Perindopril-Richter

Perindopril-Richter is an antihypertensive medication; the active ingredient is perindopril, which inhibits the effect of the angiotensin-converting enzyme, which is a catalyst for the conversion of angiotensin-1 into angiotensin-2 (peptide component), which has a vasoconstrictor effect. The result is a blockage of its stimulating effect on adrenal secretion of aldosterone.

Perindopril demonstrates therapeutic activity due to the metabolic component perindoprilat. The rest of the metabolic products do not slow down the action of ACE in vitro. [1]

Indications Perindopril-Richter

It is used to treat the following disorders:

• increased blood pressure indicators ;
• HF (to increase survival, reduce the need for hospitalizations and delay the progression of pathology);
• prevention of recurrence of ischemic stroke in persons with cerebrovascular disease;
• prevention of complications associated with the work of CVS in people with stable coronary artery disease (diagnosed).

Release form

The release of the medicinal substance is made in tablet form (volume 4 or 8 mg), 10 pieces each inside the cell plate. There are 3 such records inside the box.

Pharmacodynamics

Perindopril slows down the action of ACE, which converts angiotensin-1 to angiotensin-2.

The ACE element (or kininase 2) is an exopeptidase that promotes the transformation of angiotensin-1 into the vasoconstrictor component of angiotensin-2, and in addition to this, the destruction of bradykinin (has a vasodilating effect) to an inactive heptapeptide. Slowing down the action of ACE causes a decrease in the plasma values of angiotensin-2, which leads to an increase in the activity of plasma renin (the principle of "negative feedback") and a decrease in the volume of released aldosterone. [2]

In connection with the inactivation of bradykinin under the influence of ACE, with the inhibition of the latter, an increase in the activity of the tissue and circulating kallikrein-kinin structure is observed; along with this, the activation of the steam generator system is carried out. There is an assumption that this effect is an integral part of the developing hypotensive effect of ACE inhibitors and the appearance of certain negative symptoms characteristic of this class of drugs (for example, cough). [3]

Increased blood pressure values.

Perindopril has been shown to be highly effective in treating increased blood pressure of any degree of intensity. When using it, there is a decrease in the level of diastolic and systolic blood pressure (with vertical and horizontal positions of the patient).

Perindopril weakens the severity of OPSS, resulting in a decrease in blood pressure; at the same time, the speed of peripheral blood circulation increases (without changing the heart rate values).

Often, the medication increases the rate of renal circulation; in this case, the CF rate remains unchanged.

The antihypertensive effect of Perindopril-Richter reaches its peak level after 4-6 hours from the moment of a single oral administration and lasts for a period of 24 hours. After 24 hours, a significant (approximately 87-100%) residual slowdown in ACE action occurs.

A decrease in blood pressure values is noted quite quickly. In persons with a positive reaction to therapy, these values stabilize after a month, remaining without the appearance of tachyphylaxis.

After the end of therapy, there is no “rebound” reaction.

Perindopril demonstrates a vasodilating effect, helping to restore the elasticity of large arteries, as well as the structure of the vascular membranes of small arteries. Along with this, the drug weakens the left ventricular hypertrophy.

Use in combination with thiazide-type diuretics potentiates the intensity of the hypotensive effect. At the same time, the combination of an ACE inhibitor with a thiazide diuretic reduces the likelihood of hypokalemia associated with the introduction of diuretic drugs.

Taking medicine for CHF.

The medication stabilizes cardiac function by reducing post- and preloading relative to the heart. In persons with CHF who took perindopril, it is noted:

• a decrease in the level of filling pressure within the right and left cardiac ventricles;
• decrease in the intensity of OPSS;
• an increase in heart index and cardiac output.

It was revealed that the change in blood pressure values with the 1st use of drugs in a portion of 2.5 mg in people with CHF (grade 2-3 according to the NYHA registry), in accordance with statistics, was the same as in the placebo group.

Cerebrovascular pathology.

In people with a history of cerebrovascular disease, active use of drugs for a period of 4 years (monotherapy or a combination with indapamide), in addition to standard treatment, led to a decrease in blood pressure (diastolic and systolic). In addition, there was a significant decrease in the likelihood of developing fatal or disabling strokes, the main complications associated with CVS (among these, myocardial infarction, which can also lead to death), dementia due to stroke, and in addition to this pronounced deterioration of cognitive activity.

The above effects were observed in individuals with elevated blood pressure and normal blood pressure, without reference to gender and age, as well as a type of stroke and the absence / presence of diabetes mellitus.

Stable form of ischemic heart disease.

In people with a stable type of coronary artery disease, the administration of drugs at a dosage of 8 mg per day for a period of 4 years caused a noticeable decrease in the absolute probability of complications (death from CVD diseases, not leading to a lethal outcome of myocardial infarction or cardiac arrest with successful resuscitation) - by 1.9%.

