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Chapter: Modern Medical Toxicology: Miscellaneous Drugs and Poisons: Anti-Infectives

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Griseofulvin - Antifungal

Griseofulvin is a fungistatic antibiotic which can be admin-istered orally.

Griseofulvin

Griseofulvin is a fungistatic antibiotic which can be admin-istered orally. It is derived from Penicillium griseofulvin and Penicillium janczewskii, and is effective in the treatment of avariety of dermatophytoses, (especially against various species of Microsporum, Epidermophyton, and Trichophyton) . It is presumed to act by disrupting the fungal mitotic spindle struc-ture and arrest fungal growth in the M phase of the life cycle.

Griseofulvin is also said to be beneficial in the treatment of Raynaud’s disease, systemic sclerosis, lichen planus, herpes zoster, and molluscum contagious. The recommended daily dose for children is 10 mg/kg and for adults 500 mg to 1 gram daily. Peak plasma levels are noted about 4 to 6 hours following a therapeutic dose, and the plasma half-life is about 24 hours. Griseofulvin is metabolised in the liver and excreted in the urine. A major portion of orally administered griseofulvin is eliminated unchanged in the faeces.

Adverse effects include confusion, fatigue, dry mouth, headache, anorexia, vomiting, abdominal cramps, diarrhoea,

vertigo, blurred vision, lethargy, insomnia, albuminuria and cylindruria without evidence of renal insufficiency, and haematological disturbances (leukopenia, neutropenia). Hepatotoxicity has also been reported. Hypersensitivity reac-tions include urticaria, angioedema, and erythema multiforme. Cross-reactivity with penicillin is a possibility.

There is insufficient information in the literature to accurately characterise the syndrome following griseofulvin overdosage. However, limited toxicity can be expected. Hyperamylasaemia and elevated liver enzymes have been reported following griseof-ulvin overdose. Griseofulvin is a microsomal enzyme inducer, produces an alcohol intolerance reaction, and has been associated with development of porphyria. Concomitant intake of alcohol along with griseofulvin can induce a disulfiram-like reaction.

Efficacy of oral contraceptives may be affected and there can be amenorrhoea or intermenstrual bleeding. Griseofulvin is said to be foetotoxic and should not be administered to pregnant women. There have been reports of mongolism and conjoined twins.

Treatment of overdose is symptomatic and supportive. Activated charcoal, cathartics, or extracorporeal methods of elimination do not appear to be beneficial, though early stomach wash may help. Intensive care therapy is desirable in serious overdose with constant respiratory and cardiac monitoring. Mild to moderate allergic reactions may be treated with antihis-tamines with or without inhaled beta agonists, corticosteroids or adrenaline.


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