Induction of treatment in serious fungal infections is mostly done by:
POLYENE ANTIBIOTICS: The name polyene is derived from their highly double-bonded structure. Amphotericin B is described as the prototype. Amphotericin B (AMB): It is obtained from Streptomyces nodosus. Chemistry and mechanism of action The polyenes possess a macrocyclic ring, one side of which has several conjugated double bonds and is highly lipophilic, while the other side is hydrophilic with many OH groups. A polar aminosugar and a carboxylic acid group are present at one end in some. They are all insoluble in water and unstable in aqueous medium. Pharmacokinetics: AMB is not absorbed orally; it can be given orally for intestinal candidiasis without systemic toxicity. Administered i.v. as asuspension made with the help of deoxycholate (DOC), it gets widely distributed in the body, but penetration in CSF is poor. It binds to sterols in tissues and to lipoproteins in plasma and stays in the body for long periods. Administration and dose Amphotericin B can be administered orally (50-100 mg QID) for intestinal moniliasis; also topically for vaginitis, otomycosis, etc.: FUNGIZONE OTIC 3% ear drops. For systemic mycosis, it is available as dry powder along with DOC for extemporaneous dispersion before use: FUNGIZONE INTRA VENOUS, MYCOL 50 mg l It is first suspended in 10 rnl water and then diluted to 500 ml with glucose solution (saline tends to make the suspension coarse). Initially 1 mg test dose is injected i.v over 20 minutes. If no serious reaction follows, 0.3 mg/kg is infused over 4-8 hours. Daily dose may be gradually increased to 0.7 mg/kg depending on tolerance of the patient. The total dose of AMB for majority of cases is 3- 4 g given over 2-3 months. Intrathecal injection of 0.5 mg twice weekly has been given in fungal meningitis. New amphotericin B formulations In an attempt to improve tolerability of i.v. infusion of AMB, reduce its toxicity and achieve targeted delivery, 3 new lipid formulations of AMB have been produced. (a) Amphotericin B lipid complex (ABLC): Contains 35% AMB incorporated in ribbon like paicles of dimyristoyl phospholipids. ( b ) Amphotericin B colloidal dispersion (ABCO). Disc shaped paicles containing 50% each of AMB and cholesteryl sulfate are prepared as aqueous dispersion (c) Lpi osomal amphotericin B (small unilamellar vesicles SUV): Consists of 10% AMB incorporated in uniform sized (60-80 nM) unilamellar liposomes made up of lecithin and other biodegradable phospholipids. The special features of these preparations are: * They, except ABCD, produce milder acute reaction (especially liposomal formulation) on i.v. infusion. * They can be used in patients not tolerating infusion oi conventional AMB formulation. * They have lower nephrotoxicity. * They cause minimal anaemia. * The liposomal preparation delivers AMB paicularh* to reticuloendothelial cells in liver and spleen-----especialh valuable for kala azar and in immunocompromised patients. However, some preparations, especially ABLC and ABCD, produce lower AMB levels and their clinical efficacy relative to conventional formulations appear to be lower. ESSENTIALS OF MEDICAL PHARMACOLOGY K.D.TRIPATHI SIXTH EDITION PAGE NO:757,758
IV amphotericin
B Ketoconazole
5-flucytosine
Fluconazole
Chemotherapy