Tài liệu Color Atlas of Pharmacology (Part 11): Vasodilators pdf

Vasodilators–Overview

The distribution of blood within the cir￾culation is a function of vascular caliber.

Venous tone regulates the volume of

blood returned to the heart, hence,

stroke volume and cardiac output. The

luminal diameter of the arterial vascula￾ture determines peripheral resistance.

Cardiac output and peripheral resis￾tance are prime determinants of arterial

blood pressure (p. 314).

In A, the clinically most important

vasodilators are presented in the order

of approximate frequency of therapeu￾tic use. Some of these agents possess

different efficacy in affecting the venous

and arterial limbs of the circulation

(width of beam).

Possible uses. Arteriolar vasodila￾tors are given to lower blood pressure in

hypertension (p. 312), to reduce cardiac

work in angina pectoris (p. 308), and to

reduce ventricular afterload (pressure

load) in cardiac failure (p. 132). Venous

vasodilators are used to reduce venous

filling pressure (preload) in angina pec￾toris (p. 308) or cardiac failure (p. 132).

Practical uses are indicated for each

drug group.

Counter-regulation in acute hy￾potension due to vasodilators (B). In￾creased sympathetic drive raises heart

rate (reflex tachycardia) and cardiac

output and thus helps to elevate blood

pressure. Patients experience palpita￾tions. Activation of the renin-angioten￾sin-aldosterone (RAA) system serves to

increase blood volume, hence cardiac

output. Fluid retention leads to an in￾crease in body weight and, possibly,

edemas. These counter-regulatory pro￾cesses are susceptible to pharmacologi￾cal inhibition (!-blockers, ACE inhibi￾tors, AT1-antagonists, diuretics).

Mechanisms of action. The tonus

of vascular smooth muscle can be de￾creased by various means. ACE inhibi￾tors, antagonists at AT1-receptors and

antagonists at "-adrenoceptors protect

against the effects of excitatory media￾tors such as angiotensin II and norepi￾nephrine, respectively. Prostacyclin an￾alogues such as iloprost, or prostaglan￾din E1 analogues such as alprostanil,

mimic the actions of relaxant mediators.

Ca2+ antagonists reduce depolarizing in￾ward Ca2+ currents, while K+

-channel ac￾tivators promote outward (hyperpolar￾izing) K+ currents. Organic nitrovasodi￾lators give rise to NO, an endogenous

activator of guanylate cyclase.

Individual vasodilators. Nitrates

(p. 120) Ca2+-antagonists (p. 122). "1-

antagonists (p. 90), ACE-inhibitors, AT1-

antagonists (p. 124); and sodium nitro￾prusside (p. 120) are discussed else￾where.

Dihydralazine and minoxidil (via

its sulfate-conjugated metabolite) dilate

arterioles and are used in antihyperten￾sive therapy. They are, however, unsuit￾able for monotherapy because of com￾pensatory circulatory reflexes. The

mechanism of action of dihydralazine is

unclear. Minoxidil probably activates K+

channels, leading to hyperpolarization

of smooth muscle cells. Particular ad￾verse reactions are lupus erythemato￾sus with dihydralazine and hirsutism

with minoxidil—used topically for the

treatment of baldness (alopecia androg￾enetica).

Diazoxide given i.v. causes promi￾nent arteriolar dilation; it can be em￾ployed in hypertensive crises. After its

oral administration, insulin secretion is

inhibited. Accordingly, diazoxide can be

used in the management of insulin-se￾creting pancreatic tumors. Both effects

are probably due to opening of (ATP￾gated) K+ channels.

The methylxanthine theophylline

(p. 326), the phosphodiesterase inhibi￾tor amrinone (p. 132), prostacyclins (p.

197), and nicotinic acid derivatives (p.

156) also possess vasodilating activity.

118 Vasodilators

Lüllmann, Color Atlas of Pharmacology © 2000 Thieme

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