List of calcium channel blockers. Overview of calcium channel blockers: general description, types of group drugs. Indications for the appointment of calcium channel blockers in cardiology practice

calcium antagonists(abbreviated as AK) is an important group of drugs in cardiology. They are primarily used to treat arterial hypertension(AG). Calcium antagonists have another name (synonym) - calcium channel blockers(abbreviated - BKK). The term BKK is used less frequently than AK. Be sure to remember that BKK is the same as AK.

Mechanism of action of calcium antagonists

There are several types of cell membranes in our body. calcium channels, which are able to pass Ca 2+ ions in one direction (inward or outward). calcium channels are several types. All calcium antagonists used in cardiology act only on slow L-type channels, which are in striated myocardial muscle cells(both in conductive and contractile cells) and in smooth muscle of blood vessels. calcium channels are activated catecholamines (epinephrine, norepinephrine). Thus, for the normal functioning of calcium channels, calcium ions and (nor) adrenaline are simultaneously required, therefore, the simultaneous use of calcium antagonists and beta-blockers is fraught with excessive inhibition of the activity of calcium channels (in relation to blood vessels, this is not so terrible, but a double effect on the myocardium can lead to to slow atrioventricular conduction with the development of AV blockade of various degrees).

calcium antagonists(gr. anti- against, agon- struggle; literal translation - calcium fighters) block the flow of calcium through calcium channels in cell membranes from the intercellular space to the muscle cells of the heart and blood vessels. Calcium is essential for muscle contraction. The higher the concentration of calcium in the cell, the higher the force of contraction.

Calcium supplements (eg. calcium chloride) it is forbidden to inject intramuscularly because of the danger of uncontrolled strong and prolonged muscle contraction, which will lead to clamping of blood vessels and necrosis (necrosis) of the muscle with the formation of an abscess (large abscess). Calcium supplements are allowed only intravenously.

Due to the energy-consuming work to remove calcium ions from the cell Ca 2+ concentration outside is 25 times higher than inside the cell (we are talking about the heart). Due to the difference in concentrations, calcium ions constantly strive by hook or by crook to get inside the cell. At the end of muscle contraction, calcium ions are actively removed from the cell. ion pumps against the difference in concentrations, which requires the expenditure of energy (ATP).

It is appropriate here to recall rigor mortis mechanism. It is sure sign of death, refers to early cadaveric changes and consists in the hardening and stiffness of the muscles of the corpse. After death, the supply of oxygen to the cells stops, ATP is no longer formed. Calcium ions gradually seep into the cell due to the difference in concentrations. In this case, calcium cannot be removed from the cell by ion pumps, because it is an energy dependent process. As a result, a few hours after death, the calcium concentration inside the muscle cells passively rises to the desired level, and rigor mortis begins. It reaches maximum one day after death and then begins to gradually weaken due to the enzymatic destruction of muscle proteins. If before death there were convulsions, then intravital muscle contraction straightaway passes into rigor mortis.

Dietary calcium intake and blood pressure

Research scientists have shown that diet rich in calcium(for example, with a high intake of dairy products), can lower blood pressure levels at 3-5 mmHg. It is believed that hormones that increase the level of calcium in the body ( parathyroid hormone, atriopeptide, and vitamin D3), also increase blood pressure by vasoconstriction and activation of the sympathoadrenal system. A diet rich in calcium feeds back the levels of these hormones, and consequently, the level of blood pressure. However, the effect of a calcium-rich diet is seen only in people with low baseline calcium levels in the blood.

Animal studies have shown that excessive calcium levels in the blood can also lead to arterial hypertension.