In individuals who had previously had myocardial infarction or revascularization, the absolute probability decrease was 2.2% compared with the placebo category.

Pharmacokinetics

Absorption.

After oral administration, perindopril is absorbed at a high rate inside the gastrointestinal tract, reaching the plasma level Cmax after 1 hour. The term plasma half-life is 1 hour. Perindopril does not show drug activity.

About 27% of the total volume of the absorbed substance penetrates into the circulatory system in the form of the active metabolic element perindoprilat. In addition to perindoprilat, 5 more metabolic components are formed that do not have medicinal activity.

Plasma indicator Cmax of perindoprilat is observed after 3-4 hours from the moment of oral administration. Eating food decreases the rate of transformation of perindopril to perindoprilat, which changes the bioavailability value. Because of this, the medicine should be taken orally once a day, in the morning, before breakfast.

It was found that the size of the dosage of the drug and its plasma level have a linear relationship.

Distribution processes.

The distribution volumes of free-flowing perindoprilat are approximately 0.2 l / kg. Among proteins, the substance is synthesized mainly with ACE - it is equal to 20% and depends on the portion size of the drug.

Excretion.

Perindoprilat is excreted via the kidney, with a terminal half-life of the free fraction of about 17 hours; thus, the equilibrium values of the drug are noted after 4 days.

Pharmacokinetic parameters in certain categories of patients.

In the elderly and those with kidney failure or CHF, the excretion of perindoprilat is slowed down. The dialysis clearance of perindoprilat is 70 ml / min.

In persons with hepatic cirrhosis, the level of intrahepatic clearance of perindopril is halved. But the total volume of the forming perindoprilat does not change, which is why the dosage regimen does not need to be adjusted.

Dosing and administration

Perindopril-Richter is taken 1 time per day, orally (recommended in the morning, before meals). The initial dosage is 2-4 mg, and the maintenance dosage is 8 mg.

• Application for children

Perindopril-Richter is prohibited to appoint in pediatrics.

Use Perindopril-Richter during pregnancy

The medication is not used when planning conception, pregnancy, and also during breastfeeding.

Contraindications

It is contraindicated to use the medicine in the presence of intolerance to its elements.

Caution is required for such violations:

• hereditary or idiopathic type of Quincke's edema;
• allergy to other medicines from the ACE inhibitors subgroup;
• Quincke's edema, which developed after the use of drugs (in history);
• aortic stenosis;
• cardio- or cerebrovascular pathologies (including insufficiency of cerebral blood flow processes, coronary heart disease and coronary insufficiency);
• narrowing of the arteries of both kidneys (bilateral stenosis) or stenosis affecting the artery of a single kidney, as well as the condition after kidney transplantation;
• severe stages of autoimmune collagen type (scleroderma or SLE);
• suppression of hematopoietic processes inside the bone marrow associated with the introduction of immunosuppressants;
• diabetes;
• CRF (especially when combined with hyperkalemia);
• conditions against which there is a decrease in the BCC;
• elderly age.

Side effects Perindopril-Richter

The following side signs may be noted:

• decrease in blood pressure values, fatigue, headaches, fainting, dizziness;
• nausea, xerostomia, glossitis, diarrhea, abdominal pain, dysfunction of taste buds;
• muscle spasms, myalgia, vasculitis, arthritis, or arthralgia;
• dry type cough, bronchial spasm, itching, rashes, hyperhidrosis, urticaria, psoriasis, Quincke's edema, erythema multiforme, alopecia, photosensitivity and allergic dermatitis;
• anemia, agranulocytosis, thrombocyto- or leukopenia;
• cholestatic jaundice, an increase in hepatic transaminases, urea, plasma creatinine, cholestatic or hepatocellular type hepatitis, liver failure and pancreatitis;
• sinusitis, bronchitis, runny nose, change in voice timbre, pneumonia or alveolitis of the eosinophilic type;
• proteinuria, anuria or oliguria, as well as renal dysfunction;
• tachycardia, orthostatic symptoms, palpitations, fever and arrhythmia;
• impotence or gynecomastia.

Overdose

Signs of poisoning include agitation, decreased blood pressure, shock and anxiety, vascular insufficiency, fainting and bradycardia, as well as dizziness, cough, kidney / liver failure, arrhythmia, salt balance disorder, and hyperventilation.

It is necessary to carry out procedures that allow the excretion of the drug from the body (gastric lavage and the use of enterosorbents). The patient must be placed in a horizontal position. Excretion can be done through dialysis.

Interactions with other drugs

The likelihood of hyperkalemia increases in the case of the combined use of drugs with other substances that can provoke this violation: potassium salts or potassium-sparing diuretics, aliskiren, as well as aliskiren-containing agents, heparin, trimethoprim, ACE inhibitors, NSAIDs, antagonists among the endings of angiotensin-2 and immunodepressants tacrolimus or cyclosporine).

