What Is Losartan?

Losartan (Kosova) (English name: Losartan; alias: Kosua, Losartan, Losartan) Production method: 2-butyl-4-chloro 5-hydroxymethylimidazole and sodium methoxide in methanol The solution was stirred for reaction. The resulting sodium salt was then stirred with 4-bromomethyl-2-cyanobiphenyl in dimethylformamide. The resulting compound was etherified and reacted with sodium azide in It is reacted in dimethylformamide to obtain losartan through acidic hydrolysis. Uses: Kosovo was first marketed in 1994 and has been approved for use in 93 countries to treat hypertension. Oral non-peptide angiotensin II receptor antagonist. It is mainly used for essential hypertension. Coxia is the first angiotensin II receptor antagonist (AIIA) antihypertensive drug. Properties: light yellow solid, melting point 183.5 184.5 .

Losartan (Kosova) (English name: Losartan; alias: Kosua, Losartan, Losartan) Preparation: 2-butyl-4-chloro 5-hydroxymethylimidazole and sodium methoxide The solution was stirred for reaction. The resulting sodium salt was then stirred with 4-bromomethyl-2-cyanobiphenyl in dimethylformamide. The resulting compound was etherified and reacted with sodium azide in It is reacted in dimethylformamide to obtain losartan through acidic hydrolysis. Uses: Kosovo was first marketed in 1994 and has been approved for use in 93 countries to treat hypertension. Oral non-peptide angiotensin II receptor antagonist. It is mainly used for essential hypertension. Coxia is the first angiotensin II receptor antagonist (AIIA) antihypertensive drug. Properties: light yellow solid, melting point 183.5 184.5 .

Drug Name: Losartan
Alias: Kosua, Losartan, Rosati
Foreign name: Losartan

Whether prescription drugs: prescription
Main indications: Treating hypertension
CAS: 124750-92-1

Introduction to Losartan Compounds

Losartan is the first angiotensin II receptor antagonist (AIIA) antihypertensive drug. Coxia blocks angiotensin II, a key sex hormone that regulates blood pressure in the body. ^[1]

Losartan Basic Information

Chinese name: Losartan

Chinese alias: Losartan carboxylate; 2-butyl-4-chloro-1-[(2- (1-H-tetrazol-5-yl) [1,1-biphenyl] -4-yl) formaldehyde Phenyl] -1-H-imidazole-5-carboxylic acid;

English name: 2-butyl-5-chloro-3-[[4- [2- (2H-tetrazol-5-yl) phenyl] phenyl] methyl] imidazole-4-carboxylic acid

English alias: 1H-Imidazole-5-carboxylic acid, 2-butyl-4-chloro-1-((2 '-(1H-tetrazol-5-yl) (1,1'-biphenyl) -4-yl) methyl ); Losartan carboxylic acid; 2-n-butyl-5-chloro-3- [2 '-(2H-tetrazol-5-yl) -biphenyl-4-ylmethyl] -3H-imidazole-4-carboxylic acid; E- 3174; Exp3174;

CAS number: 124750-92-1

Molecular formula: C ₂₂ H ₂₁ ClN ₆ O ₂

Molecular weight: 436.89400

Exact mass: 436.14100

PSA: 109.58000

LogP: 4.47270

Physicochemical properties of Losartan

Appearance and properties: light yellow solid

Density: 1.41g / cm

Melting point: 130-132ºC

Boiling point: 707.8ºC at 760mmHg

Flash point: 381.8ºC

Refractive index: 1.695

Vapor pressure: 5.04E-21mmHg at 25 ° C ^[2]

Losartan Toxicology Data

Male mice received oral losartan potassium with an LD50 of 2248 mg / kg (6744 mg / m2) (1124 times the maximum recommended daily dose for adults). The significant minimum lethal doses of this product in mice and rats are 1000mg / kg (3000mg / m2) and 2000mg / Kg (11800mg / m2), respectively, which are 500 times and 1000 times the maximum recommended daily dose for adults *. The potential toxicity of losartan potassium was evaluated by conducting a series of toxicity tests on monkeys for three months, rats and dogs, with multiple oral administrations for one year, and was found not to impede medication at therapeutic dose levels. ^[1]

Losartan related drug label information

Losartan

Kosovo; Losartan potassium; Losartan; Losartan; Losartan

Losartan

Losartan, Cozaar, Novartis

Losartan ingredients

Losartan potassium

Losartan pharmacological action

Losartan can specifically antagonize the angiotensin AT1 receptor, block the effects of angiotensin (AG) on arterial vasoconstriction, sympathetic nerve excitability, and increased baroreceptor sensitivity in circulating and local tissues. And continuous lowering of blood pressure, so that systolic and diastolic blood pressure. Still can reduce left ventricular hypertrophy, inhibit myocardial cell proliferation, delay or reverse myocardial remodeling, and improve left ventricular function. No adverse effects on blood glucose and blood lipid metabolism. It also has the function of improving renal hemodynamics, reducing renal vascular resistance, selectively expanding the arterioles, reducing the pressure in the glomeruli, reducing proteinuria, increasing renal blood flow and glomerular filtration rate, and protecting the kidneys. Delaying the process of chronic renal insufficiency, in particular, has a reverse effect on the deterioration of diabetic nephropathy.

