Name polyene is derived from highly double bonded structure
amphotericin B combines avidly with lipids (ergosterol) along the double bond-rich side of its structure and associates with water molecules along the hydroxyl-rich side. This amphipathic characteristic facilitates pore formation by multiple amphotericin molecules, with the lipophilic portions around the outside of the pore and the hydrophilic regions lining the inside. The pore allows the leakage of intracellular ions and macromolecules, eventually leading to cell death. Some binding to human membrane sterols does occur, probably accounting for the drug's prominent toxicity.
Dermatophytes are inhibited in vitro but conc of AMB attained inskin are low and ineffective
Bile salt –doc60% metabolized in liver, excretion occurs slowly in both urine and bile
Started at 0.3 mg/kg – 0.7 mg/kg , 1 mg test dose injected over 20 min to see acute reaction
Owing to its broad spectrum of activity and fungicidal action, amphotericin B remains a useful agent for nearly all life-threatening mycotic infections, although newer less toxic agents have largely replaced amphotericin B for most conditions. It is often used as the initial induction regimen in order to rapidly reduce fungal burden and is then replaced by one of the newer azole drugs (described below) for chronic therapy or prevention of relapse. Such induction therapy is especially important for immunosuppressed patients and those with severe fungal pneumonia, severe cryptococcal meningitis, or disseminated infections with one of the endemic mycoses such as histoplasmosis or coccidioidomycosis. Once a clinical response has been elicited, these patients then often continue maintenance therapy with an azole; therapy may be lifelong in patients at high risk for disease relapse. For treatment of systemic fungal disease, amphotericin B is given by slow intravenous infusion at a dosage of 0.5–1 mg/kg/d. It is usually continued to a defined total dose (eg, 1–2 g), rather than a defined time span, as used with other antimicrobial drugs.
ameliorated by slowing the infusion rate or decreasing the daily dose. Premedication with antipyretics, antihistamines, meperidine, or corticosteroids can be helpful. When starting therapy, many clinicians administer a test dose of 1 mg intravenously to gauge the severity of the reaction. This can serve as a guide to an initial dosing regimen and premedication strategy.
Used in superficialcandidiasis,
Torula, chromoblastomyces, candida some strains
Available as Cream, gel, spray, lotion, pessary ,. ( pedis, cruris, corporis, versicolor)
Most toxic among azoles so not used so much triazolespreferedAcidic environment favours absorption so orange juice increases absorption and proton pump inhibitors decrease absorption. But saturation of metabolism occurs shortly which prolongs the its half life and permits once daily dosing , since small amount of drug appears in urine it is not suitable for
Not used in fungal meningitis
Much less toxic than AMB but more side effects than fluconazole, itraconazoleNausea etc can be minimized by taking with food
Proton pump inhibitors : decrease absorption Rifampicin, phenytoin increase metabolism With sulfonylureas can cause hypoglycemia Nephrotoxicity can occur with cyclosporine H2 receptor blockers ↑ Srconc of cisapride, terfenadine, astemizole, quinidinePhenytoin toxicity Sulfonylureas: hypoglycemiaCyclosporine: nephrotoxicityWarfarin: bleeding Rifampicin, phenytoin ↑ metabolism of ketoconazoleShould not combine with AMB
200 mg OD Also tried in dermal leshmaniasis
Oral candidiasis : fluconazole 200 mg on first day then 100 mg daily for atleast 2 weeksCryptococcosis: 400 mg daily 8 weeks after stabilization with amb , after 8 weeks dose is reduced to 200 mg for life aids related only Coccodiodal meningitis: drug of choice Fluconazole has activity against histoplasma, blasto, sporotrich , ring worm but efficacy less Nor against aspergillusAll azoles not against mucormycosis. Children doses = 3-6 mg/kg
Capsule form of drug better absorbed in fed state , invasive aspergillosis outside the CNSIN treating deep mycosis two 100 mg capsules given twice daily with food , divided doses increase the AUC WHY PULSE THERAPY: retention of active drug in nail keratin . Daily therapy prefered for recurring infection. Terbinbafine 250 mg OD better in onychomycosis than itraconazole
effective against candida & aspergillosis
Not effective in hyperkeratinized lesions like tineapedis , tineacapitis , tineaunginum as poor penetration , symptomatic relief occurs early with tolnaftate but if discontinued before fungal bearing tissue is shed relapses occur
Active against malasesseziafurfur