Supplements blockers of slow calcium channels. Calcium channels: a clinical pharmacologist's perspective. Interaction of BPC with drugs of other groups

Arterial hypertension is a disease that requires mandatory drug therapy. Pharmaceutical companies from year to year are working on the creation of new, more effective drugs to fight this disease. And today there are a huge number of drugs that can regulate blood pressure. Slow calcium channel blockers (CCBs) or calcium antagonists are one of the groups of drugs that are widely used for this purpose.

General characteristics of calcium channel blockers

Calcium antagonists have a diverse chemical structure, but do not differ in their mechanism of action. It consists in blocking the entry of calcium ions into the cells of the myocardium and the walls of blood vessels through special slow calcium channels. Representatives of the group not only reduce the number of ions of this element that enter the cells, but also affect their movement inside the cells. As a result, the peripheral and coronary blood vessels expand. Due to this pronounced vasodilating effect, a decrease in pressure occurs.

Calcium antagonists are one of the most effective drugs for the treatment of hypertension, belonging to the "first line". They are preferred for the treatment of elderly people with stable angina pectoris, systolic hypertension, dyslipidemia, peripheral circulatory disorders, lesions of the kidney parenchyma.

Why Block Calcium?

Calcium ions play a significant role in regulating the functioning of all organs of cardio-vascular system. They control the heart rate, regulate cardiac activity and the contractile function of myocytes. If there is an excess of ions of this microelement or the processes of its removal from cells are disturbed, then the specific functions of the cell are disrupted, which causes disturbances in the pumping activity of the heart, resulting in increased pressure.

How are drugs classified?

CCBs are classified according to various criteria - chemical structure, duration of action, tissue specificity. Yet the most commonly used classification of calcium channel blockers is based on their chemical structure. According to it, they distinguish:

phenylalkylamines;
dihydropyridines;
benzothiazepines.

Dihydropyridine calcium channel blockers have a predominant effect on the vessels and almost do not reveal it on the myocardium. Due to their vasodilating action, they increase the rate of heart contractions, which makes it impossible for them to be taken by hypertensive patients with heart problems. This negative effect is practically not expressed in drugs of the 2nd and 3rd generation, which have a longer half-life. The ability of drugs of the dihydropyridine series to have an antioxidant, antiplatelet, angioprotective effect, reduce the manifestations of atherosclerotic lesions and increase the effect of statins has been proven. Long-acting dihydropyridines effectively lower blood pressure and show practically no side effects.

This group includes: nifedipine, isradipine, amlodipine, felodipine, lercanidipine, nitrendipine, lacidipine.

Benzothiazepines and phenylalkylamines, on the contrary, lower the heart rate due to the same effect on the myocardium and blood vessels. This has made them the means of choice for the treatment of patients with hypertension in association with stable angina pectoris.

Preparations of these non-dihydropyridine groups suppress the automatism of the sinus node, lower the contractility of the heart, and prevent spasm coronary arteries, reduce peripheral resistance in the vessels. This group includes verapamil and diltiazem.

BKK Generations

There is another classification of calcium antagonists. It is based on the characteristics of the effect on the body, the duration of their action and tissue selectivity. There are calcium channel blockers:

1st generation (diltiazem, nifedipine, verapamil);
2nd generation (nifedipine SR, felodipine, diltiazem SR, nisoldipine, verapamil SR, manidipine, benidipine, nilvadipine, nimodipine);
3rd generation (lacidipine, lecarnidipine, amlodipine).

The first generation is used to a limited extent due to low bioavailability, high risk the development of side effects, as well as a short-term effect.

The second generation is more perfect in these indicators, however, some representatives also have a short action. When creating the 3rd generation, all the shortcomings of the previous ones were taken into account. As a result, preparations with long-term action, high bioavailability and high tissue selectivity were obtained.

BPC properties

Calcium antagonists are very diverse in their chemical structure, and therefore can have different effects:

lowering blood pressure;
regulation of the heart rate;
reduction of mechanical stress in the myocardium;
improve cerebral circulation in atherosclerosis of the head vessels;
prevent thrombosis;
suppress excessive insulin production;
lower pressure in the pulmonary artery.