Losartan pharmacokinetics

Losartan is rapidly absorbed orally, reaching its peak plasma concentration in 0.5 h to 1 h, with a peak plasma concentration of 80 ng / ml, a significant first pass effect in the liver, a bioavailability of 33% to 37%, and a plasma protein binding rate of 98.7%. It is difficult to cross the blood-brain barrier. Elimination half-life is 1.5h ~ 2h. E-3174, a pharmacologically active product, is formed in the liver through cytochrome P450 enzyme metabolism. Its activity is about 15 to 30 times stronger than that of the parent, the protein binding rate is greater than 99%, and the half-life is about 6 to 9 hours, which further strengthens the hypotensive effect. And lasting. Most of losartan and its metabolites are excreted by the liver and urinary tract. After oral administration of a 14C-labeled losartan, about 35% of the radioactivity appears in the urine and 58% in the feces.

Losartan adverse reactions

Other adverse reactions that have been reported after the listing of this product include:

Allergic reactions: Angioedema (including swelling of the throat and glottis that causes airway obstruction, and / or swelling of the face, lips, pharynx, and / or tongue) has been reported in a very small number of patients taking losartan. Some of these patients have previously experienced angioedema due to taking other drugs, including ACE inhibitors. Vasculitis, including Henoch-Schönlein (Hen-Sheer's) purpura, has been rarely reported.

Gastrointestinal reactions: hepatitis (rarely reported), abnormal liver function.

Blood system: Anemia.

Musculoskeletal System: Myalgia.

Nervous / Mental System: Migraine.

Respiratory system: Cough.

Skin: hives, itching.

Losartan laboratory test results

In clinically controlled trials of essential hypertension, few patients who use this product have clinically significant changes in laboratory parameters. Hyperkalemia occurred in 1.5% of patients (serum potassium> 5.5mEq / L). ALT elevations are rare and return to normal after discontinuation.

Losartan drug interactions

In clinical pharmacokinetic studies, it has been confirmed that there is no clinically significant drug interaction with hydrochlorothiazide, digoxin, warfarin, cimetidine, phenobarbital, ketoconazole, and erythromycin. Rifampicin and fluconazole have been reported to reduce active metabolite levels. The clinical outcomes of these interactions have not been evaluated.

As with other drugs that inhibit angiotensin and its effects, this product is used in combination with potassium-sparing diuretics (such as spironolactone, ampicillin, amiloride), potassium supplements, or potassium substitutes Can lead to elevated potassium.

Like other antihypertensive drugs, the nonsteroidal anti-inflammatory drug indomethacin reduces the antihypertensive effect of losartan.

Losartan precautions

Those who are allergic to this product are prohibited, pregnant women are prohibited. For patients with blood volume depletion who may have symptoms of hypotension after starting this product, consider reducing the dose or improving the symptoms before using this product.

1. Symptomatic hypotension can occur in patients with hypotension and inadequate vascular volume due to electrolyte / body fluid imbalance (such as those treated with high-dose diuretics). These conditions should be corrected before using this product, or a lower starting dose should be used. (See Dosage and Administration).

2. Liver function impairment

Pharmacokinetic data indicate that the plasma concentration of losartan in patients with liver cirrhosis is significantly increased, so patients with a history of liver impairment should consider using lower doses (see Dosage and Administration).

3 Impaired renal function

Due to the inhibition of the renin-angiotensin system, changes in renal function, including renal failure, have been reported in sensitive individuals; these changes in renal function can be restored after treatment is discontinued. For patients with bilateral renal artery stenosis or patients with unilateral kidney and renal artery stenosis, other drugs affecting the renin-angiotensin system can increase their blood urea and serum creatinine levels. There have been similar reports on the use of this product. These changes in kidney function can be restored after stopping treatment.

Losartan indication

hypertension.

Losartan dosage usage

Oral administration:

(1) For most patients, the starting and maintenance dose is usually 50 mg once daily. Maximum antihypertensive effect can be achieved after 3 to 6 weeks of treatment.

(2) In some patients, increasing the dose to 100 mg once daily can produce a further antihypertensive effect.

(3) For patients with insufficient vascular volume (such as those treated with high-dose diuretics), a starting dose of 25 mg once a day may be considered.

(4) For elderly patients or patients with renal impairment, including patients undergoing hemodialysis, it is not necessary to adjust the starting dose.

(5) Patients with a history of liver impairment should consider using lower doses.

(6) Can be used with other antihypertensive drugs.

(7) May be taken with or without food.

Losartan Taboo

Children, pregnant and lactating women.

Losartan specifications

Tablets 50mg x 7 tablets. ^[3-4]

Losartan application

Kosovo was first marketed in 1994 and is currently approved for use in 93 countries to treat hypertension. Hygeia has also been approved for use in 74 countries, including the United States.

Merck is currently in the process of applying for indications for Kosova for heart failure in some countries outside the United States. It is also registered in 12 countries for patients who are no longer suitable for treatment with angiotensin-converting enzyme inhibitors (ACEI).

Kosua and Hygea are the most prescribed drugs in the AIIA category, ranking third in sales of antihypertensive drugs worldwide. Since the advent of the drug, more than 10 million patients have been taking Coxusia and Hygea. As the most widely studied drug in this class, Cosco has published more than 4,000 scientific papers. Both Kosua and Hygea were developed by Merck.

In order to evaluate the efficacy of Kosova's treatment, especially in improving survival and reducing disability in patients with hypertension, heart failure and recent heart attacks, a series of large-scale endpoint studies have been conducted, including LIFE (Kosova Survival Treatment for Hypertension) and OPTIMAAL (Post-Infarction Study in Kosovo).

The Corsoline Kidney Protection Study (RENAAL) was presented at the annual meeting of the American Hypertension Association. This new landmark study has reached its main goal, demonstrating for the first time the protective effect of Kosova on the kidneys of patients with type 2 diabetic nephropathy with hypertension. The risk of end-stage renal disease was reduced by 28% in patients in the Kosoval subgroup. Usually these patients require dialysis and kidney transplantation to survive. ^[5]