home Folk remedies A new word in cardiology is left-handed isomers. Possibilities of amlodipine isomer in the treatment of arterial hypertension

A new word in cardiology is left-handed isomers. Possibilities of amlodipine isomer in the treatment of arterial hypertension

Levamlodipine INN

International name: Levamlodipine

Dosage form: tablets

Pharmachologic effect:

BMKK, dihydropyridine derivative, S (-) isomer of amlodipine; has a more pronounced pharmacological effect than R (+) amlodipine. Blocks Ca2+ channels, inhibits the transmembrane transition of Ca2+ into the cell (to a greater extent into vascular smooth muscle cells than into cardiomyocytes). It has an antianginal effect, as well as a long-term dose-dependent hypotensive effect. A single dose provides a clinically significant decrease in blood pressure 2-4 hours after administration, which persists for 24 hours (in the supine and standing position).

Pharmacokinetics:

The absorption of levamlodipine in the gastrointestinal tract does not change with food intake. Bioavailability - 65%; has an effect through the liver. Cmax - 7.229-9.371 ng/ml, TCmax - 1.85-3.61 h. TCss - 7 days. Protein binding - 93%. Volume of distribution - 21 l/kg; Most of it is distributed in the tissues, the smaller part is distributed in the blood. Penetrates through the BBB. Metabolism is 90% carried out in the liver (slow but extensive) with the formation of inactive metabolites. Total clearance - 0.116 ml/s/kg (7 ml/min/kg, 0.42 l/h/kg). After the first dose, T1/2 is 14.62-68.88 hours, with repeated doses, T1/2 is 45 hours. For liver failure, T1/2 is 60 hours (long-term use increases the accumulation of the drug). In patients over 65 years of age, T1/2 is 65 hours (which has no clinical significance). It is excreted by the kidneys (60% in the form of metabolites, 10% unchanged), intestines (20-25%), and also with breast milk. It is not removed by hemodialysis.

Indications:

Arterial hypertension stage I (in monotherapy or in combination with other antihypertensive drugs).

Contraindications:

Hypersensitivity, Prinzmetal's angina, severe arterial hypotension, collapse, cardiogenic shock, age up to 18 years (efficacy and safety have not been established), pregnancy, lactation. With caution. SSSU, CHF of non-ischemic etiology in the stage of decompensation, moderate arterial hypotension, aortic and mitral stenosis, HOCM, myocardial infarction (and within 1 month after), diabetes mellitus, lipid metabolism disorders, liver failure, old age.

Dosage regimen:

Orally, initial dose - 2.5 mg 1 time per day, maximum dose - 5 mg 1 time per day.

Side effects:

From the cardiovascular system: palpitations, shortness of breath, marked decrease in blood pressure, fainting, vasculitis, swelling of the lower extremities, blood to the skin of the face, rarely - arrhythmia (bradycardia, ventricular tachycardia, atrial fibrillation), chest pain, orthostatic hypotension, very rarely - development or worsening HF, migraine. From the nervous system: dizziness, headache, fatigue, drowsiness, emotional lability; rarely - convulsions, loss of consciousness, hyperesthesia, nervousness, paresthesia, tremor, vertigo, asthenia, malaise, insomnia, depression, unusual dreams; very rarely - ataxia, apathy, agitation, amnesia. From the digestive system: nausea, vomiting, epigastric pain; rarely - increased enzyme activity and jaundice (caused by cholestasis), pancreatitis, dry mouth, flatulence, hyperplasia of the gingival mucosa, constipation or diarrhea; very rarely - gastritis, increased appetite. From the genitourinary system: rarely - pollakiuria, painful urge to urinate, nocturia, decreased potency; very rarely - dysuria, polyuria. From the skin: very rarely - xeroderma, alopecia, dermatitis, purpura, skin discoloration. Allergic reactions: maculopapular erythematous rash, urticaria, skin itching, angioedema. From the musculoskeletal system: rarely - arthralgia, arthrosis, myalgia (with long-term use); very rarely - myasthenia. From the senses: blurred vision, conjunctivitis, diplopia, eye pain, impaired accommodation, xerophthalmia; tinnitus, impaired taste, rhinitis, parosmia. Other: rarely - gynecomastia, hyperuricemia, weight gain/loss, thrombocytopenia, leukopenia, hyperglycemia, back pain, dyspnea, nosebleeds, hyperhidrosis, thirst; very rarely - cold sticky sweat, cough. Overdose. Symptoms: marked decrease in blood pressure, tachycardia, excessive peripheral vasodilation. Treatment: gastric lavage, taking activated charcoal, monitoring the functions of the cardiovascular system, respiratory and excretory systems, and bcc. It is necessary to give the patient a horizontal position with raised limbs; vasoconstrictor drugs (in the absence of contraindications); IV calcium gluconate (to eliminate blockade of Ca2+ channels).

Special instructions:

During the treatment period, it is necessary to control body weight, Na+ intake (appropriate diet), maintain dental hygiene, and visit the dentist (to prevent pain, bleeding and hyperplasia of the gum mucosa). In elderly patients, T1/2 and drug clearance are prolonged, so careful monitoring is necessary when increasing the dose. Despite the absence of BMCC syndrome, a gradual dose reduction is recommended before stopping treatment. During the treatment period, care must be taken when driving vehicles and engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Interaction:

Inhibitors of microsomal oxidation increase the concentration of the drug in the blood plasma, increasing the risk of side effects, while inducers of microsomal liver enzymes reduce it. Alpha adrenergic agonists, estrogens (Na+ retention), sympathomimetics weaken the hypotensive effect. Thiazide and diuretics, beta-blockers, verapamil, ACE inhibitors, nitrates enhance the antianginal and hypotensive effects. Amiodarone, quinidine, alpha-blockers, neuroleptics, BMCC may enhance the hypotensive effect. Li+ preparations - risk of increased neurotoxicity (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus). Ca2+ preparations may reduce the effect of BMCC. Procainamide, quinidine and other drugs that cause prolongation of the QT interval enhance the negative inotropic effect and increase the risk of significant prolongation of the QT interval.

According to modern recommendations for the treatment of arterial hypertension (AH), long-acting dihydropyridine CCBs are one of five classes of antihypertensive drugs, the effectiveness and safety of which have been proven in clinical studies in recent years. Long-acting dihydropyridine CCBs are highly effective in preventing major cardiovascular events and stroke. Drugs of this class are well tolerated and can be used without significant restrictions as monotherapy or in combination with other antihypertensive drugs in patients with mild, moderate and severe hypertension, regardless of age. Today, dihydropyridine CCBs are indicated as the drugs of choice in elderly patients with isolated systolic hypertension, left ventricular myocardial hypertrophy, peripheral vascular diseases, during pregnancy, and atherosclerosis of the carotid and coronary arteries.

