-
Antifungal 3 main MOA
- 1. alter cell membrane permeability
- 2. block nucleic acid synthesis
- 3. disrupt microtubule function
-
Antifungals that effect cell wall permeability (4)
- 1. Azoles
- 2. Allylamines
- 3. Polyenes
- 4. Glucan synthesis inhibitor
-
Antifungals that block nucleic acid synthesis (1)
pyrimidine analogs
-
Antifungals that disrupt microtubule function
Griseofulvin
-
Azoles
A. Imidazoles (3)
B. Triazoles (4)
- A.
- 1. ketoconazole
- 2. miconazole (topical)
- 3. clotrimazole(topical)
- B.
- 1. Itraconazole
- 2. fluconazole
- 3. voriconazole
- 4. Posiconazole
-
Fluconazole
- -only azole drug to penetrate CNS
- -IV & PO
-used for candida infections and cryptococcal meningitis
-150mg stat dose for vulvovaginal candidiasis
-
Ketoconazole
- PO, Topical
- for mucocutaneous candidiasis, seborhea, tinea versicolor, tinea skin infections
- less selective for fungal CYP P450 so AE and DI (drug interactions)
- hepatotoxicity (monitor LFTs)
- GI side effects ARE COMMON
-endocrine effects
-
Itraconazole
-IV, PO
-is most potent with widest spectrum
-for onychomycosis, tx of endemic histoplasmosis and blastomycosis
-watch DI
-AE: GI, edema, rash, hepatotoxicity, so mointor LFTs
-
Voriconazole (Vfend)
- new Triazole agent
- for invasive aspergillosis, candidemia, esophageal candidiasis
AE: well tolerated; occasional elevated LFTs, rash, visual disturbances
DI: metabolized by CYT P450 so many drug interactions
-
Posiconazole
Newest Azole
Oral Triazole for IC (Immunocompromised) pts w/ aspergillus and candida prophylaxis for severe IC pts
AE: N/V and liver dmg
-
Topical azoles (3)
- 1. Clotrimazole
- 2. Miconazole
- -both for vulvovaginal candidiasis, tinea infections
3. ketoconazole cream, shampoo for tinea skin infections and seborrhea
-
Caspofungin acetate
-new glucan inhibitor
-MOA: inhibits beta 1,3 D-glucan in fungal cell wall
-IV for REFRACTORY invasive aspergillosis infections
- AE:
- -allergic rxns with feve, flushing, GI effects
- -infusion vein inflammation (phlebitis)
-
Anidulafungin (Eraxis)
- -IV
- -for severe esophageal candidiasis (2nd to fluconazole), candidemia, and other Candidida
- AE:
- -diarrhea
- -hypokalemia
- -evelated ALT
-
Micafungin (Mycamine)
-IV for Candida prophylaxis in pts undergoing stem cell transplant
-2nd for esophageal candidiasis
-
Amphotericin B
- -Polyene antibiotic
- broadest spectrum antifungal
- -drug choice for life threatening fungal infections
MOA: binds to ergosterol in fingal membrane and alters permability
Toxicity: ampho "terrible" infusion related; fever, chills, muscle spasms, HA, hypotension; Slower toxicities: renal dmg common
-
Nystatin
- -Polyene antibiotic
- -mostly used for topical application
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