VASODILATORS — the pharmaceuticals causing expansion of blood vessels.
There is no standard classification of S. of page. By the principle of action distinguish neurotropic, myotropic S. of page, the antagonists of calcium and S. of page influencing humoral regulation of a vascular tone.
Pages carry the drugs influencing an efferent innervation of vessels to neurotropic S. Include in this group first of all the drugs having anti-adrenergic properties, i.e. oppressing an adrenergic innervation of vessels. Alpha adrenoblockers, alpha and the beta adrenoblockers, sympatholytics and other substances influencing various links of a sympathetic innervation belong to their number. alpha Adrenoblockers — Prazozinum, phentolamine (see), Tropaphenum (see) etc. — cause a vazodilatation owing to blockade of alpha adrenoceptors of vessels. They not only suppress an adrenergic innervation, but also prevent humoral adrenergic influences on vessels. Prazozinum (a synonym Minipressum) which is the selection alpha 1 - adrenoblocker is of special interest. Unlike phentolamine and Tropaphenum it blocks only postsynaptic agadrenoretseptor and does not influence on presynaptic alpha 2 - adrenoceptors. In this regard the vasodilating effect of Prazozinum is not followed by strengthening of emission of noradrenaline from the terminations of adrenergic nerves, and the reflex tachycardia arising against the background of its action has moderate character.
To alpha and to beta adrenoblockers belongs labetalol (a synonym trandat), to-ry at the same time blocks as α-, and β-adrenoceptors and thereof has a number of advantages before α-adrenoblockers.......... At its use, e.g., there is no compensatory tachycardia in response to vasodilatation since drug blocks β-adrenoceptors of heart. Besides, in connection with existence of β-adrenoceptor blocking activity labetalol possesses more expressed hypotensive action.
Expansion of peripheral vessels is observed also at prolonged use propranolol (see) and other β-adrenoblockers, though in an initiation of treatment them the general vascular resistance can increase a little. Decrease in vascular resistance at use of β-adrenoblockers is regarded as compensatory reaction in response to the reduction of cordial emission caused by them. Besides, these drugs reduce secretion of a renin, and nek-ry of them exert the oppressing impact on the vasculomotor centers.
Except adrenoblockers, the vasodilating effect is caused by the drugs influencing other links of an adrenergic innervation. Treat their number sympatholytics (see), acting on the terminations of postganglionic sympathetic (adrenergic) fibers, ganglioblokiruyushchy means (see), breaking momentum transfer in vegetative (and including sympathetic) gangliya, and the substances lowering activity of the vasculomotor centers, napr katapresan (see), Methyldopa (see).
To drugs, the vasodilating effect to-rykh is definitely connected with anti-adrenergic action, can be conditionally carried diuretics (see), causing a moderate vazodilatation generally at arterial hypertension. The mechanism of their vasodilating effect is connected, apparently, with the fact that they reduce the maintenance of ions of sodium and water in walls of vessels (hl. obr. arterioles) and thereof lower sensitivity of the last to vasopressor action of catecholamines.
Except anti-adrenergic substances, the vazodilatation is caused by the pharmaceuticals stimulating nek-ry types of receptors of a vascular wall. Treat them, e.g., β2-адреномиметики bametan (see. Bametansulfat ) and Isoxuprinum, exciting β2-адренорецепторы vessels. Dopamine (dopamine), stimulating dopamine receptors, causes expansion of hl. obr. brain, mezenterialny, renal and coronary vessels. Dopamine excites also β-adrenoceptors of a myocardium and in this regard causes cardiotonic effect. Thanks to a combination of the specified properties dopamine renders expressed to lay down. action at different types of shock, including cardiogenic shock. Dopamine stimulates α-adrenoceptors of a vascular wall in high doses and therefore can cause vasoconstriction. Properties C. of page also m cholinomimetics, m - and N cholinomimetics have (see. Cholinomimetic substances ) and antikholinesterazny means (see), the vasodilating effect to-rykh is caused by excitement of m-holinoretseptorov of vessels. Unlike substances with anti-adrenergic action the listed pharmaceuticals did not find broad application as vasodilators.
Myotropic VASODILATORS affect directly unstriated muscles of a vascular wall and cause their relaxation (see. Antispasmodics ). Pharmaceuticals from different classes of chemical connections concern to this group C. of page: nitrites and nitrates — nitroglycerine (see), aerinite (see), Nitrosorbidum (see), etc.; purines and pyrimidines — Euphyllinum (see), Xantinoli nicotinas (see), etc.; derivatives of isoquinoline — papaverine (see), Nospanum (see); derivative an imidazole — Dibazolum (see).