The use of CCBs is indicated in the treatment of coronary heart disease (CHD): stable angina pectoris, vasospastic angina. The use of dihydropyridine CCBs is accompanied by an effective reduction in the frequency, intensity and duration of anginal episodes and episodes of silent myocardial ischemia. These drugs have a significant coronary dilating effect, which helps to increase blood delivery to the myocardium; cause peripheral vasodilation, reduce total peripheral vascular resistance and reduce left ventricular afterload, which ultimately leads to a decrease in myocardial oxygen consumption. The PREVENT study proved the effect of CCBs on reducing the progression of atherosclerosis of the carotid arteries: amlodipine had an independent anti-atherosclerotic effect and helped reduce the risk of developing coronary complications in patients with coronary artery disease. It is discussed that the antiatherogenic effect of CCBs is associated with their antioxidant and antiproliferative properties, with a decrease in the deposition of cholesterol esters in the vascular wall. Typically, these properties are inherent exclusively to the dextrorotatory R(+) isomer. A meta-analysis by J.G. Wang et al. (2005), showed that dihydropyridine CCBs, to a greater extent than other antihypertensive drugs, reduce the thickness of the intima-media complex of the carotid arteries.

Recent meta-analyses have shown that CCBs are more effective in preventing stroke than ACE inhibitors, and their effectiveness in reducing the risk of stroke goes well beyond lowering blood pressure.

The VALUE study, comparing amlodipine with valsartan in high-risk hypertensive patients, showed a reduction in the incidence of stroke with the use of CCBs, which, however, is partly explained by better blood pressure control.

The large-scale clinical trial ASCOT, which examined the effectiveness and safety of long-term antihypertensive therapy in hypertensive patients at high risk of cardiovascular complications, showed a significant advantage of combination treatment based on CCBs in preventing major cardiovascular complications - myocardial infarction and stroke.

In the CAMELOT study, in 2000 patients with normal blood pressure, the use of a CCB for 2 years reduced the incidence of stroke or transient cerebrovascular accident by 50.4% compared with patients taking an ACE inhibitor. The anti-stroke effectiveness of CCBs may be due to their anti-sclerotic effect. It is believed that the anti-atherosclerotic effect of CCBs is realized by restoring impaired vascular tone and the condition of the vascular wall, which is associated with the ability of CCBs to positively influence endothelial dysfunction, which is the beginning of the development of atherosclerosis and atherothrombosis.

Dihydropyridine CCBs are metabolically neutral, do not change plasma concentrations of glucose, uric acid, creatinine, basic electrolytes, do not have a negative effect on lipid metabolism, bronchial muscle tone, central nervous system activity, digestive system, sexual function, which suggests the possibility of their use in various concomitant pathologies in a wide range of patients with hypertension. In some cases, limiting the use of dihydropyridine CCBs may cause side effects in the form of peripheral edema. To solve this problem, new modern representatives of the third generation of dihydropyridine BCCs, lercanidipine and manidipine, were created.

Recently, drugs representing levorotatory stereoisomers (enantiomers) of S-amlodipine have appeared on the Ukrainian pharmaceutical market, and therefore the effectiveness and safety of their use, clinical benefits and evidence base are actively discussed.

Stereoisomers first became known in the mid-19th century, when L. Pasteur separated and demonstrated isomers of tartaric acid. Stereoisomerism, or spatial isomerism, is based on the existence of compounds with the same molecular formulas and the sequence of atoms in the molecule, but with different arrangements of atoms in space. The property of molecules not to be combined with their mirror image is called chirality (molecules that exist in such forms are called chiral from the Greek χειρ - hand). Each of the two stereoisomers of a chiral molecule is called an enantiomer, and they are classified into R- and S-species depending on whether the plane of the polarized beam bends to the right (clockwise) or to the left (counterclockwise). A mixture of equimolecular amounts of enantiomers is called racemic (racemate). Optical isomers (enantiomers) of a racemic drug can have different pharmacokinetic and pharmacodynamic characteristics, which are largely determined by the stereospecificity of its action. Modern methods make it possible to obtain specific isomers in pure form and select those that have the most pronounced effects and/or the least toxicity. Additional isomers in a mixture are no longer considered "silent passengers" but potential impurities.

Amlodipine is a racemic compound (1:1) of its S- and R-enantiomers, which have different pharmacological properties. S(-)-amlodipine has greater pharmacological activity; only this isomer is able to block slow L-type calcium channels and have a vasodilator effect. At the same time, the attachment to dihydropyridine receptors is stereoselective and the connection with the S (-) isomer is 1000 times stronger than with the R (+) isomer, the duration of the half-life of amlodipine is also related to the activity of the S isomer. The hope of using only the therapeutically active form of a drug, as opposed to a mixture of active and inactive forms, is based on the fact that removing the inactive component in terms of lowering blood pressure may reduce the incidence of side effects. The use of the pure levorotatory pharmacologically active S(-)-isomer of amlodipine instead of the racemic mixture has, according to some authors, certain advantages: in particular, the required dose and systemic toxicity can be reduced. Evidence of this is provided by clinical trials to study the clinical effectiveness, safety and tolerability of S(-)-amlodipine drugs, conducted in India, Korea, Russia, and Ukraine. To date, in economically highly developed countries (USA, Canada, Japan, advanced European countries), S(-)-amlodipine has not yet found clinical use, probably because there is no serious evidence base (studies with hard end points) for this drug.

A randomized, open-label, two-phase comparative crossover study conducted in Korea involving 18 healthy volunteers aged 21-26 years to compare pharmacokinetic and pharmacodynamic characteristics and safety profile showed that S-amlodipine has pharmacokinetics comparable to amlodipine and has a pharmacodynamic profile comparable to amlodipine racemate , both drugs were tolerated equally.

Post-marketing surveillance of 4089 patients in India (SESA 1859 and SESA II 2230 participants) confirmed the safety and improved tolerability of S-amlodipine 2.5/5.0 mg in the treatment of essential hypertension. A series of small randomized studies, including in Russia and Ukraine, confirmed the antihypertensive and antianginal effect of S-amlodipine: it was shown that to achieve the optimal therapeutic effect of S-amlodipine, doses of the drug are required 2 times lower than those of racemic amlodipine, the comparability of pharmacokinetic and pharmacodynamic properties and safety profile of 5 mg S-amlodipine and 10 mg amlodipine racemate in healthy volunteers.

