Antifungals Flashcards
Amphotericin B
MOA
* Binds ergosterol
* Pore formation in fungal membranes
* Leakage of electrolytes & lysis of the fungal cell
Uses
* Treating systemic fungal infections
Adverse effects:
Acute
* IV phlebitis =local vein inflammation after infusion
* Fever & chills
* Hypotension
Chronic
* Anemia
* Nephrotoxicity – tubular necrosis, decrease in GFR, increase in BUN/creatinine (hydration is key)
* Electrolyte imbalances – hypokalemia & hypomagnesemia
NB
* Liposomal amphotericin B has fewer side effects
Nystatin
MOA
* Binds ergosterol
* Pore formation in fungal membranes
* Leakage of electrolytes & lysis of the fungal cell
Clinical Use
* Topical use only
* Candidiasis – swish/swallow for roal thrush & topical for diaper rash or vaginal candidiasis
Lab Settings
* Used in Thayer-Martin media to inhibit yeast growth and isolate Neisseria
Adverse effects:
* Skin irritation
* Hypersensitivity
Flucytosine
Inhibits fungal DNA & RNA synthesis.
MOA
* Is converted into 5-FU by cytosine deaminase
* 5-FU analog inhibits DNA/RNA Polymerase
* Renal clearance
Cryptococcal meninigitis
* Combo: Flucytosine + Amphotericin B
Adverse effects
* Bone marrow suppression – sometimes used as chemotherapy w/ similar effects on one marrow
* Anemia, thrombocytopenia, leukopenia
* Nephrotoxocity – cases of concomitant Amphotericin B use
* Hepatotoxicity – check liver enzymes
* N/V
Azoles
Inhibits fungal ergosterol synthesis.
MOA
* Inhibit 14-a-demethylase (CYP-450 enzyme) which converts Lanosterol to Ergosterol
* Result: inhibited formation of the fungal cell membrane
Uses
* Local and less serious mycoses
Adverse effects
* Anti-androgen – inhibits testosterone synthesis, gynecomastia (especially ketoconazole)
* Hepatotoxicity – check liver enzymes
* GI upset
* Inhibition of CYP450 enzymes – drug interactions (theophylline, warfarin)
Terbinafine
Inhibits fungal ergosterol synthesis.
MOA
* Inhibits fungal squalene epoxidase which inhibits the synthesis of cell membrane precursor Lanosterol
* Result: fungal cell death
* Excreted via liver metabolism
Uses – Tinea
* Dermatophytosis tinea pedis (athlete’s foot) & tinea cruris (jock itch) – topical form
* Onychomycosis – oral form
Adverse effects
* GI upset
* Loss of taste
* Headaches
* Hepatotoxicity – abnormal LFTs
Echinocandins
The Fungins.
- Caspofungin
- Micafungin
MOA
* Inhibit fungal beta-glucan synthesis (tight cross links for cell wall synthesis)
* Excreted via liver metabolism
Uses
* Candida – severe disseminated infection
* Invasive Aspergillus infections
Adverse effects
* Hepatotoxicity – abnormal LFTs
Griseofulvin
MOA
* Disrupts microtubules – inhibiting mitosis in fungi
* Deposits in nails and other keratin-contaning tissues
*
Uses
* Oral treatment of superficial fungal infections
* Tinea (dermatophytes)–onychomycosis
Adverse effects
* Induces CYP450 enzymes – drug interactions w/ Theophylline, Warfarin
* Teratogen – contraindicated in all pregnant women
* Photosensitive rash
* Disulfiram-like reaction to alcohol
Clinical implications of hypomagnesemia:
- Related to kidney injury
- Can cause arrhythmias
- muscle spasms & cramps
Clinical implications of hypokalemia:
- Related to kidney injury
- Fatigue & muscle cramps
- ECG: prolonged QT-interval & deadly arrhythmias
List of Azoles
Fluconazole
* Cryptococcal meninigitis in AIDS (maintenance)
* Candida
Itraconazole
* Blastomyces
* Coccidioides
* Histoplasma
* Sporothrix schenckii
Voriconazole
* Aspergillus
Clotrimazole/Miconazole
* Topical fungal infections
Ketoconazole
Ketoconazole has what weird side effect, that is sometimes exploited in the endocrine clinic?
Anti-androgenic effects & gynecomastia
What 2 side effects are Azoles (as a class overall) associated with?
- GI upset
- Liver toxicity