Indications for use

BKK can be used:

in mono- or combination therapy of hypertension;
to eliminate systolic hypertension, especially in elderly patients;
with arterial hypertension and coronary heart disease against the background of diabetes, gout, kidney disease, bronchial asthma;
with vasospastic angina;
for the treatment of stable angina pectoris;
as an alternative for intolerance to beta-blockers.

Side effects

Medicines of this group have both common and characteristic for individual subgroups. side effects. So, absolutely all BKKs can cause:

allergic reactions;
dizziness;
excessive pressure drop;
headache;
peripheral edema (shins and ankles are especially often swollen in elderly patients);
feeling of "hot flashes" and redness of the face.

Dihydropyridine calcium antagonists can also provoke tachycardia. Most of all this negative effect characteristic of nifedipine.

Non-dihydropyridine representatives of CCB can disrupt atrioventricular conduction, cause bradycardia, and reduce the automatism of the sinus node. Verapamil also often causes constipation and toxic effects on the liver.

Contraindications for use

Reception of BCC is prohibited when:

severe hypotension;
systolic dysfunction of the left ventricle;
acute myocardial infarction;
severe aortic stenosis;
hemorrhagic stroke;
atrioventricular blockade of 2-3 degrees;
in the 1st trimester of pregnancy;
while breastfeeding.

With caution and taking into account all the risks, CCB can be applied:

in the 3rd trimester of pregnancy;
with cirrhosis of the liver;
with angina pectoris.

It should be borne in mind that drugs of the non-dihydropyridine group cannot be taken simultaneously with beta-blockers, and dihydropyridine blockers must not be combined with the intake of nitrates, prazosin, magnesium sulfate.

CCB preparations

A joint list of calcium channel blockers used in the treatment of hypertension:

Verapamil (Isoptin, Lekoptin, Finoptin);
Diltiazem (Dilren, Cardil, Dilzem);
Nifedipine (Corinfar, Adalat, Cordaflex, Cordipin-retard);
Amlodipine (Amlo, Stamlo, Amlovas, Normodipin, Norvasc);
Felodipine (Felodip, Plendil);
Nitrendipine (Unipress, Bypress);
Lacidipine (Lacidip);
Lercanidipine (Lerkamen).

In no case should you prescribe any drugs yourself. Be sure to undergo an examination and get a prescription from a doctor, taking into account all the characteristics of the body, the severity of the course of the disease and the presence of concomitant diseases.

Potassium or calcium blockers?

It is not uncommon for patients to confuse calcium channel blockers with potassium channel blockers. But they are completely different substances. Potassium channel blockers are medications 3 classes of antiarrhythmic drugs. They exert their effect by slowing down the current of potassium through the membranes of cardiomyocytes. This lowers the automatism of the sinus node and inhibits atrioventricular conduction. This group of drugs on the shelves of pharmacies is represented by amiodarone (Cordarone, Amiocordin, Cardiodarone), sotal (Sotalex, SotaGeksal).

Calcium channels: a clinical pharmacologist's perspective

Kukes V.G., Sychev D.A., Ramenskaya G.V., Starodubtsev A.K.

MMA them. THEM. Sechenov, IKF NTsEGKLS

Abstract.

Drugs from the group of slow calcium channel blockers are widely used in medicine. They are used not only in therapy cardiovascular diseases(CHD, arterial hypertension, arrhythmias), but also in neurological, gastroenterological practice and in other areas of medicine. Recently, with the results of multicenter controlled studies proving the high efficiency of this group of drugs, a kind of "renaissance" of slow calcium channel blockers has begun. In this regard, interest has increased in calcium-regulating cell structures as potential pharmacological targets for more effective and safe drugs.

Key words: calcium, slow calcium channels, slow calcium channel blockers.

