CENTOR

Centor - a drug from the category of angiotensin 2 antagonists.

[1], [2]

Indications Sentor

It is used in the treatment of such disorders:

• heart failure, having a chronic degree (it is possible to use only in combination therapy or if the patient is intolerant with regard to the drugs ACE inhibitors);
• increased values of blood pressure (this includes patients with the first type of diabetes mellitus in combination with proteinuria).

Release form

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

Pharmacodynamics

Losartan is an artificial antagonist of the endings of angiotensin 2 (type AT1), which is applied orally. The angiotensin 2 element is a vasoconstrictor with a potent effect, as well as the active hormone PAC - one of the most important pathophysiological factors for increasing blood pressure. This component is synthesized with the termination of AO1, located inside a variety of tissues (for example, inside the smooth muscles of blood vessels, and in addition to the heart with kidneys and adrenal glands), promoting the development of many important biological reactions, including the release of aldosterone and vasoconstriction. Together with this, angiotensin 2 has a stimulating effect on the process of reproduction of smooth muscle cells.

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

With the introduction of losartan, the plasma values of renin increase, resulting in an increase in similar values of angiotensin 2 (a similar effect is associated with the disabling of the negative retroactive effect provoked by angiotensin 2). But even with these effects in mind, the effect of drugs in the form of a decrease in blood pressure and a decrease in aldosterone values persists. This demonstrates the effectiveness of the drug in blocking the activity of the end of angiotensin 2.

Losartan demonstrates selective synthesis with the termination of AO1, not synthesizing and not blocking other hormonal endings or ion channels important from the regulation of the function of the CCC. At the same time, this element does not block the ACE activity (kininase 2, splitting bradykinin), which allows it to avoid the development of certain manifestations that do not have a direct connection with the blockade of the AT1 end (meaning the potentiation of reactions caused by bradykinin, such as the tendency to develop swellings ).

Losartan blocks the development of effects provoked by the action of angiotensin 1 and 2, without affecting the effects of bradykinin. In this case, ACE inhibits the effects caused by angiotensin-1, and potentiates the reaction 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 and losartan.

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

The active element of the drug maintains high-speed glomerular filtration rates, and at the same time reduces the filtration fraction. It also lowers intraplasma urea levels (mean value is <24 μmol / L), which remain at the same level with prolonged treatment.

Losartan does not affect the autonomic reflexes, but in addition to the plasma values of noradrenaline.

The drug in a dose of not more than 150 mg once a day does not affect the values of cholesterol with triglycerides, as well as the level of serum cholesterol in people with hypertension. Similar doses of losartan did not affect the blood sugar values when administered on an empty stomach.

[3], [4]

Pharmacokinetics

Absorption.

When administered orally, the absorption of losartan is quite good. The substance undergoes the process of primary metabolism, during which 1 active carboxyl degradation product and other metabolites that do not have drug activity are formed. The level of bioavailability of the substance is about 33%. The peak values of losartan, together with its active metabolic product, are noted after approximately 1 hour and 3-4 hours, respectively. The use of food does not lead to a significant change in pharmacokinetic parameters of drugs.

Distribution processes.

More than 99% of the active element with its active metabolic product is synthesized with proteins present in the blood plasma (mainly - with albumins). The distribution volume of the substance is 34 liters. Tests in 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 ingested portion is converted to an active degradation product. After oral administration of 14C-labeled losartan, the level of radioactivity of 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%) of losartan, the minimum volume of the metabolic product is formed.

In addition to the pharmacoactive decay product, a number of metabolites that do not have activity are also formed. The main ones are formed by the hydroxylation of the butyl side chain, while the less significant component is N-2-tetrazole-glucuronide.

Excretion.

The clearance level of the active substance is 600 ml / minute, and its active metabolite is 50 ml / minute. The clearance of these elements inside the kidneys is equal to 74 and 26 ml / minute, respectively. After taking drugs, about 4% of the unchanged component and 6% of the active decomposition product are excreted in the urine. The substances exhibit linear pharmacokinetic properties.

When you use medicines inside, the values of the active substance with its metabolite decrease polyexponentially. The terminal half-life of losartan is about 2 hours, the metabolic product is approximately 6-9 hours. At a daily dose of 0.1 g, there is no significant cumulation of both active elements of the drug inside the blood plasma.

Losartan, along with its metabolites, is excreted through the urethra, and also with bile.

After ingestion of 14C-losartan labeled with an isotope, about 35% of radioactivity is recorded in the urine, and in feces - another 58%.

