Vasodilation can be produced with a variety of drugs. The major classes of vasodilators, along with representative agents, are listed in Table 46–1. Some of these drugs act primarily on arterioles, some act primarily on veins, and some act on both types of vessel. The vasodilators are widely used, with indications ranging from hypertension to angina pectoris to heart failure. Many of the vasodilators have been discussed in previous chapters. Three agents—hydralazine, minoxidil, and nitroprusside—are introduced here.

In approaching the vasodilators, we begin by considering concepts that apply to the vasodilators as a group. After that we discuss the pharmacology of individual agents.

Basic concepts in vasodilator pharmacology

Selectivity of vasodilatory effects

Vasodilators differ from one another with respect to the types of blood vessels they affect. Some agents (eg, hydralazine) produce selective dilation of arterioles. Others (eg, nitroglycerin) produce selective dilation of veins. Still others (eg, prazosin) dilate arterioles and veins. The selectivity of some important vasodilators is summarized in Table 46–2.

TABLE 46–2 

Vasodilator Selectivity

	Site of Vasodilation
Vasodilator	Arterioles	Veins
Hydralazine	+
Minoxidil	+
Diltiazem	+
Nifedipine	+
Verapamil	+
Prazosin	+	+
Terazosin	+	+
Phentolamine	+	+
Nitroprusside	+	+
Captopril	+	+
Enalapril	+	+
Losartan	+	+
Aliskiren	+	+
Nesiritide	+	+
Nitroglycerin		+
Isosorbide dinitrate		+

The selectivity of a vasodilator determines its hemodynamic effects. For example, drugs that dilate resistance vessels (arterioles) cause a decrease in cardiac afterload (the force the heart works against to pump blood). By decreasing afterload, arteriolar dilators reduce cardiac work while causing cardiac output and tissue perfusion to increase. In contrast, drugs that dilate capacitance vessels (veins) reduce the force with which blood is returned to the heart, which reduces ventricular filling. This reduction in filling decreases cardiac preload (the degree of stretch of the ventricular muscle prior to contraction), which in turn decreases the force of ventricular contraction. Hence, by decreasing preload, venous dilators cause a decrease in cardiac work, along with a decrease in cardiac output and tissue perfusion.

Because hemodynamic responses to dilation of arterioles and veins differ, the selectivity of a vasodilator is a major determinant of its effects, both therapeutic and undesired. Undesired effects related to selective dilation of arterioles and veins are discussed below. Therapeutic implications of selective dilation are discussed in Chapters 47, 48, 51, 53, and 107—the chapters in which the primary uses of the vasodilators are presented.

Overview of therapeutic uses

The vasodilators, as a group, have a broad spectrum of uses. Principal indications are essential hypertension, hypertensive crisis, angina pectoris, heart failure, and myocardial infarction. Additional indications include pheochromocytoma, peripheral vascular disease, pulmonary arterial hypertension, and production of controlled hypotension during surgery. The specific applications of any particular agent are determined by its pharmacologic profile. Important facets of that profile are route of administration, site of vasodilation (arterioles, veins, or both), and intensity and duration of effects.

Adverse effects related to vasodilation

Postural hypotension

Postural (orthostatic) hypotension is defined as a fall in blood pressure brought on by moving from a supine or seated position to an upright position. The underlying cause is relaxation of smooth muscle in veins. Because of venous relaxation, gravity causes blood to “pool” in veins, thereby decreasing venous return to the heart. Reduced venous return causes a decrease in cardiac output and a corresponding decrease in blood pressure. Hypotension from venous dilation is minimal in recumbent subjects because, when we are lying down, the impact of gravity on venous return is small.

Patients receiving vasodilators should be informed about symptoms of hypotension (lightheadedness, dizziness) and advised to sit or lie down if these occur. Failure to follow this advice may result in fainting. Patients should also be taught that they can minimize hypotension by avoiding abrupt transitions from a supine or seated position to an upright position.

Reflex tachycardia

Reflex tachycardia can be produced by dilation of arterioles or veins. The mechanism is this: (1a) arteriolar dilation causes a direct decrease in arterial pressure or (1b) venous dilation reduces cardiac output, which in turn reduces arterial pressure; (2) baroreceptors in the aortic arch and carotid sinus sense the drop in pressure and relay this information to the vasomotor center of the medulla; and (3) in an attempt to bring blood pressure back up, the medulla sends impulses along sympathetic nerves instructing the heart to beat faster.

Reflex tachycardia is undesirable for two reasons. First, tachycardia can put an unacceptable burden on the heart. Second, if the vasodilator was given to reduce blood pressure, tachycardia would raise pressure and thereby negate the desired effect.

To help prevent vasodilator-induced reflex tachycardia, patients can be pretreated with a beta blocker (eg, propranolol), which will block sympathetic stimulation of the heart.

Expansion of blood volume

Prolonged use of arteriolar or venous dilators can cause an increase in blood volume (secondary to prolonged reduction of blood pressure). The increase in volume represents an attempt by the body to restore blood pressure to pretreatment levels.

Why does blood volume increase? First, reduced blood pressure triggers secretion of aldosterone by the adrenal glands. Aldosterone then acts on the kidney to promote retention of sodium and water, thereby increasing blood volume. Second, by reducing arterial pressure, vasodilators decrease both renal blood flow and glomerular filtration rate; because filtrate volume is decreased, the kidney is able to reabsorb an increased fraction of filtered sodium and water, which causes blood volume to expand.

Increased blood volume can negate the beneficial effects of the vasodilator. For example, if volume increases during the treatment of hypertension, blood pressure will rise and the benefits of therapy will be canceled. To prevent the kidney from neutralizing the beneficial effects of vasodilation, patients often receive concurrent therapy with a diuretic, which prevents fluid retention and volume expansion.

Pharmacology of individual vasodilators

In this section we focus on three drugs: hydralazine, minoxidil, and sodium nitroprusside. All of the other vasodilators are discussed at length in other chapters, and hence discussion of them here is brief. Diazoxide [Hyperstat IV], discussed in previous editions of this book, has been withdrawn.

Hydralazine

Cardiovascular effects

Hydralazine [Apresoline] causes selective dilation of arterioles. The drug has little or no effect on veins. Arteriolar dilation results from a direct action on vascular smooth muscle (VSM). The exact mechanism is unknown. In response to arteriolar dilation, peripheral resistance and arterial blood pressure fall. In addition, heart rate and myocardial contractility increase, largely by reflex mechanisms. Because hydralazine acts selectively on arterioles, postural hypotension is minimal.

< div class='tao-gold-member'>

Only gold members can continue reading. Log In or Register to continue

Share this:

• Click to share on Twitter (Opens in new window)
• Click to share on Facebook (Opens in new window)

Related

Related posts:

1. Orientation to pharmacology
2. Drug therapy of infertility
3. Drug abuse III: nicotine and smoking
4. Review of the immune system

Stay updated, free articles. Join our Telegram channel

Join