Classification of calcium channel blockers

A classification by chemical structure is usually used, but it is difficult to remember (for example, dihydropyridine preparations), so I simplistically prefer to divide the calcium channel blockers used in cardiology, for 2 groups by parent drugs and general properties:

№ 1. Verapamil group(drugs act on both the muscle tissue of the heart and on the vessels):

• verapamil(the only available drug of the group),
• gallopamil(not available in pharmacies in Russia and Belarus according to the search for pharmacies on the websites www.poisklekarstva.ru or tab.by),
• diltiazem(available in pharmacies. It differs in chemical structure from verapamil and gallopamil, but belongs to this group in its properties),
• klentiazem(not available in pharmacies of the Russian Federation and the Republic of Belarus, chemical structure similar to diltiazem).

№ 2. Nifedipine group, or dihydropyridine preparations(act only on the smooth muscles of the blood vessels):

• nifedipine(ancestor of the group)
• amlodipine, lercanidipine(these are modern drugs of a new generation with a frequency of administration 1 time per day),
• felodipine, nimodipine(registered in the Russian Federation, but not in the Republic of Belarus),
• nitrendipine, lacidipine, nicardipine, isradipine(all of them are not available in pharmacies of the Russian Federation and the Republic of Belarus).

Of the entire BKK classification, it is desirable for non-specialists to know three main things (I will go into more detail later):

1. differences in the points of application of drugs (heart or blood vessels) lead to large differences in side effects and contraindications,
2. drugs from the group verapamil act both on the myocardium and on the vessels, so they NOT compatible(!) With ,
3. drugs from the group nifedipine(dihydropyridine derivatives) act only on the vessels, therefore combination with beta-blockers is possible and even recommended for nifedipine.

If approached strictly scientifically, then verapamil the effect on vascular smooth muscle exceeds the effect on the myocardium by 1.4 times, in diltiazema- 7 times and nifedipine- 14 times. That's why verapamil stronger than all other AK acts on the myocardium, diltiazem simplistically attributed to the verapamil group, and the effect of nifedipine on the myocardium is neglected due to its insignificance.

Comparison of calcium antagonists with beta-blockers

How calcium channel blockers work similar to, but their effects depend on which group of drugs it is (group verapamil or nifedipine). L-type calcium channels can pass calcium into the cell only after they are activated by catecholamines ( epinephrine, norepinephrine). This means that the combined use of CCB and beta-blocker potentiates(dramatically enhances) the effect of each drug separately. For the verapamil group, this combination is quite dangerous. Verapamil and diltizem should never be given to the same patient concomitantly with beta-blockers due to the risk of serious atrioventricular conduction block (AV block) and cardiac arrest.

Unlike beta-blockers, all calcium antagonists:

• do not narrow the bronchi and therefore are safe to use in patients with bronchial asthma,
• do not worsen the blood lipid profile (i.e., do not increase the content), to some extent reduce blood viscosity.

L-type calcium antagonists also include drugs dilating cerebral vessels: cinnarizine, flunarizine. Pharmacies sell only the first drug ( cinnarizine), which improves blood circulation in the brain and reduces headaches, tinnitus, increases the resistance of nerve cells to lack of oxygen. Cinnarizine acts mainly on cerebral vessels and has almost no effect on blood pressure and heart rate. It is prescribed for atherosclerosis of cerebral vessels, for the treatment of ischemic strokes, vestibular disorders (dizziness, tinnitus, etc. due to problems in the inner ear), peripheral circulation disorders (i.e., in the limbs).

Calcium channel blockers are often prescribed against high blood pressure, as well as a number of other diseases. These drugs have clear indications for use and require mandatory compliance with contraindications.

Preparations and their types

Calcium antagonists, or calcium channel blocking agents (CCBs), are a large group of drugs with the same mechanism of action, but differing from each other in composition, structure, and some properties (absorption, excretion, effect on the work of the heart). Another correct name for the group is slow calcium channel blockers.

The described drugs belong to the first line, they are used as antihypertensive drugs.

