Sentor

Sentor is a medication from the category of angiotensin 2 antagonists.

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Indications Centora

It is used in the treatment of the following disorders:

• chronic heart failure (can only be used as part of combination therapy or if the patient is intolerant to ACE inhibitors);
• elevated blood pressure values (this includes patients with type 1 diabetes mellitus in combination with proteinuria).

Release form

The release is made in the form of tablets, in the amount of 10 pieces inside a blister plate. The box contains 1 or 3 such plates.

Pharmacodynamics

Losartan is an artificial angiotensin 2 (AT1 type) terminal antagonist that is administered orally. The angiotensin 2 element is a potent vasoconstrictor and an active RAS hormone, one of the most important pathophysiological factors in increasing blood pressure. This component is synthesized with the AO1 terminal, which is located inside many tissues (for example, inside the smooth muscles of blood vessels, and also in the heart with kidneys and adrenal glands), promoting the development of many important biological reactions, including the release of aldosterone and vasoconstriction. Along with this, angiotensin 2 has a stimulating effect on the process of smooth muscle cell proliferation.

Losartan is selectively synthesized with the AO1 ending. In vitro and in vivo tests, this element with its pharmacoactive metabolic product (carboxylic acid) blocks all physiologically significant effects of angiotensin 2, without reference to the binding pathway and the source of its occurrence.

When losartan is administered, plasma renin values increase, resulting in an increase in similar values of angiotensin 2 (a similar effect is associated with the shutdown of the negative reverse action provoked by angiotensin 2). But even taking into account such effects, the effect of the drug in the form of a decrease in blood pressure and a decrease in aldosterone values is preserved. This demonstrates the effectiveness of the drug in blocking the activity of the angiotensin 2 terminal.

Losartan demonstrates selective synthesis with the AO1 ending, without being synthesized or blocking other hormonal endings or ion channels that are important for the regulation of the cardiovascular system function. At the same time, this element does not block the activity of ACE (kininase 2, which breaks down bradykinin), which allows it to avoid the development of some manifestations that are not directly related to the blockade of the AT1 ending (meaning the potentiation of reactions caused by bradykinin - such as the tendency to develop edema).

Losartan blocks the development of effects caused by the action of angiotensin 1 and 2, without affecting the effects of bradykinin. At the same time, ACE inhibitors block the effects caused by angiotensin 1 and potentiate the response to the action of bradykinin, while not affecting the corresponding effect of angiotensin 2. It is this effect that underlies the pharmacodynamic difference between ACE inhibitors and losartan.

In people with elevated blood pressure (without diabetes, but with proteinuria), the use of potassium losartan leads to a significant reduction in proteinuria, as well as periodic secretion of proteins with immunoglobulin type G.

The active element of the drug maintains the glomerular filtration rate and at the same time reduces the filtration fraction. It also reduces intraplasmic urea levels (average value - <24 μmol/l), which remain at the same level during prolonged treatment.

Losartan does not affect autonomic reflexes or plasma norepinephrine levels.

The drug in a dose of no more than 150 mg once a day does not affect the values of cholesterol with triglycerides, as well as the level of serum HDL-C in people with hypertension. Similar doses of losartan did not affect the values of sugar in the blood when taken on an empty stomach.

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Pharmacokinetics

Absorption.

When taken orally, losartan is absorbed quite well. The substance undergoes a process of primary metabolism, during which 1 active carboxyl decay product and other metabolites that do not have medicinal activity are formed. The level of bioavailability of the substance is approximately 33%. Peak values of losartan together with its active metabolic product are noted after approximately 1 hour and 3-4 hours, respectively. Food intake does not lead to a significant change in the pharmacokinetic parameters of the drug.

Distribution processes.

More than 99% of the active element with its active metabolic product is synthesized with proteins in the blood plasma (mainly with albumins). The distribution volume of the substance is 34 liters. Tests on rats have shown that only a small part of losartan can pass through the BBB (or it does not pass at all).

Exchange processes.

About 14% of the dose taken orally is converted into the active decay product. After oral administration of 14C-labeled losartan, the level of radioactivity in the blood plasma increases under the influence of the active element of the drug with its metabolite. In a small number of people (about 1%), a minimal amount of the metabolite is formed from losartan.

In addition to the pharmacoactive breakdown product, a number of inactive metabolites are also formed. The main ones are formed by hydroxylation of the butyl side chain, and a less significant component is N-2-tetrazole glucuronide.

Excretion.

The clearance rate of the active substance is 600 ml/minute, and its active metabolite is 50 ml/minute. The clearance of these elements in the kidneys is 74 and 26 ml/minute, respectively. After oral administration of the drug, approximately 4% of the unchanged component and 6% as an active decay product are excreted in the urine. The substances demonstrate linear pharmacokinetic properties.

When the drug is taken orally, the values of the active substance with its metabolite decrease polyexponentially. The terminal half-life of losartan is about 2 hours, the product of metabolism is about 6-9 hours. With a daily dose of 0.1 g, no significant accumulation of both active elements of the drug in the blood plasma is observed.