Administration together with aliskiren in diabetics or persons with renal dysfunctions (GFR index <60 ml / minute) increases the likelihood of hyperkalemia, a decrease in renal activity and an increase in the incidence of CVD diseases and mortality from them (in persons from these categories, this combination is prohibited).

Literary sources report that in persons with diagnosed atherosclerotic pathology, HF or diabetes mellitus, which are accompanied by lesions in the target organs, the administration of an ACE inhibitor together with the endings of angiotensin-2 leads to an increase in the incidence of syncope, hypotension, hyperkalemia and a weakening of renal activity ( this includes ARF) in comparison with the use of only one drug that affects the RAAS. The blockade of the double type (for example, when combining an ACE inhibitor with an antagonist of the endings of angiotensin-2) must be limited to individual situations when careful monitoring of renal activity and blood pressure and potassium parameters is performed.

Use together with estramustine can provoke an increase in the likelihood of side signs (among them Quincke's edema).

The combination of medication with lithium substances can reversibly increase serum lithium levels and the resulting toxic symptoms (therefore, such a compound is not used).

Administration together with antidiabetic drugs (oral hypoglycemic drugs and insulin) should be done with extreme caution, since ACE inhibitors, including perindopril, are capable of potentiating the antidiabetic activity of these drugs, up to the appearance of hypoglycemia. Typically, this effect develops during the first weeks of combination treatment in people with renal dysfunction.

Baclofen potentiates the antihypertensive effect of the drug; in the case of such a combination of drugs, it may be necessary to adjust the portion of the latter.

In persons using diuretics (especially excreting salts or liquid), at the initial stage of treatment with Perindopril-Richter, a strong decrease in blood pressure values is possible (this risk can be reduced by eliminating the diuretic and replenishing the loss of salts or liquid before using the drug). In addition, a method with the introduction of perindopril in a small initial portion, followed by its gradual increase, can be used.

In the case of CHF, when using diuretics, the drug is administered in low portions, possibly after reducing the potassium-sparing type of diuretic administered in combination. With any scheme, during the first weeks of using an ACE inhibitor, it is necessary to monitor renal activity (creatinine level).

The use of spironolactone or eplerenone in portions of 12.5-50 mg per day, as well as ACE inhibitors (among them perindopril) in small dosages.

In the case of treatment of HF 2-4 functional type according to the NYHA rating with a left ventricular ejection fraction of <40%, as well as previously used ACE inhibitors and loop-type diuretics, there is a possibility of hyperkalemia (possibly fatal), especially if instructions are not followed, concerning this combination. Before using the specified combination, you should make sure that the patient does not have renal dysfunction and hyperkalemia. It is required to constantly monitor blood levels of potassium and creatinine - every week during the 1st month of therapy, and then every month.

The use of the drug in combination with NSAIDs (aspirin in a dosage with anti-inflammatory activity, indiscriminate NSAIDs and substances that slow down the action of COX-2) can provoke a decrease in the hypotensive activity of ACE inhibitors.

The administration of an ACE inhibitor in combination with NSAIDs causes a deterioration in renal function (for example, ARF) and an increase in serum potassium levels, especially in people with impaired renal function. This combination is used with caution in the elderly. Patients need to consume a sufficient amount of fluids; it is required to closely monitor renal function (at the beginning of therapy and in its further process).

The antihypertensive effect of perindopril is potentiated in the case of combined use with other antihypertensive drugs and vasodilators (including nitrates with a prolonged and short type of effect).

The use of ACE inhibitors in combination with gliptins (saxagliptin with linagliptin, vitagliptin and sitagliptin) increases the likelihood of Quincke's edema due to the inhibition exerted by gliptin in relation to the action of dipeptidyl peptidase-4.

Taking medication with antipsychotics, tricyclics and substances for general anesthesia can potentiate the hypotensive effect.

The introduction of sympathomimetics can reduce the hypotensive activity of Perindopril-Richter.

The use of ACE inhibitors in people who are injected intravenously with gold substances (such as aurothiomalate Na) causes the development of a symptom complex, against the background of which vomiting, facial hyperemia, a decrease in blood pressure and nausea are noted.

Storage conditions

Perindopril-Richter is required to be stored at temperatures within 15-30 ° C.

Shelf life

Perindopril-Richter can be used for a 36-month term from the date of sale of the therapeutic agent.

Analogs

Analogs of drugs are the medicines Viakoram, Kosirel and Amlessa with Bi-Prestarium, and besides this Coverex, Peristar with Amlodipine + Perindopril, Parnavel and Amlopress. In addition, the list includes Perlikor, Noliprel and Arentopress, Perinpress with Ko-Prenessa, Erupnil and Hypernik with Ordilat, as well as Hyten and Pyristar.