Usually, with arterial hypertension, these drugs normalize the level of blood pressure, and if they are ineffective, they are replaced or combined with other drugs (beta-blockers, ACE inhibitors). It is preferable to treat them with people in old age, in the presence of peripheral blood flow disorders, kidney damage, angina pectoris. There are several groups of calcium antagonists, here are the main ones:

Also, all drugs can be divided into those that increase heart rate, or those that reduce it (the latter are similar in mechanism to beta-blockers). According to the time of development, four generations of drugs are distinguished. Nifedipine belongs to the first, Nimodipine to the second, Amlodipine to the third, Cilnidipine can be attributed to the last generation drugs.

Nifedipine group - drugs

Calcium ions play an important role throughout the body. Calcium is needed for bones, helps to heal them with fractures, along with magnesium helps with leg cramps. The element also controls heart contractions - it is responsible for the normal function of myocytes. If there is an excess of the element or if its excretion is disturbed, a failure of the pumping function and an increase in pressure occur. BKK helps to solve the problem.

Most often among the list of drugs, doctors prescribe dihydropyridine derivatives, which are otherwise called the Nifedipine group. The latter is the first developed BPC that has a positive effect on blood vessels. It has the following effects:

• slows down the penetration of calcium into cardiomyocytes, smooth muscle fibers of arteries;
• gives antianginal, hypotensive action;
• reduces the tone of the arteries without affecting the tone of the veins;
• expands the lumen of peripheral and coronary vessels;
• reduces myocardial oxygen demand.

The drugs do not affect the rhythms of the heart, do not inhibit conduction. In patients with heart failure, diabetes mellitus, in those who are on hemodialysis, the drug is used only in a hospital setting. Main indications:

• relief of angina attacks;
• hypertension;
• Raynaud's disease;
• hypertensive crisis.

With the same medicinal substance, more expensive preparations have been developed that differ in the degree of purification, type of release and brand of the manufacturer - Nifecard, Kordaflex, Kordipin, Corinfar, Calcigard, their cost is 200-600 rubles. The group of dihydropyridines also includes Nimodipine (Nimotop), Amlodipine (Amlovas, Norvask).

Verapamil group - representatives

Verapamil derivatives belong to the group of phenylalkylamines, they have a pronounced effect on the conductivity in the myocardium. Their distinctive feature is the effect on the sinus node - the pacemaker, since the work of cell membranes in it is due to the presence of calcium ions.

Verapamil has no effect on the conduction system of the ventricles - depolarization there depends on sodium ions.

Verapamil has a strong antianginal effect - it manifests itself as a result of the direct action of the drug, as well as due to the effect on arterial tone in the periphery. The drug is prescribed as an additional remedy for cardiomyopathy, as it reduces the tone of the myocardial walls. Other indications:

• supraventricular arrhythmias;
• stable angina pectoris without vasospasm;
• paroxysmal and other types of tachycardia;
• tachyarrhythmia is atrial;
• atrial flutter;
• supraventricular extrasystole;
• hypertension, crisis conditions;
• pulmonary hypertension.

There are also a number of other drugs based on Veropamil - Isoptin (440 rubles), Tarka (760 rubles). The second generation of drugs in this group is represented by gallopamil and a drug based on it, which is called Procorum.

Diltiazem and its analogues

Benzodiazepines are weaker than Nifedipine, affect the blood vessels, the heart. It is believed that they occupy a middle position between Verapamil and Nifedinin, they are third-generation drugs. Distinctive features:

• moderate suppression of the sinus node;
• moderate decrease in the function of the atrioventricular node;
• mild decrease in blood pressure.

The group's main drug is Diltiazem (150 rubles). It has antianginal, hypotensive, antiarrhythmic properties, reduces myocardial contractility, reduces heart rate, increases coronary blood flow and reduces the heart's need for oxygen. Also, the drug contributes to an increase in renal and cerebral blood flow. After taking the drug, the amount of calcium ions in myocardial cells decreases, which provides the effects described above.

Diltiazem is available in the form of regular tablets and extended-release formulations (Diltiazem SR). Most often it is prescribed for angina pectoris, combined with arterial hypertension, with coronary artery disease, Prinzmetal's angina. It is undesirable to make combinations of drugs with beta-blockers, so it is possible to increase the negative effect on the conduction system of the heart.

