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The “silent” health problem, as they call it, requires mandatory medical intervention. The best minds in the world are constantly in search of new and new drugs that regulate blood pressure, improve blood circulation and prevent such dangerous consequences of hypertension as or. There are many different groups of pharmaceuticals that are assigned this task.

Calcium antagonists (AAs) represent one of these groups and, having a number of positive qualities, are considered one of the best options among antihypertensive drugs in general. They are relatively mild, they are not rich in side effects, which, if they do occur, are rather weak.

When is there too much calcium?

The drugs of this group (calcium antagonists) are called by experts as they like: blockers of "slow" calcium channels (CCC), blockers of calcium ion entry, calcium ion antagonists. However, what does calcium have to do with it, why shouldn't it be allowed into the cell if it contracts the muscles, including the heart, where these channels are located, why is there so much attention to them and, in general, what is the essence of the mechanism of action of these drugs?

Physiological activity is characteristic exclusively of ionized calcium (Ca ++), that is, not associated with proteins. Muscle cells are in great need of Ca ions, which use it for their functioning (contraction), therefore, the more of this element is in cells and tissues, the more contraction force they have. But is it always useful? Excessive accumulation of calcium ions leads to excessive tension of muscle fibers and overload, therefore, in the cell, it must be in constant quantity, otherwise the processes dependent on this element will be disrupted and lose their periodicity and rhythm.

scheme of cardiomyocyte overload with calcium ions

Each cell itself maintains the concentration of calcium (sodium, potassium) at the required level through channels located in the phospholipid membrane that separates the cytoplasm from the intercellular space. The task of each channel is to control the passage in one direction (either inside the cell, or outside) and the distribution of certain ions (in this case, calcium) in the cell itself or outside it. As for calcium, it should be noted that it has a very high desire to get into the cell from the intercellular space by any means. Hence, some CCs need to be blocked so that they do not allow excess calcium ions trying to enter the cell and thus protected muscle fibers from excessive tension (mechanism of action of AK).

For the normal functioning of calcium channels, in addition to Ca ++, catecholamines (adrenaline and norepinephrine) are necessary, which activate CC, however, in this regard, the combined use of calcium ion antagonists and β-blockers (with the exception of drugs belonging to the nifedipine group) is undesirable , since excessive inhibition of the function of the channels is possible. The blood vessels will not suffer much from this, but the myocardium, having received a double effect, can respond with development.

There are several types of calcium channels, but the mechanism of action of calcium ion antagonists is directed only to slow CC (L-type), which contain various smooth muscle tissues:

• Sinoatrial pathways;
• Atrioventricular pathways;
• Purkinje fibers;
• Myofibrils of the heart muscle;
• Smooth musculature of the blood vessels;
• Skeletal musculature.

Of course, complex biochemical processes take place there, the description of which is not our task. We just need to note that:

The automatism of the heart muscle is supported by calcium, which, being in the cells of the muscle fibers of the heart, triggers the mechanism of its contraction, therefore, a change in the level of calcium ions will inevitably lead to a disruption in the work of the heart.

Abilities of calcium antagonists

Calcium channel antagonists are represented by various chemical compounds that, in addition to reduction, they have a number of other possibilities:

1. They are capable regulate heart rate, therefore, they are often used as antiarrhythmic drugs.
2. It is noticed that medicines of this pharmaceutical group have a positive effect on cerebral blood flow when in the vessels of the head and for this purpose are used to treat patients after a stroke.
3. By blocking the path of ionized calcium into cells, these drugs reduce mechanical stress in the myocardium and reduce its contractility. Due to the antispastic effect on the walls of the coronary arteries, the latter expand, which helps to increase blood circulation in the heart. The impact on peripheral arterial vessels is reduced to a decrease in upper (systolic) blood pressure and, of course, peripheral resistance. Thus, as a result of the influence of these pharmaceuticals, the oxygen demand of the heart muscle decreases, and the supply of the myocardium with nutrients and, first of all, oxygen, increases.
4. Calcium antagonists, due to inhibition of Ca ++ metabolism in cells, inhibit platelet aggregation, that is, prevent the formation of blood clots.
5. The drugs of this group have antiatherogenic properties, reduce pulmonary artery pressure and cause the expansion of the bronchi, which makes it possible to use them not only as antihypertensive drugs.

Scheme: mechanism of action and capabilities of 1-2 generations AK

Pioneers and followers

Medicines used for treatment arterial hypertension and heart diseases, belonging to the class of selective calcium ion antagonists, are classified into three groups in the classification:

Table: list of calcium antagonists registered in the Russian Federation

It is interesting that there is another group of calcium ion antagonists, which is not listed as such in the classification and is not included in them. It - non-selective AA, including piperazine derivatives (cinnarizine, belredil, flunarizine, etc.). The most popular and well-known in the Russian Federation is cinnarizine. It has long been sold in pharmacies and is often used as a vasodilator for headaches, dizziness, tinnitus, and impaired coordination of movements caused by spasm of the head vessels, which impedes cerebral circulation. The drug practically does not change blood pressure, patients love it, they often note a noticeable improvement in the general condition, therefore, it is taken for a long time with, upper and lower extremities, as well as after an ischemic stroke.

Phenylalkylamine derivatives

The first group of calcium channel blockers - phenylalkylamine derivatives or the verapamil group makes a small list of drugs, where the most famous and frequently used is verapamil itself (isoptin, finoptin).

Verapamil

The drug is capable of exerting an effect not only on blood vessels, but also on the heart muscle, while reducing the frequency of myocardial contractions. Verapamil lowers blood pressure in usual doses, therefore it is used to suppress conduction along the atrioventricular pathways and depression of automatism in the sinus node, that is, basically, this mechanism of action of the drug is used when heart rhythm disorder (supraventricular)... In injection solutions (intravenous administration), the drug begins to act in 5 minutes, so it is often used by ambulance doctors.

The effect of isoptin and finoptin tablets begins two hours later, in this regard, they are prescribed for home use in patients with exertional angina, with combined forms and supraventricular rhythm disturbances, but in the case of Prinzmetal's angina, verapamil is considered the drug of choice. Patients do not prescribe such drugs to themselves, this is the business of a doctor who knows that for elderly people the dose of verapamil should be reduced, since their metabolic rate in the liver is reduced. In addition, the drug can be used to correct blood pressure in pregnant women, or even as an antiarrhythmic agent for tachycardia in the fetus.

