75%

Via cytochrome P-450 inhibition

Inhibits the P450 enzyme 14a demethylase a

which leads to inhibition of the the conversion of lenosterol to ergosterol. This inhibits ergosterol synthesis in the cell membrane.

Inhibits triglyceride and phospholipid biosynthesis, inhibits cell wall chitin synthesis

fungi static, Can take 10 to 14 days to reach full affect

At high concentrations may be fungicidal and also will inhibit 11 hydroxylase blocking the conversion of deoxycorticosterone to corticosterone and also has anti-inflammatory effects

V/D, hepatotoxicity, rare thrombocytopenia, lightening of the hair coat, reduced synthesis of cortisol and testosterone, impotence/anestrus, Cataracs

Do not use with significant liver disease, pregnancy or in cats. Do not give with rifampicin, mitotane, theophylline and will alter the metabolism of cyclosporine and barbiturates

Absorbed better with a meal when there is acid in the stomach. Avoid giving with antacids

Inhibits the P4 50 enzyme 14 a demethylase which prevents the conversion of lanosterol to ergosterol which therefore inhibits ergosterol synthesis and incorporation into the cell membrane of fungi

Potent/more active than ketoconazole - The potency of each azole depends on it affinity for binding the P450 moiety, relative toxicity depends on it’s selectivity of action on mammalian versus fungal enzymes

Dermatophytes, systemic fungal infections including histoplasmosis Blastomycosis and Coccidioides, Malassezia

First choice for treatment of cats with dermatophyte infection

V/D, hepatotoxicity, drug reactions possible

generally better tolerated than ketoconazole As it does not inhibit mammalian P450 as strongly

In one study up to 7.5% of dogs developed vasculitis on a higher end of the dose range (10mg/kg)

Do not give with antacids or proton pump inhibitors, do not use compounded products

Will not lower cortisol levels

Inhibits the P4 50 enzyme 14 a demethylase which prevents the conversion of lanosterol to ergosterol which therefore inhibits ergosterol synthesis and incorporation into the cell membrane of fungi

Improved CNS an ocular penetration; May not be as effective for dermatophyte infections

Systemic fungal infections including histoplasmosis Blastomycosis and Coccidioides, Malassezia

Because it has improved penetration into the CNS it is used for treating cryptococcus in cats

V/D, hepatotoxicity

Do you not using pregnant animals

As with other azole drugs monitor liver enzymes

Inhibits ergosterol synthesis in the same manner as other azole drugs.

topical formulation only! Used to treat dermatophyte infections (rinse, spray or environmental treatment)…Do not let cats lick it off themselves

Can be used in the nasal passages for treatment of aspergillosis

Inhibits ergosterol synthesis in the same manner as other azole drugs.

More active and potent than fluconazole with better action against aspergillosis and fusarium

can cause neurotoxicity in cats, vomiting and hepatotoxicity; Monitor liver enzymes and CNS

Avoid in pregnancy or with liver disease

Often combined with amphotericin B and used to treat cryptococcus in cats

Anemia, thrombocytopenia, do not use in dogs = causes skin eruptions

Monitor CBC

Active against most fungi including Blastomycosis and Histoplasma and coccidiomycosis as well as some protozoa including leishmania

Can cause nephrotoxicity, fever, tremors and phlebitis

Use with extreme caution in animals with renal disease or dehydration

Incorporates/binds to keratin precursors, then inhibits mitosis of fungal cells which die. Also inhibits nucleic acid synthesis and interferes with micotic spindle microtubules

Enhances the function of P4 50 enzymes, that’s enhancing clearance of other drugs

Effective in treating dermatophyte infections, poor efficacy for other fungal organisms

has anti-inflammatory and immune modulatory properties (Suppresses delayed type hypersensitivity and skin irritant reactions)

do not use in cats with FIV! Avoid with pregnancy and hepatic dysfunction

bone marrow toxicity, depression, neurotoxicity vomiting and diarrhea. Teratogenic.

Give with a fatty meal

Targets squalene epoxidase, inhibits ergosterol synthesis

What is terbinafine used to treat? What is it safety profile?

Affective against dermatophytes and yeast

Persists in the SC for long periods of time

No contraindications and minimal side effects include vomiting, nausea, anorexia

Sodium iodide is preferred

Mechanism of action is unknown

Classically used to treat sporotrichosis in dogs but can also be a adjunct of treatment for zygomycosis, fungal granulomas and fungal infections in large animals

Excessive lacrimation, swelling of eyelids, nonproductive cough, increased respiratory secretions, scruffy coat and alopecia

Iodine containing drugs should not be used in pregnant animals as they can cause abortion

Inhibits 1,3 b d glucan synthetase, this blocking fungal cell wall synthesis, inhibits hyphal growth

Fungicidal for most fungi

Dermatophytes, sporothrix, aspergillus and candida. Possibly pythium

Monitor liver enzymes

• Inhibits cell wall synthesis, nucleic acid synthesis, and mitosis; disrupts mitotic spindle formation
• micronized 25-60mg/kg PO q 12 hours (ultramicronized 2.5-15mg/kg q 12 hours)
• Give with a fatty meal 
• monitor CBC for bone marrow suppression
• do NOT use if FIV or FELV +

• Ketoconazole is an imidazole
• It inhibits p450 enzymes, blocks 14α-demethylase preventing ergosterol synthesis and other actions
• 5-10mg/kg PO q 24 hours
• Give with food, not recommended for cats 
• monitor for hepatotoxicity (rare)
• be aware of drug interactions

• Continue treatment until three negative cultures have been obtained (weekly intervals)

• Itraconazole is an triazole
• It inhibits p450 enzymes, blocks 14α-demethylase and other actions
• 5-10 mg/kg PO q 24 hours, may use every other week
• Give with food, do not use if hepatic disease, up to 7.5% of dogs develop vasculitis (10mg/kg) 
• Monitor liver enzymes

• Fluconazole is a bis-triazole
• It inhibits p450 enzymes, blocks 14α-demethylase
• 10mg/kg PO q 24 hours
• penetrates into CNS and eyes; monitor liver enzymes

• Terbinafine is an allyalamine
• It inhibits ergosterol biosynthesis and squalene epoxidase
• 20-30 mg/kg PO q 24 hours
• Monitor liver enzymes

• Inhibits chitin synthesis
• 80-100mg/kg PO q 30 days
• insufficient proof of efficacy to recommend use in treatment of dermatophytosis

• Polyene antifungal 
• Fungistatic
• Binds to ergosterol---> membrane depolarization and increased membrane permeability
• Given IV, nephrotoxic
• Formulations:
  • Fungizone (colloid with bile salt deoxycholate)
  • Amphocil-complexed with cholesterol sulfate
  • AmBisome-encapsulated with liposomes
  • Abelcet- complexed with lipids
• Monitor renal function

• history of travel to endemic area
• cytology: organisms seldom found
• spherule (20-200um) and endospore (2-5um)
• biopsy
• culture is not recommended
• serology not consistently reliable
• Antigen detection

• Virulence factors
  • Polysaccharide capsule
  • Melanin
  • Mannitol
  • Lactose
  • Phenol oxidase
• Route of exposure
  • Inhalation
  • Direct skin penetration
• Risk factors
  • Corticosteroids/Immunosuppression
  • Retroviral infection