Cinnarizine group

This drug and its analogues have slightly different indications for use. They expand, for the most part, the vessels of the brain, and have an indirect and insignificant effect on the heart.

Cinnarizine can be used for headaches and migraines - it removes vascular spasm.

Among the indications for treatment with Cinnarizine are dizziness, memory loss, tinnitus, impaired attentiveness. The drug in complex therapy is indicated for Meniere's disease, labyrinthitis, nystagmus of various etiologies. Other indications:

• seasickness;
• disorders of cerebral circulation (chronic);
• failures of peripheral circulation;
• Raynaud's disease;
• acrocyanosis;
• ulcers on the extremities in diabetes, varicose veins.

Cinnarizine is also part of the drug Stugeron, and in combination with piracetam - in the drug Fecetam, Omaron. The second generation of the group is represented by the active substance flunarizine, which provided the basis for the creation of a number of drugs for migraine.

The fourth generation of drugs includes a rather limited list. Cilnidipine is on the list of the latest generation of calcium channel blockers. The drug belongs to the group of dihydropyridines, therefore, it is most widely prescribed for the treatment of arterial hypertension, coronary artery disease. The drug has a high selectivity for slow calcium tubules.

Cilnidipine is a promising drug that was developed by Japanese scientists in the 2000s. It is most widely used in Japan, in Russia it is represented by the original and various generics. The advantages of the drug are:

• safety for patients;
• high efficiency against hypertension;
• no adverse effects on heart rate, pulse;
• improvement of the properties of arterial walls;
• suitability for use in the elderly.

The medicine helps with stress hypertension, with a morning increase in pressure. It also has a nephroprotective effect and can be used in patients with diabetes mellitus. With coronary artery disease, the agent gives an additional effect in the form of an improvement in the lipid profile.

Contraindications and side effects

Most calcium antagonists are forbidden to drink in the acute period of myocardial infarction, if these contraindications are neglected, the risk of cardiac death is greatly increased. Also among the prohibitions on therapy are:

• pre-infarction state, unstable angina;
• arterial hypotension;
• tachycardia - for a group of drugs with nifedipine;
• bradycardia - for a group of drugs with verapamil;
• acute heart failure;
• age up to 12-18 years, depending on the drug group and the specific drug;
• lactation, pregnancy;
• the last stages of renal, hepatic insufficiency (the ban is not relevant for all drugs).

Side effects are with each remedy, most often they include headache, fever, severe pressure drop. A number of patients have peripheral edema, the development of tachycardia. Many drugs, when taken for a long time, manifest themselves as constipation, an increase in liver tests, and a skin rash. Cinnarizine may increase the symptoms of Parkinson's disease.

Drugs that lower the amount of calcium ions inside cells are called calcium blockers (slow calcium channels). Three generations of these drugs have been registered. Used to treat coronary disease, high blood pressure and tachycardia, hypertrophic cardiomyopathy.

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General information about calcium channel blockers

Medicines of this group have a different structure, chemical and physical properties, therapeutic and side effects, but they are united by a single mechanism of action. It consists in inhibition of the transfer of calcium ions through the membrane.

Among them are drugs with a predominant effect on the heart, blood vessels, selective (selective) and non-selective action. Often in one drug there is a blocker in combination with a diuretic.

Calcium channel blockers (CCBs) have been used for treatment in cardiology for about 50 years, this is due to the following advantages:

• clinical efficacy in myocardial ischemia;
• treatment and prevention,;
• reducing the risk of complications and mortality from heart disease;
• good tolerability and safety even for long courses;
• lack of addiction;
• there is no negative effect on metabolic processes, accumulation of uric acid;
• can be used in patients with bronchial asthma, diabetes, kidney disease;
• do not reduce mental or physical activity, potency;
• have antidepressant effects.

