2Infectious diseases caused by fungi are called mycoses Infectious diseases caused by fungi are called mycoses. They are often chronic in nature.Superficial mycotic infections are common and involve only the skin (cutaneous mycoses)Systemic mycoses are difficult to treat.Fungi are eukaryotic.Cell wall is made of chitin.Cell membrane is made of ergosterol rather than cholesterol found in mammals.
3> in incidence of fungal infections in the last two decades Candidemia is the fourth common cause of septicemia.> incidence because of organ transplants,Chemotherapy and HIV.Newer anti mycotics have helped.
4ANTIFUNGAL DRUGS DRUGS FOR S.C & SYSTEMIC MYCOSIS Amphotericin B FlucytosineFluconazoleItraconazoleKetoconazoleVoriconazoleDRUGS USED FOR SUPERFICIAL MYCOSISClotrimazoleGriseofulvinMiconazoleNystatin
5Antifungals - systemic Amphotericn BNaturally occuring produced by streptomyces nodosus.Mechanism - Binds with ergosterol in the plasma membrane of sensitive fungal cell. There they form pores which alter the permeability of membrane leading to cell death.
6Toxicity is common . Therefore it is used in combination with flucytosine Effective against c.albicans, H.capsulatum, C.Neoformans and many strains of aspergillus.Resistance is rare because of the decreased ergosterol content of fungal membrane.
7Amphotericin b is administered slow iv Amphotericin b is administered slow iv . Dangerous intrathecal route reserved for serious meningitis.Does not cross the placenta.Adv effects.Fever and chillsRenal impairmentHypotension. care when given with digitalisAnemiaThrombophlebitis can occur
8FLUCYTOSINE MECH : INHIBITS THYMIDYLATE SYNTHETASE Very useful in treatment of meningitisSPECTRUM : CRYPTOCOCCUS, CANDIDA, BLASTOMYCOSISORAL ROUTE, CROSSES BBBRESISTANCE PRESENTSE :HEPATO TOXICITYANEMIA & GIT DISTRESS.BONE MARROW DEPRESSION
9KETOCONAZOLEIt was the first orally active azole available for the treatment of systemic mycoses.They are fungistatic.They block the demethylation of ianosterol to ergosterol.It inhibits human gonadal and adrenal steroid synthesis.Does not enter csf
10Most effective against histoplasmosis. Has been largely replaced by itraconazole.But is more economical than others.It is given orally. It requires gastric acid for dissolution.Antacids, h2 receptor blockers and proton pump inhibitors impair absorption.
11Inhibits the cytochrome p-450 It can potentiate the drug toxicities of rifampin, phenytoin and warfarin.It should not be used with amphotericin B.SE:GITENDOCRINE – Gynecomastia, impotence, menstrual abnormalitiesHEPATIC DYSFUNCTION
12FLUCONAZOLEIt is clinically important because of the lack of endocrine side effects.Given prophylactically in recipients of bone marrow transplants.Effective against all forms of mucocutaneous candidiasis.Can be given orally or i.vHas no endocrine effects and does not inhibit cytochrome p450.
13ITRACONAZOLE Recent addition to the azole family of antifungals. Broad spectrum.Mechanism is same as that of the other azoles.Drug of choice for blastomycosis, aspergillosis, histoplasmosis.Unlike ketoconazole it is effective against aids associated histoplasmosis.
14EchinocandinsInterfere with the synthesis of the fungal cell wall by inhibiting the synthesis of beta –D-glucan leading to lysis and cell death.Caspofungin, micafungin andanidula fungin come in this category.
15DRUGS FOR CUTANEOUS MYCOTIC INFECTIONS TERBINAFINEThe drug of choice for treating dermatophytoses and onchomycoses.Inhibits fungal squaline epoxidase thereby decreases the synthesis of ergosterol.Primarily fungicidal.Limited to dermatophytes and C.albicans. Therapy is for 3 months
16GRISEOFULVINCauses disruption of mitotic spindle and inhibition of fungal mycosis.Therapy is for months.Induces hepatic cytochrome p450 activity.Indication for dermatophytes, tinea.Se : allergy, hepatotoxicityCI Acute intermittent porphyriaAlcohol consumption strictly restricted.
17NYSTATIN Polyene antibiotic. Structure and chemistry resembles amphotericin b.Restricted to topical treatment of candidaBecause of systemic toxicity never given parenterally.
18MICONAZOLETopically active drugs that are only rarely administered parenterally because of their severe toxicity. The mechanism of action is same as that of ketoconazole.Topical use is associated with contact dermatitis.Potent inhibitor of warfarin metabolism and has resulted in bleeding, even on topical application.