176. Antifungal Therapy Flashcards
What are some negative aspects of antifungal therapy?
Antifungal drugs are costly, require long-term administration, and have relatively high toxicity rates
Which anti fungal is considered as the gold standard?
Amphotericin B is produced by the microorganism Streptomyces nodosus and is considered the gold standard for antifungal therapy.
What is the route of administration of Amphotericin B and why?
Parenteral as GI absorption is poor. Protein-bound, redistributed from the blood to tissues
How does it work?
AMB binds to ergosterol in fungal cell membranes, increasing membrane permeability to cause cell death.
What is the main toxicity and what’s its MOA?
Nephrotoxicity. The drug binds to cholesterol in the proximal tubular cells causing renal vasoconstriction and renal tubular acidosis
How is it administered to reduce nephrotoxicity?
To reduce nephrotoxicity, AMB is most commonly infused in 5% dextrose and administered intravenously over 1 to 5 hours.
How does azole group work against fungi?
The azole antifungal drugs inhibit lanosterol 14α-demethylase, the fungal P-450 enzyme necessary for development of ergosterol in fungal cell walls.
What anti fungal are included in the azole group and give some examples of each
triazoles (e.g., itraconazole, fluconazole, voriconazole, posaconazole) and imidazoles (e.g., ketoconazole, clotrimazole, enilconazole, miconazole)
Which one has an higher effect on mammalian sterol synthesis?
The imidazoles have more endocrine adverse effects and greater effects on mammalian sterol synthesis.
In general, the triazoles have less effect on mammalian sterol synthesis and longer elimination times.
What is the administration route of azole?
Orally, recommended with food, acidic pH better (less absorption when used with meds which decrease pH of stomach)
Azole distribute well in most tissues except?
CNS and urine
Which agent is best to use in case of bastomycosis?
Azole: itraconazole, AMB (parenteral only and risk of nephrotoxicity) or fluconazole
Which agent is best to use in case of histoplasmosis?
Azole: itraconazole (GI absorption variable in healthy cats).
Treatment should be continued for at least 60 days, or until 1 month following resolution of clinical signs. Treatment for 6–8 months is common.
Which agent is best to use in case of Coccidioidomycosis?
Difficult to cure, requiring lifelong therapy. Azole antibiotics and AMB. Early initiation of therapy in primary respiratory coccidioidomycosis may be appropriate because dissemination is possible. Generally, treatment should continue for 3 to 6 months beyond resolution of clinical signs.
Which agent is best to use in case of cryptococcosis?
Fluconazole has become the drug of choice for cryptococcosis in cats because of its combination of efficacy and safety compared with other treatment regimens.