1. The physiological role of calcium

Calcium ions occupy a special place in the maintenance of cellular life processes. Due to their unique physicochemical properties (the ability to selectively bind to complex bioorganic molecules and change their conformation), they are the most versatile mediators connecting processes on the cell membrane surface with intracellular mechanisms. Each living cell spends a significant part of its metabolic energy on the excretion of calcium ions through systems of special calcium pumps, maintaining their very low level in the cytoplasm at rest (about 10–8 M). The resulting huge transmembrane gradient of calcium ions can “inject” these ions into the cell at high speed and create a short-term increase in their concentration there (“calcium signal”), which in turn can trigger or modulate almost all cell functions. One of the most important physiological function of calcium ions is to ensure the conjugation of the processes of excitation and contraction in smooth muscle cells and skeletal muscle cells. Calcium ions are also necessary for the processes of platelet aggregation, the release of neurotransmitters, ensure the normal functioning of endo- and exocrine glands, etc. The main structure that provides the generation of calcium signals are specialized protein molecules embedded in cell membranes and capable of opening the way for movement under the influence of external influences. ions along the electrochemical gradient - ion channels.

2. Calcium channels and their role in conjugation of excitation and contraction

2.1 Classification of calcium channels

According to their location, calcium channels can be divided into cytoplasmic or sacrolemmal located on the surface of the cytoplasmic membrane (sarcolemma) and intracellular. The latter are localized mainly in the sarcoplasmic reticulum (SPR).

In turn, among the cytoplasmic calcium channels, according to the mechanism of activation, it is customary to distinguish receptor-dependent calcium channels and potential-dependent or voltage dependent calcium channels.

Receptor-dependent calcium channels are linked via a G-protein system to various receptors. After the interaction of a specific agonist with the corresponding receptor, conformational changes occur in the receptor itself, G-proteins, and finally the receptor-dependent calcium channel, which leads to its opening, the entry of calcium ions into the cell and the realization of a biological or pharmacological effect.

Voltage-gated calcium channels open in response to depolarization of the cytoplasmic membrane. The entry of calcium ions through voltage-gated calcium channels after depolarization is slower than the entry of sodium ions through sodium channels, so voltage-gated calcium channels still called slow calcium channels. To provide calcium signals, voltage-dependent calcium channels, which open under the influence of changes in the membrane potential and have a high selectivity for calcium ions, are of particular importance. It is the activation of these channels that underlies the launch of such important vital functions as the contraction of muscle fibers of the myocardium, smooth muscles, striated (skeletal) muscles, the pacemaker activity of the cells of the conduction system of the heart, the release of mediators by nerve cells, the secretion of enzymes and hormones by exo- and endocrine cells etc. Therefore, the search for means to control the function of calcium channels opens up the most effective ways to influence the corresponding functions. Potential-dependent calcium channels according to their structure and electrophysiological properties are divided into channels of the following types:

L-type calcium channels

T-type calcium channels

P-type calcium channels

N-type calcium channels

R-type calcium channels.

The voltage-dependent channels of the L-type and T-type are the most well studied. P-, N-, R-type channels are neuronal and their physiology and biochemistry are not well understood.

Voltage-gated calcium channelsL-type localized on the surface of the cytoplasmic membrane of working cardiomyocytes of the myocardium, cells of the sinus and atrioventricular nodes of the conduction system of the heart, cells of smooth and striated muscles. As already indicated, voltage-gated L-type calcium channels open in response to depolarization of the cytoplasmic membrane. The electrophysiological features of L-type calcium channels are a high threshold (therefore, this type of calcium channels is also called high threshold calcium channels) and slow inactivation. The main function of voltage-dependent L-type calcium channels in the myocardium, smooth and striated muscles is the conjugation of the processes of excitation and contraction, in the cells of the sinus - providing pacemaker activity, in the cells of the atrioventricular node - atrioventricular conduction (table 1). Potential-gated L-type calcium channels are pharmacological targets for slow calcium channel blockers, phenylalkylamine derivatives, dihydropyridine, and benzothiazepane.

In this article, you will learn about calcium channel blockers and the list of these drugs, for which diseases they are prescribed. Different groups of these drugs, differences between them, their mechanism of action. Detailed description most commonly prescribed calcium channel blockers.

Article publication date: 07/01/2017

Article last updated: 06/02/2019

Calcium channel blockers (abbreviated as CCBs), or calcium antagonists (abbreviated as AKs) are a group of medicines that prevent calcium from entering cells through calcium channels. BKK act on:

Cardiomyocytes (cells of the heart muscle) - reduce the contractility of the heart.
The conduction system of the heart - slow down the heart rate (HR).
Vascular smooth muscle dilates the coronary and peripheral arteries.
Myometrium - reduce the contractile activity of the uterus.

