Lecture 24: Antifungal Agents Flashcards
What are the most commonly used classes of antifungals in vetmed
- Polyenes
- Azoles
What are the therapeutic challenges with anti-fungal treatments
- Rigid fungal cell wall with chitin and polysaccharides
- Cell membrane contains sterols such as ergosterol which influences efficacy and resistance to drugs
- Infections located inside host cells
- Discontinuing treatment after signs resolved but infection not eradicated
- Fungistatic- rely on host immune response to clear
- Longer treatment= host toxicity
What is the mechanism of action of polyene antifungals
Interaction with sterol of fungal membrane, ergosterol that results in loss of intracellular components—> pore forming
What are the 3 polyene antifungals
- Amphotericin B
- Nystatin
- Natamycin
Is amphotericin B broad or narrow spectrum? Fungicidal or fungistatic
Broad spectrum, fungicidal
What organisms ins amphotericin B effective against
Aspergillus, blastomyces, coccidiosis, cryptococcus, histoplasma
What are the uses for amphotericin B
- Systemic fungal infections and fungal keratitis in dogs, cats, horses, rabbits, reptiles and birds
- Combined therapy with
- ketoconzole, fluconazole or itraconazole to reduce toxicity
- flucytosine for CNS, bone or ocular infections
T or F: amphotericin B distributes to CNS, eye and bone
False
Amphotericin B is excreted slowly by the ___, therefore ___
Kidney, Nephrotoxic
What are some adverse effects of amphotericin B
- Renal toxicity- produces renal vasoconstriction, decrease GFR
What antifungal should only be considered for progressive or potentially fatal fungal infections due to severe renal toxicity
Amphotericin B
Weekly monitoring of renal function is required with what antifungal
Amphotericin B
What species has lack of Nephrotoxicity with amphotericin B due to shorter t1/2
Birds
What are some therapeutic uses for nystatin and natamycin
Fungicidal to yeast infections caused by Candida spp and Malassezia spp
How are nystatin and natamycin administered
- Topically for yeast infections of eye, ear and skin
- Orally for treating mucosal heart infections of mouth and GI tract
What are some therapeutic uses for nystatin
- Feed additive in poultry to prevent crop mycosis and mycotoxins diarrhea
- Administered orally for oral or GI candida infections in dogs, cats, horses, reptiles and birds
T or F: nystatin can be used alone when applied topically
False
What are some therapeutic uses for natamycin
- Ocular mycotoxins infections
- Drug of choice for equine fungal keratitis caused by Fusarium
What is the mechanism of action of azoles
Inhibits synthesis of ergosterol leads to depletion of ergosterol in the cell membrane and accumulation of toxic intermediate sterols causing increase membrane permeability and inhibition of fungal growth
Are azoles fungistatic or fungicidal and what pathogens do they tx
Fungistatic against infections such as Blastomyces, Coccidiodes, cryptococcus and histoplasma
Which azoles have excellent CNS penetration
Fluoconazole and voriconazole
What is ketoconazole used for
- Dogs cats, horses, reptiles and birds for systemic mycoses and severe yeast infections
Is ketoconazole broad or narrow spectrum
Broad