Second generation drugs

Other drugs of the verapamil group, belonging to the second generation drugs, have also found their application in clinical practice:

1. Anipamil differs in a more powerful (compared to verapamil) action, which lasts about 1.5 days. The drug predominantly affects the heart muscle and vascular walls, but does not affect atrioventricular conduction.
2. Falipamil selectively acts in relation to the sinus node, practically does not change blood pressure, therefore, it is mainly used in the treatment of supraventricular tachycardia, angina pectoris of rest and tension.
3. Tiapamil in power it is 10 times inferior to verapamil, tissue selectivity is also not typical for it, but it can significantly block sodium ion channels, and therefore it has proven itself well for the treatment of ventricular arrhythmias.

Dihydroperidine derivatives

The list of dihydropyridine derivatives includes:

Nifedipine (corinfar, adalat)

Refers to an active systemic vasodilator, which has practically no antiarrhythmic abilities inherent in drugs of the verapamil group.

Nifedipine lowers blood pressure, slightly raises the heart rate (reflexively), has antiaggregatory properties, as a result of which it prevents unnecessary thrombus formation. Due to its antispastic abilities, the drug is often used to eliminate spasms that occur with vasospastic angina at rest, as well as for prophylactic purposes (to prevent the development of an attack) if the patient has exertional angina.

In clinical practice, rapidly dissolving forms of nifedipine (adalat-retard, procardia XL, nifikard) are widely used, which begin to act in about half an hour and retain the effect for up to 6 hours, but if you chew them, the medicine will help in 5-10 minutes, however, antianginal its effect will still not be as pronounced as that of nitroglycerin. Nifedipine tablets with the so-called two-phase release begin to act in 10-15 minutes, while the duration can be about a day. Nifedipine tablets are sometimes used to quickly lower blood pressure (10 mg under the tongue - the effect occurs from 20 minutes to an hour).

Now in European clinics, long-acting nifedipine is becoming more and more popular, due to the fact that side effects he has less, but you can take it once a day. However, the unique system for the use of continuous-release nifedipine is recognized as the best, which ensures a normal concentration of the drug in the blood plasma for up to 30 hours and is successfully used not only as an antihypertensive agent for the treatment of high blood pressure, but also participates in the relief of paroxysms of angina pectoris at rest and tension. It should be noted that in such cases, the number of undesirable manifestations is halved when comparing continuous release nifedipine with other forms of this drug.

Nicardipine (Perdipine)

The vasodilating effect is considered to be predominant; the drug is mainly included in the therapeutic measures in the fight against angina pectoris and arterial hypertension. In addition, nicardipine is suitable as a fast-acting relief agent.

Nisoldipin (baymikard)

The mechanism of action resembles nicardipine.

Nitrendipine (bypress)

Structurally very similar to nifedipine, has a vasodilating effect, does not affect the atrioventricular and sinus nodes, and can be combined with beta-blockers. When used simultaneously with digoxin, bypress is able to double the concentration of the latter, which should not be forgotten if a combination of these two drugs becomes necessary.

Amlodipine (Norvasc)

Some sources attribute it to the 3rd generation drugs, although others claim that, along with felodipine, isradipine, diltaezem, nimodipine, it belongs to the second generation calcium antagonists. However, this is not so important, since the determining factor is the fact that the listed drugs act mildly, selectively and long-term.

Amlodipine has high tissue selectivity, ignoring the myocardium, atrioventricular conduction and sinus node and lasts up to one and a half days. Along with amlodipine, you can often find lacidipine and lercanidipine, which are also used for the treatment of arterial hypertension and are classified as calcium ion entry blockers of the 3rd generation.

Felodipine (plendil)

It has a high selectivity in relation to blood vessels, which is 7 times higher than that of nifedipine. The drug combines well with beta-blockers and is prescribed for the treatment of coronary heart disease, vascular insufficiency, arterial hypertension in a dose prescribed by a doctor. Felodipine can increase the concentration of digoxin by up to 50%.

Isradipine (lomir)

The duration of antianginal action is up to 9 hours, when taken orally, side effects in the form of facial hyperemia and swelling of the feet may be noted. In case of circulatory failure caused by stagnation, intravenous administration (very slow!) In the dose calculated by the doctor is advisable (0.1 mg / kg of body weight per minute - 1 administration, then 0.3 mg / kg - 2 administration). Obviously, the patient himself cannot make such calculations, or inject the drug, therefore, injection solutions of this drug are used only in a hospital setting.

Nimodipine (nimotop)

The drug is rapidly absorbed, the hypotensive effect occurs in about an hour. A good effect of intravenous administration of the drug on initial stage and in case. The use of nimodipine for the treatment of cerebral catastrophes is due to the high tropism of the drug to the vessels of the brain.

New Calcium Antagonist Drugs

Diltiazem

New types of calcium ion blockers, which can also be called 3rd generation drugs, include diltiazem. He, as indicated earlier, occupies the position: "verapamil - diltiazem - nifedipine". It is similar to verapamil in that it is also “not indifferent” to the sinus node and atrioventricular conduction, suppressing, albeit to a lesser extent, their function. Like nifedipine, diltiazem lowers blood pressure but does so more gently.

Diltiazem is prescribed for Prinzmetal's angina pectoris and various types of hypertension, moreover, reducing only high pressure (upper and lower). With normal blood pressure, the drug remains indifferent to the vessels, so there is no need to fear an excessive drop in pressure and the development of hypotension. The combination of this medication with thiazide diuretics enhances the hypotensive capacity of diltiazem. However, despite the numerous advantages of the new remedy, a number of contraindications to its use should be noted:

1. Cardiogenic shock;
2. Signs;
3. Violation of AV conduction;
4. Pregnancy;
5. Lactation period.

Ravaged

The drug bepredil has a unique ability to block slow calcium and sodium channels. which due to this can affect both the vascular wall and the conducting system of the heart. Like verapamil and diltiazem, it acts on the AV node, however, in the event that it can lead to the development of ventricular arrhythmia, therefore, when prescribing rape, these qualities are taken into account, and the level of magnesium and potassium ions is constantly monitored. It should be noted that this drug generally requires special care, it is not combined with thiazide diuretics, quinidine, sotalol, some antidepressants, therefore, patients' self-activity threatens with various consequences and will be completely inappropriate.

Foridon

To the list of drugs, I would like to add an original antianginal drug produced in the Russian Federation, called foridone, which in adequate doses can replace nifedipine and diltiazem.