The mechanism of action of drugs

The main pharmacological action of CCB is the inhibition of the transition of calcium ions from the extracellular space to the muscle fibers of the heart and vascular walls through slow type L channels. With calcium deficiency, these cells lose their ability to actively contract, therefore, relaxation of the coronary and peripheral arteries occurs.

In addition, the use of drugs manifests itself in the following way:

• myocardial oxygen demand decreases;
• improves exercise tolerance;
• low resistance of arterial vessels leads to a decrease in the load on the heart;
• blood flow is activated in ischemic zones, the damaged myocardium is restored;
• the movement of calcium in the nodes and fibers of the conducting system is inhibited, which slows down the rhythm of contractions and the activity of pathological foci of excitation;
• platelet adhesion and thromboxane production slow down, blood fluidity increases;
• there is a gradual regression of left ventricular hypertrophy;
• the peroxidation of fats is significantly reduced, and hence the formation of free radicals that destroy the cells of blood vessels and the heart.

The influence of calcium antagonists on the process of atherosclerotic lesions of arteries and veins allows you to influence the main cause of coronary and hypertension.

Medicines in the initial stages prevent the formation of a plaque that clogs the arteries, prevent the coronary vessels from narrowing and stop the growth of the smooth muscles of the vascular wall.

Use of antianginal or selective blockers

The main indications for the use of BPC are such diseases:

• primary and symptomatic hypertension, including during a crisis (drops or a tablet lowers blood pressure in 10 minutes);
• angina pectoris at rest and exertion (with bradycardia and blockade, hypertension, Nifedipine is used, and - or Diltiazem);
• tachycardia, flickering, treated with Verapamil;
• acute disorders of cerebral blood flow (Nimotop);
• chronic cerebral ischemia, encephalopathy, motion sickness, migraine headache (Cinnarizine);
• (Amlodipine, Nifedipine, Procorum);
• (Corinfar, Lacipil).

No less effective was the use of calcium antagonists for bronchospasm, stuttering, allergies (Cinnarizine), complex treatment of senile dementia, Alzheimer's disease, and chronic alcoholism.

Watch the video about the choice of drugs for hypertension:

Contraindications

There are general restrictions for prescribing calcium channel blockers. These include:

• sinus node depression syndrome,
• , heart attack (risk of complications),
• low blood pressure,
• acute manifestations of heart failure,
• severe renal or hepatic pathology,
• pregnancy, breastfeeding, childhood.

In addition, drugs containing Verapamil or its analogues are contraindicated in case of blockade of impulse conduction, and Nifedipine in case of tachycardia.

For patients with heart failure, heart attack, short-acting drugs such as Nifedipine are of particular danger. Severe circulatory failure is not treated with Verapamil or Diltiazem.

Types of slow calcium channel blockers

Since the BPC group combines heterogeneous drugs, several classification options have been proposed. There are three generations of medicines:

• the first - Isoptin, Corinfar, Diltiazem;
• the second - Gallopamil, Lacipil, Foridon, Klentiazem;
• the third - Lerkamen, Zanidip, Naftopidil.

According to the influence on the main clinical symptoms, the following subgroups are distinguished:

• expanding peripheral arterioles - Nifedipine, Felodipine;
• improving coronary blood flow - Amlodipine, Felodipine;
• lowering myocardial contractility - Verapamil;
• inhibitory conductivity and automatism - Verapamil.

Depending on the chemical structure, BPCs are subdivided into:

• Nifedipine group - Corinfar, Norvasc, Lacipil, Loxen, Nimotop, Foridon. Predominantly expand the peripheral arteries.
• Verapamil group - Isoptin, Veranorm, Procorum. They act on the myocardium, inhibit the conduction of a heart impulse through the atria, do not affect the vessels.
• Diltiazem group - Cardil, Klentiazem. Equally affect the heart and blood vessels.
• Cinnarizine group - Stugeron, Nomigrain. Expand mainly cerebral vessels.

