Antifungal Drugs Flashcards
Drug Classifications (3)
systemic
systemic for mucocutaneous
topical
Antifungal drug targets (3)
- cell membrane (amphotericin B, nystatin, azoles, allylamines)
- cell wall (ß-1,3-glucoside) (echinocandins)
- DNA synthesis (flucytosine)
Amphotericin B (structure, mechanism)
- macrolide amphipathic structure
- binds ergosterol (via mycosamine sugar), creating ion leak pores in membrane
- broad spectrum antifungal
Amphotericin B clinical use (spectrum, resistance, type of infection treated)
- broad spectrum (yeast: candida + cryptococcus, endemic fungi: blastomyces, histoplasma, coccidiodes, molds: Aspergillus + Mucor
- resistance: intrinsic among some, or develop with modified ergosterol binding
- drug of choice for life-threatening systemic fungal infection, mycotic keratitis, fungal arthritis
Amphotericin B pharmacokinetics (solubility, administration method, half life, CSF distribution, renal dysfunction, side effects, drug interactions)
- water insoluble
- given via IV
- 1/2 life of 16 days
- Systemic distribution except CSF
- no renal dysfunction (since eliminated so slow, cant overload kidney)
- side effects: fever, chills, headaches, vomiting, nausea (treat by decreasing dose/pretreat with antipyretics). Later toxicities are renal, anemia, liver damage.
- drug interactions with other nephrotoxic drugs
Flucytosine (drug class, mechanism, administration, 1/2 life, systemic distribution, synergy, spectrum, toxic effects, drug interactions)
antifungal targets DNA synthesis
- mechanism: uptaken by cytosine permease, –>5FU by cytosine deaminase, –>FUPT/FdUMP which inhibit DNA/RNA synthesis
- given orally
- 1/2 life 3-6 hours via kidney
- systemic distribution including CSF
- synergy with amphotericin B, itroconazole
- limited spectrum: candida, cryptococcus
- Toxicities: decrease bone marrow (leukopenia/cytopenia), rash, GI (due to effect on GI bacteria)
- Drug interactions: bone marrow suppressing drugs
Antifungal Azoles (categories, specific within each, mechanism)
Imidazoles and triazoles
- imidazoles: KCM (ketoconazole, clotrimazole, miconazole)
- triazoles: IVF (itraconazole, fluconazole, voriconazole)
- mechanism: inhibit ergosterol synthesis by Erg11 inhibition, also causing toxic byproducts that inhibit these enzymes
Azoles pharmacokinetics (side effects, spectrum, drug interactions, administration, 1/2 life, distribution, toxicity)
side effects: GI distress, drug induced hepatitis (from liver enzyme abnormality)
Spectrum: broad spectrum, especially for amphotericin-resistant stuff
Drug interactions: anything else processed via CYP/P450 (warfarin, cyclosporine, buspirone
-Administration: oral, better with food/gastric acid
-drug interaction: H2/proton pump blockers (since decrease gastric acid), p450 drugs
-1/2 life 30-40 hours, metabolized by CYP3A4
-Distribution: systemic, not CSF
-Toxicity: GI, teratogenic
Imidazoles (drugs, specific uses)
KCM. Ketoconazole replaced by triazoles, miconazole/clotrimazole used topically
Fluconazole
Better distribution>KCM and Itraconazole, plus CSF distribution
Echinocandins
- systemic antifungal, water-soluble derivative of pneumocandin B
- include caspofungin, micafungin, anidulafungin
- mechanism: inhibit ß-1,3-glucan synthase, weakening cell wall
- spectrum: Candida, invasive aspergillus
- Side effects: fever, nausea, flushing, vomiting
Systemic fungal infection drugs (4)
Amphotericin B, Azoles, Echinocandins (caspofungin), flucytosine
Mucocutaneous antifungal drugs (1) - (drug, mechanism, synergy)
Terbanifine
- Inhibit squaline epoxidase (erg1) to prevent ergosterol synthesis. Accumulates in mucocutaneous areas
- synergeistic with triazoles
Topical antifungals (drugs (3), specific uses)
Nystatin: amphotericin derivative, same mechanism -used for topical candida Terbanifine -used for dermatophyte tinea Clotrimazole/micanazole -oral/vaginal candidia, dermatophyte