Features to keep in mind

Calcium antagonists have not so many contraindications, but they still exist should be considered:

• Typically, nifedipine is not given for low baseline pressure, sinus weakness, or pregnancy.
• They try to bypass verapamil if the patient is diagnosed with abnormalities of AV conduction, sick sinus syndrome, severe heart failure and, of course,.

Although cases of an overdose of calcium channel blockers have not been officially recorded, if a similar fact is suspected, the patient is injected intravenously with calcium chloride. In addition, drugs of this group, like any pharmacological agent, give some side effects:

1. Redness of the face and décolleté area.
2. Decrease in blood pressure.
3. "Hot flashes", as with menopause, heaviness and pain in the head, dizziness.
4. Bowel disorders (constipation).
5. Increased heart rate, swelling, affecting mainly the ankle and lower leg - a side effect of nifedipine;
6. The use of verapamil can result in a decrease in heart rate and atrioventricular block.

Table: side effects of AK and contraindications

Considering the fact that calcium channel blockers are often prescribed in combination with and, it is necessary to know the undesirable effects of their interaction: beta-blockers potentiate a decrease in the pulse rate and a violation of atrioventricular conduction, and diuretics enhance the hypotensive effect of AK, which must be borne in mind when choosing the dosage of these medicinal funds.

Video: the role of calcium in the human body

A heterogeneous group of drugs or calcium channel blockers are the latest generation drugs, the list of which is numerous. CCBs are widely used in the treatment of cardiovascular diseases.

In the human body, calcium is one of the most demanded minerals. It ranks 5th among all minerals. It is found almost entirely in the bones. Only 1% is found in teeth and muscles. A small part of calcium ions (0.1-0.3%) enters the extracellular fluid.

The mineral is involved in the development of the skeletal system, teeth. He is responsible for the state of the nervous and muscular systems, spreads nerve impulses. Calcium ions are also involved in many functions of the muscular system, thus regulating the heart rate.

Without calcium, the human body would be shapeless.

The regulator of calcium levels is the body itself, especially the thyroid gland. But there are situations when the human body cannot cope with the amount of macronutrient entering it.

Consequences of excess calcium:

• urge to vomit;
• loss of appetite;
• indigestion;
• irregular heartbeats;
• impaired renal function;
• psychoemotional disorder;
• prostration.

Excess calcium is removed from the human body very slowly on its own. It accumulates in the kidneys, which leads to the formation of stones. Excess minerals collect inside the vascular walls, which triggers the process of narrowing of the veins and arteries. Muscles are affected by the abundance of calcium.

Why you need calcium channel blockers

Once in the cell, calcium particles increase the body's metabolism, increase the use of oxygen, lead to muscle spasm, and increase nervousness.

What happens under the influence of BPC:

• relaxation of arterial and venous vessels;
• improvement of cardiac and cerebral circulation;
• the amount of fluid secreted by the body increases;
• the process of gluing platelets is delayed;
• irregular heartbeats are restored;
• spasms of smooth internal and external muscles pass.

BPC composition

Calcium channel blockers (the list of the latest generation drugs will be discussed later in the article) have a diverse composition. Calcium antagonists have one active substance, but a number of "auxiliary" compounds that are needed to create drugs with a narrow or broad profile action.

They also produce medicines consisting of several active substances. These forms of BCC, in addition to the main active ingredient, also include salts of nitric acid. Such combinations are used in cardiological practice.

Calcium channel blockers are available in different form... The list of the latest generation of drugs includes capsules used under the tongue, drugs for injections and droppers.

Groups, classification of CCL

Pharmacological agents from the LBC group are widely used in medical practice.

With the help of CCBs they treat:

Calcium channel blockers (the list of drugs of the latest generation is divided into several subtypes) are divided according to their pharmacological composition.

There are 4 main classes of drugs:

1. Dihydropyridines that do not slow down the work of the heart muscle.
2. Slowing heart contractions - diphenylalkylamines.
3. Increasing blood flow to the heart and restoring the rhythm - benzodiazepines.
4. Improving vascular circulation in the brain - diphenylpiperazine.

Generation BKK

At this stage of pharmacological advances, there are 4 classes of CCBs.

These classes are divided into 1st, 2nd and 3rd generations:

1. The oldest of all are selective calcium antagonists. Patients need to apply them every 6 hours.
2. The second generation has a longer duration. They are applied 2 times a day after 12 hours. Second-generation drugs have fewer negative effects when compared with the previous group.
3. Calcium channel blockers - the list of drugs of the latest generation exceeds their predecessors in terms of strength and duration of work in the body. Their action is 24 hours, which makes medication easier.

Mechanism of action

CCCs show their restraining force by preventing calcium ions from entering smooth muscle cells. The active ingredients expand the cardiovascular system, which increases the blood flow rate. As a result, the heart receives more oxygen, metabolic products are excreted.

By reducing the heart rate and contractile ability of the heart, CCBs limit the oxygen demand of the myocardium. The medicine helps the heart muscle relax. Superficial vessels (arteries) dilate, which suppresses the symptoms of hypertension.

There are calcium channel blockers that restore the heart rate. Medicines of this class slow down the process of platelet adhesion, which prevents blood clots from appearing in the blood vessels of the heart. Calcium antagonists help to collect "wrong" cholesterol and remove it from the bloodstream, thereby increasing cholesterol metabolism in the body.

Indications for use

The spectrum of administration of calcium channel blockers is large.

Common pathologies include:

All CCBs have vasodilating properties. Separately, a group of calcium channel blockers is distinguished, which have antihistaminic qualities. They are prescribed for allergic itching. These drugs include Cinnarizine.

Spasms of the vascular system accompany all of the above pathologies. This leads to impaired blood circulation in the body. As a result, the death of cells and tissues occurs, local or global necrosis leads to a heart attack.

Exertional angina

Angina pectoris is a disease in which a lack of oxygen develops in the heart, as a result, myocardial dystrophy. Pathology is accompanied by sharp bouts of pain in the chest, neck, axillary region. This process is supervised by excess calcium, which leads to vasospasm. It can be triggered by both emotions and physical fatigue.

All calcium antagonists increase cardiovascular circulation, which helps prevent another attack. Calcium antagonists help the patient withstand emotional and physical stress.

With systemic therapy, the patient must be prescribed Diltiazem in an individually selected dosage and regimen.

With angina pectoris, combined with heart rhythm disturbances and hypertension, dihydropyridines (corinfar, nifedipine) should be prescribed. In many cases, it is Nifedipine that is the primary drug in the treatment of pathology.