Pages of myotropic action carry to S. also magnesium sulfate, apressine (see), diazoxide, minoksi-dit, Natrium nitroprussicum. Depending on preferential influence on arterial or venous vessels among S. pages of myotropic action distinguish so-called arteriolar and arteriolar and venous vazodilatator. Carry apressine, diazoxide to arteriolar vazodilatator and minoksidit. They lower the general peripheric resistance, affecting preferential arterioles. Diazoxide differs in high activity and bystry development of effect, however its action is fully shown only at intravenous administration. At intake it is much less active in this connection it is applied by hl. obr. intravenously for stopping of hypertensive crises. Minoksidil surpasses diazoxide in activity and unlike it is effective at intake. Works for a long time (24 hours and more) since selectively collects in a vascular wall. Minoksidil quite often is effective when other drugs do not give desirable effect, napr, at malignant hypertensia.
Nitrites and nitrates, and also Natrium nitroprussicum which is the most active myotropic S. page belong to arteriolar and venous vazodilatator. It is effective only at intravenous administration and works shortly in this connection it is used by hl. obr. for stopping of hypertensive crises, appointing intravenously (kapelno).
Pages of myotropic action distinguish the drugs exerting preferential impact on a tone of coronary vessels of heart, so-called myotropic coronarodilator means, napr, Dipiridamolum, Carbocromenum, diphryl, lidoflazinum, etc. from S. On a tone of vessels of a big circle of blood circulation and the general the ABP (see. Blood circulation ) these drugs influence slightly.
Pages from group of antagonists of calcium belong to S. verapamil (see), nifedipine, diltiazem, etc. The mechanism of vasodilating effect of these drugs is connected with blockade of calcium channels that leads to difficulty of penetration of calcium ions in a cell and to relaxation of smooth muscles. From among antagonists of calcium in medical practice verapamil and nifedipine are widely used, to-rye apply generally as anti-anginal means (see).
For use as S. also medicines, vasodilating action are offered page to-rykh it is connected with elimination of influence on vessels pressor or with «imitation» of effect of depressor biologically active endogenous agents. Antagonists of angiotensin carry to number C. of the page interfering effect of endogenous pressor substances. These pharmaceuticals render the expressed vasodilating effect of hl. obr. in the conditions of the increased content of angiotensin II (e.g., at renovascular hypertensia). On the mechanism of action distinguish blockers of angiotenzinovy receptors from antagonists of angiotensin (saralazin) and the inhibitors of angiotenzinkonvertiruyushchy enzyme interfering formation of II angiotensin of angiotensin I (captopril). Wide use of a saralazin is limited to need to enter it intravenously kapelno. Captopril is offered for systematic treatment of the arterial hypertension caused by the increased formation of angiotensin II.
The expressed vasodilating action nek-ry endogenous substances from group possess prostaglandins (see), napr, E2, D2 prostaglandins and prostacyclin. Use of prostacyclin as S. of page is limited in connection with short duration of its effect. Has rather bigger duration of action karbatsiklin, close on chemical structure to prostacyclin.
Depending on features of action of S. of page apply in medical practice with various purposes, napr, at arterial hypertension, stenocardia, diseases of peripheral vessels, acute and chronic heart failure.
At treatment of arterial hypertension use S. of page of various groups. For systematic treatment use drugs, effective at intake and the actions having sufficient duration, napr, the adrenoblockers, diuretics, sympatholytics and substances lowering a tone of the vasculomotor centers. From group C. of page of myotropic action with the same purpose use Dibazolum, apressine, minoksidit. The pages which are characterized by bystry development of effect, napr, diazoxide, Natrium nitroprussicum, ganglioblokator, alpha adrenoblockers apply S. to stopping of hypertensive crises. At therapy of arterial hypertension preference is given by S. to the pages causing preferential expansion of arterial vessels since drugs with the expressed influence on a tone of veins can cause orthostatic hypotension.
As anti-anginal means use nitrates and nitrites, antagonists of calcium and myotropic coronarodilator means. At diseases of peripheral vessels (a Raynaud's disease, an obliterating endarteritis, etc.) apply ganglioblokator, alpha adrenoblockers, nek-ry myotropic means.
At heart failure — alpha adrenoblockers, nitroglycerine (sublingual and intravenously), Natrium nitroprussicum. Expediency of appointment of these S. of page at heart failure is caused by the fact that they, causing dilatation of veins and arteries, promote reduction of load of heart and by that reduce its metabolic cost. Villages of the village use also at a fluid lungs and nek-ry forms of cardiogenic shock.
Bibliography: Mashkovsky M. D. Pharmaceuticals, p.1, page 377, etc., M., 1977; Cardiovascular pharmacology, ed. by M. J. Antonaccio, N. Y., 1977; The pharmacological basis of therapeutics, ed. by A. G. Gilman a. o., N. Y., 1980; Van Z w i e t e n P. A. Vasodilator drugs, Progr. Pharmacol., v. 3, p. 69, 1980.
E. Yu. Lemina, V. K. Muratov.