusion rxns least severe)
• Drug interactions:
• Notes: insoluble in water (bile salts help); lipid products less nephrotoxic. Not given orally. Drug is from Streptomyces nodoses. Long t1/2 (15d) This is the OH SHIT DRUG! Concentrates in liver and spleen
Amphoteracin B (Fungizone)
• Therapeutic Use: Cryptococcus neoformans, Candida spp, Chromoblastomycosis
• MOA: converted to 5-fluorouracil to inhibit DNA and RNA synthesis. Can penetrate the BBB. Admin orally. Vd = total body water.
• AE: Dose related bone marrow toxicity.
• Drug interactions:
• Notes: Activity based on cytosine permease uptake and activation dependent on cytosine deaminase.
o Used in combo with ampho B for cryptococcus meningitis or systemic candidiasis.
Flucytosine (ancoban)
- Therapeutic Use: Candida and Aspergillus spp.
- MOA: inhibits synthesis of B (1,3)-D-Glucan cell wall becomes permeable.
- AE: Same as other antifungals, Teratogenic
- Drug interactions: No interaction with P450 and no clinically significant drug interactions
- Notes: Selectivity based on absence of mammalian cell wall. Admin IV. Binds albumin
Caspofungin, anidulafungin, micafungin
- Therapeutic Use: fungistatic for mucocutaneous (skin, nail, hair) infection (dermatophytes).
- MOA: Antimitotic (M-phase)
- AE: Teratogenic, HA, NV
- Drug interactions: induces hepatic P450 isoforms.
- Notes: Keratophilic=binds keratin and protects skin and nails from further infection
griseofulvin
- Therapeutic Use: Fungicidal to Mucocutaneous infections
- MOA: inhibits squalene epoxidaseblocking ergosterol synthesisimpaired cell membrane synthesis.
- AE: Teratogenic, hepatotoxicity
- Drug interactions: Does not affect P450 isoforms
- Notes: High 1st pass effect; highly lipophilic, Long t1/2 = 200-400 hrs. Keratophilic. Maftifine was original. Very effective against dermatophytes. Don’t use with occlusive dressings.
Terbinafine (Lamisil)