Heart attack

Myocardial infarction is one of the forms of dystrophic changes in the heart. The cause of the pathological process is the narrowing of the vessels of the main muscle of the body and, as a result, thrombus formation.

Preparations of a heterogeneous drug group have a relaxing effect on many organs and systems, leading to the expansion of the spasmodic vascular system.

Medicines lower blood pressure. Verapamil is distinguished from the most effective and inexpensive drugs. In severe and unpredictable disease, it is necessary to combine this group of calcium antagonists with other anti-ischemic drugs.

Hypertension

Hypertension is a chronic disease manifested by persistent vasoconstriction.

The need to use calcium channel blockers is due to the fact that they block the access of calcium to the blood vessels.

Therapy for the chronic form of pathology is lifelong and contributes to the achievement of a steady state:

When treating hypertension, it makes sense to use all 4 classes of blockers.

Each group of drugs has a number of distinctive properties:

1. Dihydropyridines (nifedipine, amlodipine). Their action relaxes the walls of blood vessels. At very high pressure, the appointment of these drugs quickly stabilizes the patient's condition. Possible side effects - with prolonged use, edema may appear.
2. Definylalkylamines (verapamil, halopamil). Medicines of this group relax the heart spasm, normalize the heart rate.
3. Benzodiazepines (diltiazem). Reduces the force of the heart contraction and the tension of the heart muscle. Diltiazem therapy must be carried out under the strict supervision of a physician, since the drug constricts blood vessels, which can negatively affect therapy as a whole.
4. Diphenylpiperazines. The appointment of Cinnarizine is advisable in violation of cerebral circulation, since it helps to normalize the blood flow rate.

Heart rhythm dysfunctions

The vast majority of cardiac arrhythmias or arrhythmias are the consequences of a primary pathology or disease. Treating the underlying cause can help deal with arrhythmias.

The main drugs in the treatment of cardiac contractions are Finoptin and Diakordin.

Precautions

When using drugs from the group of calcium antagonists, precautions must be taken.

Contraindications

As with any drug, calcium antagonists have their own contraindications. They are divided into absolute (in full) and relative (conditional).

Absolute restrictions on admission:

Relative (conditional) constraints:

• the use of Diakordin and Finoptin at the end of pregnancy;
• malignant transformation of the liver;
• Heart rate less than 55 beats per minute;
• progressive form of angina pectoris;
• thickening of the interventricular septum;
• a combination of taking BKK with magnesia.

Side effects

Side effects also vary with different groups of calcium antagonists.

All groups of pharmacological drugs cause similar complications:

To avoid adverse reactions, it is necessary to choose the correct dosage of the drug.

Withdrawal syndrome

Calcium antagonist drugs differ in chemical formula, therefore, they have different severity of withdrawal syndrome:

Dihydropyridine CCBs

Dihydropyridine calcium blockers are drugs that do not slow down the heart.

These include:

• Amlodil;
• Corinfar;
• Phenoptin;
• Diakordin.

Phenylalkylamines

Calcium blockers of this class have been subdivided into several generations.

Each of them has a selective effect on the heart muscle.

Benzodiazepines

This type of calcium antagonist affects the entire cardiovascular system. Decreases the heart rate.

Benzodiazepines are divided into 2 generations.

1. First generation - Diakordin, Aldizem.
2. Second generation - Altiazem RR, Brocalcin.

Selective CCBs

Selective in another way means selective. Each drug in the class of calcium channel blockers has tissue selectivity.

These calcium antagonists are classified into several subtypes.

Calcium blockers with a primary effect on arteries and veins: dihydropyridines and others:

• amlodipine;
• nilvadipine;
• cilnidipine.
• pozikor.

Calcium blockers with a primary effect on heart muscles: phenylkylamines and benzothiazepines.

Phenylkylamines:

Benzothiazepines:

• diacordin;
• lerkamen;
• lercanidipine.

List of latest generation calcium channel blockers

Calcium channel blockers	Antiarrhythmic result	Antianginal result	Antihypertensive result
Amlodipine	—	+	+
Lercanidipine	—	+	+
Lacidipine	—	+	+

Calcium channel blockers (the list of the latest generation drugs of which is presented above) increase blood circulation in the heart muscle, eliminate spasm of veins and arteries. The duration of their action is from 30-50 hours, which is much higher than their predecessors.

List of slow calcium channel blockers

"Slow" calcium blockers are of 2 types:

• non-selective;
• combined.

BMCC non-selective:

• phenoxane;
• cordium;
• lidoflazine;
• perhexiline.

BMKK combined:

• indapamide;
• corinfar;
• amlodipine with a combination diuretic.

Can CCB be taken without a doctor's prescription?

Before prescribing this or that drug, the doctor conducts a full diagnosis, therefore, self-administration of drugs without prior consultation is prohibited.

When talking with a doctor, it is necessary to accurately answer all his questions, tell what worries. Based on a face-to-face examination, examination, an established diagnosis and concomitant diseases, the doctor prescribes calcium channel blocker therapy.

In the course of treatment, it may be necessary to measure arterial deviations, heart rate. Calcium antagonists or calcium blockers are serious medications that do not allow self-medication. Their effect on the body of a particular patient is individual.

Calcium channel blockers are effective in the treatment of pathologies of the heart muscle, veins and arteries.

The list of the latest generation drugs, which was given in the article, is not a complete list. existing drugs... Each product has unique properties, which allows you to choose a treatment regimen individually for all patients.

Article design: Mila Friedan

Video about CC blockers:

Deadly couples: beta blockers and verapamil:

Calcium is an important trace element necessary for the normal and full functioning of the human body. However, in some diseases, it becomes necessary to "slow down" the action of this component. For this, special medications are used - calcium antagonists.

Calcium is an active participant in the transmission of signals from nerve receptors to intracellular structures, which contribute to the fact that cells tense and contract. One of the reasons for the development of hypertension, according to modern doctors, is a change in the ratio of calcium in cells and in blood plasma. The amount of calcium in the blood plasma is often low, while in the cells it is increased. This is fraught with the fact that the cells of the heart and blood vessels react more intensively than required to stimuli, hormones and other biologically active components.

Drugs - calcium antagonists, or AK, will help to cope with this problem. This is a group of drugs for hypertension, which differ in chemical composition, but have a common mechanism of action. It consists in the inhibition of the process of penetration of calcium ions through special calcium channels into the cells of the heart and blood vessels.