Calcium channels are proteins in the cell membrane that contain pores that allow calcium to pass through. Due to the entry of calcium into the cells, muscle contraction, the release of neurotransmitters and hormones occur. There are many types of calcium channels, but most CCBs (except cilnidipine) only act on their slow L-type. It is this type of calcium channels that plays the main role in the entry of calcium ions into smooth muscle cells and cardiomyocytes.

Click on photo to enlarge

There are also other types of calcium channels:

P-type - located in the cells of the cerebellum.
N-type - localized in the brain.
R - located in the cells of the cerebellum and other neurons.
T - are located in neurons, cells with pacemaker activity, osteocytes (bone tissue cells).

CCB is most often prescribed for the treatment of arterial hypertension (AH) and angina pectoris (CHD), especially when these diseases are combined with diabetes mellitus. AKs are used to treat certain arrhythmias, subarachnoid hemorrhage, Raynaud's syndrome, cluster headache prevention, and prevention of preterm delivery.

Most often, CCBs are prescribed by cardiologists and therapists. Independent use of BPC is prohibited due to the risk of developing serious complications.

BKK groups

In clinical practice, the following groups of BCC are distinguished:

Dihydropyridines (nifedipine group) - act mainly on blood vessels, therefore they are used to treat hypertension.
Phenylalkylamines (verapamil group) - act on the myocardium and the conduction system of the heart, therefore they are prescribed mainly for the treatment of angina pectoris and arrhythmias.
Benzodiazepines (the diltiazem group) are an intermediate group that has the properties of dihydropyridines and phenylalkylamines.

There are 4 generations of BKK:

1st generation - nifedipine, verapamil, diltiazem.
2nd generation - felodipine, isradipine, nimodipine.
3rd generation - amlodipine, lercanidipine.
4th generation - cilnidipine.

Mechanism of action

CCBs bind to slow calcium channel receptors through which most of the calcium ions enter the cell. Calcium is involved in the functioning of the sinus and atrioventricular nodes (regulate the heart rhythm), in contractions of cardiomyocytes and vascular smooth muscles.

By influencing these channels, BPC:

They weaken the contractions of the heart, reducing its need for oxygen.
They reduce vascular tone and eliminate their spasm, reducing blood pressure (BP).
Reduce the spasm of the coronary arteries, thereby increasing the blood supply to the myocardium.
Slow down heart rate.
Impair platelet aggregation.
They counteract the formation of new atherosclerotic plaques, inhibit the division of smooth muscle cells of the vascular wall.

Each of the individual drugs does not have all these properties at once. Some of them affect the vessels more, others - on the heart.

Indications for use

Doctors prescribe calcium channel blockers to treat the following conditions:

AG (high blood pressure). By causing vasodilation, CCBs reduce systemic vascular resistance, which lowers blood pressure. These drugs affect mainly the arteries and have minimal effect on the veins. CCBs are included in the five main groups of antihypertensive drugs.
Angina pectoris (pain in the region of the heart). CCBs dilate blood vessels and decrease the contractility of the heart. Systemic vasodilation caused by the use of dihydropyridines reduces blood pressure, thereby reducing the load on the heart, which leads to a decrease in its oxygen demand. CCBs that act primarily on the heart (verapamil, diltiazem) reduce heart rate and weaken heart contractions, which leads to a decrease in its oxygen demand, making them effective means from angina. CCBs can also dilate the coronary arteries and prevent their spasm by improving myocardial blood supply. Due to these effects, CCBs - together with beta-blockers - are the mainstay of pharmacotherapy for stable angina.
supraventricular arrhythmias. Some CCBs (verapamil, diltiazem) affect the sinus and atrioventricular node, so they can effectively restore a normal heart rhythm in patients with atrial fibrillation or flutter.
Raynaud's disease (spastic vasoconstriction, most often affecting the hands and feet). The use of nifedipine helps to eliminate arterial spasm, thereby reducing the frequency and severity of attacks of Raynaud's disease. Sometimes amlodipine or diltiazem is used for this purpose.
Cluster headache (recurring attacks are very severe pain on one side of the head, usually around the eye). Verapamil helps reduce the severity of seizures.
Relaxation of the muscles of the uterus (tocolysis). Doctors sometimes use nifedipine to prevent preterm labor.
Hypertrophic cardiomyopathy (a disease in which there is a strong thickening of the walls of the heart). Calcium channel blockers (verapamil) weaken the contraction of the heart, so they are prescribed for the treatment of hypertrophic cardiomyopathy if patients have contraindications to taking beta-blockers.
(increased pressure in the pulmonary artery). Pulmonary hypertension is treated with nifedipine, diltiazem, or amlodipine.
Subarachnoid hemorrhage (bleeding into the space surrounding the brain). To prevent vasospasm, nimodipine is used, which has a selective effect on cerebral arteries.

