Imidazole antifungal drugs

Khashaba et al. [34] suggested the use of sample spectrophotometric and spectrofluorimetric methods for the determination of miconazole and other antifungal drugs in different pharmaceutical formulations. The spectrophotometric method depend on the interaction between imidazole antifungal drugs as -electron donor with the pi-acceptor 2,3-dichloro-5,6-dicyano-l,4-benzoquinone, in methanol or with p-chloranilic acid in acetonitrile. The produced chromogens obey Beer s law at Amax 460 and 520 nm in the concentration range 22.5-200 and 7.9-280 pg/mL for 2,3-dichloro-5,6-dicyano-l,4-benzoquinone and p-chloranilic acid, respectively. Spectrofluorimetric method is based on the measurement of the native fluorescence of ketoconazole at 375 nm with excitation at 288 nm and/or fluorescence intensity versus concentration is linear for ketoconazole at 49.7-800 ng/mL. The methods... 

It is orally effective broad spectrum imidazole antifungal drug. It is useful in both dermatophytosis and deep mycosis. Oral absorption is facilitated by gastric acidity. It is highly protein bound, metabolised in liver and metabolites are excreted in urine and faeces. Its spectrum is similar to that of miconazole and is more active against Coccidioides. 

Kan PB, Hirst MA, Feldman D (1985) Inhibition 2210. of steroidogenic cytochrome P-450 enzymes in rat testisby ketoconazole and related imidazole antifungal drugs. J Steroid Biochem 23 1023-1029... 

Antifungal drugs are classified according to their mode of action and/or their chemical class. Four chemical classes have mainly contributed to the actual armentory of antifungal drugs the broadest class is the one of azoles (imidazoles and triazoles), followed by polyenes, allylamines and morpholines. Some individual compounds are used in dermatology. 

Miconazole is an imidazole antifungal agent used as miconazole base or miconazole nitrate for the treatment of superficial candidiasis and of skin infections dermato-phytosis and pityriasis versicolor. The drug has also been given intravenously by infusion for the treatment of disseminated fungal infections. Miconazole can be given by mouth in a dose of 120-240 mg, as oral gel four times daily after food, for... 

A number of other substituted imidazolium ions have also been reported. [MIM-C2H50CH3]Br and [MIM-CH30CH3]Br, liquids at room temperature, were recently reported to be good solvents for carbohydrates and proteins (47). The diversity of organic cations was extended even to include the antifungal drug miconazole, which contains an imidazole ring. By the reaction of the miconazole with alkyl iodide, bioactive cations were obtained that were subsequently used to form ionic liquids with PF (9). 

Azole antifungal drugs are synthetic compounds with broad-spectrum fungistatic activity. Azoles can be divided into two groups the older imidazole agents, in which the hve-member azole nucleus contains two nitrogens, and the newer triazole compounds, fluconazole and itraconazole, in which the azole nucleus contains three nitrogens. 

Macrae, P.V. Kinns, M. Pullen, F.S. and Tarbit, M.H. Characterization of a quaternary N-glucuronide metabolite of the imidazole antifungal, tioconazole. Drug Metab Dispos 16 1100-1102, 1990. 

Noncompetitive inhibition caused by slow reversible binding of lipophilic ligands to the heme iron (e.g., imidazole-based drugs such as cimetidine and antifungals), or to reversible binding to an allosteric site. 

Some of the imidazole antifungals that are on the list of drugs that qualified, registered podiatrist can access and supply are discussed in Chapter 8. 

Many Hj antihistamines are metabolized by CYPs. Thus, inhibitors of CYP activity such as macrolide antibiotics (e.g., erythromycin) or imidazole antifungals (e.g.,ketoconazole) can increase Hj antihistamine levels, leading to toxicity. Some newer antihistamines, such as cetirizine, fexofenadine, levocabastine, and acrivastine, are not subject to these drug interactions. 

Imidazoles arc wide-spectnim antifungal drugs to which resistance rarely develops. Except for ketoconazolc. the imidazoles are poorly absorbed orally. Clotrimazole, econii/ule and miconazole are widely used lopic-aliy in the Ireatment of dennaiophyle and Candida alhicam infections. Miconazole is used intravenously in systemic infections in patients who cannot tolerate amphotericin. It may cause nausea and vomiting, faintness and anaphylaxis. Ketoconazole is well absorbed orally, and has been used in Ihe crealment of local and systemic mycoses. Enthusiasm for ketoconazole has declined because it may cause hepatic necrosis and adrenal suppression. 

Some of imidazoles and triazoles are the potential inhibitors of 14-demethylase, a key enzyme in the sterol biosynthesis pathway, thus directly interfere with cell wall biosynthesis in Leishmania. Fluconazole, a triazole antifungal drug used in the treatment and prevention of superficial and systemic fungal infections, has been used for the treatment of L. major in Old World. Similarly, ketoconazole has been used in the New World against L. panamensis and L. mexicana. Itraconazole... 

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