Action on the human body

Calcium antagonists are considered one of the best medications among antihypertensive drugs... They do an excellent job with the main task - bringing blood pressure indicators back to normal. However, they also have other positive effects on the body:

1. They are able to normalize the indicators of the heart rate, due to which calcium antagonists are used as antiarrhythmic agents.
2. AK are prescribed to patients who have had a stroke, since the drugs have a positive effect on the blood flow to the brain, which is especially important for atherosclerosis of the vessels of the head.
3. They prevent the formation of blood clots, since they cause inhibition of Ca metabolism in the cells, which contributes to the inhibition of platelet aggregation.
4. Calcium antagonists are able to reduce the pressure in the pulmonary artery and cause bronchodilation. The presence of antiatherogenic properties makes it possible to use AK not only as antihypertensive agents.
5. Reduce tension in the myocardium and its contractility. The antispastic action causes the expansion of the coronary arteries, resulting in increased blood circulation in the heart. And this helps to increase the supply of oxygen and nutrients to the myocardium.

Indications

The main indications for prescribing AK drugs are:

• hypertension;
• pulmonary hypertension;
• Ischemic heart disease (coronary heart disease);
• angina pectoris;
• disorder of the cerebral and peripheral circulation;
• hypertrophic cardiomyopathy;
• chronic diseases of the carotid arteries;
• tachycardia and other abnormalities in the heart rhythm;
• raynaud's disease;
• AK is also prescribed to prevent headache attacks.

Calcium antagonist classification

There are many classifications of calcium blockers based on - chemical composition, duration of action of drugs, etc. In 1996, experts proposed a new classification of AK. Calcium blocker medications were divided into three groups - drugs of the first, second and third generation. Let's take a closer look.

1. To medicines first generation include: Verapamil, Diltiazem and Nifedipine. These drugs have a strong antihypertensive effect, especially Nifedipine, which often limits their effective use. The drugs of the first generation have low bioavailability, a short period of exposure, and they quite often provoke the development of undesirable effects: they cause headaches, redness of the skin, and increase the heart rate.
2. List of drugs - calcium antagonists second generation wide enough: Benidipine, Isradipine, Manidipine, Nicardipine, Nilvadipine, Nimodipine, Nisoldipine, Nitrendipine, Felodipine. These funds are more effective, but also have drawbacks: for many, the effect is short-lived, the peak concentration is reached at different times, it is often not possible to determine in advance the effectiveness for patients.
3. AK third generation created taking into account the shortcomings of previous generations of medicines. The list of drugs of the latest generation includes the following drugs: Amlodipine, Lacidipine, Lekarnidipine. These drugs have the following advantages: high bioavailability, long half-life from the body, high tissue selectivity.

If we take into account the practical characteristics of drugs, then depending on the effect of the drugs used on the heart rate and on the tone of the sympathetic nervous system AK is divided into two subgroups:

• dihydropyridine preparations - those that reflexively increase heart rate (for example, Nicardipine, Amlodipine, Lacidipine);
• nondihydropyridine - reduce heart rate (for example, Verapamil, Diltiazem) and are similar in their effects to beta-blockers.

Mode of application

Let's get acquainted with the way of using some drugs.

1. Nifedipine... It is used orally at a dose of 5 to 10 mg after meals 3-4 times throughout the day, and to stop the hypertensive crisis - 5-10 mg under the tongue.
2. Nifedipine retard (Corinfar retard). It is prescribed 10-20 mg twice a day after meals.
3. Nifedipine GITS (continuous action drug). It is used at 60 - 90 mg once a day.
4. Felodipine... It is prescribed after meals, 2.5-10 mg once a day. The tablets should be taken with water, and they should not be crushed or chewed, but should be taken whole. The dose is increased gradually if necessary.
5. Amlodipine... It is used after a meal, 2.5-10 mg once a day. If necessary, increase the dose gradually. The maximum allowable is daily dose 10 mg.
6. Lacidipine. The starting dose for adults is 2 mg per day. If possible, you need to take the drug at the same time, preferably in the morning. The full effect develops after 3-4 weeks of regular use.
7. Nizoldipin... At the beginning of treatment, the dosage is 5-10 mg twice a day. According to indications, after 3 - 4 weeks, it can be increased to 20 mg per dose. The drug is taken with meals in the morning and evening. You can not chew, you need to drink plenty of water.
8. Gallopamil... It is prescribed 50 mg 2 times a day. It should be taken either with food, or immediately after it, the maximum allowable dose per day is 200 mg.
9. Diltiazem... It is taken 60 - 90 mg three times throughout the day. The tablets should not be chewed, they should be taken before meals and with plenty of water. The daily maximum dosage is 360 mg (4 times 90 mg).
10. Diltiazem SR... It is used one to two times during the day, 120 - 180 mg during a meal.

Application during pregnancy and lactation

Taking calcium antagonist medications during pregnancy and breastfeeding undesirable, since studies, which would be strictly controlled, have not been carried out on this group of patients. It is worth considering that some drugs can penetrate both into breast milkand through the placenta. When administered intravenously, the mother may develop hypotension, which causes fetal distress.

However, in some cases, the potential benefit of using calcium antagonist drugs for the treatment of pregnant women may be justified. The decision on treatment is made by the attending physician, taking into account both the mother's condition and the characteristics of the pregnancy.

Contraindications

For all calcium antagonist drugs, the following contraindications have been identified:

• low blood pressure;
• often the period of gestation (with the exception of Verapamil, Nifedipine);
• heart failure with reduced functionality of the left ventricle of the heart.

Side effects

The most common side effects that develop with AK are:

• hyperemia of the skin of the face;
• a sharp drop in blood pressure indicators;
• swelling of the limbs;
• decrease in systolic activity of the left ventricle.

Dihydropyridine drugs can provoke the development of the following adverse reactions:

• reflex tachycardia;
• peripheral edema;
• hypertrophy of the gums;
• migraine;
• hyperemia of the skin of the face.

Non-dihydropyridine calcium antagonists can cause:

• violation of sinus rhythm;
• lowering the automatism of the sinus node;
• atrioventricular conduction disorder;
• stool problems, hepatotoxicity (Verapamil).

Calcium antagonists are effective drugs that are successfully used to treat diseases of the heart and blood vessels. To get the maximum benefit from the use of drugs, it is necessary to systematically monitor blood pressure, heart rate, AV conduction, and it is also important to control the presence and severity of heart failure. An important point is the implementation of the doctor's recommendations, and you should also remember that self-medication is unacceptable.

