Torasemide

348.42000

348.42

W31X2H97FB

DTXSID2023690

C29506

QC03CA04|C03CA04|C - Cardiovascular system

2935009090

108.57000

2.7

Solid

1.283 g/cm3

163-164 °C

1.594

Water soluble

Store in original container in a cool dark place.

7.1None

7.1

NONH for all modes of transport

2

R36

S26; S37/39

UT7938000

Xi

P305 + P351 + P338

H319

|Warning|H319 (88.57%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]|P201, P202, P264, P280, P281, P305+P351+P338, P308+P313, P337+P313, P405, and P501|Aggregated GHS information provided by 108 companies from 9 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

The oral LD50 of torasemide in the rat is 5 g/kg. When overdose occurs, there is a marked diuresis with the danger of loss of fluid and electrolytes which has been seen to lead to somnolence, confusion, hypotension, hyponatremia, hypokalemia, hypochloremic alkalosis, hemoconcentration dehydration and circulatory collapse. This effects can include some gastrointestinal disturbances. There is no increase in tumor incidence with torasemide and it is proven to not be mutagenic, not fetotoxic or teratogenic.

Torasemide is found to be highly bound to plasma proteins, representing over 99% of the administered dose.

Torasemide is indicated for the treatment of edema associated with congestive heart failure, renal or hepatic diseases. From this condition, it has been observed that torasemide is very effective in cases of kidney failure. Edema is considered when swelling is observed due to the trap of fluid in the body tissue. It is mainly located in feet, ankles and legs but it can also be extended to other parts such as face, hands and abdomen or even the whole body. As well, torasemide is approved to be used as an antihypertensive agent either alone or in combination with other antihypertensives. Hypertension is defined by the presence of high blood pressure. This is caused by an increase in the amount of blood pumped which in order produces the narrowing of the arteries.|FDA Label|For treatment of clinical signs related to congestive heart failure in dogs, including pulmonary oedema.|For treatment of clinical signs, including oedema and effusion, related to congestive heart failure in dogs.|Treatment of heart failure, Treatment of hypertension

It is widely known that administration of torasemide can attenuate renal injury and reduce the severity of acute renal failure. This effect is obtained by increasing urine output and hence, facilitating fluid, acid-base and potassium control. This effect is obtained by the increase in the excretion of urinary sodium and chloride. Several reports have indicated that torasemide presents a long-lasting diuresis and less potassium excretion which can be explained by the effect that torasemide has on the renin-angiotensin-aldosterone system. This effect is very similar to the effect observed with the administration of combination therapy with [furosemide] and [spironolactone] and it is characterized by a decrease in plasma brain natriuretic peptide and improved measurements of left ventricular function. Above the aforementioned effect, torasemide presents a dual effect .in which the inhibition of aldosterone which donates torasemide with a potassium-sparing action. Torasemide has been shown to reduce extracellular fluid volume and blood pressure in hypertensive patients suffering from chronic kidney disease. As well, some reports have indicated that torasemide can reduce myocardial fibrosis by reducing the collagen accumulation. This effect is suggested to be related to the decrease in aldosterone which in order has been shown to reduce the production of the enzyme procollagen type I carboxy-terminal proteinase which is known to be overexpressed in heart failure patients.

Drugs used in the treatment of acute or chronic vascular HYPERTENSION regardless of pharmacological mechanism. Among the antihypertensive agents are DIURETICS; (especially DIURETICS, THIAZIDE); ADRENERGIC BETA-ANTAGONISTS; ADRENERGIC ALPHA-ANTAGONISTS; ANGIOTENSIN-CONVERTING ENZYME INHIBITORS; CALCIUM CHANNEL BLOCKERS; GANGLIONIC BLOCKERS; and VASODILATOR AGENTS. (See all compounds classified as Antihypertensive Agents.)|Agents that promote the excretion of urine through their effects on kidney function. (See all compounds classified as Diuretics.)|Agents that inhibit SODIUM-POTASSIUM-CHLORIDE SYMPORTERS which are concentrated in the thick ascending limb at the junction of the LOOP OF HENLE and KIDNEY TUBULES, DISTAL. They act as DIURETICS. Excess use is associated with HYPOKALEMIA and HYPERGLYCEMIA. (See all compounds classified as Sodium Potassium Chloride Symporter Inhibitors.)

Torasemide is the diuretic with the highest oral bioavailability even in advanced stages of chronic kidney disease. This bioavailability tends to be higher than 80% regardless of the patient condition. The maximal serum concentration is reported to be of 1 hour and the absorption parameters are not affected by its use concomitantly with food.|Torasemide is mainly hepatically processed and excreted in the feces from which about 70-80% of the administered dose is excreted by this pathway. On the other hand, about 20-30% of the administered dose is found in the urine.|The volume of distribution of torasemide is 0.2 L/kg.|The clearance rate of torasemide is considerably reduced by the presence of renal disorders.

Torasemide is extensively metabolized in the liver and only 20% of the dose remains unchanged and it is recovered in the urine. Metabolized via the hepatic CYP2C8 and CYP2C9 mainly by reactions of hydroxylation, oxidation and reduction 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.|Torasemide has known human metabolites that include N-[(4-{[3-(hydroxymethyl)phenyl]imino}-1,4-dihydropyridin-3-yl)sulfonyl]propane-2-carbamimidic acid.

The average half-life of torasemide is 3.5 hours.

As mentioned above, torasemide is part of the loop diuretics and thus, it acts by reducing the oxygen demand in the medullary thick ascending loop of Henle by inhibiting the Na+/K+/Cl- pump on the luminal cell membrane surface. This action is obtained by the binding of torasemide to a chloride ion-binding site of the transport molecule. Torasemide is known to have an effect in the renin-angiotensin-aldosterone system by inhibiting the downstream cascade after the activation of angiotensin II. This inhibition will produce a secondary effect marked by the reduction of the expression of aldosterone synthase, TGF-B1 and thromboxane A2 and a reduction on the aldosterone receptor binding.

1-isopropyl-3-((4-(3-methylphenylamino)pyridine)-3-sulfonyl)urea

Veterinary drugs -> Isemid -> EMA Drug Category|High-ceiling diuretics, Sulfonamides, plain -> Veterinary pharmacotherapeutic group|Veterinary drugs -> UpCard -> EMA Drug Category|Sulfonamides, plain, High-ceiling diuretics -> Veterinary pharmacotherapeutic group|Human Drugs -> EU pediatric investigation plans|Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients|Pharmaceuticals