Calcium channel blockers (calcium ion antagonists)

Calcium ions play an important role in the regulation of life
Organism. Penetrating into cells, they activate intracellular bioenergetics.
Getic processes (conversion of ATP to cAMP, phosphorylation of proteins
And others) that ensure the realization of the physiological functions of these cells.
Transmembrane transport of calcium ions occurs through specific
Channels, which are macromolecular proteins, dissecting
Peptide biosols of the cell membrane, and containing specific
Sites (receptors) that recognize calcium ions. Call them calcium
Or "slow" channels (unlike "fast" channels, through
Which are transported by other ions).
In the body, the flow of Ca B2 + through membranes is regulated by a number of endo-
Gene factors (neurogenic, mediators - acetylcholine, catechola-
Mines, serotonin, histamine, etc.).
In the late sixties of the current century,
Some exogenous pharmacological substances inhibit the passage
Ca B2 + through "slow" channels. The first such substances were the derivatives
Phenylalkylamine - prenylamine (difrene) and verapamil, proposed
Originally as coronary dilatation. At present
A number of compounds having a similar effect are known. Their
Grouped under the group name "calcium channel blockers,"
"Blockers" of slow "channels", "calcium intake blockers," and others.
The name "Uantagonists of calcium ions" is adopted.
The main (typical) representatives of this group are in
Present preparations verapamil, nifedipine (phenygidine), diltiazem.
In accordance with the chemical structure, these and related drugs
Are divided into 3 subgroups: 1) phenylalkylamines (verapamil, gallopamil, etc.);
2) dihydropyridines (nifedipine, nicardipine, etc.); 3) benzothiazepines
(Diltiazem, etc.).
To antagonists of calcium ions also include cinnarizine (see),
Flumarizine (see) and other medicines, but in connection with
Indiscriminateness of their actions do not refer to "typical" drugs
This group.
In recent years, calcium ion antagonists have found wide
Application in various fields of medicine. A wide range of their actions
Is explained by the variety of physiologically regulated calcium ions
Processes. Calcium ions contribute to increased myocardial contractility,
Affect the activity of the sinus node and the atrioventricular conductivity,
Cause vasoconstriction and increased vascular resistance,
Increase the tone of the bronchi and gastrointestinal tract,
Ureters and urinary tract; Stimulate the secretion of hormones of hypo-
Fizas and adrenal release of catecholamines, as well as aggregation
Thrombocytes, etc. Calcium ions participate in the process of neuroma-
Diathers with presynaptic nerve endings.
At pathological conditions (ischemia, hypoxia, etc.) ions Ca '+,
Especially at their increased concentration, can over-exaggerate
Processes of cellular metabolism, increase the need for tissues in acid-
And cause various destructive processes. In these conditions
Antagonists of calcium ions can exert pathogenetic pharmacokinetics.
Therapeutic effect.
Despite the commonness of the main property (the blockade of "slow"
Channels), the antagonists of Ca B2 + differ in pharmacological action,
Which is due to the peculiarities of their chemical structure and physico-chemical
Properties, the ability to directly affect intracellular
Processes.
Currently, different types of calcium channels are isolated
(L, T, N, P), which have different biophysical properties. Pola-
Different types of channels contain discrete receptors for
Different groups of calcium ion antagonists, with which in a certain
The degree of their specific effects on physiological processes.
In the most general form, the differences in the action of the main antagonists
Ca B2 + on the cardiovascular system are expressed in a stronger
The influence of verapamil on atrioventricular conductivity and in lesser -
On smooth muscles of blood vessels; Nifedipine has more effect on muscles
Vessels and less - on the conduction system of the heart; Diltiazem approximately
Equally affects the muscles of the vessels and the conducting system; Nitrene-
Dipin almost selectively affects the peripheral vessels and does not affect
On excitability and the conduction system of the heart.
In addition, the drugs of this group differ in other
Pharmacological parameters, pharmacokinetics, side effects.
Thus, most drugs have a short half-life, and
They have to be taken 3 to 4 times a day, and in nitrendipine this
The period is 8 to 12 hours, and it is enough to take 1 or 2 times
in a day. The drug amlodipine with a half-life of 35-50 hours has been created.
Of the side effects when taking verapamil, constipation is often observed
(According to statistical data, more than 40% of patients); Upon admission
Nifedipina - flushes of blood, reddening of the face (up to ZO% of patients),
Headache (up to 80%); These phenomena are similar to side effects,
Observed when taking nitroglycerin (see). Although data on terato-
Gene action of Ca2 + antagonists is not present, these preparations (as well as others
Relatively new drugs) should not be prescribed
Belt and with breastfeeding.
The main application of calcium ion antagonists is as
Cardiovascular agents. Causing vasodilation and diminishing
Peripheral vascular resistance, they reduce blood pressure, improve
Coronary blood flow, have an antianginal effect. Preparations,
Affect the excitability and conductivity of the heart, are used in
Quality of antiarrhythmic drugs. They are isolated in a special (IV)
Group of antiarrhythmics (See Antiarrhythmics.).
Important properties of calcium ion antagonists are their anti-
The ability to reduce aggregation of platelets,
Promote their disaggregation; They increase the elasticity (deforma-
In the erythrocyte, reduce the viscosity of the blood. There are data on
Hypolipidemic and antisclerotic action of these drugs.
With the accumulation of new data on the role of calcium ions in patho-
And the creation of new Ca2 + + antagonists are refined and
The indications for their use are expanding. There is evidence of a positive
Action of calcium antagonists in bronchiolospasm (According to available data,
Arresting action in bronchiolospasm these drugs (nifedipine, verapamil)
Do not have, but they can be used as a supportive
Therapy, especially in patients with bronchial asthma, combined with IHD. They
Patients with increased bronchoconstrictive
- with cold, postnagruzochnom bronhiolospazme, etc.) and violations
Cerebral circulation. There are drugs with relatively selective
Cerebrovascular action (nimodipine) (See Tools that improve
Cerebral circulation.). The efficacy of verapamil, nifedi-
Pin, nimodipine for migraine. The possibility of applying pre-
Of this group in epilepsy, dyskinesia in patients with schizophrenia and
Other diseases of the central nervous system.
Recently, a number of new calcium ion antagonists have been developed
(Nisoldipine, amlodipine, felodipine, etc.).