At the same time, a number of researchers, having failed to obtain a reduction in peripheral edema in patients taking S-amlodipine, believe that there is currently insufficient adequate data on the safety and effectiveness of this drug, and data obtained on other populations cannot be extrapolated to all populations. since results can vary significantly due to genetics, race, lifestyle, eating habits, etc. It is discussed that the occurrence of peripheral edema when taking amlodipine is associated with the body's response to the therapeutic effects of S-amlodipine, so the use of this enantiomer alone is unlikely to reduce the incidence of edema. The mechanism of edema when using CCBs is an increase in intracapillary pressure due to selective arteriolar vasodilation, for which the levorotatory isomer is responsible.

The current literature discusses the only possible mechanism for reducing the incidence of peripheral edema - reducing the "excessive" production of nitric oxide (NO) by the dextrorotatory isomer, citing a study from the American College of Cardiology. When we turned to the original source, it turned out that in this work we are not talking about excessive release of NO due to the use of this molecule, but about an unexpected finding of researchers, which the authors interpret as “a potentially important property that provides increased release of nitric oxide by Ca antagonists, which contributes to their wider use in the treatment of cardiovascular diseases." R-amlodipine, acting through kinin-dependent mechanisms, stimulates the synthesis of nitric oxide by endothelial cells, and this effect is dose-dependent. As is known, drugs that directly stimulate NO synthesis (nebivolol) or NO donors, such as nitrates, do not have peripheral edema as an adverse reaction. Scientifically substantiated potential mechanisms by which S-amlodipine may be better tolerated than racemate have not been described in the current literature.

Based on the above, today the R-enantiomer, despite its lack of calcium channel blocking properties, cannot currently be considered as isomeric ballast. It is known that CCBs have the property of inhibiting the migration of SMCs. In experimental models of atherosclerosis, the CCB isradipine has been shown to be able to reduce SMC migration and proliferation and neointimal formation due to endothelial cell damage in the vascular wall during atherosclerosis after balloon angioplasty, and therefore CCBs were expected to be useful in the treatment of conditions associated with SMC migration, including atherosclerosis and restenosis after angioplasty.

It has now been established that R(+)-amlodipine, despite its lack of calcium channel blocking activity, is a powerful inhibitor of SMC migration, as declared in US patent 6080761 “Inhibition of SMC migration by (R)-amlodipine”, its use is justified for treatment of atherosclerosis and restenosis, its activity is 2 times higher than that of racemic amlodipine. The authors declared that the use of R(+)-amlodipine serves as a means of treating and preventing conditions requiring inhibition of vascular SMC migration. It has been established that to achieve the result, the effective daily dose is 2-20 mg of the R(+)-isomer, which is comparable to that for treatment racemate of AG. Thus, as shown by the results of numerous epidemiological studies and their meta-analyses, high blood pressure, both diastolic and systolic, is associated with an increased risk of stroke, all forms of coronary artery disease, heart failure, chronic renal failure, aortic dissection and other lesions of extracardiac arteries and is associated with an increase in cardiovascular mortality. Moreover, this relationship is linear, starting from a blood pressure level of 110/70 mm Hg. . Therefore, the main goal of treating a patient with hypertension is to reduce the overall risk of cardiovascular morbidity and mortality. Along with achieving target blood pressure levels, the main task of the doctor today is to influence all risk factors and treat concomitant pathologies.

That is why a drug devoid of the dextrorotatory isomer cannot have the full range of organoprotective properties. Study results demonstrating a high level of cardiovascular and overall safety and a positive effect on cardiovascular prognosis are presented for traditional amlodipine and other dihydropyridine CCBs, which are a racemic mixture of R- and S-isomers. The validity of transferring these data to S-amlodipine requires further study. In the class of dihydropyridine calcium antagonists, in terms of additional (independent of blood pressure reduction) organ protection, one of the most modern drugs, lercanidipine, attracts attention. In particular, in a retrospective Australian study, it was shown for the first time that of the four representatives of this class (amlodipine, felodipine, extended-release nifedipine, lercanidipine), the maximum reduction in overall mortality was achieved precisely as a result of the use of lercanidipine. As a working hypothesis to explain this result, we can consider the independent neuroprotective properties of the drug, which have been repeatedly discussed in the literature, which in clinical practice is usually expressed in a decrease in the number of cerebrovascular complications. Today, regarding the neuroprotective properties of lercanidipine, we have new data from Japanese scientists, which appeared already in 2011. This study demonstrates for the first time that during experimental 10-minute bilateral carotid artery occlusion, lercanidipine significantly prevents late (1 week after ischemia) death of hippocampal neurons. At the same time, despite an almost equal reduction in blood pressure, neuronal death could not be prevented with the help of lisinopril, valsartan and nicardipine. An interesting clinical conclusion made by Japanese scientists is that lercanidipine can effectively reduce dementia caused by ischemic microstrokes in patients with hypertension. All of the above allows us to conclude that only drugs consisting of two isomers in the CCB class can be considered as first-line drugs in the treatment of hypertension.

Nesukai E.G., professor, doctor of medical sciences, Kyiv

Bibliography

For quotation: Baryshnikova G.A. Possibilities of amlodipine isomer in the treatment of arterial hypertension // RMZh. 2009. No. 7. P. 431

Despite recent advances in the treatment of cardiovascular diseases (CVD), they continue to remain the leading cause of death. Arterial hypertension (AH) is the most important risk factor for CVD due to its high prevalence (more than 40 million people suffer from hypertension in Russia) and the insufficient effectiveness of therapy. Epidemiological studies show that even with a slight increase in blood pressure (BP), the risk of stroke, myocardial infarction, heart failure, and cardiovascular death increases.

For many years, calcium antagonists (CA) have been among the main 5 groups of antihypertensive drugs (ACE inhibitors, angiotensin II receptor blockers, AA, beta-blockers, diuretics). AKs are both chemically and pharmacologically a heterogeneous group of drugs. There are verapamil with diltiazem (pulse-lowering AKs) and a large group of dihydropyridine AKs, many of which (but not amlodipine!) are capable of increasing the heart rate. All AKs, being peripheral vasodilators (to a greater extent - dihydropyridine, to a lesser extent - verapamil and diltiazem), affect the main pathophysiological mechanism of arterial hypertension - increased total peripheral vascular resistance.

