Studies on the mechanism and characteristics of action of a new phthalimidine diuretic, clorexolone

doi:10.1002/cpt196672212

Paper

Studies on the mechanism and characteristics of action of a new phthalimidine diuretic, clorexolone

Published Mar 1, 1966 · W. Baba, A. Lant, G. Wilson

Clinical Pharmacology & Therapeutics

Q1 SJR score

8

Citations

0

Influential Citations

Full textSemantic Scholar

Abstract

A study aimed at investigating the mechanism and characteristics of action of a new phthalimidine diuretic, clorexolone, has been undertaken in rats and in a group of twenty‐three normal human subiects under various experimental conditions. Hydroflumethiazide, a typical benzothiadiazine analogue, has been used as a standard of comparison. The pharmacological properties of clorexolone have been found to resemble closely those of hydroflumethiazide. Duration of clorexolone‐induced diuresis is, however, longer. At maximally effective doses, the natriuretic responses achieved by both drugs are not statistically different. Orally administered clorexolone is without effect on GFR and its action upon the nephron appears to be directed primarily at a tubular level. The cellular mechanism of clorexolone action does not involve significant inhibition of renal carbonic anhydrase in vivo since urinary bicarbonate excretion and pH remain unchanged after its administration. The natriuretic effect occurs independently of aldosterone antagonism and is, at least in part, due to selective inhibition of sodium reabsorption without water at the urinary diluting sites in the distal part of the nephron. The data do nat exclude the possibility of an additional interference with proximal processes of isoosmotic sodium reabsorption. The extent of the urinary potassium loss induced by clorexolone is linked to the degree of mineralocorticoid stimulation of the distal nephron K+‐H/Na+ competitive exchange system. In addition, significant increase in potassium excretion also occurs after clorexolone administration in adrenalectomized animals, a finding which implicates a direct action upon tubular handling of potassium ion independent of mineralocorticoid participation.

Non-RCT

Animal Study

Study Snapshot

Clorexolone acts as a natriuretic agent without significant inhibition of renal carbonic anhydrase, primarily at a tubular level, without affecting GFR or urinary bicarbonate excretion.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

Sign up to use Study Snapshot

Consensus is limited without an account. Create an account or sign in to get more searches and use the Study Snapshot.

Create an account

Paper

Studies on the mechanism and characteristics of action of a new phthalimidine diuretic, clorexolone

Sign up to use Study Snapshot

References

RENAL TUBULAR TRANSFER OF SODIUM, CHLORIDE AND POTASSIUM.

Single nephron studies provide unique insight into renal tubular transport of sodium, chloride, and potassium, revealing the countercurrent nature of the urinary concentrating mechanism and excluding the transtubular colloid-osmotic pressure gradient.

The relation between enzyme inhibition and physiological response in the carbonic anhydrase system.

Carbonic anhydrase is the dominant receptor in tissues for monosulfonamides, with 99% inhibition needed for physiological effects.

Renal Clearance of Polythiazide

Polythiazide has a low renal clearance due to high drug binding by plasma proteins and extensive reabsorption in the distal segment, with some secretion by the renal tubule.

Effect of chlorothiazide on electrolyte excretion in intact and adrenalectomized rats.

Chlorothiazide's diuretic effect is not due to mineralocorticoid antagonism, but rather a result of increased urine pH, sodium, chloride, bicarbonate, total solute, and water excretion in both intact and adrenalectomized rats.

The effects of infusions of chlorothiazide on urinary dilution and concentration in the dog.

Chlorothiazide infusions in dogs increase urinary sodium concentration and dilution, but do not lower TCH2O at any level of solute excretion.

Observations on Mechanism of Potassium Excretion due to Administration of Hydrochlorothiazide

Hydrochlorothiazide's potassium loss in rats is influenced by small amounts of diuretic-like steroids, with kaliuresis occurring only at large doses.

Citations

Studies on the mechanism and characteristics of action of a uricosuric diuretic, indacrinone (MK-196).

Indacrinone (MK-196) is a long-acting diuretic with uricosuric properties, increasing urinary volume and excretion of Na+ and Cl-, while maintaining urinary K+, Ca2+, Mg2+, and uric acid levels.

On the clinical evaluation of diuretics with particular reference to a new phthalimidine diuretic, clorexolone

Clorexolone is a potent diuretic with natriuretic action lasting at least 48 hours after oral administration, comparable to benzothiadiazine group diuretics, and no potentially adverse effects observed during prolonged therapy with potassium supplements.

Diuretics: Mechanism of Action and Clinical Application

Diuretics can be divided into four main groups based on their action on sodium reabsorption in the kidney, and their use in non-oedematous conditions like hypertension, diabetes insipidus, and hypercalciuria is increasing.

Insanity - a medical-legal enigma?

Insanity as a defense in criminal cases is primarily concerned with responsibility: does the accused suffer from mental disease so severe that he should not be held responsible for his act?