Contraindications

Calcium channel blockers drugs have their own contraindications, which are clearly spelled out in the instructions for the drug. For example:

Means from the groups of verapamil and diltiazem are contraindicated in patients with bradycardia, pathology of the conduction system of the heart or systolic heart failure. Also, they should not be given to patients already taking beta-blockers.
All calcium antagonists are contraindicated in patients with low blood pressure, unstable angina, severe aortic stenosis.
CCB is not used in pregnant and breastfeeding women.

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Side effects

Side effects of BPC depend on the properties of the group of these drugs:

Action on the myocardium can cause hypotension and heart failure.
Action on the conduction system of the heart can lead to blockades or arrhythmias.
The effect on the vessels sometimes causes hot flashes, swelling, headaches, rashes.
Other side effects include constipation, gynecomastia, increased sensitivity to sunlight.

Dihydropyridine CCBs

Dihydropyridines are the most commonly prescribed calcium antagonists. These drugs are mainly used to lower blood pressure. The most famous drugs from this group include:

Nifedipine is one of the first CCBs that acts primarily on blood vessels. Assign to reduce blood pressure in hypertensive crises, eliminate the symptoms of vasospastic angina, treat Raynaud's disease. Nifedipine rarely exacerbates heart failure, since the deterioration in myocardial contractility is compensated by a decrease in the load on the heart. There are long-acting drugs that are used to treat hypertension and angina pectoris.
Nicardipine - this drug, like nifedipine, affects blood vessels. Used to prevent angina attacks and treat hypertension.
Amlodipine and felodipine are among the most commonly prescribed CCBs. They act on blood vessels, do not worsen the contractility of the heart. They have a long-term effect, making them convenient for the treatment of hypertension and angina pectoris. Their use is especially useful in vasospastic angina. Side effects associated with the expansion of the arteries (headache, hot flashes), they can pass in a few days.
Lercanidipine and isradipine - similar in characteristics to nifedipine, are used only for the treatment of arterial hypertension.
Nimodipine - this drug has a selective action of the cerebral artery. Due to this property, nimodipine is used to prevent secondary spasm of cerebral arteries in subarachnoid hemorrhage. For the treatment of others, nimodipine is not used, since there is no evidence of its effectiveness for these purposes.

Side effects of all dihydropyridine CCBs are associated with vasodilation (headache, hot flashes), they may disappear within a few days. Edema in the legs also often develops, which is difficult to eliminate with diuretics.

Phenylalkylamines

Calcium channel blockers from this group mainly affect the myocardium and the conduction system of the heart, therefore, they are most often prescribed for the treatment of angina pectoris and arrhythmias.

Verapamil is practically the only CCA from the group of phenylalkylamines used in clinical medicine. This drug worsens the contractility of the heart, and also affects the conduction in the atrioventricular node. Because of these effects, verapamil is used to treat angina pectoris and supraventricular tachycardia. Side effects include worsening heart failure, bradycardia, a drop in blood pressure, worsening conduction disturbances in the heart. Verapamil is contraindicated in patients already taking beta-blockers.

Benzodiazepines

Benzodiazepines are intermediate between dihydropyridines and phenylalkylamines, so they can both dilate blood vessels and impair cardiac contractility.

An example of a benzodiazepa is diltiazem. This drug is most often used for angina pectoris. There is a form of release of prolonged action, which is prescribed for the treatment of hypertension. Since diltiazem affects the conduction system of the heart, it should be combined with caution with beta-blockers.