[5], [6]

Dosing and administration

For any prescribed indications, tablets should be taken once a day at the same time of day. The medicine is allowed to use without binding to the reception of food, washing down tablets with ordinary water (1 glass).

Increased blood pressure.

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

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

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

To reduce the likelihood of complications and the risk of death, such patients should be prescribed 50 mg of the drug with a one-time use per day. In view of the changes in blood pressure, a small portion of hydrochlorothiazide can be added or dosage of losartan can be increased to 0.1 g once a day.

Providing protection of the kidneys in people with type 1 diabetes mellitus and proteinuria.

The size of the initial portion is 50 mg once a day. Taking into account the parameters of blood pressure, a single dose can be increased to 0.1 g.

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

With a heart failure.

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

Conditions in which hypovolemia is noted.

People with reduced BCC (for example, due to the introduction of high dosages of diuretics) should initially take the CENTOR in a daily dose equal to 25 mg (one-time intake).

Use in people with disorders of hepatic activity.

Persons with a history of these disorders should consider the option of using a lower dose of drugs.

Data on the use of the drug in people with severe forms of disorders are absent, therefore it is forbidden to assign it to this category of persons.

Childhood.

Information regarding the safety and drug effectiveness of the drug in the treatment of high blood pressure in children aged 6-18 years is limited. Little information is also available on the pharmacokinetic parameters when using drugs in infants older than 1 month with a high blood pressure level.

Children who are able to swallow tablets whole, and whose weight is in the range of 20-50 kg, should use CENTOR in a dose of 25 mg (once a day). In exceptional situations, dosage may be increased to the maximum allowable - 50 mg once per day. The portion size should be adjusted taking into account the influence of drugs on the values of blood pressure.

Children weighing more than 50 kg should take 50 mg once a day. If necessary, it is possible to increase the dosage to the maximum value - a single dose of 100 mg per day.

Children were not evaluated for daily doses larger than 1.4 mg / kg or 0.1 g. It is forbidden to prescribe drugs to children, the glomerular filtration rate is <30 ml / minute / 1.7Zm ², because There is also no corresponding information about such use.

Do not administer losartan to children who have liver problems.

[11]

Use Sentor during pregnancy

The sensor should not be given to pregnant women or to those who are at the planning stage of pregnancy. If pregnancy was detected at the stage of therapy, you should immediately stop taking the drug and replace it with an alternative drug that is allowed for use in pregnancy.

Since there is no data regarding the use of losartan in lactation, it is forbidden to prescribe it to nursing mothers. It is recommended to choose an alternative therapy with the use of medicines, whose safety profile for lactation reception has been studied more thoroughly. This applies especially to newborns and premature babies.

Contraindications

The main contraindications:

• the presence of high sensitivity with respect to the active element of the drug or other components thereof;
• functional hepatic disorders in severe degree.

[7], [8]

Side effects Sentor

Elevated values of blood pressure.

In tests in which adults with an essential form of hypertension took losartan, these side effects were identified:

• violations in the work of the National Assembly: often there is vertigo or dizziness. Sometimes headaches develop, muscle cramps, insomnia or a feeling of drowsiness;
• disorders of the heart: sometimes there is angina, palpitation or tachycardia;
• problems with vascular function: sometimes hypotonic syndrome develops (especially in persons with intravascular dehydration - people with heart failure in the severe stage, or during therapy with large portions of diuretics), rashes and dosage-dependent orthostatic collapse;
• disorders affecting digestive activity: occasionally there are dyspeptic symptoms, abdominal pains or constipation;
• manifestations affecting respiratory activity: rhinitis with pharyngitis and sinusitis, as well as cough and infection in the upper part of the respiratory ducts;
• general disorders: often a feeling of weakness, asthenia and swelling;
• indications of laboratory tests: clinically significant changes in standard laboratory values can occasionally be caused by drug use. Among these, a rare increase in ALT values (stabilization often occurs after withdrawal) and hyperkalemia (serum potassium levels> 5.5 mmol / l).

The patient has cardiac left ventricular hypertrophy.

Among the negative reactions:

• lesions of the NA function: often dizziness occurs;
• disorders of the functioning of the auditory organs: Vertigo often develops;
• systemic disorders: often there is a feeling of weakness or asthenia.

If the patient has CHF.

