Exam 3: Antifungals Flashcards
What drugs have activity against dermatophytes?
Topical: Lime-sulfur ---Must be diluted Azoles (clotrimazole, miconazole, enilconazole, ketoconazole, posaconazole) Thiabendazole Chlorhexadine Iodine
Systemic: Griseofulvin Azoles Terbinafine Lufenuron
What drugs have activity against yeasts?
Topically, orally, or vaginally: Nystatin or clotrimazole ---Too toxic to use systemically Azoles ---Posaconazole ---Silver sulfadiazine Terbinafine
Systemic: Antimetabolites ---Fluorocytosine Polyenes ---Amphotericin B Azoles ---Ketoconazole ---Itraconazole ---Fluconazole ---Posaconazole ---Voriconazole Iodides ---Sodium and potassium iodide
What drugs have activity against systemic mycoses?
Antimetabolites ---Fluorocytosine Polyenes ---Amphotericin B Azoles ---Ketoconazole ---Itraconazole ---Fluconazole ---Posaconazole ---Voriconazole Iodides ---Sodium and potassium iodide
What is the major life-threatening toxicity associated with griseofulvin use?
Hematologic
—Most serious side effect is bone marrow suppression
Teratogen
—Do not use during pregnancy
What species is most susceptible to toxicity griseofulvin use?
Cats are more prone to bone marrow suppression
—FeLV or FIV infection may increase likelihood of this severe side effect
What is the effect of the diet on absorption with griseofulvin use?
GI absorption is variable and incomplete
- –Absorption may be enhanced twofold by administration with a fat-containing meal, margarine, or by using formulations containing polyethylene glycol (PEG)
- –Particle size greatly affects oral absorption
a. Microsized
b. Ultra-microsized particles (2x absorbed in human trials)
What are the methods/formulations used to minimize amphotericin induced nephrotoxicity?
Maintain GFR during amphotericin treatment
—Mannitol pretreatment
—Saline pre and post treatment diuresis
Amphotericin-lipid complexes formulations decrease damage to the kidney
—Liposomal, ABLC, and ABCD
How do food and/or acid suppressors affect the bioavailability of ketoconazole?
Absorption is increased by low gastric pH, so do NOT use acid suppressors
Absorption may be increase by a high fat meal
How do food and/or acid suppressors affect the bioavailability of itraconazole?
Absorption from capsules enhanced by food and a low gastric pH
How do food and/or acid suppressors affect the bioavailability of fluconazole?
Oral absorption is not affected by food or gastric pH
How do food and/or acid suppressors affect the bioavailability of posaconzaole?
Oral absorption enhanced by food, but gastric pH has minimal impact
How do food and/or acid suppressors affect the bioavailability of voriconazole?
Fatty diet may increase absorption
Describe ketoconazole in terms of the effect on testosterone and cortisol production, rate of onset of action, ability to cross tissue barriers, and entry into urine.
Inhibits testosterone and cortisol production
Slower onset of action than other azoles
Poor penetration into CNS
Describe itraconazole in terms of the effect on testosterone and cortisol production, rate of onset of action, ability to cross tissue barriers, and entry into urine.
More rapid onset than ketoconazole
Does not inhibit testosterone or cortisol production
Better tissue penetration than ketoconazole, but still often subtherapeutic for CNS infection
Describe fluconazole in terms of the effect on testosterone and cortisol production, rate of onset of action, ability to cross tissue barriers, and entry into urine.
Similar to itraconazole in onset and side effects
—More rapid than ketoconazole and does not inhibit testosterone or cortisol production
Wide tissue distribution
—Enters eye, CNS, and urine