Along with a powerful hypotensive effect, AA have an organoprotective (primarily cardio- and angioprotective) effect, reduce the severity of left ventricular hypertrophy (LVH), prevent the progression of atherosclerosis, do not have a negative effect on the level of electrolytes, carbohydrate, lipid and purine metabolism, and reduce bronchial hyperreactivity . According to the Russian recommendations “Diagnostics and Treatment of Arterial Hypertension” (third revision) of the VNOK Expert Committee (2008), the primary indications for the use of dihydropyridine ACs in hypertension are: ISAH (elderly), coronary artery disease, LVH, atherosclerosis of the carotid and coronary arteries, pregnancy ( Fig. 1). In a number of situations, AKs are prescribed due to the presence of contraindications to the use of other drugs. For example, AK can be prescribed for obstructive pulmonary diseases, intermittent claudication, type 1 diabetes mellitus, when taking b-blockers is contraindicated or undesirable. AKs do not cause metabolic disorders: they do not affect blood sugar levels (like diuretics), the level of potassium in the blood (like diuretics and ACE inhibitors), or the level of uric acid (like diuretics). AKs do not cause impotence (like b-blockers and diuretics) or cough (like ACE inhibitors).

Due to their high efficiency and a small range of contraindications for their use (there are no absolute contraindications to the use of dihydropyridine AKs), AKs quickly gained popularity among doctors and patients and by the mid-90s of the 20th century they became one of the most frequently prescribed drugs in cardiology for hypertension. However, at the same time, discussions began about the safety of long-term use of AKs, the reason for which was data on the ability of short-acting dihydropyridine AKs to negatively affect the outcome of the disease in patients with unstable angina and acute myocardial infarction. It was soon shown that short- and long-acting AA prescribed for the treatment of hypertension have different effects on the risk of myocardial infarction (Fig. 2). In 2000, the Lancet published data from an analysis showing that long-term use of long-acting ACs in patients with hypertension is not only safe, but also leads to a significant reduction in the likelihood of developing cerebral stroke and complications of coronary artery disease. Currently, according to the well-known classification of AK T. Toyo-Oka, W.G. Nayler, 1996 (Table 1) all AKs are divided into 3 generations. The first generation includes the parent AKs (verapamil, diltiazem, nifedipine), all of them are short-acting and are not recommended for use in the treatment of hypertension (use is possible only in urgent situations, for example, to relieve a hypertensive crisis). According to this classification, amlodipine belongs to the third generation of AKs.

Amlodipine is one of the most frequently prescribed drugs from the group of dihydropyridine AKs, successfully used for the treatment of hypertension. Like other dihydropyridine AKs, amlodipine does not affect the function of the sinus node and atrioventricular conduction, increases coronary blood flow, reduces myocardial oxygen demand, providing an anti-ischemic and antianginal effect. Amlodipine has, among other AKs, unique pharmacokinetic properties (Table 2): the longest half-life (35-50 hours) and volume of distribution (21 l/kg body weight), which ensures the duration of the hypotensive and antianginal effects of the drug. Of important clinical importance is the pharmacokinetic parameter such as the time to reach the maximum concentration in the blood plasma, which determines the rate of development of the therapeutic effect. This time after oral administration of amlodipine ranges from 6 to 12 hours, which guarantees the gradual development of the vasodilating effect without a pronounced reflex increase in the activity of the sympathetic-adrenal system, characteristic of the short-acting form of nifedipine, with the development of sinus tachycardia and other side effects characteristic of the rapid vasodilating effect ( headache, dizziness, palpitations, transient hypotension). If you accidentally miss the next dose of amlodipine, there is no withdrawal syndrome in the form of a pronounced rise in blood pressure, which once again proves the safety of therapy with this drug.

Amlodipine is one of the most well-studied AKs from the perspective of evidence-based medicine. In numerous controlled studies on long-term treatment of hypertension, amlodipine was usually used as an antihypertensive agent. The TOMHS study in patients with mild hypertension (grade I increase in blood pressure) compared the effectiveness of representatives of the main classes of antihypertensive drugs (amlodipine, enalapril, chlorthalidone, acebutolol, doxazosin) and placebo. Amlodipine demonstrated the same effectiveness as β-blockers, diuretics, ACE inhibitors and α-blockers, and the decrease in DBP in the group of patients treated with amlodipine was the greatest.

In the ALLHAT study, in which the effect of AA, ACE inhibitor, diuretics and α-blockers on the likelihood of complications of hypertension was studied over 6 years in more than 42 thousand patients, amlodipine was also chosen as a calcium antagonist. This study demonstrated that amlodipine was no different from chlorthalidone in its effect on overall mortality, the incidence of coronary artery disease and its complications, and cerebral stroke, although amlodipine was inferior to chlorthalidone in the incidence of heart failure.

The VALUE study, which lasted about 4 years, included 15,245 hypertensive patients over 50 years of age who had an increased risk of cardiovascular complications. Half of the patients included in the study received the angiotensin II receptor antagonist valsartan 80-160 mg/day as the main antihypertensive drug, and half received amlodipine 5-10 mg/day. It was assumed that with the same reduction in blood pressure, valsartan would be more effective in preventing complications of hypertension, but the incidence of cardiovascular complications during therapy with valsartan and amlodipine was almost the same (10.6 and 10.4%, respectively). The incidence of stroke was lower in the amlodipine group. It should be noted that in the first months of treatment, the hypotensive effect of amlodipine was more pronounced.

The PREVENT and CAMELOT studies demonstrated the ability of amlodipine to slow the progression of atherosclerosis in the carotid and coronary arteries, which is important when prescribing it to patients with hypertension and concomitant coronary artery disease.

The ASCOT-BPLA multicenter randomized controlled trial compared the effects of two therapeutic strategies on the incidence of cardiovascular events in 19,257 patients with hypertension and three or more cardiovascular risk factors. In this study, patients with hypertension aged 40-79 years were divided into two groups. Patients of the first group (n=9639) received amlodipine 5-10 mg/day, to which, if necessary, perindopril was added at a dose of 4-8 mg/day; patients of the second group (n=9618) were prescribed atenolol 50-100 mg/day, to which, if necessary, the thiazide diuretic bendroflumethiazide 1.25-2.5 mg/day was added. The duration of the study was 5.5 years. Endpoints were nonfatal myocardial infarction and cardiovascular death. Amlodipine-based therapy led to a significant reduction in the incidence of fatal and non-fatal strokes, overall cardiovascular outcomes or revascularization procedures, and overall mortality. Along with this, in the amlodipine group there was a decrease in the incidence of new cases of diabetes mellitus and renal failure. It was concluded that the observed differences in the incidence of secondary endpoints cannot be explained solely by differences in blood pressure levels (systolic blood pressure in the amlodipine group was lower by 2.7 mmHg, diastolic blood pressure by 1.9 mmHg). . compared to the atenolol group), but are determined by the additional properties of amlodipine (effect on endothelial function, anti-atherosclerotic effect, metabolic neutrality, etc.).

