Antifungals Flashcards
Indications:
■ Blastomyces dermatitidis
■ Histoplasma capsulatum
■ Coccidioides immitis
■ Cryptococcus neoformans
■ Candida spp.
■ Aspergillus (may have resistance/high MIC)
■ Leishmania
Mechanism of Action:
■ Fungistatic
■ Steroid (primarily ergosterol) binding in cell membrane
■ Altered permeability leading to leakage of K and other cellular
constituents
Pharmacokinetics:
■ Poor GI absorption (IV or SC administration)
■ Highly protein-bound (>90%)
■ Does not penetrate well to CNS, bone, joints, pancreas, muscle, etc.
○ Adverse Effects:
■ AKI (common)
■ Vomiting
■ Tremor
■ Pyrexia
■ Anorexia
■ Calcinosis cutis
■ CK elevations
Comments:
■ Liposomal formulation is more selective and less toxic
■ Different formulations: deoxycholate, lipid complex, cholesteryl sulfate
Indications:
■ Yeast, systemic fungi, dermatophytes
○ Mechanism of Action:
■ CYP450 inhibition
■ Inhibition of ergosterol formation
■ Weakens fungal cell membrane
Pharmacokinetics:
■ Good PO absorption but variable bioavailability
■ Acidic environment enhances absorption
■ Variable tissue distribution
Adverse Effects:
■ GI issues
■ Hepatotoxicity
■ Altered metabolism of other drugs
Comments:
■ Hepatotoxicity more common in cats
■ Not usually used in cats
Indications:
■ Systemic and cutaneous mycosis
Mechanism of Action:
■ Similar to other azoles
○ Pharmacokinetics:
■ Bioavailability influenced by pH and food
■ High protein binding, very lipophilic
■ Many drug interactions
Adverse Effects:
■ Idiosyncratic hepatotoxicity in cats
■ Hepatopathy in 10% of dogs
■ Vasculitis, skin lesions, thrombocytopenia
○ Comments:
■ More potent than ketoconazole
■ Available in capsules and suspension
Indications:
■ Effective against Cryptococcus and coccidiosis
Pharmacokinetics:
■ High PO absorption
■ Low protein binding, high distribution
■ Elimination through kidneys
Indications:
■ Variety of fungal infections, particularly Blasto, Crypto, and Aspergillus
Mechanism of Action:
■ Similar to other azoles
Pharmacokinetics:
■ High bioavailability
■ Can cross the CNS
■ Liver metabolism with main metabolite
Comments:
■ Cats seem prone to adverse reactions
■ Complex elimination
○ Indications:
■ Systemic or severe fungal infections
Mechanism of Action:
■ Similar to other azoles
Pharmacokinetics:
■ Adequate bioavailability
■ Moderate protein binding
Adverse Effects:
■ GI issues, ALT elevation, PLTpenia
○ Comments:
■ Second-generation triazole
■ Cost prohibitive
Amphotericin B (Fungizone):
○ Indications: Blastomyces dermatitidis, Histoplasma capsulatum, Coccidioides
immitis, Cryptococcus neoformans, Candida spp., Aspergillus, Leishmania
○ Mechanism of Action: Fungistatic, binds primarily to ergosterol in cell
membrane
○ Pharmacokinetics: Poor GI absorption, highly protein-bound (>90%), limited
penetration to various tissues
○ Adverse Effects: AKI, vomiting, tremor, pyrexia, anorexia, calcinosis cutis, CK
elevations
○ Comments: Liposomal formulation for more selectivity, different formulations
available
Ketoconazole:
○ Indications: Yeast, systemic fungi, dermatophytes
○ Mechanism of Action: CYP450 inhibition, weakens fungal cell membrane,
anti-inflammatory
○ Pharmacokinetics: Good PO absorption, variable bioavailability, metabolized
in the liver
○ Adverse Effects: GI disturbances, hepatotoxicity, altered metabolism of other
drugs
○ Comments: Hepatotoxicity more common in cats, not typically used in cats
Itraconazole (Sporanox):
○ Indications: Systemic and cutaneous mycosis
○ Mechanism of Action: Similar to other azoles
○ Pharmacokinetics: Bioavailability influenced by pH and food, high protein
binding, many drug interactions
○ Adverse Effects: Idiosyncratic hepatotoxicity in cats, hepatopathy in dogs,
skin reactions, thrombocytopenia
○ Comments: More potent than ketoconazole, available in capsules and
suspension
Fluconazole:
○ Indications: Effective against cryptococcus and coccidiosis
○ Pharmacokinetics: High PO absorption, low protein binding, elimination
through kidneys
Voriconazole:
○ Indications: Variety of fungal infections, particularly Blasto, Crypto, and
Aspergillus
○ Mechanism of Action: Similar to other azoles
○ Pharmacokinetics: High bioavailability, can cross CNS, liver metabolism
○ Comments: Cats prone to adverse reactions, complex elimination
Posaconazole:
○ Indications: Systemic or severe fungal infections
○ Pharmacokinetics: Adequate bioavailability, moderate protein binding
○ Adverse Effects: GI issues, ALT elevation, PLTpenia
○ Comments: Second-generation triazole, cost prohibitive
Amphotericin B - Mechanism of Action:
○ Binds primarily to ergosterol in the fungal cell membrane
○ Induces altered permeability, leading to leakage of cellular constituents
Itraconazole - Adverse Effects:
○ Idiosyncratic hepatotoxicity in cats
○ Hepatopathy in 10% of dogs, skin lesions, thrombocytopenia
Posaconazole - Pharmacokinetics:
○ Adequate bioavailability with moderate protein binding
○ Prolonged t1/2 in cats, associated with GI issues and ALT elevation
Voriconazole - Mechanism of Action:
Inhibition of 24-methylene dehydrolanosterol demethylation in molds,
resulting in increased antifungal activity
Fluconazole - Pharmacokinetics:
○ High PO absorption, low protein binding, significant elimination through
kidneys
Ketoconazole - Pharmacokinetics:
○ Good PO absorption, variable bioavailability, extensive liver metabolism
Itraconazole - Comments:
○ More potent than ketoconazole
○ Available in both capsules and suspension formulations
Posaconazole - Adverse Effects:
○ GI issues, ALT elevation, platelet abnormalities identified in dogs
○ Considered a second-generation triazole with a cost-prohibitive profile
