Imidazoles - Antifungal

Imidazoles

All imidazoles act by inhibiting the conversion of lanosterol to ergosterol, the main sterol of fungal cell membranes.

Clotrimazole is usually not associated with serious toxicity. Nausea, vomiting, and diarrhoea are frequent side effects following oral administration of clotrimazole. Depression, drowsiness, disorientation, visual alterations, abnormal liver function tests have occurred.

Fluconazole can be given orally or parenterally for a number of systemic fungal infections. It causes nausea, abdominal discomfort, headache, vertigo, delirium, convulsions, skin rash, and hepatic damage sometimes progressing to fatal hepatic necrosis. Long-term use is associated with alopecia. Hypokalaemia is common. Treatment involves symptomatic and supportive measures. Haemodialysis may be of value.

Ketoconazole was the first synthetic broad-spectrum oral antifungal drug to be introduced into practice and has been around since 1981. It is effective in the treatment of a number of systemic fungal infections. Adverse reactions include hepatitis, anaphylaxis, vomiting, rashes, headache, fever, photophobia, and gynaecomastia. Concomitant alcohol intake can cause nausea and flushing. Deaths have been reported even from therapeutic doses (due to hepatotoxicity). Incidentally, one of the many metabolites of ketoconazole is paracetamol, which is itself a hepatotoxic drug. Treatment involves symptomatic and supportive measures. Extracorporeal methods of elimina-tion are not likely to be useful since much of the parent drug is metabolised. Though paracetamol is one of its metabolites, the use of N-acetylcysteine is not recommended at present.

Miconazole was formerly used intravenously and occa-sionally induced arrhythmias, hyponatraemia, and seizures. Today it is only used as a local application. Less commonly used imidazole antifungals include bifonazole, butoconazole, croconazole hydrochloride, econazole nitrate, fenticonazole nitrate, omoconazole nitrate, oxiconazole nitrate, sertacona-zole nitrate, sulconazole nitrate, and tioconazole. Overdose experience is limited with these agents. Due to minimal oral absorption and limited systemic toxicity, severe toxic effects following oral overdose is not anticipated. Ingestion of even large quantities should produce only minor GI symp-toms. Treatment is usually unnecessary. Dermal application, however, may produce local irritation. Patients treated with imidazole antifungal vaginal products have reported (rarely): dysuria, slight urinary frequency, lower abdominal cramping, and dyspareunia. An objectionable odour has been reported in up to 20% of patients using butoconazole. Some of these agents are teratogenic.