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Acute effects of alkylating agents on canine renal function. 1. [4-(2-Bromoalkanoyl)phenoxy]acetic acids.

A group of [4-(2-bromoalkanoyl)phenoxy]acetic acids was studied to determine if there was an association between the alkylating ability and the diuretic activity of its members. Acute studies in dogs revealed that there is not a consistent correlation in the alkylating potential of these alpha-bromo ketones and their ability to induce a diuretic response. In addition, pretreatment of dogs with the various alpha-bromo ketones did not alter the diuretic activity normally observed with ethacrynic acid (EA). The role of chemical-induced renal tissue alkylation in the initiation of a diuresis or a nephrotoxic response is discussed.

Alkylating Agents↗

[Unconventional treatment of severe heart failure in the elderly].

In the elderly, congestive heart failure is common and associated with significant morbidity and mortality. Comprehensive management of heart failure improves functional status and decreases mortality. Diuretics remain the mainstay in treating congestive heart failure. However, some patients are resistant to diuretics. This is a serious problem as it seems to represent a final manifestation of congestive heart failure. In an 85-year-old woman diuretic resistance was recognized as the cause of failure of conventional diuretic therapy. When the dose of furosemide was rapidly increased from 120 mg per os to 1000 mg i.v. within 4 days, diuresis began and there was dramatic improvement in her condition. The dose was then gradually decreased until a conventional maintenance dose of 200 mg/day per os was reached. This dose was sufficient to keep her heart failure under control.

Aged↗

Aquaretic agents: a new potential treatment of dilutional hyponatremia in cirrhosis.

An impairment in the renal capacity to excrete water is a common finding in patients with cirrhosis and ascites. In some patients this abnormality is minor since it is only detectable by measuring urine volume or free water clearance after a water load and is not associated with changes in plasma osmolality and serum sodium concentration. In other patients the intensity of the disorder is such that they are not able to eliminate their regular water intake, and develop dilutional hyponatremia and hypoosmolality. The renal capacity to excrete water is one of the most useful prognostic indicators in patients with cirrhosis and ascites. The main pathogenic factors of the impaired water excretion in human cirrhosis are an increased plasma concentration of AVP, a reduced renal synthesis of prostaglandins and a reduced delivery of filtrate to the ascending limb of the loop of Henle. At present, no effective therapy exists for the management of this complication. Two types of drugs have recently been reported that selectively increase renal water excretion, antagonists of the AVP V2 receptors and kappa-opioid agonists. Experimental studies have shown that both substances improve water excretion in rats with cirrhosis and ascites. Therefore, these drugs may represent a novel therapeutic tool in the management of spontaneous hyponatremia in cirrhosis and in the treatment or prevention of diuretic-induced hyponatremia in these patients.

Animals↗

[Anti-ischemic action of diuretics].

Rat experiments were conducted for comparative study of the effect of diuretics, injected into the organism in a single dose prior to two-and-a-half-hour ischemia of an only kidney and after it, on the extent of the kidney affection and survival of the animals. It was established that furosemid, etacryn acid and mannitol exert a preventive protective effect in ischemia of the kidneys and considerably increase the survival of rats as compared to the control-group. Analysis of the renal function in the first five days of the postischemic period testifies to the property of the above-mentioned diuretics for normalizing excretory processes on the 2nd-4th days of the action of the injuring agent, and for relieving or shortening the oligoanuric phase of acute renal failure. The significance of metabolic shifts, intratubular hydrodynamics and vascular microcirculation in the mechanism of the protective effect of diuretics in ischemia of the kidneys is discussed.

Animals↗