Venous dilatation, drugs causing

INAMRINONE AND MILRINONE Parenteral formulations of inamrinone (previous name amrinone) and milrinone are approved for short-term support of the circulation in advanced heart failure. Both drugs are bipyridine derivatives and relatively selective inhibitors of PDE3, the cyclic GMP-inhibited cyclic AMP PDE. These drugs cause direct stimulation of myocardial contractility and acceleration of myocardial relaxation. In addition, they cause balanced arterial and venous dilation with a consequent fall in systemic and pulmonary vascular resistances, and left and right heart filling pressures. Cardiac output increases due to the stimulation of myocardial contractility and the decrease in left ventricular afterload. As a result of this dual mechanism of action, the increase in cardiac output with milrinone is greater than that seen with nitroprusside at doses that comparably reduce systemic resistance. Conversely, the arterial and venous dilator effects of milrinone are greater than those of dobutamine at doses that produce comparable increases in cardiac output. 

The drug at therapeutic dose levels, causes vasodepression which is primarily the outcome of arteriolar dilatation, in order that the ensuing orthostatic hypotension is normally minimal. However, certain extent of venous dilatation invariably occurs, which occasionaly is responsible to afford orthostatic hypotension. It has been duly observed that the smooth muscle-relaxing effects are usually caused due to the hyper-polarization of vascular smooth muscle by activating ATPase-sensitive K-channels. Hence, it is mostly used in IV as a hypotensive drug in situations arising from acute hypertensive crises. 

Hydralazine (apresoline) causes direct relaxation of arteriolar smooth muscle, possibly secondary to a fall in intracellular Ca concentrations. The drug does not dilate epicardial coronary arteries or relax venous smooth muscle. Hydralazine-induced vasodilation is associated with powerful stimulation of the sympathetic nervous system, likely due to baroreceptor-mediated reflexes, which results in increased heart rate and contractility, increased plasma renin activity, and fluid retention all of these effects counteract the antihypertensive effect of hydralazine. Although most of the sympathetic activity is due to a baroreceptor-mediated reflex, hydralazine may stimulate NE release from sympathetic nerve terminals and augment myocardial contractility directly. Most of hydralazine s effects are confined to the cardiovascular system the decrease in blood pressure after administration is associated with a selective decrease in vascular resistance in the coronary, cerebral, and renal circulations, with a smaller effect in skin and muscle. Because of preferential dilation of arterioles, postural hypotension is not common, and hydralazine lowers blood pressure equally in the supine and upright positions. 

Minoxidil (loniten) is efficacious in patients with the most severe and drug-resistant forms of hypertension. A small fraction of minoxidil is metabolized by hepatic sulfotransferase to the active molecule, minoxidil N-O sulfate. Minoxidil sulfate activates the ATP-modulated channel in smooth muscle, causing hyperpolarization and relaxation of arteriolar smooth muscle. Minoxidil produces arteriolar vasodilation with essentially no effect on capacitance vessels. Minoxidil preferentially increases blood flow to skin, skeletal muscle, the GI tract, and the heart. The disproportionate increase in blood flow to the heart may have a metabolic basis, in that administration of minoxidil is associated with a reflex increase in myocardial contractility and in cardiac output. The cardiac output can increase by as much as three- to fourfold, primarily due to enhanced venous return to the heart. The increased venous return probably results from enhanced flow in vascular beds with a fast response for venous return to the heart. The adrenergic increase in myocardial contractility contributes to the increased cardiac output, but is not the predominant factor. The renal effects of minoxidil are complex it dilates renal arteries, but systemic hypotension produced by the drug actually can decrease renal blood flow. Renal function usually improves in patients who take minoxidil for the treatment of hypertension, especially if renal dysfunction is secondary to hypertension. Minoxidil potently stimulates renin secretion, an effect mediated by renal sympathetic stimulation. 

Vasodilator drugs relax the smooth muscle in blood vessels, which causes the vessels to dilate. Dilation of arterial vessels leads to a reduction in systemic vascular resistance, which leads to a fall in arterial blood pressure. Dilation of venous vessels decreases venous blood pressure. 

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