What antifungals target membrane function?
What drugs target ergosterol synthesis?
What drugs target nucleic acid synthesis?
What drugs target cell wall synthesis?
What are the options to treat superficial dermatophyte infections?
- Azoles - Either Triazoles or imidazoles
What are the options to treat superficial Candida infections?
- Azoles - Triazoles or Imidazoles
What are the options to treat deep fungal infections?
Triazoles or Amphotericin B
What are the two drugs that are generally used to treat Candida? Dermatophytes?
- Candida - Polyenes, Azoles
- Dermatophytes - Allylamines, Azoles
MOA of imidazoles and allylamines?
- Inhibit ergosterol synthesis by blocking lanosterol demethylase
Spectrum of imidazoles and allylamines?
- imidazoles - broad - candida and dermatophytes
- Allylamines - narrow - eradicate only dermatophytes
What are the topically applied cell wall synthesis inhibitors?
- imidazoles - clotrimazole
- Allylamines - tolnaftate
What are the systemically administered cell wall synthesis inhbitors?
- Triazoles - fluconazole
- Allylamines - Terbinafine
Spectrum of triazoles as systemically administered drugs?
Broad spectrum - eradicate fungi causing deep mycoses and dermatophytes
Spectrum of allylamines as systemically administered drugs?
Used systemically for nail infections (fungi causing onchomycosis)
Why is clotrimazole limited to topical application?
Due to toxicity
What are the adverse effects of both triazoles and allylamines when used systemically?
- Rarely hepatotoxicity
- Drug interactions thru inhibition of CYP isoforms
What drug is used for azole-resistant candida and aspergillus?
What is the MOA of caspofunginin?
It inhibits the glucan synthase complex which is responsible for fungal cell wall synth in the plasma membrane
What is caspofungin reserved for?
Life-threatening fungal infections unresponsive to older agents (candida/aspergillus)
What is the mechanism of the polyenes?
Pores formed in the fungal cell membrane allowing leakage of K+ and Mg++
What are the polyenes and their particular route of administration?
- Nystatin - limited to topical use
- Amphotericin B - systemically
For what infectious agent is nystatin used?
Only efficacious against candidiasis. Not dermatophytes
For what type of infection is amphotericin B used? Tx strategy of deep mycoses in IC patients?
Life-threatening deep mycoses
- Amphotericin B
Acute and chronic toxicities of amphotericin B
- Acute - (During IV infusion) -> Fever/chills, potential for hypotension
- Chronic - fall in Cr clearance, Mg and K wasting, renal tubular acidosis, bone marrow: normocytic anemia
Patient in DKA with elevated blood sugar. Likely Dx? Tx?
Mucormycosis (bad mammajamma); Amphotericin B
What is the MOA of flucytosine?
Cytosine deaminase (in fungi) eventually gets converted into 5-FdUMP which inhibits fungal thymidylate synthase
SEs of flucytosine?
Sloughing of GI mucosa, centrolobular hepatitis and BM cytopenia