Antifungal Drugs Flashcards
What is the classification of Amphotericin B?
Polyene antibiotic
Systemic use
anti fungal
What is the mechanism of action of Amphotericin B?
Binds selectively to ergosterol, which alters permeability of cell by forming pores in cell membrane, results in the loss of intracellular ions + macromolecules which leads to cell death.
What are the therapeutic indications of Amphotericin B?
most organisms responsible for systemic mycoses
What is the solubility of Amphotericin B?
soluble in water
How is Amphotericin B administered?
IV, oral for candidiasis infections within the lumen of GIT, topically
What are the 2 formulations of Amphotericin B?
- colloidal suspension of amphotericin B and sodium deoxycholate (IV)
- amphotericin complexed with lipids or encapsulated in liposomes
What % of Amphotericin B is bound to plasma proteins?
> 90%
Describe the distribution of Amphotericin B
widely distributed in tissues, crosses BBB poorly (except when meninges are inflamed)
What is the half-life of Amphotericin B?
24-hours, up to 15 days with repeated dosages
How is Amphotericin B excreted?
excreted very slowly via the urine, 2-5% in an active form
What are the adverse effects of Amphotericin B?
- fever, headache, tinnitis, nausea
and vomiting and chills (immediate) - renal toxicity (slower)
What is the classification of Ketoconazole?
Imidazole
Systemic use
anti fungal
What is the mechanism of action of Ketoconazole?
inhibits of the cytochrome P450 enzyme system of fungal cells
What are the therapeutic indications of Ketoconazole?
yeast and dermatophyte infections
Describe the absorption of Ketoconazole
Oral absorption (varies among individuals)
What % of Ketoconazole is bound to plasma proteins?
99%
Describe the distribution of Ketoconazole
widely distributed in tissues and body fluids
What is the half-life of Ketoconazole?
8 hours
How is Ketoconazole metabolised and excreted?
metabolized in the liver and excreted in bile, a small amount is also excreted in urine
What are the adverse effects of Ketoconazole?
- fatal liver damage
- gynecomastia, infertility, and menstrual irregularities
- alters metabolism of other drugs (increases concentration and toxic effects)
What is the classification of Fluconazole?
Triazole
Systemic use
Antifungal
What is the mechanism of action of Fluconazole?
inhibits of the cytochrome P450 enzyme system of fungal cells
What are the therapeutic indications of Fluconazole?
- Orally: oropharyngeal and eosophageal candidiasis
- IV: systemic candidiasis and cryptococcal infections including cryptococcal meningitis
- Mainly candida and cryptococcus
How is Fluconazole administered?
Orally and IV
Describe the distribution of Fluconazole
Crosses BBB
What are the adverse effects of Fluconazole? (5)
- nausea
- vomiting
- abdominal pain
- diarrhea
- headache
What is the classification of Griseofulvin?
Antibiotic
Systemic use
antifungal
What is the mechanism of action of Griseofulvin?
inhibits mitosis in fungal cells by binding to tubulin
What are the therapeutic indication of Griseofulvin?
dermatophyte (micosporum) infections of the skin, hair and nails
- fungistatic
- fungicidal
What is the spectrum of activity of Griseofulvin?
narrow
How is Griseofulvin administered?
orally
Describe the absorption of Griseofulvin
poorly soluble in water and absorption is improved when the agent is taken with a fatty meal
What is the half life of Griseofulvin?
24 hours, detectable in the skin for longer
What are the adverse effects of Griseofulvin?
- GIT disturbances
- headache
- photosensitivity
- induces cytochrome P450 enzymes (causes drug interactions)
What is the classification of Nystatin?
Polyene antibiotic
topical use
anti fungal
What is the classification of Clotrimazole?
Topical Use
Imidazoles
anti fungal
