Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
15 Cards in this Set
- Front
- Back
|
Why is ergesterol important.
|
Cholesterol equivalent in fungi. It's only one step away from cholesterol.
|
|
|
Polyenes
|
Has very hydrophilic side and one very hydrophobic side. High binding affinity for ergosterol in fungal membranes. Alters membrane permeability.
|
|
|
Nystatin
|
Locally administrated polyene. Too toxic for systemic use.
|
|
|
Amphotericin B
|
Toxic but systemically administered. Gold standard of antifungals. Not absorbed orally. Stored in tissues. Slowly excreted in urine. Half life of 15 days. Nephrotoxicity by direct damage to distal tubular membrane leading to Na, K and Mg wasting. It also constricts afferent arteriole leading to lowered GFR.
|
|
|
Liposomal Amphotericin B.
|
Three formulations on the market that are supposed to be less nephrotoxic. Extremely expensive though.
|
|
|
Azole antifungals.
|
Inhibitors of lanosterol 14a-demethylase: a p450. This is part of the ergosterol synthesis pathway. There is an accumulation of toxic sterols.
|
|
|
Azole resistance
|
Altered p450 or overexpression.
|
|
|
Ketoconazole
|
First gen azole. Large doses inhibit human sex steroid biosynthesis and inhibits drug metabolism. Need high stomach acidity for better absorbtion.
|
|
|
Fluconazole
|
2nd gen azole. High bioavailability. High aqueous solubility. Used in thrush and candida where the infection is in a mucus area and the solubility helps. Least likely to give guys boobs.
|
|
|
Itraconazole
|
Highly lipophilic 2nd gen azole. Inhibits drug metabolism. Has mainly replaced ketoconazole.
|
|
|
Voriconazole
|
3rd gen azole. Invasive resistant aspergillosis.
|
|
|
Allylamines
|
Inhibitors of squalene eposidase: a p450. 2nd step in ergosterol synthesis.
|
|
|
Terbinafine
|
Allylamine used to treat dermatophytes and onychomycosis (nasty nails). Less hepatotoxicity than itraconazole. Can give synergism with other drugs in the pathway.
|
|
|
Flucytosine
|
Allylamine with Required metabolic activation within fungal cells. Activated to 5-fluorouracil by cytosine deaminase. Inhibits thymidylate synthase which inhibits DNA synthesis. Can also insert as a replacement for Uracil in mRNA. Quick resistnace so gives with something else. Can get bone marrow depression.
|
|
|
Echinocandins (Caspofungin, anidulafungin, and micafungin)
|
Inhibit fungal wall synthesis.Inhibit synthesis of B-1,3-D-diglucans. Wall can't form. Cause cell lysis. Azole resitant invasive aspergillosis is its use. Very expensive.
|
