Pharmacology - Antifungal Flashcards
Antifungal drugs
Griseofulvin
Amphotericin B
Azole antifungals **
Terbinafine
Antiviral drugs
Antiherpetic drugs
Anti-influenza drugs
Diagnosis of fungal diseases
Difficult to diagnose
Difficult to treat - fungi reaches highly protected sites that few drugs can reach
Treatment is long & expensive
Factors for increased fungal incidence
Immunosuppression
Radiation therapy
Chemotherapy
Prolonged corticosteroid use
Mechanism and action of griseofulvin
Dermatophytes - microsporum, Trichophyton
Inhibits mitosis of fungal cells, fungalstatic
What route of absorption is ideal for griseofulvin?
Oral, enhanced w meal - lipophilic drug
Micronized (25-70%)
Ultramicronized (100%)
Formulation effects dosing / absorption
Distribution of griseofulvin
To skin, deposits in stratum corneum by 48-72 hrs, persists for weeks = fewer doses required
Adverse effects of griseofulvin
Cats & horses
Cats: bone marrow suppression, esp in FeLv
Teratogenic in pregnant animals = no use
Horses: teratogenic in early pregnancy
Amphotericin B
Polyene antifungal, reserved for severe illness
Mechanism of Amphotericin B
Binds to sterols in fungal cells - toxicity binding to cholesterol
Cell membrane = more permeable
Fungicidal
Common adverse effects in Amphotericin B
Renal injury - always monitor function during administration
Acute injury - altered blood flow, azotemia
Chronic (cumulative) injury - ischemia, cell death
Less common adverse effects of Amphotericin b
Fever
Thrombophlebitis
Nausea, vomiting, anorexia
Anemia
How to decrease Amphotericin B toxicity
Fluid pretreatment
Slow IV infusion
Liposomal formulations
Drug interactions with Amphotericin b
- flucytosine
Synergistic
Treat refractory CNS cryptococcus infections
Combo can decrease dose/ toxicity of Amphotericin
Drug interactions with Amphotericin b
- azole
Treat w ampB first, allow switching to azole for out of hospital treatment/recovery use
XX using azole first, binds/alters receptor site
Azole antifungal drugs mechanism
Inhibits what enzyme? And what synthesis?
Inhibit 14alpha demethylase
Synthesis of fungal cell sterols, inhibit ergosterol synthesis
Fungistatic
Common ADRs of azole drugs
Hepatotoxicity, not safe during pregnancy
Older azole drugs
Imidazoles
- ketoconazole: systemic
Newer azole drugs
Triazoles
- itraconazole
- fluconazole
- voriconazole
(Posaconazole)**
Dimorphic fungi spectrum drugs
Blastomyces
Histoplasma
Cryptococcus
Sporothrix
(Most lipophilic will treat)
Dermatophytes spectrum drugs
Filamentous fungi (+/-)
Aspergillus
Fusarium
Depends on drugs
PK of ketoconazole
Oral absorption enhanced by food
Inhibited by anti acids
Not absorbed in horses
AE of ketoconazole
Cheapest & most adverse effects
Nausea, vomiting, diarrhea
Heptotoxicosis
Cataracts
Fetal death
Adverse effects mechanism of ketoconazole
Inhibits? Decreases?
Inhibits steroid synthesis (CYP450 mediated)
Decreases testosterone & cortisol
Short term management of Cushings disease