In recent years, a new promising direction of modern cardiology has been actively developing - the targeted clinical use of pure chiral forms of drugs. It has long been known about the existence of stereoisomerism, or chirality, when a molecule exists in two structurally identical forms (stereoisomers), which are mirror images of each other, which, however, when spatially oriented in the same plane, cannot be superimposed on each other. Each of the two stereoisomers of a chiral molecule is called an enantiomer, or isomer. Enantiomers are divided into R- and S-species depending on whether they deflect the plane of the polarized beam to the right (clockwise) or to the left (counterclockwise). According to traditional technology, most drugs are obtained in the form of undivided chiral molecules, that is, a mixture of their left- and right-handed enantiomers in a 1:1 ratio (racemic mixture, or racemate). Optical isomers (enantiomers) of a racemic drug, despite the same composition and sequence of chemical bonds of atoms, may differ in pharmacokinetic and pharmacodynamic properties. With the development of experimental and clinical pharmacology, data were obtained on the different roles of the R- and S-enantiomers of many racemic drugs used in practice in the implementation of both their beneficial and undesirable effects. In this regard, the production of pure optical isomers has become a very pressing chemical-technological problem, and the clinical use of chiral molecules is proposed to be considered as a new direction in pharmacotherapy. A new impetus to the development of the “chiral” direction in clinical medicine was given by the development of advanced technology for the separation of optical stereoisomers by W. Noles, R. Noyori and B. Charpless (Nobel Prize in Chemistry for 2001).

It has been established that amlodipine is also a racemic compound and consists of two isomers (S and R). A study of amlodipine showed that binding to dihydropyridine receptors is stereoselective (Fig. 3) and the binding to the S-isomer is 1000 times stronger than to the R-isomer. It was found that it is the S-isomer of amlodipine that has a vasodilating effect, i.e. has greater pharmacological activity. It is obvious that the use of pure levorotatory pharmacologically active S-isomer of amlodipine instead of a racemic mixture has important advantages, because in this case, the dose and, accordingly, the risk of side effects may be reduced. It also turned out that the active S-form differs from the inactive R-form by a longer half-life (49.6 hours versus 34.9 hours). As a factor predisposing to greater safety of treatment with the pure S-isomer of amlodipine, the significant circumstance that its clearance is subject to less individual variations than the clearance of the R-isomer is considered.

A number of clinical studies have been conducted to study the clinical efficacy, safety and tolerability of S(-)amlodipine. One of the largest studies is the multicenter SESA (Safety and Efficacy of S-Amlodipine) study, the purpose of which was to evaluate the effectiveness and tolerability of S(-)amlodipine in the treatment of essential hypertension. The study included 1859 patients with hypertension; patients were divided into 2 groups receiving S(-)amlodipine 2.5 or 5 mg/day. within 4 weeks. This study demonstrated that the antihypertensive effect of S(-)amlodipine is largely dose-dependent (Fig. 4). As part of the SESA study, the effectiveness and safety of S(-)amlodipine in the treatment of isolated systolic hypertension (ISAH) was analyzed - the MICRO-SESA-1 study. The SESA database identified 90 ISAH patients with a mean age of 54.6 ± 12.5 years. All patients received S(-)am-lodipine 2.5-5 mg for 4 weeks. S(-)amlodipine significantly reduced systolic blood pressure (SBP). The average decrease in SBP compared to baseline was 21.5±13.9 mmHg. The response rate to treatment was 73.3%. None of the patients experienced lower extremity edema or other adverse events. 82 out of 90 patients received S(-)amlodipine at a dose of 2.5 mg once daily, and only 8 patients required an increase in dose to 5 mg. Thus, S(-)amlodipine is a safe and effective drug for the treatment of ISAH. Moreover, in elderly patients, compared to younger patients, there was a more pronounced decrease in SBP compared to the initial level. These data are especially important given the fact that in elderly people suffering from hypertension, ISAH predominates (more than 50%), and the risk of cardiovascular complications increases significantly with increasing pulse rate. An additional analysis in the SESA study was conducted to determine the safety and effectiveness of S(-)amlodipine in the treatment of hypertension in 339 elderly patients (mean age 70.4±5.7) overall - MICRO-SESA II. After 4 weeks from the start of taking S(-)amlodipine at a dose of 2.5-5 mg once a day, the average decrease in SBP was 37.8 ± 19.6, DBP - 17.8 ± 12.2 mm Hg. (p<0,001). Доля «ответчиков» составила 96,46%. У 33 пациентов с сопутствующим сахарным диабетом удалось добиться более выраженного снижения САД (41,1±21,4 мм рт.ст.; p<0,0001) и ДАД (24,1±18,8 мм рт.ст.; p<0,0001). Как хорошо известно, жесткий контроль над уровнем АД у пациентов с СД обеспечивает дополнительное значительное снижение риска сердечно-сосудистых осложнений. Таким образом, S(-)amlodipine is a safe and effective drug for the treatment of hypertension in elderly patients, including those with diabetes.

It should be noted that the SESA study included 314 patients who had previously developed edema while taking racemic amlodipine. After switching them to S(-)amlodipine, edema remained in only 4 patients, i.e. compared with racemic amlodipine, a reduction in the development of edema was found by 98.7% (Fig. 5). The same results were obtained in another clinical study, in which replacing amlodipine racemate (5 mg/day) in 256 patients with S(-)amlodipine (2.5 mg/day) caused the disappearance of previously detected edema in 252 (98 .43%) patients. This striking effect on peripheral edema is associated with the lack of vasodilating effect of S(-)amlodipine on precapillaries, and as is known, it is the expansion of precapillaries without a corresponding expansion of postcapillaries that leads to an increase in hydrostatic pressure with the appearance of peripheral edema. The frequent development of pretibial edema against the background of racemic amlodipine is also associated with the formation of nitric oxide under the influence of R-amlodipine, which enhances the dilatation of precapillaries.

It has been established that excessive dilatation of the precapillary-arteriolar link of the vessels of the lower extremities, caused by excessive formation of NO, neutralizes the implementation of an important physiological mechanism that prevents the development of edema of the tissues of the lower extremities when the body is in an upright position - the so-called precapillary postural vasoconstrictor reflex.

In general, only 1.61% of patients experienced the development of side effects, which were mild and did not require discontinuation of the drug. Thus, S(-)amlodipine in doses of 2.5 mg and 5 mg is an effective drug for the treatment of hypertension with the additional advantage of significantly fewer adverse events (primarily edema of the lower extremities). S(-)amlodipine was well tolerated by elderly and senile patients; no dose adjustment of S(-)amlodipine was required in this age group.

