ID:201510317Student’sname: Altaf Hani In pregnancy itcan only be given when the benefits exceed the harm of it on the pregnancy, itis also not known if it passes to the baby through the breast milk, so patientshould not breastfeed during using the drug.
Blood and Livertoxicities may occur with 5-FC intake, but can be minimized by monitoring serumconcentrations and by managing the dose carefully in pts with renal impairment.When its not available to check for serum concentration, careful monitoring forcytopenias is necessary.· Pts with bone marrow failure and liver failure shouldbe treated with caution.
· Pts withkidney disease should take flucytosine in reduced doses.· Pts who areusing this drug have deacresed bone marrow function , so should be treatedcarefully. CBC should bedone frequently.
S. E. :After an oral intake of 2 gm peak serum levels are obtained afterapprox. 6 h, the time to peak level goes down with cont. therapy. The drug is excretedfrom the kidneys. In healthy pts flucytosine has a half-life of 2.
5 to 6hs. Inpatients with renal failure, more serum levels are noted & the medicineaccumulate. It is mainly excreted without change in the urine and onlymetabolized and excreted in the feces.Flucytosine is absorbed from the GIT. Taking it with meals slow the absorption,but will not decrease the amount absorbed.Pharmacokinetics· Flucytosinegoes conversion into 5-FDUP that inhibits fungal DNA synthesis.· Flucytosineis intrafungally converted into the cytostatic fluorouracil that goes for further steps of activation and finally interacts as 5-FUTwith RNA biosynthesis soi t changes the organisation of some important proteins.
Two mechanisms have beenreported :ActionFlucytosine, as5-fluorocytosine (5-FC), it is an antifungal drug . It has to be used in a company with amphotericin B, in serious Candida infections and cryptococcosis. Pt can use it byitself or with other antifungals for chromomycosis. Flucytosinecan be given orally or I.V.
· Teratogenic, so should be avoided in pregnancy· It isnecessary to adjust the dose in liver diseaseNot to go for it :· No need tochange the dose based on age, gender, race· Does notaffect those with renal failure and hemodialysis· minimum amount of toxicity· extended half-life(alpha phase 1–2 h + beta phase 9–11 h + gamma phase 40–50 h)· Wide range (speciallyagainst Candida), To go for it :All echinocandins have minimal oral bioavailability & the only wayof administration is via intravenous route. Because no one of the medicines isexcreted by the kidneys, the dose does not need to be changed for those withrenal failure or problem. In mild to moderate hepatic failure, the dose ofcaspofungin has to be changed but this change is not as important foranidulafungin & micafungin.PharmacokineticsThe echinocandins play a roleof a non competitive inhibitors of ? – (1, 3) – D-glucan synthase,an important component of the fungal cell wall. Uncapability of the organism to synthesize ? – (1, 3) -D-glucan will lead to osmotic abnormalities & the cell will die.ActionAspergillus species, echinocandins shows fungistatic affect same asamphotericin B & trizoles, that shows fungicidal affect.
Echinocandinresistance, is not common, was only recorded with C. glabrata & C.Parapsilosis.Echinocandins shows good fungicidal affect against Candida albicans,Candida parapsilosis & Candida guilliermondii. A good resultrecorded against amphotericin B-resistant & fluconazole-resistant Candidaglabrata.
Echinocandins are basically groupof semisynthetic, cyclic lipopeptides with an N-linked acyl lipid side chain,involving subtypes : caspofungin, micafungin & anidulafungin.Antifungal spectrum