|
Treatment
of systemic mycotic infections in dogs and cats |
Amphotericin B (fungicidal)
Amphotericin B was one of the first antifungal drugs used to
combat systemic mycotic infections. It acts by binding to ergosterol
in the fungal cell wall, causing increased permeability and leakage
>>> cell death.
- given by IV infusion over 4-6 hours
- SERIOUS side effects:
- anorexia
- nausea
- thrombophlebitis
- cardiac arrhythmias
- RENAL TOXICITY
- renal vasoconstriction and tubular dysfunction- The BUN and/or
creatinine levels must be monitored closely and treatment stopped
if significant azotemia develops.
- Renal effects may be lessened by concurrent treatment with
mannitol, dopamine or furosemide.
- A liposome-encapsulated form of amphotericin is less toxic
and very efficacious, but very expensive.
- sometimes combined with 5-flucytosine (5-FC) for Cryptococcus
infections---Apparently the amphotericin enhances the penetration
of 5-FC into the fungal cell. (5-FC is not effective against
the other systemic mycoses.)
Newer imidazole drugs (fungistatic)
These drugs result in increased membrane permeability as well
as other metabolic effects on the fungal cell.
Ketoconazole (Nizoral®):
- should be administered with food for best absorption (low
pH)
- can be used in combination therapy with amphotericin B to
reduce amphotericin's dose and side-effects
- ketoconazole side effects:
- nausea
- diarrhea
- reversible alopecia; lightening of the haircoat
- hepatotoxicity
- In addition to use against systemic mycotic infections, ketoconazole
is also used to treat pyodermas and otitis caused by yeast infections.
Itraconazole (Sporanox®):
- should be administered with food for best absorption (low
pH)
- drug of choice for systemic mycoses in dogs and cats today
- less toxicity, longer half-life than ketoconazole
- also the best choice for systemic aspergillosis in dogs
- Note: both ketoconazole and itraconazole are highly
protein bound and, therefore, do not reach the CNS efficiently.
Fluconazole (Diflucan®):
- absorption is independent of food/pH
- used extensively in humans, but more limited experience in
dogs
- One advantage over keto- and itraconazole is that it penetrates
the CNS and the eye because it is not strongly protein bound.
- Hence, fluconazole is used for treatment of CNS and ocular
mycotic infections. It is also used for treatment of renal cryptococcosis
in cats.
- It is eliminated through the kidneys and, therefore, is
also used for treatment of renal cryptococcosis in cats.