The main negative manifestations:

• disturbances in the work of the National Assembly: sometimes there are headaches or dizziness. Occasionally, paresthesia develops;
• problems with cardiac function: occasionally there is a stroke, syncope and atrial fibrillation;
• disorders of vascular activity: sometimes there is a decrease in blood pressure (this also includes orthostatic collapse);
• signs on the part of the organs of the sternum and mediastinum, as well as the respiratory system: sometimes dyspnea appears;
• disorders of digestive activity: occasionally there is nausea, diarrhea or vomiting;
• lesions of subcutaneous tissues and epidermis: sometimes there are rashes, hives or itching;
• systemic disorders: often a feeling of weakness or asthenia;
• Laboratory test data: Urea or serum creatinine or potassium levels sometimes increase.

People with elevated values of blood pressure and type 1 diabetes, against which kidney diseases are noted.

Among the violations:

• disorders affecting the work of the National Assembly: often there is dizziness;
• problems in the field of the vascular system: often lowering the level of blood pressure;
• systemic lesions: often there is a feeling of weakness or asthenia;
• information laboratory tests: often develops hyperkalemia or hypoglycemia.

Data from postmarketing research.

In postmarketing tests, the following negative manifestations were identified:

• disorders of lymphatic and hematopoietic functions: development of thrombocytopenia or anemia;
• damage to the auditory organs: the appearance of an ear ring;
• Immune disorders: Occasionally, symptoms of intolerance appear (such as Quincke's edema (this includes swelling in the area of the glottis and larynx, which causes obstruction of the respiratory ducts, and in addition swelling in the face, pharynx with tongue or lips) and anaphylactic manifestations);
• reactions from the NA: dysgeusia or migraine;
• symptoms affecting the sternum with mediastinum and the 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. Possible problems with liver function;
• lesions of the epidermis and subcutaneous layer: erythroderma or urticaria, and in addition to rashes, itching and photosensitivity;
• disruption of the function of connective tissue and musculoskeletal activity: arthralgia or myalgia, as well as rhabdomyolysis;
• disorders affecting the breast and reproductive organs: the development of impotence;
• problems with the work of the urinary system and kidneys: due to the slowing of the activity of the RAS, there were changes in the functioning of the kidneys, among which kidney failure is in people at risk. Such disorders are reversible if the treatment is stopped immediately;
• mental disorders: the state of depression;
• laboratory data: development of hyponatremia.

[9], [10]

Overdose

Among the signs of poisoning - taking into account the amount of intoxication, bradycardia or tachycardia can develop, as well as decrease the level of blood pressure. But in general, reports of the development of an overdose were not noted.

The form of therapy for poisoning depends on the duration of the time interval that has elapsed since the use of drugs, and in addition to the nature and severity of the manifestations of the disorder.

The most important thing in case of intoxication is to stabilize the CCC. It is necessary to appoint the victim to receive the appropriate portion of activated carbon. Next, you need to regularly monitor vital functions, adjusting these processes, if necessary. Remove losartan with its active decay products by hemodialysis will not work.

Interactions with other drugs

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

There are some data suggesting that the combination of the Centor with rifampicin, as well as fluconazole, leads to a decrease in the indices of the disintegration product of losartan within human blood. At the same time there is no officially confirmed information on these data.

Simultaneous use of drugs and diuretic preparations of potassium-sparing type (such as spironolactone, triamterene or amiloride) can lead to the development of hyperkalemia.

Combination with NSAIDs can cause disorders of kidney activity, and in addition increase the values of potassium. Such reactions can be eliminated. The combination of this category of drugs in the elderly requires constant monitoring of renal function during the entire period of therapy.

Simultaneous reception with lithium salts causes a curable increase in the values of lithium inside the blood, which is why its indicators must be constantly monitored.

The sensor can be combined with other antihypertensive medications, including insulin, diuretics and other drugs that are actively used to treat diabetes.

[12]

Storage conditions

The sender should be kept in a dry place, closed from the access of children. Temperature values are a maximum of 25 ° C.

Shelf life

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

[13]

Use in children

The efficacy and safety of medicinal use in children younger than 6 years of age are not defined, so this age category is not prescribed.

Analogues

Analogues of the medication are such drugs as Angisartan, Losar and Angizaar with Cosaar, Bloktran and Lorista, and besides Lozap, Tarnazol, Ripeys and others.

Reviews

The CENTOR receives good reviews about its drug effectiveness, and is positively evaluated because of its simplicity and ease of use. Among the advantages are the availability of a large number of different analogs that can replace the drug if necessary.

Among the shortcomings are the presence of a sufficiently large list of negative symptoms, and in addition to this contraindication.