Anti Fungal Flashcards
(37 cards)
What is the mechanism of action of Amphotericin B?
Amphotericin B binds to ergosterol in the plasma membranes of sensitive fungal cells to forms pores (channels). The pores disrupt membrane function, allowing electrolytes (particularly potassium) and small molecules to leak from the cell, resulting in cell death.
What does Amphotericin B cover?
It’s a broad spectrum anti fungal. Covers Candida albicans (candidiasis), histoplasmosis, cryptococcus neoformans, aspergillus (aspergillosis).
How is Amphotericin B administered?
Parenterally
What formulations of Amphotericin B are there?
Amphotericin B is insoluble in water and must be coformulated with either sodium deoxycholate (conventional) or artificial lipids to form liposomes. The liposomal preparations have reduced renal toxicity but are costly.
What are some adverse effects of Amphotericin B?
- Infusion related toxicity: Fever and chills
- Nephrotoxicity: Despite the low levels of the drug excreted in the urine, conventional amphotericin B (ie, not the lipid formulations) causes renal vasoconstriction and can reduce the glomerular filtration rate (GFR) by more than half. Concurrent therapy with other nephrotoxic agents can increase the risk further. Renal function usually returns with discontinuation of the drug. Hydrate patients adequately.
Can switch to liposomal formulation. - thrombophlebitis
- Bone marrow suppression
Can Amphotericin B be used in pregnancy?
Yes, cat B, generally safe.
What is the mechanism of action of 5-Flucytosine?
5-flucytosine enters fungal cells through cytosine specific permeases and is then converted, by cytosine deaminase, to its metabolically active form 5-fluorouracil (5-FU).
Conversion of 5-FU into 5-fluorouridine triphosphate (FUTP). FUTP
is incorporated into fungal RNA in place of uridylic acid; and inhibits
protein synthesis.
Metabolism of 5-FU into 5-fluorodeoxyuridine monophosphate
(FdUMP), a potent inhibitor of thymidylate synthase, which is a
key enzyme for DNA synthesis.
How is the spectrum of activity like for 5-FC?
Narrow spectrum. Need cytosine specific permeates to enter fungal cells and needs cytosine deaminase to form 5-FU.
What combination of 5-FC is used?
It is effective in combination with amphotericin B for treating candidiasis and cryptococcosis (meningitis and pulmonary infections).
Gold standard for cryptococcal meningitis.
How is 5-FC given?
Oral. It penetrates well into CSF
Is 5-FU used as a single agent?
No, leads to resistance
Adverse effects of 5-FC?
- GI effects
- Bone marrow suppression
- Hepatotoxicity
What are examples of echinocandin?
- caspofungin, 2. micafungin 3. anidulafungin
Mechanism of action of echniocandin ?
Echinocandins inhibit the activity of the glucan synthase complex, resulting in loss of the structural integrity of the cell wall.
How are echinocandins administered?
Parenteral. They cannot penetrate CSF.
Adverse effects of echinocandins
Minor. generally safe. Includes GI symptoms, fever, chills, etc.
Two types of azoles
Triazoles and imidazoles
Mechanism of action of azoles
They inhibit C-14 α- demethylase (CYP450 enzyme), thereby blocking the demethylation of lanosterol to ergosterol, the principal sterol of fungal membranes. The inhibition of ergosterol biosynthesis disrupts membrane structure and function and inhibits fungal cell growth.
What are the 3 triazoles
Fluconazole, Itraconazole, Voriconazole
How are triazoles administered
Oral.
What are the uses of fluconazole?
Single dose oral treatment for vulvovaginal candidiasis. Cryptococcal meningitis (useful as alternative to Amphotericin B + 5-FC, good CSF penetration) Candida infections.
How is fluconazole cleared
Renally.
3 adverse effects associated with triazoles
- GI
- Hepatotoxicity
- QT prolongation
What forms of oral medication is itraconazole used in
Oral capsules -> take after full meal and with coke (acidic pH)
Oral solution -> take on empty stomach
