Glyceryl mononitrate

Servent and colleagues [52] reported that GTN is metabolised in rat liver microsomes by an NADPH-dependent cytochrome P-450 system, yielding GDN, glyceryl mononitrate (GMN) and NO. Moreover, Schroeder and Schroer [53] showed that inhibitors of cytochrome P-450 reduce cGMP stimulation by GTN in kidney epithelial cells. 

Glyceryl mononitrates are stable substances which do not undergo decomposition when heated to a moderate temperature. In a sealed tube they decompose explosively at a temperature of about 170°C. 

Glyceryl trinitrate was converted by rabbits to the mono-and 1,3-dinitrate derivatives, which were excreted in the urine. The isomeric 1,2-glyceryl dinitrate was not detected as a metabolite of glyceryl trinitrate. After the administration of 1,2-glyceryl dinitrate, only glyceryl mononitrate (isomeric position unknown) was detected. The metabolism of penta-erythritol trinitrate (IV), an active metabolite of pentaerythritol tetra-nitrate, was studied in dogs. The major metabolites in the urine were pentaerythritol mononitrate and pentaerythritol only the latter compound was present in the feces. An oral dose of pentaerythritol was excreted unchanged by the dog. ... 

The oldest class of clinically used NO donors are the organic nitrates (R-ONO2) (Fig. 20.3), which are nitric acid esters of mono and polyhydric alcohols, including glyceryl trinitrate (GTN A.l), pentaerithrityl tetranitrate (PETN A.2), isosorbide dinitrate (ISDN A.3), and isosorbide-5-mononitrate (ISMN A.4). Metabolites of GTN, viz., glyceryl mononitrate (GMN) and glyceryl dinitrate (GDN), are pharmacologically active, but less potent than GTN. 

A number of organic nitrates are potent vasodilators and have been used clinically for over lOOyears, particularly for the relief of the symptoms of angina (Fig. 8.6). The most widely used is glyceryl trinitrate (GTN) but the group includes pentaerythrityl tetranitrate (PETN), isosorbide mononitrate (ISMO) andisosorbide dinitrate (ISDN). 

Drug therapy may be adapted to the time of attacks, e.g. nocturnal (transdermal glyceryl trinitrate, or isosorbide mononitrate orally at night). 

Nitrates were used to produce a favourable effect on portal hypertension isosorbide dinitrate, isosorbide mononitrate (55,69,134,136,145,217,218) and glyceryl trinitrate (92, 149). Glyceryl trinitrate can easily be controlled owing to its short half-life of 5 minutes. It is also effective upon transdermal application (10 mg/day). 

Nitrates have been produced in many chemical forms, but the current choice lies between the rapid-onset, short-acting glyceryl trinitrate (nitroglycerin) and the longer-acting isosorbide mononitrate and isosorbide dinitrate. 

The adverse effects of the nitrates are unaffected by the chemical form or by the route of administration. The spectrum and frequency of adverse effects for the individual drugs, such as glyceryl trinitrate, isosorbide dinitrate, and isosorbide-5-mononitrate, appear to be similar. 

The butoconazole nitrate vaginal cream, 2%, contains butoconazole nitrate 2%, an imidazole derivative with antifungal activity. Its chemical name is ( )-l-[4-(p-chlo-rophenyl)-2-[(2,6-dichlorophenyl)thio]butyl] imidazole mononitrate. It contains 2% butoconazole nitrate in a cream of edetate disodium, glyceryl monoisostearate, methylparaben, mineral oil, polyglyceryl-3 oleate, propylene... 

The organic nitrates are denitrated in the liver after oral administration. Glyceryl dinitrate and isosorbide mononitrate are active metabolites. The latter agent is available as a separate drug. The answer is (C). 

The phosphodiesterase type-5 inhibitors potentiate the hypotensive effects of nitrates in a proportion of patients, which might re-suit in potentiaiiy serious hypotension or even precipitate myocardiai infarction. Therefore, the concurrent use of sildenafil, tadalafil or vardenafil with organic nitrates (glyceryl trinitrate (nitroglycerin), isosorbide dinitrate, isosorbide mononitrate, etc.) is contraindicated. The concurrent use of nicorandil and all phosphodiesterase type-5 inhibitors is also contraindicated. 

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