Losartan, together with its metabolites, is excreted through the urinary system, and also with bile.

Following oral administration of isotopically labeled 14C-losartan, approximately 35% of the radioactivity is detected in the urine and another 58% in the feces.

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Dosing and administration

For any prescribed indications, the tablets should be taken once a day at the same time of day. The medicine can be taken without reference to food intake, washing down the tablets with plain water (1 glass).

Elevated blood pressure.

Often, patients are prescribed a single dose of 50 mg of the drug per day (starting and maintenance dose). The maximum antihypertensive effect is achieved after 3-6 weeks of using Sentora. Some patients can increase the dosage to 0.1 g/day (taken in the morning).

The drug can be combined with other antihypertensive medications, especially diuretics (such as hydrochlorothiazide).

With elevated blood pressure values (in people with left ventricular hypertrophy diagnosed using ECG).

To reduce the likelihood of complications and the risk of death, such patients should be prescribed 50 mg of the drug once a day. Taking into account changes in blood pressure indicators, a small dose of hydrochlorothiazide can be added or the dosage of losartan can be increased to 0.1 g once a day.

Providing kidney protection in people with type 1 diabetes and proteinuria.

The initial dose is 50 mg once a day. Depending on blood pressure readings, the single dose can be increased to 0.1 g.

The drug can be combined with other antihypertensive drugs (such as Ca channel blockers, diuretics, drugs with central action or α- and β-adrenergic blockers), as well as with insulin and other drugs used for diabetes therapy (glitazones, sulfonylurea derivatives and α-glucosidase inhibitors).

For heart failure.

To eliminate this disorder, it is necessary to use the medicine in a starting dose of 12.5 mg/day. This dosage should be increased at weekly intervals and taking into account the patient's tolerance (it is necessary to reach the maintenance dose level, which is a single dose of 50 mg per day). The maximum permissible daily dose is 150 mg.

Conditions in which hypovolemia is observed.

People with reduced BCC (for example, due to the administration of high doses of diuretics) should initially take Sentor in a daily dose of 25 mg (single dose).

Use in people with liver dysfunction.

Individuals with a history of such disorders should consider using a lower dose of the drug.

There is no data on the use of the drug in people with severe forms of disorders, so it is prohibited to prescribe it to this category of people.

Childhood.

Information on the safety and medicinal efficacy of the drug in the treatment of high blood pressure in children aged 6-18 years is limited. There is also little information on the pharmacokinetic parameters when using the drug in infants over 1 month old with high blood pressure.

Children who are able to swallow tablets whole and whose weight is between 20 and 50 kg should take Sentor in a 25 mg dose (once per day). In exceptional situations, the dosage may be increased to the maximum permissible dose of 50 mg once per day. The dose size should be adjusted taking into account the effect of the drug on blood pressure values.

Children weighing more than 50 kg should take 50 mg of the drug once a day. If necessary, the dosage can be increased to the maximum value - a single dose of 100 mg per day.

No studies have been conducted in children with daily doses exceeding 1.4 mg/kg or 0.1 g. The drug should not be administered to children with a glomerular filtration rate of <30 ml/min/1.73 ^m2, as there is no relevant information on such use.

Losartan should not be given to children with liver problems.

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Use Centora during pregnancy

Sentor is prohibited to prescribe to pregnant women or those who are planning pregnancy. If pregnancy is detected at the stage of therapy, it is necessary to immediately stop taking the drug and replace it with an alternative drug that is approved for use during pregnancy.

Since there is no data on the use of losartan during lactation, it is prohibited to prescribe it to nursing mothers. It is recommended to select alternative therapy using medications whose safety profile for use during lactation has been studied more thoroughly. This is especially true for newborns and premature infants.

Contraindications

Main contraindications:

• the presence of high sensitivity to the active element of the drug or its other components;
• severe functional liver disorders.

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Side effects Centora

Elevated blood pressure values.

In tests in which adults with essential hypertension took losartan, the following side effects were found:

• disorders of the nervous system: vertigo or dizziness often appears. Sometimes headaches, muscle cramps, insomnia or a feeling of drowsiness develop;
• Cardiac disorders: sometimes angina pectoris, palpitations or tachycardia occur;
• problems with vascular function: sometimes hypotonic syndrome develops (especially in people with intravascular dehydration - people with severe heart failure; or during therapy using large doses of diuretic drugs), rashes and dose-dependent orthostatic collapse;
• disorders affecting digestive activity: dyspeptic symptoms, abdominal pain or constipation occasionally appear;
• manifestations affecting respiratory activity: rhinitis with pharyngitis and sinusitis, as well as cough and infection in the upper respiratory tract;
• general disorders: a feeling of weakness, asthenia and edema is often noted;
• Laboratory test results: clinically significant changes in standard laboratory values may occasionally be caused by taking the drug. These include rare increases in ALT values (which often stabilize after stopping the drug) and hyperkalemia (serum potassium levels >5.5 mmol/L).

The presence of left ventricular hypertrophy in the patient.

