化合物信息

Drug Groups

approved

Description

Torasemide (rINN) or torsemide (USAN) is a pyridine-sulfonylurea type loop diuretic mainly used in the management of edema associated with congestive heart failure. It is also used at low doses for the management of hypertension. It is marketed under the brand name Demadex. [Wikipedia]

Indication

For the treatment of edema associated with congestive heart failure, renal disease, or hepatic disease. Also for the treatment of hypertension alone or in combination with other antihypertensive agents.

Pharmacology

Torasemide (INN) or torsemide (USAN) is a novel loop diuretic belonging to pridine sulphonyl urea. It differs form other thiazide diuretics in that a double ring system is incorporated into its structure. Like thiazides, loop diuretics must be secreted into the tubular fluid by proximal tubule cells. In the thick ascending loop Na+ and Cl- reabsorption is accomplished by a Na⁺/K⁺/2Cl^- symporter. The thick ascending limb has a high reabsorptive capacity and is responsible for reabsorbing 25% of the filtered load of Na⁺. The loop diuretics act by blocking this symporter. Because of the large absorptive capacity and the amount of Na⁺ delivered to the ascending limb, loop diuretics have a profound diuretic action. In addition, more distal nephron segments do not have the reabsorptive capacity to compensate for this increased load. The osmotic gradient for water reabsorption is also reduced resulting in an increase in the amount of water excreted.

Toxicity

Symptoms of overdose include dehydration, hypovolemia, hypotension, hyponatremia, hypokalemia, hypochloremic alkalosis, and hemoconcentration. Oral LD₅₀ in rat is 5 g/kg, and intravenous LD₅₀ in rat is 500 mg/kg.

Affected Organisms

Biotransformation

Metabolized via the hepatic CYP2C8 to 5 metabolites. The major metabolite, M5, is pharmacologically inactive. There are 2 minor metabolites, M1, possessing one-tenth the activity of torasemide, and M3, equal in activity to torasemide. Overall, torasemide appears to account for 80% of the total diuretic activity, while metabolites M1 and M3 account for 9% and 11%, respectively.

Absorption

Rapidly absorbed following oral administration. Absolute bioavailability is 80%. Food has no effect on absorption.

Half Life

3.5 hours

Protein Binding

> 99%

Elimination

Torsemide is cleared from the circulation by both hepatic metabolism (approximately 80% of total clearance) and excretion into the urine (approximately 20% of total clearance in patients with normal renal function).

Distribution

* 12 to 15 L [normal adults or in patients with mild to moderate renal failure or congestive heart failure]

References

External Links