Fungal II Flashcards
What was 5-fluorocytosine initially used for?
Cancer treatment - 1957
What takes up 5-FC into fungal cells?
Fungal specific cytosine permease
What converts 5-FC to 5-Fluorouracil?
Deaminase
What process does 5-FU interfere with?
Translation - incorporated into RNA
What is 5-FC active against?
Mainly yeasts - cryptococcus
What is 5-FC not active against?
Aspergillis, candida krusei, histoplasma capsulate and most moulds
How is 5-FC administered?
IV
What is 5-FC used in combination with?
Amphotericin B or Fluconazole
What is 5-FC licensed for?
Use against systemic infections
Is 5-FC water soluble?
Yes - gets into the CSF very quickly
What risk is there with too high level of serum 5-FU?
Depletion of bone marrow
May lead to high phenytoin levels
What drug prevents the degradation of 5-FU?
Brivudine
What can prevent the conversion of 5-FC?
Mutations in uracil phosphoribosyl transferase
What to polyenes include?
Amphotericin B and nystatin
How doe polyenes damage cells?
Increase cell permeability
They bind sterols and distort the membrane bilayers leading to leakage
How can amphotericin B cause damage?
Oxidative damage through auto-oxidation
What does amphotericin B damage?
Yeasts and moulds
What is resistant to amphotericin B?
Aspergillus and scedosporium spp.
What is sensitive to nystatin?
Most yeasts
What are the formulations of amphotericin B?
IV and lipid fornulation
What are the formulations of nystatin?
Topical cream, too toxic for IV, not absorbed orally
What can amphotericin B be used for?
empirical treatment of suspected infections
What can nystatin be used for?
Oral and Vaginal candidosis
How often and in which way is ambisome delivered?
IV and one daily
How much of ambisome is protein bound?
95% - mainly unchanged
What is the half life of ambisome?
24 hours
How is ambisome eliminated?
43% in the bile and 21% in the urine
Can ambisome cause nephrotoxicity?
Yes
What are the drug interactions?
Nephrotoxic agents may induce neurotoxicity
Muscle relaxants - hypokalaemia
Corticosteroids - hypokalaemia
Flu cytosine - nephrotoxicity
How do molecules become resistant?
Reduced levels of ergosterol content of membranes (mutations in ERG3 gene coding for sterol desaturase)
