Boards 2018 Flashcards
(40 cards)
What is the main side effect noted with Amphotericin B?
Nephrotoxicity. This drug has a low therapeutic index. There is direct tubular damage. Recommend monitoring for renal function - K+ loss, renal tubular acidosis. It’s best to use this in a lipid formulation as it may reduce toxicity.
This drug binds to Ergosterol in cell membrane creating a pore. The K+ and other small molecules leak from the fungal cells. There is some binding to mammalian cells
What is Amphotericin B?
This is given via IV. There is infrequent resistance.
What are two polyene macrolide antibiotics that have anti fungal actions?
Amphotericin B and Nystatin
This antibiotic has some anti fungal properties however it does not include ringworm treatment. This is limited to topical administration
Nystatin
What antifungals are fungistatic?
Azoles, Griseofulvin
What is the mechanism of action of all azoles
All azaleas block the fungal CYP450 pathway responsible for synthesis of ergosterol, increase membrane permeability, and interference with action of membrane associated enzymes. They inhibit Candidia yeast into hyphae.
What part of the ergosterol pathway do the azoles affect?
They block the cytochrome P450 pathway which happens just around the Lanosterol point in the pathway.
What potential side effects are seen with ketoconazole?
Gastrointestinal, hepatotoxicity, cataractes, pruritus, alopecia, teratogenic, mutagenic
What kind of environment is favourable for ketoconazole administration?
Requires an acidic environment, therefor decreased food is better.
Ketoconazole can be used to treat HAC - why?
Ketoconazole can inhibit synthesis of androgens and adrenal steroids. Fluconazole has minimal effects on adrenal steroidgenesis
How longs does Ketoconazole take to reach it’s steady state?
10-14 days
What antifungals penetrate the CNS?
Ketoconazole (enter CSF), Fluconazole (low protein binding, enters CSF. It is also seen in the nails, skin, saliva, and vagina)
How is Ketoconazole metabolized?
Liver
How is Fluconazole metabolized?
Liver and excreted in the bile and urine.
What has the longer half life? Ketoconazole or Itraconaozle?
Itraconazole (28-30 hrs).
Is fluconazole bioavailability affected by food intake?
No it’s not affected.
What azole is in the imidazole group and how many N’s are in the azole ring?
Ketoconazole. 2N’s in the azole ring
What azole is in the triazole group and how many N’s are in the azole ring?
Itraconazole, Posaconazole. 3N’s in the azole ring
What azole is in the bistriazole group ?
Fluconazole, Voriconazole (synthetic derivative of fluconazole)
What is a broad-spectrum triazole?
Posaconazole.
What species should we use caution when using Posaconazole?
Cats. This broad spectrum Triazole is eliminated by glucoronidation and biliary excretion.
What adverse effects are noted with Posaconazole?
Dogs - hepatotoxicity, hypokalemia, thrombocytopenia, anemia, cardiac abnormalities. Cats - erythema, pruritus of face and pinna, retinotoxicity, neurologically, cardiac abnormalities.
What is the mechanism of action of Voriconazole?
It inhibits sterol and CYP450 synthesis as well as inhibiting 24-metylene dehydrolanosterol demthylation. Is efficacious with dimorphic and filamentous fungi.
What kind of drugs are Terbinafine or Lamisil? What is the mechanism of action.
Allylamines. Squalene Epoxidase Inhibitors. It decreases the synthesis of ergosterol. Toxic amounts of squalene results in the death of fungal cells.
