Sulphonylureas selection

Acetazolamide is a carbonic anhydrase inhibitor that reduces aqueous humour production and is therefore indicated in glaucoma to reduce the intraocular pressure. Salbutamol is a selective, short-acting beta2-agonist used as a bronchodilator in asthma. Tolbutamide is a short-acting sulphonylurea used in type 2 (non-insulin dependent) diabetes mellitus. Chlorpromazine is an aliphatic neuroleptic antipsychotic drug used in schizophrenia. Zafirlukast is a leukotriene-receptor antagonist that is indicated in the prophylaxis of asthma but should not be used to relieve acute severe asthma. 

Non-selective p-receptor blockers potentiate hypo-glycaemia of insulin and sulphonylureas. 

Competing photodecomposition pathways have been observed in sulpho-namides and sulphonylureas, and the photohydrolysis of sulphonamides, via the formation of donor-acceptor ion pairs with electron-donating aromatic compounds, has been reported.Irradiation of AT-tosylmethylphenethylamine (188) in the presence of veratrol (189) in ethanol, for example, gave methyl-phenethylamine (190) in 66% yield. This procedure has also been employed in the selective detosylation of lysine peptides. 

Non-selective beta blockers can also block beta-2 receptors in the pancreas concerned with insulin-release, so that the effects of the sulphonylureas may be blocked. 

Diabetics taking oral sulphonylureas rarely seem to have serious hypoglycaemic episodes caused by beta blockers, and any reductions in the blood glucose-lowering effects of the sulphonylureas normally appear to be of little clinical importance. The selective beta blockers are probably safer than those that are non-selective. Nevertheless, always monitor concurrent use to confirm that diabetic control is well maintained, adjusting the dose of antidiabetic as necessary, and warn all patients (as above) that some of the premonitory signs of hypoglycaemia may not occur. 

Apart from mediating the action of catecholamines, cAMP and its congener cGMP are common secondary-transmitters of hormone action. For example, they play the main part in liberating insulin from the pancreas in vivo. Tolbutamide, and similar sulphonylureas, which are used to alleviate the diabetes of elderly people, somewhat selectively inhibit pancreatic phosphodiesterase and thus preserve cAMP from destruction (Goldfine et al. 1971). Activity within a series of sulphonylureas is positively correlated with lipophilicity and also with binding by serum albumin (Seydel, Ahrens, and Losert, 1975). These cyclic phosphates also mediate the diuretic effect of vasopressin, and the action of ACTH and many other hormones (Sutherland, 0ye, and Butcher, 1965). 

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