3rd generation drugs

First-generation calcium blockers are characterized by low bioavailability, insufficient selectivity of action, and rapid elimination from the body. This requires frequent administration and sufficiently high doses. The second generation is devoid of these shortcomings, since the drugs are in the blood for a long time, their absorption is much higher.

The third generation of BKK is represented by Lerkamen. It penetrates well into the cell membrane, accumulates in it and is slowly washed out. Therefore, despite the short circulation in the blood, its effect is long-lasting. Use the drug 1 time per day, which allows you to maintain a constant effect and is convenient for the patient.

The action of Lerkamen is manifested in the relaxation of the walls of blood vessels, it does not reduce the contractility of the myocardium, which makes it the safest remedy for the treatment of hypertension or angina with weakness of the heart muscle.

At the same time, the drug has other positive effects on hemodynamics:

• improves cerebral circulation,
• protects brain cells from destruction
• acts as an antioxidant
• dilates the arteries of the kidneys, inhibits their sclerosis,
• has a pronounced hypotensive effect,
• refers to cardio-nephro- and cerebroprotectors.

Side effects:

• headache,
• edema,
• pressure drop,
• facial redness,
• feelings of hot flashes,
• increased heart rate,
• inhibition of cardiac impulse conduction.

Verapamil inhibits conduction and automatism function, can cause blockade and asystole. Less common: constipation, indigestion, rash, cough, shortness of breath and drowsiness.

Blockers of slow calcium channels effectively lower blood pressure, with a long course of therapy they prevent myocardial hypertrophy, protect the inner lining of blood vessels from the atherosclerotic process, remove sodium and water due to the expansion of the renal arteries. They reduce the mortality rate and the frequency of complications in heart disease, increase exercise tolerance and have no pronounced side effects.

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As a rule, treatment is reduced to the correction of antihypertensive therapy and the appointment of drugs that improve microcirculation in tissues. With the ineffectiveness of these methods, surgical intervention is indicated.

Calcium channel blockers, or calcium antagonists (CA) are medicinal substances that inhibit the entry of calcium ions into cells through calcium channels.

Calcium channels are protein structures through which calcium ions move in and out of the cell. These charged particles are involved in the formation and conduction of an electrical impulse, and also provide contraction of the muscle fibers of the heart and vascular walls.
Calcium antagonists are actively used in therapy, hypertension and.

These drugs slow down the entry of calcium into the cells. This expands the coronary vessels, improves blood flow in the heart muscle. As a result, the supply of oxygen to the myocardium and the removal of metabolic products from it are improved.

By reducing the heart rate and myocardial contractility, AK reduce the heart's need for oxygen. These drugs improve the diastolic function of the myocardium, that is, its ability to relax.
AKs dilate peripheral arteries, helping to lower blood pressure.

Some drugs from this group (verapamil, diltiazem) have antiarrhythmic properties.
These drugs reduce the aggregation ("gluing") of platelets, preventing the formation of blood clots in the coronary vessels. They exhibit anti-atherogenic properties, improving cholesterol metabolism. AA protect cells by inhibiting lipid peroxidation and slowing down the release of dangerous lysosomal enzymes into the cytoplasm.

Classification depending on the chemical structure

AAs are divided into three groups depending on their chemical structure. In each of the groups, preparations of the 1st and 2nd generations are isolated, differing from each other in their selectivity (“targetedness”) of action and the duration of the effect.

AK classification:
Derivatives of diphenylalkylamine:

• 1st generation: verapamil (isoptin, finoptin);
• 2nd generation: anipamil, gallopamil, falipamil.

Benzothiazepine derivatives:

• 1st generation: diltiazem (cardil, dilzem, tilzem, dilacor);
• 2nd generation: Altiazem.

Derivatives of dihydropyridine:

• 1st generation: nifedipine (corinfar, cordafen, cordipin, fenigidin);
• 2nd generation: amlodipine (Norvasc), isradipine (Lomir), nicardipine (Carden), nimodipine, nisoldipine (Ciscor), nitrendipine (Bypress), riodipine, felodipine (Plendil).