Among the negative reactions:

• damage to the nervous system function: dizziness is often observed;
• disorders of the auditory organs: vertigo often develops;
• systemic disorders: a feeling of weakness or asthenia often occurs.

If the patient has CHF.

Main negative effects:

• Disorders in the functioning of the nervous system: headaches or dizziness sometimes occur. Paresthesia occasionally develops;
• problems with cardiac function: stroke, fainting and atrial fibrillation are occasionally observed;
• vascular disorders: sometimes a decrease in blood pressure values is observed (this also includes orthostatic collapse);
• signs from the organs of the sternum and mediastinum, as well as the respiratory system: sometimes dyspnea appears;
• digestive disorders: nausea, diarrhea or vomiting occasionally occur;
• lesions of subcutaneous tissues and epidermis: sometimes rashes, urticaria or itching appear;
• systemic disorders: a feeling of weakness or asthenia often appears;
• laboratory test results: sometimes urea values or serum creatinine or potassium levels are increased.

People with high blood pressure and type 1 diabetes, which is accompanied by kidney disease.

Among the violations:

• disorders affecting the functioning of the nervous system: dizziness often occurs;
• problems in the vascular system: blood pressure levels often decrease;
• systemic lesions: a feeling of weakness or asthenia often occurs;
• laboratory test results: hyperkalemia or hypoglycemia often develops.

Post-marketing research data.

The following adverse reactions were identified during post-marketing testing:

• disorders of lymphatic and hematopoietic functions: development of thrombocytopenia or anemia;
• damage to the auditory organs: the appearance of tinnitus;
• immune disorders: occasionally, symptoms of intolerance appear (such as Quincke's edema (this includes swelling in the glottis and larynx, which causes obstruction of the respiratory tract, as well as swelling in the face, pharynx with tongue or lips) and anaphylactic reactions);
• reactions from the nervous system: dysgeusia or migraine;
• symptoms affecting the sternum with mediastinum and respiratory tract: the appearance of a cough;
• digestive disorders: vomiting or diarrhea, as well as pancreatitis;
• general disorders: the appearance of a feeling of malaise;
• manifestations in the hepatobiliary system: hepatitis is occasionally observed. Problems with liver function may occur;
• lesions of the epidermis and subcutaneous layer: erythroderma or urticaria, as well as rashes, itching and photosensitivity;
• disorders of connective tissue function and musculoskeletal activity: arthralgia or myalgia, as well as rhabdomyolysis;
• disorders affecting the mammary glands and reproductive organs: development of impotence;
• urinary and renal problems: due to the slowing of RAS activity, changes in kidney function have occurred, including renal failure in people at risk. Such disorders are reversible if treatment is stopped immediately;
• mental disorders: depression;
• laboratory data: development of hyponatremia.

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Overdose

Among the signs of poisoning - taking into account the volume of intoxication, bradycardia or tachycardia may develop, and the blood pressure level may decrease. But in general, there have been no reports of overdose.

The form of therapy for poisoning depends on the length of time that has passed since the drug was taken, and in addition, on the nature and severity of the manifestations of the disorder.

The most important thing in case of intoxication is to stabilize the work of the cardiovascular system. It is necessary to prescribe the victim to take an appropriate dose of activated carbon. Then it is necessary to regularly monitor vital functions, adjusting these processes if necessary. It will not be possible to remove losartan with its active decay products by hemodialysis.

Interactions with other drugs

The combined use of the drug with such substances as warfarin, hydrochlorothiazide, ketoconazole with cimetidine, and also digoxin with phenobarbital and erythromycin, does not cause significant drug reactions.

There is some evidence that the combination of Sentora with rifampicin and fluconazole leads to a decrease in the levels of the breakdown product of losartan in human blood. However, there is no officially confirmed information regarding this data.

Concomitant use of the drug and potassium-sparing diuretics (such as spironolactone, triamterene, or amiloride) may lead to the development of hyperkalemia.

Combination with NSAIDs may cause renal dysfunction, and in addition, an increase in potassium values. Such reactions can be eliminated. Combination of this category of drugs in elderly people requires constant monitoring of renal function during the entire period of therapy.

Concomitant administration with lithium salts causes a treatable increase in lithium levels in the blood, which is why its levels must be constantly monitored.

Sentor can be combined with other antihypertensive medications, including insulin, diuretics and other drugs actively used to treat diabetes.

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Storage conditions

Sentor should be kept in a dry place, out of reach of children. Temperature values are maximum 25°C.

Shelf life

Sentor can be used for 5 years from the date of release of the therapeutic drug.

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Use in children

The efficacy and safety of medicinal use in children under 6 years of age have not been determined, therefore the drug is not prescribed to this age category.

Analogues

Analogues of the drug are such drugs as Angisartan, Losar and Angizaar with Cozaar, Bloktran and Lorista, as well as Losap, Tarnazol, Ripace and others.

Reviews

Sentor receives good reviews for its medicinal effectiveness, and is also positively assessed due to its simplicity and ease of use. Among the advantages, there is also a large number of different analogues that can replace the drug if necessary.

Among the disadvantages, there is a fairly large list of negative symptoms, as well as contraindications.