Non-mercurial diuretics

The most commonly used diuretics are invariably classified by their respective chemical class, mechanism of action, site of action, or effects on the urine contents. Nevertheless, these drugs normally exert their action rather widely with regard to their prevailing efficacy as well as their definite site of action located within the nephron. The real efficacy of a diuretic is often measured by its ability to enhance the rate of excretion of Na ions filtered usually at the glomerulus i.e., the filtered load of sodimn) and hence, must not be misunderstood with the potency, that is the actual amount of the diuretic essentially needed to cause a specific diuretic response. In other words, the efficacy of a diuretic is invariably estimated in portion by the site of action of the diuretic. 

The non-mercurial diuretics may be classified on the basis of their chemical structures together with their physical characteristics as follows  

A major breakthrough in diuretic therapy was the introduction of chlorothiazide as a reliable, oral and non-mercurial diuretic in 1955 by Nouello and Spagne in the research laboratories of Merck, 

Sharp and Dohme. A number of benzothiadiazines (I), having the following general ehemieal formula  

It has been amply observed that the thiazide diuretics enhance urinaiy excretion of both Na and H2O by specifically inhibiting Na reabsorption located in the cortical (thick) portion of the ascending limb of Henle s loop and also in the early distal tubules. Besides, they also progressively cause an increase in the excretion of Cl, and HCO3 (to a lesser extent) ions. However, the latter efiect is predominantly by virtue of their mild carbonic anhydrase-inhibitory action. Importantly, due to their site of action, they invariably interfere with the dilution whereas, the concentration of urine is not affected appreciably. 

---

Organic mercurial diuretics were widely employed prior to the introduction of thiazides and a host of other potent non-mereurial diuretics, but now have been virtually superseded by these orally aetive drugs that are found to be both potent and less toxic. 

From his studies with ethacrynic acid, Cafruny concludes that ethacrynic acid does react with protein-bound sulfhydryl of renal cells. He further states that the data indicate that ethacrynic acid occupies the same "receptors and may share the same mechanism of action as the mercurials" and that ethacrynic acid "probably blocks reabsorption of soditjm in the same way as mercurials and in most respects is the "non-mercurial mercurial" diuretic it was designed to be". 

---