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Clinical Disorders: Therapeutic Classes: Mechanism Classes:
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Vasoconstrictors
Therapeutic Use and Rationale
As the name implies, vasoconstrictor drugs contract the smooth muscle in blood vessels, which causes the vessels to constrict. Constriction of arterial (resistance) vessels increases systemic vascular resistance, which leads to an increase in arterial blood pressure. Constriction of venous (capacitance) vessels increases venous blood pressure and increases cardiac preload and cardiac output by the Frank-Starling mechanism, which increases arterial pressure. Because vasoconstrictor drugs increase arterial pressure, they are sometimes referred to as pressor drugs.
Hypotension, which is a systolic pressure of less than 90 mmHg or a diastolic pressure less than 60 mmHg, needs to be aggressively treated because blood flow to critical organs, particularly the brain, heart and kidneys may become compromised to an extent that organ failure and death occurs. Although vasoconstrictors can elevate arterial pressure, there is a drawback to their use. Unless cardiac output is increased at the same time systemic vascular resistance is increased, blood flow to some organs may actually decrease. The reason for this is that if the vascular resistance of an organ increases, for example, by 30% and mean arterial pressure increases by 30%, the organ blood flow will not change. If on the other hand, resistance is increased in some organs by 50%, and in others by only 10%, yet the arterial pressure is increased by 30%, blood flow will be increased to those organs that had the smaller increase in resistance because arterial pressure increased more than their resistance. This is precisely how pressor drugs can have a benefit in treating hypotension. Although blood flow may be reduced in some organs (e.g., to the splanchnic and muscle circulations), blood flow to critical organs (e.g., brain, heart and kidneys) may actually increase. Part of this benefit may be lost if systemic vascular resistance is increased too much with a pressor drug, especially if the hypotension is caused by cardiogenic shock, because the increase in ventricular afterload can reduce cardiac output. For a greater understanding of the hemodynamics associated with regional vasoconstriction, the reader is encouraged to read about the significance of the parallel arrangement of vascular beds in the body.
Drug Classes and General Mechanisms of Action
There are two general functional classes of vasoconstrictors, based upon their mechanism of action, that are used in the treatment of hypotension. The first class is sympathomimetic drugs that have alpha-adrenoceptor agonist (a-agonist) properties. Although many sympathomimetics possess other mechanisms that contribute to their pressor effects (e.g., b1-adrenoceptor agonist activity), a common property of several of these these drugs is that they bind to a1-adrenoceptors on vascular smooth muscle thereby promote smooth muscle contraction. A second class of vasoconstrictor that has been utilized increasingly in recent years vasopressin analogs. These drugs are a synthetic form of the naturally occurring hormone (vasopressin or antidiuretic hormone) that is released by the posterior pituitary. These drugs possess both both vasoconstrictor and antidiuretic properties, both of which contribute to elevating arterial pressure.
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