Vasodilatory Drugs Acting On Smooth Muscle

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Reduction of arterial smooth muscle tone may occur by many mechanisms, such as reduction in sympathetic tone, stimulation of ^-adrenergic receptors, or even direct action on the vasculature without interference from the autonomic innervation. Drugs acting on the arteriolar smooth muscle also increase sympathetic reflex activity, causing an increase in heart rate and cardiac output and stimulating renin release, which increases sodium retention and plasma volume. As a result, it is common to coadminister saluretics and ^-adrenergic blocking drugs with these agents.

Antihypertensive agents that produce vasodilation of smooth muscle can be divided into two categories: direct-acting and indirect-acting vasodilators. Indirect-acting vasodilators may be distinguished from direct-acting vasodilators, in that they produce their effect by interfering with the vasoconstrictor stimuli, and their primary site of action is not necessarily the vascular smooth muscle itself. Indirect-acting vasodilators include sympatholytic drugs, such as reserpine; ^-adrenergic antagonists, such as prazosin hydrochloride; ACE inhibitors; and angiotensin II receptor antagonists, such as saralysin. Direct-acting vasodilators include hydralazine hydrochloride, sodium nitroprusside, potassium channel openers, and calcium channel-blocking agents.58

Hydralazine Hydrochloride, USP. Hydralazine hydrochloride, 1-hydrazinophthalazine monohydrochloride (Apresoline hydrochloride), originated from the work of a chemist59 attempting to produce some unusual chemical compounds and from the observation60 that this compound had antihypertensive properties. It occurs as yellow crystals and is soluble in water to the extent of about 3%. A 2% aqueous solution has a pH of 3.5 to 4.5.

Hydralazine hydrochloride is useful in the treatment of moderate-to-severe hypertension. It is often used in conjunction with less potent antihypertensive agents, because side effects occur frequently when it is used alone in adequate doses. In combinations, it can be used in lower and safer doses. Its action appears to be centered on the smooth muscle of the vascular walls, with a decrease in peripheral resistance to blood flow. This results in increased blood flow through the peripheral blood vessels. It also has the unique property of increasing renal blood flow, an important consideration in patients with renal insufficiency.

Hydralazine hydrochloride acts on vascular smooth muscle to cause relaxation. Its mechanism of action is unclear. It interferes with Ca2+ entry and Ca2+ release from intracellular stores and reportedly causes activation of guanylate cyclase, resulting in increased levels of cGMP. All of these biochemical events can cause vasodilation.

Absorption of hydralazine hydrochloride taken orally is rapid and nearly complete. The maximal hypotensive effect is demonstrable within 1 hour. The drug is excreted rapidly by the kidneys, and within 24 hours, 75% of the total amount administered appears in the urine as metabolites or unchanged drug. Hydralazine hydrochloride undergoes benzylic oxidation, glucuronide formation, and N-acetylation by the microsomal enzymes in the tissues (Fig. 19.15). Acetylation appears to be a major determinant of the rate of hepatic removal of the drug from the blood and, therefore, of systemic avail-ability.61 Rapid acetylation results in a highly hepatic extraction ratio from blood and greater first-pass elimination.

Hydralazine hydrochloride is more effective clinically when coadministered with drugs that antagonize adrenergic transmission (e.g., ^-adrenergic antagonists, reserpine, guanethidine monosulfate, methyldopa, and clonidine hydrochloride). When given with diuretics, it is useful in the treatment of CHF.

Hydralazine hydrochloride is marketed as a combination therapy with isosorbide under the trade name BiDil specifically for African Americans with CHF.

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Blood Pressure Health

Blood Pressure Health

Your heart pumps blood throughout your body using a network of tubing called arteries and capillaries which return the blood back to your heart via your veins. Blood pressure is the force of the blood pushing against the walls of your arteries as your heart beats.Learn more...

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