L-type calcium channels found in the plasma membrane are structurally different from the calcium release channels in the sarcoplasmic reticulum. Both membranes contain ATP-dependent calcium pumps, which, although regulated differently, are members of the ion pump ATPase family, which also includes a sodium pump. The main system transporting from the cytosol to the extracellular space is the Na + -Ca2 + exchanger, which has no equivalent in the sarcoplasmic reticulum. Unlike the plasma membrane, where calcium flux generates an electrical current, the sarcoplasmic reticulum membrane contains non-selective anion channels that neutralize charge transfer associated with transmembrane calcium movement.

Plasma membrane ion channels, which are usually named for the ion transported, are oligomers containing up to 5 subunits. Ions pass the hydrophobic core of the bilayer membrane through ion-selective pores contained within large proteins.

The alpha- and c-subunits of sodium and calcium channels, as well as the potassium channel of delayed rectification, consist of four domains, each of which contains six a-helical transmembrane segments. Channel “pores” consist of a-helical transmembrane segments S5 and S6 and an intermediate amino acid sequence. The transmembrane segments of S4, which are rich in positively charged amino acids, are “voltage sensors” that open the channel in response to membrane depolarization. Several classes of ion channels are inactivated by an intracellular peptide chain linking domains III and IV, which in a depolarized cell undergo a conformational change to create an "inactivation particle" that blocks the inner pore opening. Four domains of most sodium and calcium channels of the plasma membrane are covalently linked into one large protein, while the domains of delayed rectification potassium channels, which also function as tetramers, are not covalently linked.

There are several classes of plasma membrane calcium channels. In the heart, the most important are the L-type calcium channels, so named because of their relatively long-lasting opening. These channels bind known classes of calcium channel blockers and are sometimes referred to as dihydropyridine receptors because of their high binding affinity for this class of calcium channel blockers. The second class of calcium channels, called T-channels, only open transiently; these channels play an important role in the sinoatrial junctional pacemaker, but they are practically absent in working ventricular myocytes. The content of T-type channels is increased in the hypertrophied heart, where they are thought to be involved in proliferative signaling.

The heart contains an even greater variety of potassium channels. They include potassium channels of delayed rectification, which show rectification outward. The latter term refers to the ability of these channels to open in response to membrane depolarization, which generates an electrical current that restores resting potential. Another class of potassium channels, referred to as inward rectification channels, is open when the cell is at rest but closes in response to depolarization; closing these channels lengthens the action potential of the heart and promotes the characteristic plateau phase. The main subunits of potassium channels of rectification are inwardly smaller than the subunits of potassium channels of delayed rectification and consist of regions homologous to the a-helical transmembrane segments S5 and S6 and an intermediate sequence of amino acids that correspond to the pore region of the large domains of the channels.

This information is intended for healthcare and pharmaceutical professionals. Patients should not use this information as medical advice or guidance.

Calcium channel blockers

Most of the Russian market for calcium channel blockers is formed by imported ones. The requirements for cinnarizine and nifedipine are almost entirely met by imports. 　

Mechanism of action of calcium channel blockers

Calcium ions are essential for maintaining heart function. Entering the cell, calcium ions activate metabolic processes, increase oxygen consumption, cause muscle contraction, and increase excitability and conductivity. Ca 2+ ions enter the cell through ion-selective calcium channels, which are located in the phospholipid membrane of heart cells. The membrane separates the cytoplasm from the extracellular environment. All Ca 2+ channels are divided into two large groups: voltage-gated and receptor-gated. In turn, depending on the conductivity, the lifetime in the open state, the rate of activation or inactivation, voltage-dependent Ca 2+ channels are divided into four types: dihydropyridine-sensitive Ca 2+ L-type channels, Ca 2+ channels T-, N - and P-type. In the cardiovascular system, there are L-type calcium channels, which regulate the entry of calcium into smooth muscle fibers and directly affect the contraction process. When activated, the channels form instant ion-selective pores through which Ca 2+ ions penetrate into the cell in the direction of the concentration gradient. This leads to a potential difference, which is measured as the membrane potential between the cytoplasm and the extracellular fluid. The movement of ions into and out of the cell returns the membrane potential to its original level.

With an increased load on the heart, compensatory mechanisms cannot cope with the overload and acute heart failure develops. At the same time, excessive accumulation of sodium and calcium ions inside the cells occurs in the heart muscle, a violation of the synthesis of high-energy compounds, acidification of the intracellular environment, followed by a violation of the contraction and relaxation of the heart muscle fiber. This leads to a decrease in the strength and rate of contraction of the heart muscle, an increase in the residual systolic volume and diastolic pressure, and expansion of the heart cavities. And since the contraction of vascular smooth muscle cells depends on the concentration of Ca 2+ in the cytoplasm, then if you suppress the transmembrane entry of Ca 2+ and its amount in the cytoplasm of the cell, then its readiness to contract will decrease. A critical increase in intracellular Ca 2+ can lead to cell damage and cell death due to its excessive activation with insufficient energy supply.

Calcium channel blockers (CCBs) reduce the intake of Ca 2+ through calcium L-channels. The mechanism of action of calcium channel blockers is based on the fact that they do not enter into any antagonism with calcium ions and do not block them, but affect their modulation, increasing and / or decreasing the duration of different phases of the state (phase 0 - closed channels, N1 and N2 - open channels) , and thus changing calcium current.

As a result, the load on the myocardium decreases and the tone of the smooth muscles of the arteries decreases (vasodilating effect), the high blood pressure decreases, the formation of the action potential changes (they affect the cardiac conduction system, normalizing the heart rate), the aggregation of platelets decreases (the risk of thrombosis decreases), the total peripheral vascular resistance (OPSS). Therefore, calcium channel blockers are widely used in modern medicine.

Calcium channel blockers or selective calcium antagonists are a group of drugs that were originally intended to treat angina pectoris. The first drug in this group, verapamil, a derivative of the well-known papaverine, was synthesized in Germany in 1962. Since the late 60s - early 70s of the last century, it has been established that calcium channel blockers have not only antianginal effects, but are also able to reduce systemic blood pressure. Since then, calcium antagonists have been widely used in the treatment of hypertension (persistent high blood pressure). Calcium channel blockers also penetrate well into the brain tissue and restrict the entry of calcium ions into nerve cells, which leads to the blocking of calcium-dependent mechanisms of neuronal death (the so-called apoptosis) in acute cerebral ischemia. This is the neuroprotective effect of calcium channel blockers.

