Diuretics Mercurial

Chloro-6-sulfonamido-4(3 f)quinazo]inones are more effective than the mercury diuretics and can be administered orally. The 1,2-dihydro derivatives are even more effective and one (59) has been marketed under the name "Quinethazone. ... 

Of historical interest, arsenical antibiotics (8.107) were once used to treat syphilis and mercurial diuretics (8.108) were once used to treat edema and to promote water excretion. Due to their high toxicity, neither is currently used. 

Organic mercurial diuretics also inhibit salt transport in the TAL but are no longer used because of their toxicity. 

There are a few common and long-known uses of heavy metal compounds which should be mentioned. The barium meal is used in gastrointestinal X-rays. It is administered as barium sulfate, the high electron scattering of barium ions providing X-ray opacity. Mercurial diuretics, derivatives of propan-2-ol, work by inhibition of sulfhydryl enzyme sites. These compounds are now becoming obsolete, however. 

Drugs that alter the pH of urine can significantly affect the renal excretion of other drugs. Acid urine increases the effectiveness of mercurial diuretics. It also accelerates the excretion of basic drugs such as meperidine, tricyclic antidepressants, amphetamines, and antihistamines. Acidic drugs, such as aspirin, streptomycin, phenobarbital, sulfonamides, nalidixic acid, and nitrofurantoin have been shown to increase renal clearance in alkaline urine (61). The possible effects of urine pH on the renal excretion of drugs has been illustrated by the observation that if urine is rendered sufficiently alkaline, the excretion of amphetamine is markedly delayed and effective blood levels, after a single dose, can be maintained for several days (62). 

Diuretic drug preparations have promoted urine formation. They are derivatives of mercury propanol RCH2CH(OH)CH2HgX, where R is a polar hydrophilic group. The mercury diuretic preparations act as ferment inhibitors (latter containing-. They also inhibit adenosine triphosphate (ATP). These properties led to the use of mercury drug compounds in the treatment of bacterial infections. In these cases, they interacted with -SH groups of the bacteria proteins. 

BatesMN. "Mercury amalgam dental fillings an epidemiologic assessment."IntJ Hyg Environ Health 2006 209 309-16 Riddle M, Gardner E, Beswick I, Filshie I. The nephrotic syndrome complicating mercurial diuretic therapy. Brit Med J 1958 1 1274-7. 

MunckO, Nissen Nl. Developmentof nephrotic syndrome during treatment with mercurial diuretics. Acta Med Scand 1956 153 397-413. 

Preedy LRK, Russel DS. Acute salt depletion associated with the nephrotic syndrome. Development during the treatment with a mercurial diuretic. Lancet 1953 2 1181-4. 

The phenoxyacetic acid structure had been found to be a good carrying moiety in organic mercury diuretics. 

The present classes of diuretic drugs have contributed much useful information to the chemist and to the biologist. From the mercurial diuretics, on the biological side, some facts have been learned about their site of action, if not the exact mechanism of action, and they have been helpful in the study of the site of the transport of various ions by the kidney. The importance of sulfhydryl enzyme systems has been demonstrated, although the specific enzyme has not been identified. On the chemical side, the chemist has learned about the structural requirements for useful activity, the nature of the carbon-mercury attachment, and the organic structures most useful as carrying moieties for mercury. 

Burston J, Darmady EM, Stranack E Nephrosis due to mercurial diuretics. Brit Med J 1958 1 1277-8. 

Ethacrynic acid (Table 10-11) is a powerful loop diuretic whose molecular mechanism of action is not fully clear. However, it has marked pharmacodynamic similarities to the mercurial diuretics such as merbaphen (see above) and mersalyl, both of which are also phenoxyacetic acid derivatives, as well as in vitro and in vivo comparability in its reaction with SH groups It competes with them for the same receptors. It is not surprising that an analogy, if not identity, of mechanism of action at the cellular level has been proposed. Equation 10.5, which illustrates a Michael-type addition, might represent a possible enzyme inactivation. 

The mercurial diuretics essentially contain in an organic molecule. They usually inhibit sodium reabsorption in the proximal tubuler and ascending loop of Henle. There may be slight effect in the distal tubule where inhibition of chloride reabsorption also occurs. The mercurials have been foimd to enhance excretion though potassium loss is less than that produced by many other diuretics. However, the overall action of mercurial diuretics is invariably increased by acidification of urine. The mercurial diuretics are not very much used in clinical practices due to their pronormced and marked side-effects viz., mercurialism, hypersensitivity and excessive diuresis which may lead to electrolyte depletion and vascular complications. Most of the mercurials are administered by intramuscular route and the availability of orally active diru etics has limited their use. 

The mechanism of action of the mercurial diuretics described under Section 13.2.1 are stated as under ... 

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. 

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