Direct-acting vasodilators

Acetylchohne is a vasodilator that acts by causing relaxation of the smooth muscle of blood vessels. However, it does not act directly on smooth muscle. A key observation was that if endothefial cells were stripped away from underlying smooth muscle cells, acetylcholine no longer exerted its vasodilator effect. This finding indicated that vasodilators such as acetylcholine initially interact with the endothelial cells of small blood vessels via receptors. The receptors are coupled to the phos-phoinositide cycle, leading to the intracellular release of... 

The answer is d. (Hardman, pp 794-795.) Hydralazine, minoxidil, diazoxide, and sodium nitroprusside are all directly acting vasodilators used to treat hypertension. Because hydralazine, minoxidil, nifedipine, and diazoxide relax arteriolar smooth muscle more than smooth muscle in venules, the effect on venous capacitance is negligible. Sodium nitroprusside, which affects both arterioles and venules, does not increase cardiac output, a feature that enhances the utility of sodium nitroprusside in the management of hypertensive crisis associated with MI. 

Nitrates (e.g., ISDN) and hydralazine were combined originally in the treatment of HF because of their complementary hemodynamic actions. Nitrates are primarily venodilators, producing reductions in preload. Hydralazine is a direct vasodilator that acts predominantly on arterial smooth muscle to reduce systemic vascular resistance (SVR) and increase stroke volume and cardiac output. Evidence also suggests that the combination may provide additional benefits by interfering with the biochemical processes associated with HF progression. 

Sodium nitroprusside is a mixed arterial-venous vasodilator that acts directly on vascular smooth muscle to increase cardiac index and decrease venous pressure. Despite its lack of direct inotropic activity, nitroprusside exerts hemodynamic effects that are qualitatively similar to those of dobutamine and milrinone. However, nitroprusside generally decreases PAOP, SVR, and blood pressure more than those agents do. 

Pharmacology Minoxidil is a direct-acting peripheral vasodilator. Minoxidil elicits a reduction of peripheral arteriolar resistance. The exact mechanism of action on the vascular smooth muscle is unknown. 

The directly acting vasodilators, with the exception of calcium channel antagonists and sympathetic nervous system depressants, receive the bulk of attention in this chapter. Other chapters offer additional information on diuretics (see Chapter 21), the renin-angiotensin system (see Chapter 18), adrenergic receptor antagonists (see Chapter 11), and the calcium channel antagonists (Chapter 19). 

Systemic heat Large whirlpool Hubbard tank Decreased muscle/joint stiffness in large areas of the body Opioid and nonopioid analgesics skeletal muscle relaxants Severe hypotension may occur if systemic hot whirlpool is administered to patients taking peripheral vasodilators and some antihypertensive drugs (eg., alpha-1 antagonists, nitrates, direct-acting vasodilators, calcium channel blockers)... 

Direct vasodilators frequently produce baroreflex-induced tachycardia, but rarely orthostatic hypotension. They are usually prescribed with a beta blocker or a centrally acting antihypertensive to minimize the reflex increase in heart rate and cardiac output. It should be noted that another member of the directly acting class of antihypertensives is minoxidil. This potent, long-acting drug has gained considerable notoriety for its use as a topical hair-restorer. Oral use can result in hirsutism (unwanted hair growth over the face as well as other parts of the body). 

Diazoxide [dye az OX ide] is a direct-acting arteriolar vasodilator. It has vascular effects like those of hydralazine. For patients with coronary insufficiency, diazoxide is administered intravenously with a p-blocker, which diminishes reflex activation of the heart. Diazoxide is useful in the treatment of hypertensive emergencies, hypertensive encephalopathy, and eclampsia. Excessive hypotension is the most serious toxicity. 

Correct answer = C. Clonidine reduces sympathetic outflow by stimulating a-adrenergic receptors. Minoxidil is a direct-acting vasodilator. Verapamil causes vasodilation by inhibiting calcium ion flow into smooth muscle. Enalapril blocks the enzyme that converts angiotensin I to angiotensin II. Hydrochlorothiazide acts by decreasing blood volume. 

Diazoxide is a direct vasodilator that acts on vascular smooth muscle to produce systemic vasodilatation. As a result there is baroreceptor-mediated activation of the sjm-pathetic nervous system and the renin-angiotensm system. 

Administer two or three additional medications such as alpha blockers, direct-acting vasodilators, or adrenergic neuron blockers. 

Direct-acting arteriolar vasodilators relax the smooth muscles of the blood vessels, causing vasodilation, which results in an increase in blood flow to the brain and kidneys. Direct-acting arteriolar can be combined with diuretics to decrease the edema. 

Nitroprusside is widely considered the agent of choice for most cases bnt can be problematic in patients with chronic kidney disease. It is a direct-acting vasodilator that decreases peripheral vascnlar resistance bnt does not increase cardiac ontpnt nnless left ventricnlar failnre is present. Nitroprusside can be given to treat most hypertensive emergencies, bnt in aortic dissection, propranolol shonld be given first to prevent reflex sympathetic activation. Since nitroprnsside is metabolized to cyanide and then to thiocyanate, which is eliminated by the kidneys, serum thiocyanate levels shonld be monitored when infnsions are continned longer than 72 honrs. Nitroprusside should... 

Peripheral resistance t Sympathetic tone Sympathoplegics, CCBs, direct-acting vasodilators, diuretics... 

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