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Modern diuretics and the kidney.

It is particularly appropriate to discuss the pharmacology and mechanisms of action of diuretic drugs in a symposium on diseases of the kidney, since diuretics were the first group of drugs to be developed for the control and manipulation of selected aspects of renal function. Despite a relatively short history of less than three decades since the discovery of the first orally acting diuretic, chlorothiazide, modern diuretic therapy continues to enjoy an everexpanding clinical demand: worldwide expenditure has been estimated at around US $800 million per annum during the last five years. Though originally introduced for the treatment of oedematous conditions it is interesting that application of diuretics to the treatment of hypertension has outstripped their use in oedema. This has happened notwithstanding the parallel discoveries of other major antihypertensive agents such as the betaadrenoceptor blocking drugs and powerful vasodilators. The advent of novel, orally effective diuretics following on the prototype benzothiadiazine, chlorothiazide, has had a major influence in stimulating progess in the basic sciences relating to nephrology or electrolyte transport in body tissues in general. Advances in fundamental knowledge have in turn given the impetus to further discoveries of new and, in some cases, unique substances possessing diuretic activity. By and large these compounds have attained a remarkable degree of sophistication while, at the same time, remaining relatively safe during long term treatment of patients. The widespread use and, at times, the regrettable abuse of any group of drugs whose primary effect is directed toward interference with the renal handling of electrolytes must inevitably generate secondary disturbances in body homeostasis which have particular relevance to the chemical pathologist. To understand these, demands an understanding of how diuretics work in the context of modern views of the functional organisation of the kidney.