The main indications for the use of calcium channel blockers are:

Essential hypertension and symptomatic arterial hypertension (with hypertensive crises, to lower blood pressure;

Exertional angina pectoris, Prinzmetal angina (a form of coronary insufficiency, characterized by prolonged (up to 1 hour) bouts of pain).

Combination of angina pectoris with bradycardia (slowing heart rate less than 60 per minute),

Angina pectoris, accompanied by supraventricular arrhythmias, tachycardia (heart rate over 100 beats per minute).

Supraventricular (sinus) tachycardia.

Extrasystole (violation of the heart rhythm, characterized by the occurrence of single or paired premature contractions of the heart (extrasystoles) caused by excitation of the myocardium). By themselves, extrasystoles are completely safe. They are called "cosmetic arrhythmias". However, in people with heart disease, the presence of extrasystoles is an additional unfavorable factor for atrial flutter and atrial fibrillation.

Acute disorders of cerebral circulation Chronic cerebrovascular insufficiency, discirculatory encephalopathy, vestibular disorders, motion sickness in transport, migraine.

Hypertrophic cardiomyopathy (primary non-inflammatory myocardial lesions of unexplained etiology (idiopathic), not associated with valvular defects or intracardiac shunts).

Raynaud's disease and syndrome (a disease of unclear etiology, characterized by paroxysmal spasms of the arteries of the fingers of the hands, less often of the feet, manifested by their paleness, pain and paresthesia (sensitivity disorders)).

Combination of paroxysmal supraventricular tachycardia, chronic atrial fibrillation with arterial hypertension.

The scope of the CCB is not limited to cardiology and angioneurology. There are other, more "narrow" and less well-known indications for the appointment of these drugs. These include the prevention of cold bronchospasm, as well as the treatment of stuttering, since the drugs in question eliminate the spastic contraction of the diaphragm. Cinnarizine has antihistaminic properties and can be used for immediate allergic reactions - itching, urticaria. It should be noted that recently, due to their neuroprotective and psychotropic properties, CCBs have been used in the complex treatment of Alzheimer's disease, Huntington's chorea, senile dementia, and alcoholism.

Let's list the most important pharmacological effects of these drugs in the field of cardiohemodynamics:

relaxation of vascular smooth muscles, which leads to a decrease in blood pressure, a decrease in post- and preload on the heart, an improvement in coronary and cerebral blood flow, microcirculation, a decrease in pressure in the pulmonary circulation; related to this hypotensive and antianginal the action of the CCL;

a decrease in myocardial contractility, which helps to reduce blood pressure and reduce the heart's need for oxygen; these effects are also required for hypotensive and antianginal action;

diuretic effect due to inhibition of sodium reabsorption (participates in lowering blood pressure);

relaxation of muscles internal organs (antispasmodic effect);

slowing down the automatism of the cells of the sinus node, inhibition of ectopic foci in the atria, a decrease in the speed of impulses along the atrioventricular node ( antiarrhythmic action);

inhibition of platelet aggregation and improvement of the rheological properties of blood, which is important for the treatment of Raynaud's disease or syndrome.

Different CCBs have different pharmacological properties. The funds under consideration are divided into 4 main groups with slightly different hemodynamic effects:

Dihydropyridines

Phenylalkylamines;

Benzothiazepines.

Flunarizines.

The subgroup of dihydropyridines is divided into 3 generations of drugs. Each subsequent generation surpasses the previous one in terms of effectiveness, safety and pharmacokinetic parameters.

Classification of calcium channel blockers.

Subgroup	Drugs	a brief description of
Dihydropyridines	1st generation: Nifedipine short-acting, Nifedipine retard (long-acting) generation: Nifedipine GITS (continuous), Felodipine generation: Amlodipine, Lacidipine, Nimodipine	These drugs have a predominant effect on vascular smooth muscles, they have less effect on the conducting system of the heart and on myocardial contractility; nimodipine (nimotop) differs in that it has a predominant expanding effect on the vessels of the brain, and is used for disorders of cerebral circulation
Phenylalkylamines	Verapamil, Verapamil retard	The effect on the cardiac conduction system is strongly expressed, namely on the sinus node, where depolarization of cell membranes depends on the entry of calcium ions, and on the atrioventricular node, in which the entry of calcium and sodium ions is important for the development of the action potential. They practically do not affect the conduction system of the ventricles, clearly reduce the contractility of the myocardium, and their effect on the vessels is weak.
Benzothiazepines	Diltiazem, Diltiazem retard	These drugs have approximately the same effect on the heart and blood vessels, but somewhat weaker than the nifedipine group.
Flunarizines	Cinnarizine	In therapeutic doses, the drugs of this group have an expanding effect mainly on the vessels of the brain, therefore they are mainly used for cerebral circulation disorders, migraines, and vestibular disorders. The influence of the considered CCBs on the vessels of other basins, as well as on the heart, is insignificant and has no significant clinical significance.

Table 1.

By the duration of the antihypertensive action, calcium antagonists can be divided into the following groups:

short acting

(up to 6-8 hours) - frequency of reception; 3-4 times a day (verapamil, diltiazem, nifedipine and others);

medium duration

(8-12 hours) - taken 2 times a day (isradipine, felodipine and others);

long acting

(up to 24 hours) - effective when taken once a day (nitrendipine and retard forms of verapamil, diltiazem, isradipine, nifedipine and felodipine);

super long action

- their antihypertensive effect lasts more than 24-36 hours (amlodipine).

The disadvantage of short-acting dosage forms is both their short duration of action and sharp drops in blood concentration, as a result of which the risk of developing a stroke or myocardial infarction increases. All calcium channel blockers are lipophilic, 90-100% absorbed in the digestive tract and excreted from the body through the liver, however, in important pharmacokinetic parameters, such as bioavailability and plasma half-life, they differ significantly from each other.

Duration of action	A drug	Bioavailability,%	Half-life in blood plasma, h	Time to reach the maximum concentration in blood plasma, h
Short acting	Verapamil	10-30	4-10	1-2
	Diltiazem	30-40	2-7	1-2
	Nifedipine	23-30	2-6	0,6
Medium duration	Felodipine	12-16	3-14	1,5
	Isradipin	17-33	7-8	1,6
	Lacidipine	3-52	7-8	1
Long-acting	Felodipine retard	12-16	10-36	2-8
	Verapamil retard	10-30	12	1-2
	Nifedipine retard	60-75	12	4
Extra long action	Amlodipine	60-80	35-52	6-12

Source: reference book of medicines.