Russia also has experience with the use of S(-)amlodipine. Thus, in a randomized comparative clinical study carried out on the basis of the Federal State Institution State Research Center for Preventive Medicine under the leadership of academician. RAMS, professor R.G. Oganov, the advantage of S(-)amlodipine at a dose of 2.5 mg was confirmed compared to the original drug containing racemic amlodipine at a dose of 5 mg. The study included 36 patients with moderate and mild hypertension, of which one group received 2.5 mg of S(-) amlodipine for 8 weeks, the second (control) group received 5 mg of racemic amlodipine. After 4 weeks of therapy, it was noted that S(-)amlodipine 2.5 mg was more effective in lowering blood pressure than racemic amlodipine 5 mg (Fig. 4), and after 8 weeks of therapy, the hypotensive effect of S(-)amlodipine 2.5 mg and racemic amlodipine 5 mg was found to be comparable (Fig. 6). Greater safety of the use of S(-)am-lo-di-pine was also noted.

It has been shown that when taking 2.5 mg of S(-)amlodipine once a day and 5 mg of racemic amlodipine in the blood, the same maximum equilibrium concentration is created. S(-)amlodipine is well tolerated by patients. Monotherapy with S(-)amlodipine does not cause activation of the sympathoadrenal system, no effect on carbohydrate and lipid metabolism was found (sugar and total cholesterol levels do not change). There was no increase in the level of creatinine in the blood, which makes it possible to prescribe this drug in the treatment of hypertension in patients with diabetes mellitus, atherogenic dyslipidemia, and renal failure. Compared to racemic amlodipine, S(-)amlodipine has a more pronounced antihypertensive effect after 4 weeks of use with a minimal risk of developing peripheral edema. The latter is extremely important, since pretibial edema is the most common side effect of amlodipine, sometimes forcing patients to abandon its use. For example, in the ASCOT-BPLA study, peripheral edema was almost 4 times more common in the amlodipine (racemic) group compared to the atenolol group (23% vs. 6%, p<0,0001), хотя не следует забывать, что к атенололу у большинства больных добавляли тиазидный диуретик. S(-)амлодипин метаболически нейтрален, благодаря хорошей переносимости обеспечивает высокую приверженность к лечению.

Pre-para-S(-)amlodipine is registered in Russia by Actavis under the name “EsCordi Core" "EsCordi Core" is the only pure levorotatory isomer of amlodipine in Russia; Available in doses of 2.5 and 5 mg per tablet, it is a highly effective and safe drug for the treatment of hypertension, the good tolerability of which is the key to high patient adherence to treatment.

Yabluchansky N.I., Editor-in-Chief of Medicus Amicus

You can't do without amlodipine. It is one of the most famous and widely used drugs in cardiological, neurological, therapeutic, pediatric clinics, as well as many related areas of medical practice.

Amlodipine is successfully used in the treatment of patients with essential and symptomatic arterial hypertension, atherosclerosis and its complications (cerebrovascular and coronary syndromes, peripheral arterial disease), arterial damage in systemic connective tissue diseases, as well as in isolated and comorbid metabolic syndrome and bronchial asthma with diabetes mellitus , critical in relation to drugs from other groups with a similar mechanism of action.

Having significant therapeutic potential, amlodipine has a positive effect on the patient’s overall health, quality and length of life.

Pharmacokinetics and pharmacodynamics of amlodipine

Amlodipine? dihydropyridine antagonist (blocker) of slow (L-type) calcium channels. By slowing down the kinetics of intracellular calcium, it suppresses the contractile activity of vascular smooth muscle cells and, as a result, lowers blood pressure in the arteries of the systemic circle without affecting the heart rate, conductivity and contractility of the myocardium.

Under the influence of amlodipine, both systolic and diastolic blood pressure decreases.

Thanks to the same action, amlodipine suppresses vasospastic reactions in coronary heart disease, atherosclerosis of the brain and other vessels. Amlodipine, when taken orally, is slowly and almost completely absorbed from the digestive tract, regardless of food intake. Its bioavailability reaches 80% with a volume of distribution of 20-21 l/kg body weight.

In the blood, 95-98% of ingested amlodipine binds to plasma proteins, with the maximum concentration in it being reached 6-12 hours after its administration.

The half-life of amlodipine is 35-50 hours. A stable equilibrium concentration (steady-state) is achieved 7-8 days after the start of administration. The duration of action is due to the slow release from binding to receptors.

Amlodipine does not affect the activity of the sympathetic part of the autonomic nervous system, the levels of norepinephrine and renin in the blood plasma.

Amlodipine is excreted by the kidneys (up to 10% unchanged and 60% in the form of inactive metabolites) and through the digestive canal. Biotransformation to inactive metabolites occurs in the liver and, if its function is impaired, is prolonged.

Pharmacodynamic effects of amlodipine

Decreased arterial smooth muscle tone
- decrease in total peripheral resistance
- lowering blood pressure
- reduction of afterload on the heart
- reduction of platelet aggregation (reducing the risk of thrombosis)
- no negative effect on lipid metabolism
- maintaining electrolyte balance
- no negative effect on the course of diabetes mellitus
- preservation of bronchial patency
- maintaining performance
- anti-ischemic effect
- antianginal effect
- organoprotective effect
- anti-atherosclerotic effect.

Examples of organoprotective action of amlodipine? cardioprotective (reversal of left ventricular hypertrophy), nephroprotective (reduction of proteinuria, reduction of renal hypertrophy, proliferation of mesangial cells, prevention of nephrocalcinosis by reducing the overload of parenchyma cells with calcium ions and slowing the progression of chronic renal failure).

Pharmacodynamic effects of amlodipine in patients with moderate arterial hypertension one year after the start of therapy (based on the TOMHS study)

Thickness of the interventricular septum, mm -0.6
Thickness of the posterior wall of the left ventricle, mm -1
Left ventricular mass index, g/m? -11.2
Internal volume of the left ventricle, mm? -0.3
Internal volume of the right ventricle, mm? -2.8
Sodium excretion in urine, mmol/hour -9.4
Increment of diastolic blood pressure, mm Hg. Art. -12.9
Increment of systolic blood pressure, mm Hg. Art. -15.6
Heart rate increment, beats/min -1.8

Amlodipine affects glucose tolerance and can be used in patients with diabetes.

Can be used in patients with bronchial asthma and gout.

Amlodipine is taken once a day in a dose of 2.5 mg to 10 mg.

When supplementing treatment with thiazide diuretics, beta-adrenergic receptor blockers, angiotensin-converting enzyme inhibitors and angiotensin receptor inhibitors, no dose adjustment is required.

Amlodipine also goes well with statins, cardiac glycosides, aldosterone antagonists, nitrates, antiplatelet agents, etc. Side effects of amlodipine that limit its clinical use include the possibility of developing leg edema and hyperemia.