Other Precautions While Using CCB

Any drug from the CCB group can be used only as directed by a doctor. The following points should be taken into account:

If you are taking a CCB drug, you should not drink grapefruit juice. This prohibition is due to the fact that it increases the amount of the drug entering the blood. As a result of this, your blood pressure may suddenly drop, which is sometimes quite dangerous. Grapefruit juice affects almost all calcium channel blockers except amlodipine and diltiazem. Juice from oranges and other fruits can be drunk.
Check with your doctor before taking any medication, including herbal medicines, in combination with calcium antagonists.
Be prepared for long-term use of CCBs in the treatment of hypertension. Some patients stop taking antihypertensive drugs on their own as soon as their blood pressure levels return to normal, but doing so can put their health at risk.
If you have angina and suddenly stop taking these blockers, you may experience heart pain.

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 ischemic disease high blood pressure blood 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;
No negative influence 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

chief pharmacological action 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, so the coronary and peripheral arteries relax.

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 senile dementia, Alzheimer's disease, 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 most safe means 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.

Classification of drugs

The Committee of Experts of the World Health Organization divided all representatives of calcium blockers into two groups - selective, non-selective. The former interact only with the calcium channels of the heart and blood vessels, the latter interact with any structures. Therefore, the use of non-selective AA is associated with a large number of adverse reactions: disruption of the intestines, gallbladder, uterus, bronchi, skeletal muscles, neurons.

The main representatives of non-selective AK are fendiline, bepridil, cinnarizine. First two medicines rarely applied. Cinnarizine improves the microcirculation of the nervous tissue, is widely used for the treatment various kinds disorders of cerebral circulation.

Selective calcium channel blockers include 3 classes of drugs:

phenylalkylamines (verapamil group);
dihydropyridines (nifedipine group);
benzothiazepines (diltiazem group).

All selective CCCs are divided into three generations. Representatives of the second differ from their predecessors in the duration of action, higher tissue specificity, and fewer negative reactions. All calcium channel antagonists of the latest generation are derivatives of nifedipine. They have a number of additional properties uncharacteristic of earlier preparations.

In clinical practice, another type of AK classification has taken root:

pulse accelerating (dihydropyridine) - nifedipine, amlodipine, nimodipine;
pulse-slowing (non-dihydropyridine) - derivatives of verapamil, diltiazem.

Principle of operation

Calcium ions are activators of many tissue metabolic processes, including muscle contraction. Large quantities minerals that have entered the cell, make it work in the most intensive mode. Excessive increase in metabolism increases its oxygen demand, quickly wears out. CCBs prevent the passage of calcium ions through the cell membrane, "closing" special structures - slow L-type channels.

"Inputs" of this class are located in the muscle tissue of the heart, blood vessels, bronchi, uterus, ureters, gastrointestinal tract, gallbladder, platelets. Therefore, calcium channel blockers interact primarily with the muscle cells of these organs.

However, due to the diversity of the chemical structure, the effect of drugs is different. Verapamil derivatives affect mainly the myocardium, the conduction of the cardiac impulse. Drugs like diltiazem, nifedipine - on the vascular muscles. Some of them interact only with the arteries of certain organs. For example, nisoldipine well expands the vessels of the heart, nimodipine - the brain.

The main effects of BPC:

antianginal, anti-ischemic - prevent, stop an attack of angina pectoris;
anti-ischemic - improve blood supply to the myocardium;
hypotensive - lower blood pressure;
cardioprotective - reduce the cardiac load, reduce the oxygen demand of the myocardium, contribute to the qualitative relaxation of the heart muscle;
nephroprotective - eliminate the narrowing of the renal arteries, improve the blood supply to the organ;
antiarrhythmic (non-dihydropyridine) - normalize heart rhythm;
antiplatelet - prevent platelet aggregation.

List of drugs

The most common representatives of the group are presented in the table below.

First generation
Representatives	Tradename
Verapamil	Isoptin; Finoptin.
Nifedipine	Adalat; Cordaflex; Corinfar; Fenigidin.
Diltiazem	Cardil
Second generation
Gallopamil	Gallopamil
Felodipine	Plendil; Felodip; Phelotens.
Nimodipine	Nimopin; Nimotop.
third generation
Amlodipine	Amlovas; Amlodac; Amlodigamma; Amlong; Karmagip; Norvask; Normodipin; Stamlo M.
Lacidipine	Lacipil; Sakur.
Lercanidipine	Zanidip; Lerkamen; Lercanorm; Lernicor.