The drug should be effective, have as few side effects as possible, and manage disease in the best possible way. If the drug meets all the requirements that apply to it, then it is considered to be of high quality.

All calcium channel blockers have a sufficient number of side effects, therefore, when choosing this drug, you must be very careful not to have the opposite effect.

Calcium channel blockers should be used systematically, therefore, certain requirements are imposed on them:

with monotherapy, the drug should effectively reduce blood pressure, maintain antihypertensive efficacy;

with long application, have a long-lasting effect, ensuring blood pressure control when administered 1–2 times a day;

be well tolerated;

do not induce withdrawal symptoms when it stops suddenly application;

do not cause undesirable metabolic effects (do not worsen lipid, carbohydrate, purine metabolism, do not disturb the balance of electrolytes);

improve health indicators of the population (reduce the incidence of complications, mortality);

be relatively inexpensive.

Calcium channel blockers do not fully satisfy these requirements, each drug has its own advantages and disadvantages, which must be carefully analyzed before prescribing any drug. Table 3 provides a comparative characteristic of the most common calcium channel blockers used in clinical practice. The basic principles that must be followed when prescribing these drugs are given in Table 4. However, when treating, it is necessary to take into account all factors that may have an adverse effect, especially individual intolerance to this drug and all concomitant diseases.

Comparative characteristics of calcium channel blocker drugs.

A drug	disadvantages	Benefits
Nifedipine	There are many more side effects than other calcium channel blockers. Symptoms associated with vasodilation (sensation of flushing, burning; tachycardia, arterial hypotension), chest pain (sometimes of the type of angina pectoris) are frequent, which requires immediate discontinuation of the drug; possible headache, visual impairment, myalgia, paresthesia in the limbs, short-term vision changes, fatigue, sleep disturbances. Prescribe carefully to patients diabetes mellitussince hyperglycemia is possible. After a sudden withdrawal of nifedipine, a hypertensive crisis or myocardial ischemia ("withdrawal phenomenon") may develop. The disadvantage of nifedipine also lies in the need to take it multiple times, which not only creates inconvenience for patients, but also causes a rather sharp daily fluctuation in blood pressure.	Increases the excretion of sodium and water from the body. In therapeutic doses, it does not inhibit myocardial conductivity. Virtually no antiarrhythmic activity. The antihypertensive effect of nifedipine is especially pronounced in patients with initially high blood pressure. Able to quickly lower blood pressure, especially when taken under the tongue. An ambulance for outpatient relief of hypertensive crises, reduction of transient increases in blood pressure. High efficiency in reducing blood pressure, the speed of the onset of the effect and low cost made nifedipine practically a folk drug for the treatment of certain forms of angina pectoris, arterial hypertension and a number of cardiovascular diseases.
Amlodipine	The maximum effect of amlodipine can be expected in a week from the start of its administration, because it is slowly absorbed after ingestion and gradually begins to act, that is, it is unsuitable for a rapid decrease in blood pressure.	High bioavailability. The duration of action due to its slow release from the connection with the receptors. It can be used in patients with diabetes mellitus, as well as bronchial asthma and gout. It has a pronounced hypotensive effect on both systolic and diastolic blood pressure. With the development of the hypotensive effect of amlodipine, there is no change in the heart rate. Has great selectivity in relation to coronary and cerebral vessels, is practically devoid of inotropic effect and influence on the function of the sinus node and atrio-ventricular conduction. Well tolerated by patients, safe and effective in patients with hypertension in combination with severe heart failure.
Lacidipine	Low bioavailability. Recently on the market, little clinical research has been done.	It has a gradual and long-term antihypertensive effect.
Felodipine	In most cases, adverse reactions are dose-dependent and appear immediately after starting treatment. These reactions are temporary and subside over time. Edema is common with this drug.	Effective and well tolerated by elderly patients, regardless of age or concomitant pathology, does not have a negative effect on blood glucose concentration and lipid profile The main pharmacodynamic feature of the drug is its strong vascular selectivity. Smooth muscle resistive muscles are especially sensitive to felodipine.
Nimodipine	The most common side effects: hypotension, tachycardia, swelling, facial redness; dyspeptic symptoms; sleep disorders, increased psychomotor activity. There is only an imported drug on the market. Dear. It is inconvenient to enter (it is administered intravenously). Practically does not affect the conductivity in the AV and SA nodes and myocardial contractility. Reflexively increases heart rate in response to vasodilatation.	Blocks calcium channels in certain areas of the brain, has a positive effect on learning ability and memory (nootropic effect). Effective in violation of cerebral circulation.
Verapamil	When using large doses, especially in predisposed patients, severe bradycardia, AV blockade, arterial hypotension, and symptoms of heart failure are possible. In patients with coronary artery disease or cerebrovascular insufficiency, an excessive decrease in blood pressure during antihypertensive therapy can lead to the development of myocardial infarction or cerebrovascular accident. With rapid intravenous administration in isolated cases - complete transverse heart block, asystole, collapse. Verapamil can cause asymptomatic grade I atrioventricular block or transient bradycardia.	The anti-ischemic effect increases with regular administration of verapamil. No orthostatic hypotension or reflex tachycardia is observed and does not cause changes in systolic cardiac function in patients with normal ventricular function. It has an effective antiarrhythmic effect in supraventricular arrhythmias. The contraction of the ventricles slows down with atrial flutter or atrial fibrillation. Restores sinus rhythm in paroxysmal supraventricular tachycardia The action of Verapamil can rarely lead to atrioventricular block II or III degrees of severity, bradycardia or, in rare cases, to asystole.
Diltiazem	The ability to quickly reach maximum concentration, the action of the drug passes just as quickly, the risk of bradycardia.	Diltiazem is one of the most effective and safe drugs in modern cardiology, which does not affect lipid and carbohydrate metabolism... Effective in supraventricular arrhythmias reduces the peripheral and renal effects of angiotensin II.
Cinnarizine	Almost does not affect blood pressure. sometimes mild drowsiness, dry mouth, gastrointestinal upset is possible; in these cases, reduce the dose. With severe arterial hypotension. In some elderly patients, extrapyramidal symptoms appear (or intensify). Strengthens the effect of sedatives and alcohol.	Few side effects. These drugs are the cheapest on the market. Increases tissue resistance to hypoxia. It has a direct antispasmodic effect on blood vessels, reduces their response to biogenic vasoconstrictor substances.