Direct vasodilators hydralazine

Direct Vasodilators Isosorbide dinitrate 20 mg and hydralazine 37.5 (BiDil) 1-2 tablets three times a day Minoxidil (Loniten) Hydralazine Heart failure (isosorbide dinitrate + hydralazine in African-Americans) A-HeFT66 Edema (minoxidil) Tachycardia Lupus-like syndrome (hydralazine) ... 

Vasodilators. Hydralazine causes direct relaxation of arteriolar smooth muscle. An important consequence of this vasodilation, however, is reflex tachycardia (T CO). It may also cause sodium retention (T plasma volume). The resulting increase in CO tends to offset effects of the vasodilator. Therefore, these drugs are most effective when administered along with sympathetic agents such as P-adrenergic receptor antagonists, which prevent unwanted compensatory responses by the heart. 

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. 

Hydralazine and minoxidil cause direct arteriolar smooth muscle relaxation. Compensatory activation of baroreceptor reflexes results in increased sympathetic outflow from the vasomotor center, producing an increase in heart rate, cardiac output, and renin release. Consequently, the hypotensive effectiveness of direct vasodilators diminishes over time unless the patient is also taking a sympathetic inhibitor and a diuretic. 

DIRECT VASODILATOR ANTIHYPERTENSIVES Case reports of t tachycardia when epinephrine was given for perioperative 1 BP in patients on hydralazine Additive effect Avoid co-administration... 

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

Direct vasodilator agents T Renal vascular resistance (hydralazine, minoxidil) Arterial vasodilation plus dilatation of venous capacitance vessels (nitroprusside) Increase in RBF and no effect on GFR Decrease in GFR and RBF (acute effect)... 

In the treatment of hypertension, a major use of beta-blockers is in combination with hydralazine. The direct vasodilators bring about reflex cardiac stimulation, and beta-blockers prevent these adverse effects (see also Figure 67). Beta-blockers also reduce blood pressure by exerting a central effect or a peripheral action, or both, which decreases renin activity. Metoprolol and atenolol are beta selective, and they are safer agents in patients with asthma, diabetes mellitus, or low-renin hypertension. Some beta-blocking agents such as pindolol have intrinsic sympathomimetic activity and may be used in the treatment of pronounced bradycardia (sick sinus syndrome). Unlike propranolol, metoprolol is not a very lipid-soluble... 

MDL 899 (26) is a direct acting arteriolar vasodilator in man, but coadministration of a beta-blocker is necessary to prevent reflex-related side effects. A clinical study with cadralazlne (ISF 2469, 27) shows this compound similar to hydralazine with fewer side effects. Two other vasodilators, budralazine (28) and pinacidil (29) may owe some of their activity to calcium channel blockade.Anthranilamlde (WIN 48,049) lowers blood pressure in monkeys without accompanying tachycardia. This compound acts primarily as a direct vasodilator but also has sympatholytic and dopaminergic activities. Compounds and 32 also lower blood pres-... 

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. 

Pharmacology Hydralazine exerts a peripheral vasodilating effect through a direct relaxation of vascular smooth muscle. 

The hemodynamic effects of diazoxide are similar to those of hydralazine and minoxidil. It produces direct relaxation of arteriolar smooth muscle with little effect on capacitance beds. Since it does not impair cardiovascular reflexes, orthostasis is not a problem. Its administration is, however, associated with a reflex increase in cardiac output that partially counters its antihypertensive effects. Propranolol and other -blockers potentiate the vasodilating properties of the drug. Diazoxide has no direct action on the heart. Although renal blood flow and glomerular filtration may fall transiently, they generally return to predrug levels within an hour. 

The vasodilating properties of captopril or hydralazine (antihypertensive agents) are mediated by the formation of EDRF or prostaglandin, or both. On the other hand, the vasodilating properties of nitroprusside (an antihypertensive agent) result directly from the formation of cyclic GMP. 

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. 

Hydralazine now has little use long-term for hypertension, but it may have a role as a vasodilator (plus nitrates) in heart failure. It reduces peripheral resistance by directly relaxing arterioles, with negligible effect on veins. In common with all potent arterial vasodilators, its hypotensive action is accompanied by a compensatory baroreceptor-mediated sjmpathetic discharge, causing tachycardia and increased cardiac output. There is also renin release with secondary salt and water retention,... 

Vasodilators have a number of different mechanisms of action. Some are smooth muscle relaxants that act directly on the blood vessels, e.g. glyceryl trinitate, hydralazine, isosorbide dinitrate, pentaerythritol tetranitrate, sodium nitroprusside and other nitrite and nitrate drugs, which are thought to mimic the actions of the endogenous mediator nitric oxide, which relaxes smooth muscle through elevation of cGMP (see nitrergic stimulants). 

Direct-acting vasodilators lower the peripheral vascular resistance mainly by causing arteriolar dilation. Drugs discussed are nitroprusside, hydralazine, minoxidil, and diazoxide. 

Hydralazine is a peripheral vasodilator that directly relaxes vascular smooth muscle to cause peripheral vasodilation, decreasing arterial BP and peripheral vascular resistance. It is used in the treatment of both essential hypertension (oral form) and severe essential hypertension (parenteral form). 

---