S(-), R(+) isomerism of amlodipine, or “clearing the wheat from the chaff”

Amlodipine is an excellent medicine, if only without side effects, and it turns out that this problem can be solved.

Most chemical compounds existing in nature have optical stereoisomerism (chirality - from right-handed to left-handed). The stereoisomers that form them are also called enantiomers. Depending on the deviation of the plane of the polarized beam (to the right - clockwise, to the left - counterclockwise), they are divided into S(-) and R(+) enantiomers. In living objects, one of the enantiomers is usually active.

Traditional technologies in the pharmaceutical industry involve the production of drugs from a mixture of unseparated left- and right-handed (chiral) enantiomer molecules in a 1:1 ratio (racemic mixture, racemate). Moreover, the pharmacological activity of most of them is associated with the action of only one enantiomer. The second enantiomer has either less activity, is inactive at all, or exhibits different pharmacodynamic effects.

The establishment of the fact of the connection between the pharmacodynamic effect of drugs and optical stereoisometry served as the basis for the FDA declaring the feasibility of developing enantiometrically pure pharmaceutical drugs (chiral switch) back in the early 1980s of the last century. These processes accelerated at the turn of the millennium when W. Noles, R. Noyori and B. Charpless proposed innovative technology for the separation of optical stereoisomers.

Conventional amlodipine, consisting of two levo-S(-) and dextrorotatory R(+) enantiomers in equal proportions, in which only the levorotatory S(-) enantiomer is pharmacodynamically active, was no exception in the development of enantiometically pure pharmaceutical drugs. It is he who has the property of blocking slow calcium channels of vascular smooth muscle cells, having a 1000 times greater affinity for calcium channel receptors than the dextrorotatory R(+) enantiomer. In addition, it turned out that the side effects of regular amlodipine are associated with the presence of the dextrorotatory R(+) enantiomer in it.

A positive result of mastering the production and introduction into clinical practice of amlodipine, represented by only one levorotatory S(-) isomer, is a twofold reduction in the dosage of the drug and a significant reduction in the likelihood of developing side effects from its use.

Clinical efficacy of amlodipine

The use of amlodipine allows you to effectively control the levels of systolic and diastolic blood pressure in mono- and combination therapy.

Monotherapy for mild and moderate arterial hypertension is effective in 60-70% of patients and is often superior to that of antihypertensive drugs from other pharmacotherapeutic groups.

According to data from the Amlodipine Cardiovascular Community Trial, amlodipine is equally effective in blacks and whites, with a stronger antihypertensive effect in females.

Due to the long half-life, a single dose of amlodipine allows you to control blood pressure throughout the day, and the antihypertensive effect of the drug itself is characterized by a linear dose-concentration relationship in the blood plasma, which is convenient for selecting its effective therapeutic dose.

With long-term therapy, the antihypertensive effect of amlodipine increases gradually, reaching a maximum 6 weeks after its start. Therefore, if blood pressure is not fully controlled, an early increase in the dose of the drug is not advisable.

The coronary artery effect of amlodipine is stronger, the greater the spasm of the coronary arteries. In stable angina, amlodipine significantly reduces the frequency, duration and severity of attacks. In addition to its coronary action, it reduces calcium overload of cardiomyocytes as one of the causes of cardiomyocyte damage. Due to these properties, it has found use in patients with stable and variant angina, including after myocardial infarction.

It has a similar effect in cerebrovascular syndromes and atherosclerotic lesions of other peripheral arteries. The clinical effectiveness of amlodipine has been confirmed in numerous authoritative international randomized controlled studies (PRAISE-1 and 2, PREVENT, ALLHAT, VALUE, ASCOT-BPLA, ACCOMPLISH, SESA, etc.).

Thus, according to the TOMHS study (Treatment of mild hypertension study), amlodipine effectively reduces the mass of the left ventricular myocardium and reduces the risk of developing cardiovascular complications in patients with arterial hypertension and left ventricular hypertrophy. As shown by data from the PREVENT study (Prospective Randomized Evaluation of the Vascular Effects of Norvasc Trial), long-term therapy with amlodipine leads to regression of the intima-medial layer of the carotid arteries, which confirms its anti-atherosclerotic effect. At the same time, the number of hospitalizations of patients due to destabilization during angina pectoris and chronic heart failure decreases, and the need for myocardial revascularization operations also decreases.

In accordance with the CAPE (Circadian Anti-ischemia Program in Europe) study, amlodipine significantly reduced the frequency of episodes of ST segment depression, total ischemic time, the frequency of painful ischemic episodes and the frequency of additional use of short-acting nitrates in patients with coronary artery disease.

The PRAISE I (Prospective Randomized Amlodipine Survival Evaluation Study) study showed that in patients with chronic heart failure of ischemic and non-ischemic origin and an ejection fraction of less than 30%, amlodipine reduced the total number of cardiovascular complications by 9% and the risk of sudden death by 9%. 16%.

Are the results even more impressive in patients with non-ischemic heart failure? reduction in the total number of cardiovascular complications by 31% and the risk of sudden death by 46%.

Today there are countless examples confirming the high clinical effectiveness of amlodipine with a low risk of adverse, and non-fatal, outcomes.

Let’s say a word about levorotatory S(-) amlodipine

One of the largest is the SESA (Safety and Efficacy of S-Amlodipine) study, which showed the effectiveness and tolerability of S(-) amlodipine in daily doses of 2.5 mg and 5 mg in the treatment of 1859 patients with arterial hypertension for four weeks. At a dose of 2.5 mg S(-), amlodipine allowed to achieve a decrease in systolic blood pressure from 161 mmHg. up to 129 mm Hg. Art., diastolic - from 100 mm Hg. Art. up to 84 mmHg, and at a dose of 5 mg, respectively, from 179 mmHg. up to 107 mm Hg. and from 107 mm Hg. up to 86 mmHg

It is important to note that while 314 patients included in the study had edema due to taking racemic amlodipine, after switching to S(-) amlodipine, they remained in only 4 patients (a 99% reduction in the incidence of edema).

In total, side effects were noted in 30 patients out of 1859 (1.6% of cases), and none of them required drug discontinuation or any special treatment.

The SESA-MICRO-SESA-1 substudy demonstrated the safety and effectiveness of S(-)amlodipine in the treatment of isolated systolic hypertension, and the SESA-MICRO-SESA II substudy demonstrated the safety and effectiveness of S(-)amlodipine in the treatment of isolated systolic hypertension.

Which amlodipine is better?

There is no doubt that amlodipine is part of modern clinical practice.

