Peripheral vasculature

Amiodarone dilates arteriolar vascular smooth muscle, especiady coronary arteries, and thus exhibits antianginal effects. Its effects on the peripheral vasculature to decrease resistance leads to a decrease in left ventricular stroke work and a decrease in myocardial oxygen consumption. The dmg rarely produces hypotension that requires discontinuation of the dmg (1,2). 

Prazosin, terazosin, and doxazosin are selective cq-receptor blockers that inhibit catecholamine uptake in smooth muscle cells of the peripheral vasculature, resulting in vasodilation. 

Protein binding also plays a role in the distribution of drugs and thus the volume of distribution. Drugs that are highly bound to plasma proteins may distribute less widely because they remain trapped in the peripheral vasculature, since the plasma proteins themselves cannot tra-... 

The antihypertensive activity of clonidine can be ascribed solely to a decrease in the sympathetic activity transmitted from the brain to the peripheral vasculature. After clonidine administration, direct measurements of sympathetic nerve activity show that electrical discharge is reduced in a number of sympathetic nerves, including the cardiac, splanchnic, and cervical nerves. 

Mechanism of Action An alpha-adrenergic agonist that stimulates alphaj-adrenergic receptors. Inhibits sympatheticcardioaccelerat or and vasoconstrictor center to heart, kidneys, peripheral vasculature. Therapeutic Effect Decreases systolic, diastolic blood pressure (BP). Chronic use decreases peripheral vascular resistance. Pharmacohinetics Well absorbed from gastrointestinal (GI) tract. Widely distributed. Protein binding 90%. Metabolized in liver. Excreted in urine and feces. Not removed by hemodialysis. Half-life 6 hr. 

Combining agonists with some local anesthetics greatly prolongs the duration of infiltration nerve block the total dose of local anesthetic (and the probability of toxicity) can therefore be reduced. Epinephrine, 1 200,000, is the favored agent for this application, but norepinephrine, phenylephrine, and other agonists have also been used. Systemic effects on the heart and peripheral vasculature may occur even with local drug administration but are usually minimal. 

Alpha-1 Receptors. A primary location of these receptors is the smooth muscle located in various tissues throughout the body. Alpha-1 receptors are located on the smooth muscle located in the peripheral vasculature, intestinal wall, radial muscle of the iris, ureters, urinary sphincter, and spleen capsule. The response of each tissue when the alpha-1 receptor is stimulated varies depending on the tissue (see Table 18-2). Research also suggests that there might be three subtypes of alpha-1 receptors, identified as alpha-1 A, alpha-IB, and alpha-ID receptors.4 Much of this research, however, has focused on the characteristics of alpha-1 receptor subtypes in various animal models. Studies are currently underway to determine the exact location and functional significance of these alpha-1 receptor subtypes in humans. 

Although the control of blood pressure is a fairly complex subject, the actual factors that determine blood pressure can be simplified. At any given time, blood pressure is the product of cardiac output and the total resistance in the peripheral vasculature. This relationship is illustrated by the following equation ... 

FIGURE 21-1 Schematic diagram of the possible mechanisms in essential hypertension. Various factors interact to turn on sympathetic outflow to the kidneys, heart, and peripheral vasculature, resulting in elevated blood pressure. Hypertension also causes structural and functional changes in the vasculature that help maintain the elevated pressure. 

Sympatholytics Various sites within the sympathetic division of the autonomic nervous system Decrease sympathetic influence on the heart and/or peripheral vasculature... 

Vasodilators Peripheral vasculature Lower vascular resistance by directly vasodilating peripheral vessels... 

Peripheral vasculature and certain organs with a functional renin-angiotensin system (heart, kidneys]... 

Diltiazem (Cardizem, Dilacor). Like the other calcium channel blockers, diltiazem is able to vasodilate the coronary arteries and the peripheral vasculature. Diltiazem also produces some depression of electrical conduction in the sinoatrial and atrioventricular nodes, an effect that may cause slight bradycardia. This bradycardia can be worsened by beta blockers or in patients with myocardial conduction problems, and diltiazem should probably be avoided in these individuals.32,45... 

Promote dilation in the peripheral vasculature, which decreases the amount of blood returning to the heart (cardiac preload] and decreases the pressure the heart must pump against (cardiac afterload]... 

Peripheral vasculature. PGI2, PGE, and PGE2 induce vasodilation in heart, kidney, skeletal muscle, and mesentery, lowering vascular resistance and blood pressure. 

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