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Antagonists of calcium ions

Calcium ions play an important role in regulation of activity of an organism. Getting into cells, they activate the intracellular biopower processes (transformation of ATP into tsAMF, phosphorylation of proteins, etc.) providing implementation of physiological functions of these cells.
Transmembrane transport of calcium ions occurs via the special channels which are the macromolecular proteins cutting peptide biolayers of a cellular membrane, and containing specific sites (receptors) distinguishing calcium ions. Call them calcic or "slow", channels (unlike "fast" channels via which other ions are transported).
In an organism the stream of Sa of B2+ through membranes is regulated by a number of internal causes (neurogenetic, mediators - acetylcholine, catecholamines, serotonin, a histamine, etc.).
In the late sixties the current century the ability of some exogenous pharmacological substances to slow down passing of Sa of B2+ via "slow" channels was found. Derivatives of a fenilalkilamin - Prenylaminum (diphryl) and the verapamil offered originally as coronarodilator means were the first such substances. Now a number of the connections having similar effect is known. They are combined under the group name "blockers of calcium channels", "blockers of "slow" channels", "calcium input blockers", etc. The name "Uantagonisty of calcium ions" is accepted.
The main (typical) representatives of this group are drugs verapamil, nifedipine (Phenihydinum), diltiazem now. According to chemical structure and related to them drugs divide these into 3 subgroups: 1) fenilalkilamina (verapamil, gallopamit, etc.); 2) dihydropyridines (nifedipine, nikardipin, etc.); 3) benzotiazepina (diltiazem, etc.).
Carry to antagonists of calcium ions also cinnarizine (see), flunarizin (see) and other medicines, however in connection with not selectivity of action do not carry them to "typical" drugs of this group.
In recent years antagonists of calcium ions found broad application in various fields of medicine. The wide range of their action is explained by variety of the physiological processes regulated by calcium ions. Calcium ions promote strengthening of contractility of a myocardium, affect activity of a sinus node and atrioventricular conductivity, cause vasoconstriction and increase in vascular resistance, promote increase in a tone of bronchial tubes and bodies of digestive tract, ureters and urinary tract; stimulate secretion of hormones of a hypophysis and release with adrenal glands of catecholamines and also aggregation of thrombocytes, etc. Calcium ions participate in process of discharge of neurotransmitters presynaptic nerve terminations.
At morbid conditions (ischemia, a hypoxia, etc.) ions of Sa "+, especially at the increased their concentration, can excessively strengthen processes of cellular metabolism, increase the need of fabrics for oxygen and cause various destructive processes. In these conditions the antagonists of calcium ions can render pathogenetic pharmacotherapeutic effect.
Despite community of the main property (blockade of "slow" channels), antagonists of Sa of B2+ differ on pharmacological action that is connected with features of their chemical structure and physical and chemical properties, with ability to influence directly intracellular processes.
Now allocate various types of the calcium channels (L, T, N, P) having different biophysical properties. Believe that various types of channels contain discrete receptors for different groups of antagonists of calcium ions what features of their action on physiological processes are to some extent connected with.
In the most general view of distinction in operation of the main antagonists of Sa of B2+ on a cardiovascular system are expressed in stronger influence of verapamil on atrioventricular conductivity and in smaller on unstriated muscles of vessels; nifedipine influences muscles of vessels less more - on the carrying-out system of heart; diltiazem approximately equally influences muscles of vessels and the carrying-out system; nitrendipin almost selectively influences peripheral vessels and does not affect excitability and the carrying-out system of heart.
Besides, drugs of this group differ on other pharmacological indicators, pharmacokinetics, side effects. So, the majority of drugs have short elimination half-life, and it is necessary to accept them 3 - 4 times a day, and at a nitrendipin this period is 8 - 12 h, and 1 or 2 times a day are enough to accept of it. Drug amlodipin with elimination half-life of 35 - 50 h is created. From side effects at intake of verapamil constipations are often observed (according to statistical data, more than at 40% of patients); at intake of nifedipine - rushes of blood, face reddening (to ZO of % of patients), a headache (up to 80%); these phenomena are similar to the side effects observed at intake of nitroglycerine (see). Though there are no antagonists of Sa given about teratogenic action B2+, these drugs (as well as other rather new medicines) it is not necessary to appoint pregnant and when feeding a breast.
Antagonists of calcium ions have the main use as cardiovascular means. Causing vasodilatation and reducing peripheric vascular resistance, they lower the arterial blood pressure, improve a coronary blood stream, have anti-anginal effect. The drugs affecting excitability and conductivity of heart find application as antiarrhytmic means. They are allocated in special (IV) group of antiarrhytmic means (See. Antiarrhytmic means.). Important properties of antagonists of calcium ions are their anti-aggregation action, ability to reduce aggregation of thrombocytes, to promote their disaggregation; they increase elasticity (deformability) of erythrocytes, reduce viscosity of blood. There are data on hypolipidemic and anti-sclerous effect of these drugs.
In process of accumulation of new data on a role of calcium ions in pathological processes and creation of new antagonists of Sa of B2+, indications to their use are specified and extend. There are data on positive action of antagonists of calcium at a bronkhiolospazma (On the available data, these drugs (nifedipine, verapamil) do not render the stopping action at bronkhiolospazma, but they can be applied as means of maintenance therapy, especially at patients with the bronchial asthma which is combined with an ischemic heart disease. They are shown also sick with the increased bronkhokonstriktorny reactivity - at a cold, post-load bronkhiolospazm, etc.) and disturbances of cerebral circulation. There are drugs with rather selective cerebrovascular effect (nimodipin) (See the Means improving cerebral circulation.). The efficiency of verapamil, nifedipine, a nimodipin in migraine is shown. The possibility of use of drugs of this group at epilepsy, diskineziya at patients with schizophrenia and other diseases of central nervous system is studied.
Recently a number of new antagonists of calcium ions is developed (nisoldipin, amlodipin, felodipin, etc.).
Diltiazem
Ispradipine
Nicardipine
Nitrendipine
Nifedipine
Sensit
Foridonum
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