Antifungals

Question 1

Indications:

Answer 1

■ Blastomyces dermatitidis
■ Histoplasma capsulatum
■ Coccidioides immitis
■ Cryptococcus neoformans
■ Candida spp.
■ Aspergillus (may have resistance/high MIC)
■ Leishmania

Question 2

Mechanism of Action:

Answer 2

■ Fungistatic
■ Steroid (primarily ergosterol) binding in cell membrane
■ Altered permeability leading to leakage of K and other cellular
constituents

Question 3

Pharmacokinetics:

Answer 3

■ Poor GI absorption (IV or SC administration)
■ Highly protein-bound (>90%)
■ Does not penetrate well to CNS, bone, joints, pancreas, muscle, etc.

Question 4

○ Adverse Effects:

Answer 4

■ AKI (common)
■ Vomiting
■ Tremor
■ Pyrexia
■ Anorexia
■ Calcinosis cutis
■ CK elevations

Question 5

Comments:

Answer 5

■ Liposomal formulation is more selective and less toxic
■ Different formulations: deoxycholate, lipid complex, cholesteryl sulfate

Question 6

Indications:

Answer 6

■ Yeast, systemic fungi, dermatophytes

Question 7

○ Mechanism of Action:

Answer 7

■ CYP450 inhibition
■ Inhibition of ergosterol formation
■ Weakens fungal cell membrane

Question 8

Pharmacokinetics:

Answer 8

■ Good PO absorption but variable bioavailability
■ Acidic environment enhances absorption
■ Variable tissue distribution

Question 9

Adverse Effects:

Answer 9

■ GI issues
■ Hepatotoxicity
■ Altered metabolism of other drugs

Question 10

Comments:

Answer 10

■ Hepatotoxicity more common in cats
■ Not usually used in cats

Question 11

Indications:

Answer 11

■ Systemic and cutaneous mycosis

Question 12

Mechanism of Action:

Answer 12

■ Similar to other azoles

Question 13

○ Pharmacokinetics:

Answer 13

■ Bioavailability influenced by pH and food
■ High protein binding, very lipophilic
■ Many drug interactions

Question 14

Adverse Effects:

Answer 14

■ Idiosyncratic hepatotoxicity in cats
■ Hepatopathy in 10% of dogs
■ Vasculitis, skin lesions, thrombocytopenia

Question 15

○ Comments:

Answer 15

■ More potent than ketoconazole
■ Available in capsules and suspension

Question 16

Indications:

Answer 16

■ Effective against Cryptococcus and coccidiosis

Question 17

Pharmacokinetics:

Answer 17

■ High PO absorption
■ Low protein binding, high distribution
■ Elimination through kidneys

Question 18

Indications:

Answer 18

■ Variety of fungal infections, particularly Blasto, Crypto, and Aspergillus

Question 19

Mechanism of Action:

Answer 19

■ Similar to other azoles

Question 20

Pharmacokinetics:

Answer 20

■ High bioavailability
■ Can cross the CNS
■ Liver metabolism with main metabolite

Question 21

Comments:

Answer 21

■ Cats seem prone to adverse reactions
■ Complex elimination

Question 22

○ Indications:

Answer 22

■ Systemic or severe fungal infections

Question 23

Mechanism of Action:

Answer 23

■ Similar to other azoles

Question 24

Pharmacokinetics:

Answer 24

■ Adequate bioavailability
■ Moderate protein binding

Question 25

Adverse Effects:

Answer 25

■ GI issues, ALT elevation, PLTpenia

Question 26

○ Comments:

Answer 26

■ Second-generation triazole ■ Cost prohibitive

Question 27

Amphotericin B (Fungizone):

Answer 27

○ 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

Question 28

Ketoconazole:

Answer 28

○ 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

Question 29

Itraconazole (Sporanox):

Answer 29

○ 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

Question 30

Fluconazole:

Answer 30

○ Indications: Effective against cryptococcus and coccidiosis ○ Pharmacokinetics: High PO absorption, low protein binding, elimination through kidneys

Question 31

Voriconazole:

Answer 31

○ 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

Question 32

Posaconazole:

Answer 32

○ 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

Question 33

Amphotericin B - Mechanism of Action:

Answer 33

○ Binds primarily to ergosterol in the fungal cell membrane ○ Induces altered permeability, leading to leakage of cellular constituents

Question 34

Itraconazole - Adverse Effects:

Answer 34

○ Idiosyncratic hepatotoxicity in cats ○ Hepatopathy in 10% of dogs, skin lesions, thrombocytopenia

Question 35

Posaconazole - Pharmacokinetics:

Answer 35

○ Adequate bioavailability with moderate protein binding ○ Prolonged t1/2 in cats, associated with GI issues and ALT elevation

Question 36

Voriconazole - Mechanism of Action:

Answer 36

Inhibition of 24-methylene dehydrolanosterol demethylation in molds, resulting in increased antifungal activity

Question 37

Fluconazole - Pharmacokinetics:

Answer 37

○ High PO absorption, low protein binding, significant elimination through kidneys

Question 38

Ketoconazole - Pharmacokinetics:

Answer 38

○ Good PO absorption, variable bioavailability, extensive liver metabolism

Question 39

Itraconazole - Comments:

Answer 39

○ More potent than ketoconazole ○ Available in both capsules and suspension formulations

Question 40

Posaconazole - Adverse Effects:

Answer 40

○ GI issues, ALT elevation, platelet abnormalities identified in dogs ○ Considered a second-generation triazole with a cost-prohibitive profile