Derivatives of diphenylalkylamine (verapamil) and benzothiazepine (dilthiazem) act on both the heart and blood vessels. They have expressed antianginal, antiarrhythmic, hypotensive action. These drugs decrease the heart rate.

Dihydropyridine derivatives dilate blood vessels, have antihypertensive and antianginal effects. They are not used to treat arrhythmias. These drugs cause an increase in heart rate. Their effect in angina pectoris is more pronounced than in the first two groups.

Currently, second-generation dihydropyridine derivatives, in particular, amlodipine, are widely used. They have a long duration of action and are well tolerated.

Indications for use

angina pectoris

For long-term therapy, verapamil and diltiazem are used. They are most indicated in young patients, with a combination of angina pectoris with sinus bradycardia, arterial hypertension, bronchial obstruction, hyperlipidemia, biliary dyskinesia, and a tendency to diarrhea. Additional indications for the choice of these drugs are cerebrovascular insufficiency.

In many cases, combination therapy is indicated, combining diltiazem and beta-blockers. The combination of AA with nitrates is not always effective. The combination of beta-blockers and verapamil can be used with great care to avoid possible severe bradycardia, arterial hypotension, cardiac conduction disturbances and reduced myocardial contractility.

myocardial infarction

In transmural myocardial infarction (“with a Q wave”), AKs are not indicated.

Hypertonic disease

AAs are able to cause reverse development, protect the kidneys, and do not cause metabolic disorders. Therefore, they are widely used in the treatment of hypertension. Derivatives of nifedipine II generation (amlodipine) are especially shown.

These drugs are especially indicated for the combination of arterial hypertension with exertional angina, lipid metabolism disorders, and obstructive bronchial diseases. They help improve kidney function in diabetic nephropathy and chronic renal failure.

The drug "Nimotop" is especially indicated for the combination of hypertension and cerebrovascular insufficiency. In case of rhythm disturbances and hypertension, it is especially recommended to use drugs of the verapamil and diltiazem groups.

Heart rhythm disorders

In the treatment of arrhythmias, drugs from the verapamil and diltiazem groups are used. They slow down the conduction of the heart and reduce the automatism of the sinus node. These drugs inhibit the re-entry mechanism in supraventricular tachycardias.

AK are used to stop and prevent attacks of supraventricular tachycardia. They also help to reduce the heart rate during. These medications are also prescribed for the treatment of supraventricular extrasystole.

With ventricular arrhythmias, AKs are ineffective.

Side effects

AKs cause vasodilation. As a result, dizziness, headache, facial flushing, and heart palpitations may occur. As a result of low vascular tone, edema occurs in the legs, ankles, and feet. This is especially true for nifedipine preparations.
AK worsen the ability of the myocardium to contract (negative inotropic effect), slow down the heart rate (negative chronotropic effect), slow down atrioventricular conduction (negative dromotropic effect). These side effects are more pronounced in derivatives of verapamil and diltiazem.

When using nifedipine preparations, constipation, diarrhea, nausea, and in rare cases vomiting are possible. The use of verapamil in high doses in some patients causes severe constipation.
It is quite rare for skin side effects to occur. They are manifested by redness, rash and itching, dermatitis, vasculitis. In severe cases, the development of Lyell's syndrome is likely.

withdrawal syndrome

After abrupt discontinuation of AC intake, the smooth muscles of the coronary and peripheral arteries become hypersensitive to calcium ions. As a result, a spasm of these vessels develops. It can be manifested by an increase in angina attacks, an increase in blood pressure. Withdrawal is less common in the verapamil group.

Contraindications

Due to the difference in the pharmacological action of drugs, contraindications for different groups differ.

Verapamil and diltiazem derivatives should not be prescribed for atrioventricular block, left ventricular systolic dysfunction, cardiogenic shock. They are contraindicated at systolic blood pressure levels below 90 mm Hg. Art., as well as with anterograde conduction along an additional path.

