Antifungals Flashcards
How is Amphotericin B administered?
IV
What is the MOA for Amphotericin B?
Interaction with ergosterol of fungal membrane, resulting in loss of intracellular components, depolarization, and pore formation
Fungicidal
What are the uses of Amphotericin B?
DOC:
Most systemic antifungal infections
What are the infusion related/immediate toxicities of Amphotericin B?
- Chills, fever, muscle spasms, V, HA (slow infusion rate/decrease dose)
What are the cumulative toxicities of Amphotericin B?
- Nephrotoxicity (excreted slowly; can lead to irreversible damage)
- Azotemia - BUN/creatinine elevated
- Jaundice, anorexia, weight loss, hypokalemia
- Hypersensitivity
What is the MOA of Flucytosine?
Converted to 5-fluorouracil which interferes with fungal DNA/RNA synthesis
What are the uses of Flucytosine?
Cryptococcus (+ amphotericin B)
What are the toxicities of Flucytosine?
- Bone marrow depression
- May elevated ALT, AST
- GI disturbances
- Renal toxicity if pt has renal impairment due to renal excretion of drug
What is the DOC for most systemic antifungal infections?
Amphotericin B
What is the DOC for Cryptococcus infections?
Flucytosine + Amphotericin B
How is Ketoconazole administered?
Oral, shampoo, cream
What is the MOA for the “azoles”?
Inhibits synthesis of ergosterol leading to increased membrane permeability and inhibition of fungal growth
What are the uses for Ketoconazole?
Broad spectrum and tried as a substitute for Amphotericin B
What are toxicities of Ketoconazole?
- Potent inhibitor of P450 = drug interactions
- Gynecomastia and impotence due to inhibition of adrenal/testicular function
- Prolonged QT
What are contraindications to Ketoconazole?
Acute or chronic hepatic disease as extensively metabolized before elimination
How is Fluconazole administered?
Oral or IV
What is significant about the penetration of Fluconazole?
Has good CNS penetration
What are the uses for Fluconazole?
DOC:
Crytococcal meningitis for suppressive and/or prophylactic therapy in HIV+ patients
- Candida
What are the toxicities of Fluconazole?
- Potent inhibitor of CYP2C9
- Headache
- Less toxic than amphotericin B or flucytosine and better tolerated than ketoconazole
- Less drug interactions than other azoles
How is Voriconazole administered?
Oral or IV
What is significant about the penetration of Voriconazole?
Modest CSF penetration
What are the uses of Voriconazole?
DOC:
Aspergillus (+ amphotericin B)
Esophageal candidiasis
What are the toxicities of Voriconazole?
Drug interactions:
- Metabolized by P450s
- Inhibits P450s
- Genetic polymorphism: CYP2C19
- Visual impairment (reversible)
What is the DOC for Crytococcal meningitis for suppressive and/or prophylactic therapy in HIV+ patients?
Fluconazole
What is the DOC for Aspergillus?
Voriconazole + Amphotericin B
How is Itraconazole administered?
Oral or IM
What are the uses of Itraconazole?
Active against many of the same fungi as ketoconazole and fluconazole, but greater against Aspergillus
Dermatophytes
Onychomycosis
What are the toxicities of Itraconazole?
- Potent inhibitor of CYP3A4 – drug interactions
- GI effects
How is Isavuconazonium administered?
Oral and IV
What are the uses for Isavuconazonium?
Indicated for treatment of mucormycosis and invasive aspergillosis
What are the toxicities of Isavuconazonium?
- Nephrotoxicity
- Short QTc interval (dose dependent)
- Drug interactions – both substrate and moderate inhibitor of CYP3A4
When is Isavuconazonium contraindicated?
In patients with familial short QT syndrome
How is Posaconazole administered?
Oral and IV
What are the uses of Posaconazole?
- Aspergillus
- Candida
What are the toxicities of Posaconazole?
- Drug interactions – both substrate and moderate inhibitor of CYP3A4
- GI effects
- Stomatitis, vaginal bleeding
- Hypokalemia, thrombocytopenia
How is Caspofungin administered?
IV, slow infusion
What is the MOA for Caspofungin?
Inhibits synthesis of major cell wall component, Beta (1,3)-D-glucan, which is not present in mammalian cells
What are the uses of Caspofungin?
Invasive Aspergillosis in refractory patients (azole or ampho B resistant fungi)
Esophageal candidiasis
What are the toxicities of Caspofungin?
Increased liver enzymes, histamine release, headache, chills, GI
How is Griseofulvin administered?
Oral
What is the MOA for Griseofulvin?
Binds to microtubules of keratin and destroys spindles
Fungistatic – prevents new skin infection
What is the DOC for Onychomycosis?
Griseofulvin
What are the toxicities of Griseofulvin?
- Headache, GI, other CNS effects
- Disulfiram-like effects
- Hematological, skin rashes, photosensitivity, albuminuria, hepatotoxicity
What are contraindications for Griseofulvin?
- Acute intermittent porphyria
- Hepatocellular failure
- Pregnancy
- Men 6 months prior to fathering child
How is Terbinafine administered?
Oral or topical
What is the MOA for Terbinafine?
Interferes with sterol biosynthesis; inhibits squalene which builds up and is toxic to fungi
Fungicidal
What are the uses of Terbinafine?
Onychomycosis
How is Nystatin administered?
Oral - GI candida
Topical - other
What are the uses for Nystatin?
Candidal infection
What are the uses for Efinaconzaole (Jublia)?
Onychomycosis of toenails caused by Trichophyton rubrum and mentagrophytes
What are the uses for Naftifine and Tolnaftate?
- Athlete’s foot
- Jock itch
What are the uses for Tioconazole, Clotrimazole, and Miconazole (topical azoles)
Skin and vaginal candidiasis
Tinea
What is the DOC for Aspergillus in azole or Ampho B resistant fungi?
Caspofungin
