Direct+Acting+Arterial+Dilators

__General Pharmacology__ The one drug in this group, **hydralazine**, does not fit neatly into the other mechanistic classes, in part, because its mechanism of action is not entirely clear and it appears to have multiple, direct effects on the vascular smooth muscle. Hydralazine, which is highly specific for arterial vessels, may work by a couple of different mechanisms. First, hydralazine causes smooth muscle hyperpolarization quite likely through the [|opening of K+-channels]. It also may inhibit [|IP3-induced release of calcium] from the smooth muscle sarcoplasmic reticulum. This calcium combines with calmodulin to activate [|myosin light chain kinase], which induces contraction. Finally, hydralazine stimulates the formation of [|nitric oxide] by the vascular endothelium, leading to cGMP-mediated vasodilation. The arterial vasodilator action of hydralazine reduces systemic vascular resistance and arterial pressure. Indirect cardiac stimulation (e.g., tachycardia) occurs with hydralazine administration because of activation of the [|baroreceptor reflex]. __Specific Drugs and Therapeutic Indications__ The direct acting vasodilator that is used clinically is **hydralazine**. This drug is used in the treatment of hypertension and heart failure. //**[|Hypertension].**// Hydralazine is used occasionally (although rarely alone) in the treatment of [|arterial hypertension]. It is not first-line therapy for arterial hypertension. Its relatively short half-life (therefore requires frequent dosing) and precipitation of reflex tachycardia make it undesirable for treating chronic hypertension. However, it is used in treating acute hypertensive emergencies, secondary hypertension caused by preecclampsia, and [|pulmonary hypertension]. It is often used in conjunction with a [|beta-blocker] and [|diuretic] to attenuate the [|baroreceptor]-mediated reflex tachycardia and sodium retention, respectively. __Side Effects and Contraindications__ Common side effects to hydralazine include headaches, flushing and tachycardia. Some patients (~10%) experience a lupus-like syndrome. Reflex cardiac stimulation can precipitate [|angina] in patients with coronary artery disease.
 * Direct Acting Vasodilators**
 * //[|Heart failure].//** Hydralazine has a role in the management of heart failure because of its ability to reduce [|afterload] and thereby enhance stroke volume and [|ejection fraction]. When used in heart failure, it is given along with a diuretic and often with a [|nitrodilator].