Antifungal Flashcards
What are the 3 most common systemic fungal infection in humans?
- Candidiasis
- Cryptococcosis
- Aspergillosis
What are the systemic drugs for subcutaneous and systemic mycoses?
- Amphotericin B
- Flucytosine
- Azoles
- Echinocandins
Amphotericin B MOA, Uses, AE
MOA: binds to ergosterol forming pores to allow leakage of intracellular ions and macromolecules > cell death
Uses: broad spectrum and fungicidal action; often uses as initial induction to reduce fungal burden follow by an azole; DOC deep fungal infections in pregnancy
AE: nearly universal fever, chills, muscle spasms, vomiting, HA, hypotension; can bind to cholesterol leading to renal toxicity (tubular acidosis) with severe magnesium and potassium wasting so is administered with saline infusion; alter LFTs, hypocromic normocytic anemia; seizures
Should monitor LFTSm, serum electrolytes, blood counts, and hemoglobin
What are the lipid formulations of amphotericin B and why are they used?
- Liposomal amphotericin B (L-AMB)
- Amphotericin B lipid complex (ABLC)
- Amphotericin B colloidal dispersion (ABCD)
Reduces nephrotoxicity
Flucytosine MOA
MOA: synthetic pyrimidine antimetabolite used by fungal enzyme cytosine permease which then inhibits thymidylate synthetase thus blocking synthesis of dTMP; also 5-FUTP inhibits protein synthesis
Uses: only for serious infections causes by susceptible strains of Candida and/or Cryptococcus; used synergistically with amphotericin B to prevent resistance
AE: bone marrow toxicity; result from metabolism to 5-fluorouracil
What are the Azoles, MOA, and AE?
Imadazoles
- Ketoconazole
- Miconazole
- Clotrimazole
Triazoles
- Itraconazole
- Fluconazole
- Voriconazole
- Posaconazole
MOA: inhibit fungal cytochrome P450 enzyme 14-alpha-sterol demethylase with triazoles being more specific than imadazole
AE: minor GI upset
Ketoconazole uses, AE, DI
Uses: superficial mycoses; rarely used for systemic mycoses because of AE and narrow specturm
AE: decrease plasma testosterone, gynecomastia, decreased libido, loss of potency in men, menstrual irregularities in women; high concentration may inhibit andrenal steroid synthesis and decrease plasma cortisol
DI: strong inhibitor of CYP3A4 so can potentiate warfarin and cyclosporin; best absorbed with antiacid/H2 blocker/PPI
Fluconazole uses, DI
Uses: DOC esophageal/oropharyngeal/vulvovaginal/urinary candidiasis, DOC candidemia, DOC coccidioidmycosis; DOC for maintenancd therapy for cryptococcal meningitis after amphotericin B, DOC initial and secondary prophylacis for cryptococcal meningitis, alternative to amphotericin B for non-severe cryptococcal meningitis; Good CSF penetration
DI: inhibitor of CYP3A4; inhibitor of CYP2C9 (can increase phenytoin, zidovudine, warfarin)
Itraconazole uses, AE,
Uses: dimorphic fungi Blastomyces, Sporothrix, Histoplasma; dermatophytoses and onychomycosis
DI: strong inhibitor of CYP3A4 can cause fatal arrhythmias when concurrently with cisapride or quinidine; absorption reduced by antacids/H2 blockers/PPIs
Voriconazole uses, DI
Uses: DOC for invasive aspergillosis
DI: inhibits CYP2C19, CYP2C9, CYP3A4
Posaconazole uses, DI
Uses: Zygomycetes such as Mucor
DI: inhibits CYP3A4
What is the Echinocandins MOA, uses?
Caspofungin
MOA: inhibits synthesis of beta(1-3)-D-glucans in fungal cell wall
Uses: Candida and aspergillus
What are the systemic drugs for superficial mycoses?
- Griseofulvin
- Terbinafine
- Ketoconazole
- Fluconazole
- Itraconazole
Griseofulvin MOA, uses, DI
MOA: disrupts mitotic spindles and inhbits mitosis
Uses: severe dermatophytoses of skin, hair, and nails
DI: induces P450 enzymes
Terbinafine MOA, Uses, AE, DI
MOA: inhibition of squalene epoxidase and accumulation of toxic levels of squalene
Uses: Onychomycosis
AE: GI upset, rash, HA, taste disturbances, elevation in serum liver transaminases
DI: inhibit CYP2D6
