Saluretics

Sulfonamides derived from sulfanilamide (p-arninoben2enesulfonainide) are commonly referred to as sulfa dmgs. Although several dmg classes are characterized by the presence of a sulfonamide function, eg, hypoglycemics, carbonic anhydrase inhibitors, saluretics, and tubular transport inhibitors, the antibacterial sulfonamides have become classified as the sulfa dmgs. Therapeutically active derivatives are usually substituted on the N nitrogen the position is generally unsubstituted. These features are illustrated by the stmctures of sulfanilamide (1) and sulfadiazine (2)... 

Muzolimine (710), a 1-substituted 2-pyrazolin-5-one derivative, is a highly active diuretic, differing from the structures of other diuretics since it contains neither a sulfonamide nor a carboxyl group. It has a saluretic effect similar to furosemide and acts in the proximal tubule and in the medullary portion of the ascending limb of the loop of Henle. Pharmacokinetic studies in dogs, healthy volunteers and in patients with renal insufficiency show that the compound is readily absorbed after oral administration (B-80MI40406). 

Diuretics (saluretics) elicit increased production of urine (diuresis). In the strict sense, the term is applied to drugs with a direct renal action. The predominant action of such agents is to augment urine excretion by inhibiting the reabsorption of NaCl and water. 

Modern diuretics (natriuretics, saluretics), as used in the treatment of hypertension and heart failure, are administered with the aim to enhance the renal excretion of sodium ions and water. Older diuretics, such as the osmotic diuretic agents, are of little interest in the treatment of the aforementioned cardiovascular disorders, but may be used to lower intracranial pressure associated with brain edema. 

IV administration of furosemide produces prompt relief in acute pulmonary edema (acute left ventricular failure, following myocardial infarction). This is due to the vasodilator action that precedes the saluretic action. 

Trichlormethiazide is often given in combination with dexamethasone because in this way effects can be achieved with a minimum dosage of trichlormethiazide, since tire two drugs are complementary in their action. Studies in humans and experimental animals have shown that trichlormethiazide presents a favorable pattern of lower potassium excretion than the other thiazides. The clinically determined saluretic potency of trichlormethiazide was estimated to be 10-20 times lower than that of hydrochlorothiazide and 100-200 times lower than that of chlorothiazide this results in decrease in the incidence of hypokalemic manifestations. 

Some saluretic-diuretic agents, like ethacrynic acid, are inactive in the rat, when given orally. Moreover, uricosuric activity in mice is less reliable than that in primates. 

Figure 2.5 In addition to its antibacterial activity, sulfanilamide 11 (Figure 2.4) inhibits the enzyme carbonic anhydrase. Acetazolamide 12 is much more potent as a carbonic anhydrase inhibitor but its clinical use as diuretic was impaired by some serious side effects. Hydrochlorothiazide 13 is the prototype of orally active saluretic sulfonamide diuretics. Furosemide (frusemide) 14 and bumetanide 15 are so-called loop diuretics .

Mannitol Stimulation of osmotic diuresis is possible using mannitol (10-20% solution). (128) Mannitol is neither metabolized in the body nor reabsorbed by the tubules and is excreted almost totally through the kidney. Renal circulation and renal filtration are raised, and by reducing tubular absorption (= osmotic diuresis), water excretion is increased ( diuresis starter ). The saluretic effect is, however, relatively small. In the case of restricted renal function, application of mannitol is contraindicated. If necessary, the mannitol test (i.v. injection of 75 ml of a 20% solution) can be carried out beforehand. With enhanced diuresis of > 40 ml/hr, the kidneys still function adequately, so that it is possible to stimulate osmotic diuresis by means of a mannitol infusion. 

Schroeder G, Sannerstedt R, Werkoe L. Clinical experiences with ethacrynic acid, a new non-thiazide saluretic agent (MK-595). Acta Med Scand 1964 175 781-6. 

The renal saluretic response to loop diuretics is partially dependent on intact intrarenal prostaglandin produchon in the thick ascending loop of Henle. The decrease in the response to loop diuretics is mediated both by removing the inhibition of sodium chloride... 

HookJB, Blatt AH, Brody MJ, Williamson HE. Effects of several saluretic-diuretic agents on renal hemodynamics. J Pharmacol Exp Ther 1966 154 667-673. 

Bourke E, Asbury MJA, O Sullivan S, Gatenby PBB.The sites of action of bumetanide in man. Eur J Pharmacol 1973 23 283-289. Karlander S-G, Henning R Lundvall O. Renal effects of bumetanide, a new saluretic agent. Eur J Clin Pharmacol 1973 6 220-223. 

Because clhacryiiic acid induces a short-term incroas ii Ihe renal excretion rate of Na . Cl. K". and Ca. I a. natriuretic, chlorurctic. saluretic, kaliurelic. and culciuiti. agent. 

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