Drugs from the verapamil and diltiazem groups are relatively contraindicated in digitalis intoxication, severe sinus bradycardia (less than 50 beats per minute), and a tendency to severe constipation. They should not be combined with beta-blockers, nitrates, prazosin, quinidine and disopyramide, because in this case there is a danger of a sharp decrease in blood pressure.

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

Calcium channel blockers

Most of the Russian market for calcium channel blockers is formed by imports. The demand for cinnarizine and nifedipine is almost completely met by imports. 　

Mechanism of action of calcium channel blockers

Calcium ions are essential for maintaining the work of the heart. Entering the cell, calcium ions activate metabolic processes, increase oxygen consumption, cause muscle contraction, 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 intercellular environment. All Ca 2+ channels are divided into two large groups: voltage-gated and receptor-gated. In turn, depending on the conductivity, 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+ channels of the L-type, Ca 2+ - and R-type. In the cardiovascular system, there are L-type calcium channels that regulate the entry of calcium into smooth muscle fibers and directly affect the contraction process. When activated, the channels form instantaneous ion-selective pores through which Ca 2+ ions penetrate into the cell in the direction of the concentration gradient. This results in a potential difference, which is measured as a 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, in the heart muscle, there is an excessive accumulation of sodium and calcium ions inside the cells, a violation of the synthesis of macroergic compounds, acidification of the intracellular environment, followed by a violation of the processes of contraction and relaxation of the cardiac muscle fiber. This leads to a decrease in the strength and speed of contraction of the heart muscle, an increase in 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, if you suppress the transmembrane entrance of Ca 2+ and its amount in the cytoplasm of the cell, then its readiness for contraction will decrease. A critical increase in intracellular Ca 2+ can lead to cell damage and death due to its excessive activation with insufficient energy supply.

Calcium channel blockers (CCBs) reduce the supply 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 by 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), high blood pressure decreases, the formation of the action potential changes (they affect the conduction system of the heart, normalizing the heart rhythm), platelet aggregation 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 for the treatment of angina pectoris. The first drug of this group, verapamil, which is a derivative of the well-known papaverine, was synthesized in Germany in 1962. Since the late 60s - early 70s of the last century, it was found that calcium channel blockers not only have an antianginal effect, but are also able to reduce systemic arterial pressure. Since then, calcium antagonists have become widely used in the treatment of arterial hypertension (persistent high blood pressure). Calcium channel blockers also penetrate well into the brain tissue, and limit the entry of calcium ions into nerve cells, which leads to the fact that calcium-dependent mechanisms of neuronal death (so-called apoptosis) are blocked during acute cerebral ischemia. In this, the neuroprotective effect of calcium channel blockers is manifested.

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

The scope of BCC is not limited to cardiology and angioneurology. There are 　other, narrower and 　less known indications for　prescribing these drugs. These include the prevention of cold bronchospasm, as well as the treatment of stuttering, since the drugs in question eliminate the spasmodic contraction of the diaphragm. Cinnarizine has antihistamine properties and can be used for immediate allergic reactions - skin itching, urticaria. It should be noted that in　recently, CCB　in connection with　their neuroprotective and　psychotropic properties　use in　complex treatment of Alzheimer's disease, Huntington's chorea, senile dementia, alcoholism.

We list the most important pharmacological effects of these drugs in the field of cardiohemodynamics:

The pharmacological properties of different CCBs are expressed differently. The drugs under consideration are divided into 4 main groups with somewhat different hemodynamic effects:

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

Classification of calcium channel blockers.

Table 1.

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

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

Source: medicine guide.

The drug must be effective, have as few side effects as possible, and deal with the 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, so 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:

Calcium channel blockers do not fully satisfy the requirements, each drug has its own advantages and disadvantages, which must be carefully analyzed before prescribing any drug. Table 3 compares the most common calcium channel blockers used in clinical practice. The basic principles that should be followed when prescribing these drugs are shown in Table 4. However, the treatment must 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 blockers.