Vasodilating antihypertensive agents

Direct vacuum gauges, 20 657 Direct vasodilators, antihypertensive agents, 5 165-166 Direct violet dyes, 9 406... 

The phthalazine ring system has yielded a pair of quite effective antihypertensive agents. Both these drugs are believed to act as vasodilators they would owe much of their effectiveness to the consequent decrease in resistance to blood flow in the periphery. Condensation of the half-aldehyde corresponding... 

There are numerous patents claiming 3-hydrazinopyridazine derivatives with amino-substituted alkoxy side-chains at C-6 as ff-blocking vasodilating agents [188,286-293]. Other 3-hydrazinopyridazine-derived antihypertensive agents are covered by patents [294-301], or described in the literature [302 306]. It should be noted that with structurally very simple hydrazino-pyridazines like 6-hydrazino-3-pyridazinecarboxamide (hydracarbazine, 2105 TH CAS 3164-47-9), antihypertensive activity has been observed. 

Reduction in blood pressure caused by treprostinil may be exacerbated by drugs that by themselves alter blood pressure, such as diuretics, antihypertensive agents, or vasodilators. Because treprostinil inhibits platelet aggregation, there is also a potential for increased risk of bleeding, particularly among patients maintained on anticoagulants. 

Vasodiiators/Antihypertensive agents Iloprost has the potential to increase the hypotensive effect of vasodilators and antihypertensive agents. 

C. Trimethaphan is a ganglionic blocking agent that will lower blood pressure very rapidly. Hydralazine is a vasodilator hydrochlorothiazide and spironolactone are diuretics and methyldopa is a sympatholytic acting in the central nervous system. All of these drugs are used clinically as antihypertensive agents. None work as rapidly as trimethaphan. Clinically, however, either nitroprusside or clonidine is used much more commonly than trimethaphan in this situation. 

The vasodilators decrease total peripheral resistance and thus correct the hemodynamic abnormality that is responsible for the elevated blood pressure in primary hypertension. In addition, because they act directly on vascular smooth muscle, the vasodilators are effective in lowering blood pressure, regardless of the etiology of the hypertension. Unlike many other antihypertensive agents, the vasodilators do not inhibit the activity of the sympathetic nervous system therefore, orthostatic hypotension and impotence are not problems. Additionally, most vasodilators relax arterial smooth muscle to a greater extent than venous smooth muscle, thereby further minimizing postural hypotension. 

Minoxidil, an antihypertensive agent, produces arteriolar vasodilation by an unknown mechanism. In limited clinical studies, minoxidil increases penile rigidity and has been used in the long-term treatment of organic impotence. 

Mechanism of Action An antihypertensive and antianginal, antiarrhythmic, and antihypertensive agent that inhibits calcium ion entry across cardiac and vascular smooth-muscle cell membranes. This action causes the dilation of coronary arteries, peripheral arteries, and arterioles. Therapeutic Effect Decreases heart rate and myocardial contractility and slows SA and AV conduction. Decreases total peripheral vascular resistance by vasodilation. 

From a clinical perspective, some of these PCO classes have attracted initial attention. Diazoxide and minoxidil have been evaluated as antihypertensive agents. These PCOs open K+ channels in the plasma membranes of vascular smooth muscle cells, causing vascular vasodilation, thereby lowering blood pressure. Cromakalim has been investigated as a smooth muscle bronchodilator for the treatment of human asthma. Nicorandil was launched in Japan in 1984 for the treatment of angina because of its perceived ability to promote vasodilation of coronary arteries. Developmental work on these and other PCOs is continuing for indications ranging from hypertension, asthma, urinary incontinence, psychosis, epilepsy, pain, and alopecia (hair loss). 

Drug Interactions Other antihypertensive agents Carbamazepine (vasodilators, ACE inhibitors, Rifampin diuretics, and beta-blockers) Phenobarbital Digoxin Cyclosporine Disopyramide Theophylline Flecainide Inhalation anesthetics Quinidine Neuromuscular blocking agents Cimetidine Lithium ... 

Other antihypertensive agents (vasodilators, ACE inhibitors, diuretics, and beta-blockers)... 

Coronary vasodilator antihypertensive Morsydomine. First mesoionic-type therapeutic agent... 

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. 

Fenoldopam is a Di receptor agonist that selectively leads to peripheral vasodilation in some vascular beds. The primary indication for fenoldopam is as an intravenously administered drug for the treatment of severe hypertension (Chapter 11 Antihypertensive Agents). Continuous infusions of the drug have prompt effects on blood pressure. 

Calcium channel blocking agents, such as verapamil and nifedipine are also satisfactory antihypertensive agents. These drugs reduce the influx of calcium ions into vascular muscle cells following excitation and so cause vasodilation. They act mainly on arterial vessels in the circulation. 

Q9 Sodium nitroprusside acts via the production of NO. It is a powerful vasodilator and a potent, rapidly acting antihypertensive agent. The drug is administered by intravenous infusion but is then converted to thiocyanate in plasma. Thiocyanate toxicity can occur with continued use consequently, sodium nitroprusside can be used only for short-term treatment. 

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