Indications for appointment

Most often, calcium antagonists are prescribed for the treatment of arterial hypertension, coronary heart disease. The main indications for the appointment:

isolated increase in systolic pressure in the elderly;
a combination of hypertension / ischemic heart disease and diabetes mellitus, bronchial asthma, kidney pathologies, gout, lipid metabolism disorders;
combination of ischemic heart disease and arterial hypertension;
IHD with supraventricular arrhythmias / some types of angina pectoris;
microinfarction (diltiazem);
elimination of attacks of accelerated heart rate (tachycardia);
decrease in heart rate during attacks of fibrillation, atrial flutter (verapamil, diltiazem);
alternative to beta-blockers in case of intolerance/contraindications.

arterial hypertension

The hypotensive effect of BPC is enhanced by others, so they are often prescribed together. The optimal combination is considered to be a combination of calcium antagonists and,. It is possible to use it with beta-blockers, other types of antihypertensive drugs, but its effect is less studied.

Cardiac ischemia

Best of all, non-dihydropyridine CCBs (derivatives of verapamil, diltiazem) and 3rd generation dihydropyridines (amplodipine) cope with insufficient blood supply to the myocardium. Preference is given to the last option: the effect of the latest generation of drugs is longer, predicted, specific.

Heart failure

In heart failure, only 3 types of calcium channel blockers are used: amlodipine, lercanidipine, felodipine. The rest of the drugs negatively affect the work of the diseased heart; reduce the force of muscle contraction, cardiac output, stroke volume.

Advantages

Due to the specific mechanism of action, calcium channel antagonists are very different from other antihypertensive drugs. The main advantages of medicines of the BPC group are that they:

do not affect the metabolism of fats, carbohydrates;
do not provoke bronchospasm;
do not cause depression;
do not lead to electrolyte imbalance;
do not reduce mental, physical activity;
do not contribute to the development of impotence.

Possible side effects

Most patients tolerate drugs well, especially 2-3 generations. The frequency of occurrence, the type of adverse reactions are very different, depending on the class. Most often, complications accompany the intake of nifedipine (20%), much less often diltiazem, verapamil (5-8%).

The most common/unpleasant side effects include:

swelling of the ankles, lower leg - especially older people who walk / stand a lot, had leg injuries or vein diseases;
tachycardia, a sudden feeling of heat, which is accompanied by reddening of the skin of the face, upper shoulders. Characteristic of dihydropyridines;
a decrease in the contractile function of the myocardium, a slowing of the heart rate, and a violation of cardiac conduction are typical for pulse-slowing CCBs.

Side effects of CCBs of various groups

Backlash	Verapamil	Diltiazem	Nifedipine
Headache	+	+	++
Dizziness	+	+	++
heartbeat	-	-	++
Skin redness	-	-	++
hypotension	+	+	++
Swelling of the legs	-	-	++
Decreased heart rate	+	+	-
Cardiac conduction disorder	+	+	-
Constipation	++	-/+	-

Contraindications

Drugs should not be prescribed for:

arterial hypotension;
systolic dysfunction of the left ventricle;
severe aortic stenosis;
sick sinus syndrome;
blockade of the atrioventricular node of 2-3 degrees;
complicated atrial fibrillation;
hemorrhagic stroke;
pregnancy (first trimester);
breastfeeding;
the first 1-2 weeks after myocardial infarction.

Relative contraindications to calcium channel blockers

It is not recommended to use drugs together with prazosin, magnesium sulfate, supplement therapy with dihydropyridines with nitrates, and non-dihydropyridine drugs with amiodarone, etacizine, disopyramide, quinidine, propafenone, β-blockers (especially when administered intravenously).

Literature

I.V. Davydova, N.A. Perepelchenko, L.V. Klimenko. Calcium channel blockers: mechanisms of action, classification, indications and contraindications for use, 2009
Giuseppe Mancia, Robert Fagard et al. Recommendations for the treatment of arterial hypertension ESH / ESC 2013, 2014
Y. Shtrygol. Calcium channel blockers in cardiology, 2004

Last updated: January 24, 2020