Anti fungal drugs Flashcards
Later toxicity of Amphotericin B Deoxycholate
Nephrotoxicity
what is the MOA of echinocandins?
inhibition of fungal cell wall synthesis
Drug of choice for cryptococcal meningitis
Amphotericin B
Side effects of ketoconazole?
- Gynexomastia
- decrease libido
Tiazole that clearance is altered by genetics
Voriconazole
Triazoles and pregnancy?
Avoid All
Synergism of nephrotoxicity of Amphotericin B with Trasplant and allograft patients
- Cyclosporin
- Sirolimus
- Tacrolimus
Azole of choice for Histo, cocci, and blasto
itraconazole
What therapy has been found to be associated with Histoplasmosis
anti-TNFalpha therapy
- infliximab
- Etanercept
What enzyme to echinocandins inhibit?
beta-(1,3) glucan synthase
mechanism of action of the Azoles
-inhibit Lanosterol to Ergosterol biosynthetic pathway
What 2 azoles have good CSF access?
Fluconazole and Voriconazole
What azole has strong cyp450 inhibition and therefore interacts with other drugs?
itraconazole and voriconazole
What is given with amphotericin B to treat cryptococcal meningitis
5-FC (5-Fluorocytosine anti metabolite)
What enzyme is inhibited by Azoles
14-alpha-demethylase (Cytochrome p450)
Fluconazole is narrow spectrum in that it only targets what?
No activity against what?
- Candida Albicans
- also Cryptococcous
No activitiy vs Aspergillus
What is the third line Azole that comes in pill form
Ketoconazole
Drug of choice for mucormycosis
Amphotericin B
Toxicity of amphotericin B deoxycholate upon onset of infusion
- chills
- fever
- anemia
- hypotension
Therapeutic indications for echinocandins?
serious opportunistic infections such as
- invasive candidiasis, candidemia
- invasive Aspirgillosis
especially if refractory to other therapies
mechanism of action for polyenes (amphotericin B)
associates with ergosterol and creates pores
What would you give an AIDS patients with oropharyngeal candidiasis who had failed to recover on fluconazole, amphotericin B, and itraconazole
Caspofungin
Azoles create a surplus of what?
Lanosterol
What does 5-FC do?
uses what fungal enzyme that humans don’t have?
uses cytosine deaminase to ultimately inhibit DNA synthesis by blocking thymidylate synthase and also inhibits proteins synthesis
Mechanisms of resistance to Azoles
- mutation or overexpression of lanosterol 14alpha demethylase
- efflux
- changes in sterol and/or phospholipid composition
Azole for cryptococcus
fluconazole
Triazoles and liver damage
All can
is Caspofungin effective against pathogenic fungal infections such as histo, cocci, and fusarium
NO
Synergism of nephrotoxicity of Amphotericin B with gram - and MRSA infections
- aminoglycosides
- vancomycin
mechanism of resistance to 5-FC
- mutated cytosine permease
- mutated cytosine deaminase
What azoles have good bioavailibility
Fluconazole and voriconazole
Synergism of nephrotoxicity of Amphotericin B with HIV patients
- Foscarnet
- Pentamidine
Triazole that disturbs vision
Voriconazole
There is a way for 5-FC to still work and get into the fungal cells even if there is a mutation in cytosine permease . . explain this
can go through the pores that are created by amphitericin B
Describe the effects of Amphotericin B on the kidney
Direct damage to DISTAL TUBULE membrane leading to Na, K, and Mg wasting and the hyponatremia leads decreased GFR and Arteriole constriction
drug to use for Candiduria
Fluconazole . . . (renal excretion and high bioavailibility)
What azole is cleared renally
fluconazole
What is the Broad spectrum Azole
Itraconazole
What is the echinocandin fungal drug?
Caspifungin
Azole used for Aspergillus
voriconazole