And if you have to choose, then perhaps between regular (racemic) and levorotatory S(-) amlodipine.

Levorotatory S(-) amlodipine is better than racemic amlodipine.

He is a new word in modern clinical pharmacology, his present and future.

Name:

Azomex (Asomex)

Pharmachologic effect:

The drug contains the levorotatory isomer of amlodipine. Amlodipine is a dihydropyridine derivative and consists of a mixture of two stereomers, but only levorotatory (S) amlodipine exhibits pharmacological activity. S-amlodipine has an affinity for dihydropyridine receptors that is 1000 times greater than the affinity of R-amlodipine for dihydropyridine receptors. The mechanism of action of the drug is associated with its ability to block slow calcium channels, due to which the penetration of calcium ions into the smooth muscle cells of blood vessels and cardiac muscle becomes impossible. Due to the blockade of calcium ion transport into smooth muscle cells, the tone of the vascular wall decreases and blood pressure decreases. Thus, S-amlodipine is characterized by a direct antihypertensive effect. In addition to the antihypertensive effect, the drug has a pronounced antianginal effect due to the complex effect of S-amlodipine on the cardiovascular system. First, the drug dilates peripheral blood vessels, thus reducing overall peripheral vascular resistance. With the expansion of peripheral vessels, the afterload decreases, and since the use of S-amlodipine does not affect the heart rate, the load on the myocardium and its oxygen demand decreases. Secondly, the drug, due to its effect on the smooth muscle layer of the vascular wall, prevents spasm of the coronary vessels and helps normalize coronary blood flow. The drug does not have a significant effect on the metabolism of lipids and carbohydrates, so the drug can be used in patients with diabetes, gout and bronchial asthma.

After oral administration, the drug is well absorbed from the gastrointestinal tract; food intake does not affect the degree of absorption of the drug. The maximum plasma concentration of amlodipine is achieved within 6-12 hours; due to the slow onset of action, the drug does not cause a sharp drop in blood pressure. The bioavailability of amlodipine is about 70-80%. After starting amlodipine therapy, a stable equilibrium concentration in the blood is observed after 7-8 days. Metabolized in the liver to form pharmacologically inactive metabolites. The half-life is approximately 35-50 hours. It is excreted primarily by the kidneys, both unchanged and in the form of metabolites.

Age does not affect the rate of achievement of the maximum concentration of the drug in the blood plasma, however, in elderly patients there is a slower excretion of the drug and an extension of the half-life. Also, the half-life increases in patients suffering from congestive heart failure.

Indications for use:

The drug is used to treat patients suffering from arterial hypertension.

In addition, the drug is used to treat coronary heart disease, including vasospastic angina, Prinzmetal's angina and stable angina.

Method of application:

The drug is taken regardless of food intake; it is recommended to swallow the tablet whole, without chewing, with a sufficient amount of water. If necessary, the tablet can be divided.

Patients with arterial hypertension and coronary heart disease are usually prescribed the drug at an initial dose of 2.5-5 mg of the drug 1 time per day. The dosage of the drug can be increased on the recommendation of the attending physician to 10 mg 1 time per day.

Adverse events:

When using the drug Azomex, the frequency and severity of side effects is significantly less than when using racemic amlodipine, however, when using the drug, some patients may develop the following side effects:

From the gastrointestinal tract: nausea, vomiting, pain in the epigastric region, stool disorders, dyspepsia, anorexia, flatulence, dry mouth. In isolated cases, when using the drug, the development of gum hyperplasia was noted.

From the liver: increased activity of liver enzymes, impaired outflow of bile, impaired liver function.

From the cardiovascular system: tachycardia, redness of the upper body and face, hypotension, arrhythmias (including bradycardia, ventricular arrhythmias, atrial fibrillation, sinus tachycardia), shortness of breath. In isolated cases, attacks of angina pectoris, collapse, and myocardial infarction (which cannot be differentiated from the course of the underlying disease) were noted. In addition, it is possible to develop edema of the extremities (most often the legs), which are significantly reduced or disappear completely after adjusting the dose of the drug.

From the central and peripheral nervous system: headache, dizziness, disturbance of sleep and wakefulness, drowsiness, fatigue, hearing and vision impairment, ringing in the ears, depression. In addition, the development of paresthesia and tremor is possible.

From the hematopoietic system: anemia, thrombocytopenia, leukopenia, agranulocytosis.

From the musculoskeletal system: asthenia, pain in muscles and joints, cramps.

Allergic reactions: skin rash, itching, erythema, hair loss, allergic dermatitis.

Others: increased frequency of urination and increased daily amount of urine, sweating, gynecomastia, impaired sexual function.

All side effects are reversible and disappear quickly after discontinuation of the drug.

Contraindications:

Increased individual sensitivity to the components of the drug,

Arterial hypotension (systolic blood pressure readings less than 90 mm Hg),

During pregnancy and breastfeeding,

Children under 18 years of age.

During pregnancy:

The drug is contraindicated for use during pregnancy and lactation. If it is necessary to use the drug during lactation, it is necessary to decide on stopping breastfeeding.

Interaction with other drugs:

Azomex can be used simultaneously with α- and β-blockers, thiazide diuretics, oral nitroglycerin, long-acting nitrates and ACE inhibitors.

The drug does not affect the pharmacological activity and pharmacokinetics of non-steroidal anti-inflammatory drugs, oral hypoglycemic drugs, digoxin and cimetidine.

Grapefruit juice helps to increase the bioavailability of the drug Azomex and enhance its hypotensive effect.

Overdose:

When taking excessive doses of the drug, patients experienced the development of excessive relaxation of the vascular wall of peripheral vessels, hypotension, and cardiac arrhythmias (the development of both tachycardia and bradycardia is possible).

There is no specific antidote. In case of an overdose of the drug, gastric lavage, administration of enterosorbent and symptomatic therapy aimed at maintaining vital functions are indicated. In case of overdose, intravenous administration of injectable solutions of calcium gluconate and dopamine is also recommended. The patient should be under constant supervision of medical personnel until the functions of the heart and lungs are completely restored. In case of overdose, it is recommended to monitor circulating blood volume and diuresis.

Hemodialysis is ineffective.

Release form of the drug:

Tablets, 10 pieces in a blister, 3 blisters in a cardboard package.

Storage conditions:

Shelf life – 2 years.

Compound:

1 tablet of Azomex 2.5 contains:

S-amlodipine – 2.5 mg,

Excipients.

1 tablet of Azomex 5 contains:

S-amlodipine – 5 mg,

Excipients.

Drugs with similar effects:

Hypril-A / Hypril-A Plus Tenox Amlo Agen Nadolol

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