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Merbaphen (NOVASUROL), which contains mercury Post Date: Wed, 15 Oct 2008 23:05:03 +0000 It was an ingredient of the famous "Guy's Hospital pill" (calomel, squill, and digitalis) and contributed greatly to the diuretic action of this combination of drugs. Despite its efficacy, calomel was displaced by the organic mercurials, because of its cathartic effect and uncertainty of intestinal absorption.Merbaphen (NOVASUROL), which contains mercury in organic linkage, was originally introduced as an antisyphilitic agent. Autor of the post: Undefined Following the introduction of potent Post Date: Wed, 15 Oct 2008 22:46:18 +0000 Its potent diuretic properties were soon discovered by Saxl and Heilig (see historical account by Vogl, 1950). For a period of approximately 30 years the organic mercurials were the preeminent diuretics. Following the introduction of potent, less toxic, oral diuretics their use greatly declined. Autor of the post: Undefined The pharmacological actions and therapeutic uses Post Date: Wed, 15 Oct 2008 22:32:32 +0000 Indeed, only two mercurial diuretics re-main as official drugs. Despite their current limited use, they will be discussed in detail since they have made major contributions to our basic understanding of renal tubular function and the therapeutic principles that underlie the mobilization of edema fluid.The pharmacological actions and therapeutic uses of all the organic mercurial diuretics are so similar that they can be discussed as a group. Autor of the post: Undefined The advantage of organic mercurials Post Date: Wed, 15 Oct 2008 22:13:35 +0000 Mechanism of Diuretic Action. The primary action of the mercurial diuretics is to depress tubular mechanisms responsible for the active reabsorption of sodium and chloride. The advantage of organic mercurials over inorganic compounds lies in the fact that they are rapidly excreted by the kidney. Autor of the post: Undefined The active form of mercurials Post Date: Wed, 15 Oct 2008 22:00:35 +0000 In this way, it is possible to produce reversible functional changes in the renal tubule with minimal danger of producing pathological lesions in the kidney or else-where that are characteristic of poisoning by the mercuric ion.Structure-Activity Relationship. The active form of mercurials has been a controversial subject. Autor of the post: Undefined (2) All diuretic organic mercurials Post Date: Wed, 15 Oct 2008 21:47:33 +0000 Present evidence suggests that the diuretic response is attributable to the intrarenal release of mercuric ions in vivo by rupture of the carbon-to-mercury bond, and that, with the drugs commonly employed, this occurs with only a minute fraction of the dose ad-ministered (Weiner et ah, 1962). This is based on the consideration of a wide variety of factors, as follows: (1) Some organic mercurials are diuretic, others are not; however, there is no specific structural configur-ation of the organic compound to which diuretic activity can be attributed. (2) All diuretic organic mercurials thus far examined are acid labile in ap-propriate in-vitro systems. Autor of the post: Undefined Most diuretic mercurials Post Date: Wed, 15 Oct 2008 21:30:20 +0000 This lability involves the rupture of the carbon-to-mercury bond and is cata-lyzed by thiols. Mercurials that are acid stable in such a system do not have diuretic activity, even though some may be rapidly excreted in the urine and may accumulate within the renal parenchyma. Most diuretic mercurials have the general formula OY I R—CH—CH2—Hg+, in which Ó is usually CH3 or another alkyl group, and R is a complex organic moiety, frequently with urea groupings or aromatic or heterocyclic rings. Autor of the post: Undefined When the beta carbon Post Date: Wed, 15 Oct 2008 21:16:52 +0000 The R substituents largely de-termine the compound's distribution and rate of excretion; they may also be of importance with re-spect to inducing hypersensitivity reactions. The type formula is acid labile. When the beta carbon is unsubstituted, as in R—CH2—CH2—Hg+, the com-pound is acid stable and nondiuretic. Autor of the post: Undefined In contrast to the organic Post Date: Wed, 15 Oct 2008 21:06:46 +0000 (3) An active diuretic has been shown to release small amounts of mercuric ion in kidney tissue (Clarkson et al, 1965). (4) Under some experimental conditions, inorganic mercuric salts are highly active as diuretics. In contrast to the organic mercurials, their effectiveness is only slightly influenced by changes in acid-base balance. Autor of the post: Undefined Mercurials are excreted as the cysteine Post Date: Wed, 15 Oct 2008 20:49:42 +0000 (5) Under a variety of different physi-ological conditions, there is a high correlation between the action of diuretic organic mercurials and the acidity of the urine. This suggests that urinary acidity may reflect the pH of an intrarenal site at which the organic compounds undergo metabolic alteration.Mercurials are excreted as the cysteine complex and probably circulate within the body fluids in combination with the thiol groups either of com-pounds of low molecular weight or of plasma pro-teins. 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