Category:Vasodilators

A vasodilator is a medicine that relaxes vascular smooth muscle, widening blood vessels and so reducing vascular resistance. The category is heterogeneous by mechanism but unified by effect: the resulting drop in resistance reduces the workload on the heart (in arterial vasodilation) or the venous return to it (in venodilation), and the resulting redistribution of blood flow can be exploited to treat a variety of conditions: systemic hypertension, angina pectoris, heart failure, pulmonary arterial hypertension, peripheral arterial disease, Raynaud's phenomenon, erectile dysfunction (where the local penile vasodilation is the therapeutic goal), and the hypertensive crises of pheochromocytoma and aortic dissection.

The vasodilators are conventionally classified by mechanism. The direct vasodilators act on vascular smooth muscle through receptor-independent mechanisms: hydralazine (Ciba, 1949) by an incompletely characterised mechanism that produces preferential arteriolar dilation, minoxidil (Upjohn, 1979) by opening of the ATP-sensitive potassium channels in smooth muscle (an additional dermatologic application as a topical hair-growth medicine emerged accidentally). The organic nitrates (nitroglycerin, isosorbide dinitrate and mononitrate) release nitric oxide, activating soluble guanylate cyclase and producing predominantly venodilation; the mechanism is described under antianginals. Sodium nitroprusside releases nitric oxide and cyanide in equimolar quantities (the cyanide is detoxified by hepatic rhodanese under normal circumstances; severe hypotension or prolonged infusion can produce cyanide toxicity); it is used by continuous infusion for hypertensive emergencies and for afterload reduction in acute heart failure.

The receptor-mediated vasodilators act on specific G-protein-coupled receptors of vascular smooth muscle. The alpha-1 adrenergic antagonists (doxazosin, terazosin, prazosin) block the sympathetic vasoconstrictor signal and produce arterial vasodilation; their principal indications are described under antihypertensives and BPH treatments. The non-selective alpha antagonists phentolamine (intravenous) and phenoxybenzamine (oral, irreversible) are used in pheochromocytoma to prevent perioperative hypertensive crisis. The calcium channel blockers block L-type calcium channels of vascular smooth muscle and produce arterial vasodilation; the dihydropyridines (amlodipine, nifedipine, nicardipine, clevidipine) are predominantly vascular-selective, the non-dihydropyridines (verapamil, diltiazem) have substantial cardiac effects as well. The angiotensin-converting enzyme inhibitors and the angiotensin receptor blockers, although usually classified as antihypertensives, are also vasodilators of arteriolar and venular smooth muscle through the angiotensin II-mediated vasoconstrictor pathway.

The phosphodiesterase inhibitors produce vasodilation by preventing the degradation of intracellular cyclic nucleotides. The PDE5 inhibitors (sildenafil, tadalafil, vardenafil, avanafil) prolong the cyclic-GMP signal from nitric oxide in vascular smooth muscle; their principal clinical use is in erectile dysfunction (the original 1998 indication for sildenafil at Pfizer, discovered serendipitously during cardiovascular trials of the medicine for angina, by patients reporting unanticipated effects), but they are also used in pulmonary arterial hypertension (where the lower-dose sildenafil and tadalafil are approved) and selectively in Raynaud's phenomenon. The PDE3 inhibitors milrinone and amrinone are used intravenously for inotropic and vasodilator support in acute decompensated heart failure; pulmonary-targeted cilostazol (also a PDE3 inhibitor) is used for intermittent claudication in peripheral arterial disease.

The pulmonary arterial hypertension pharmacopoeia is a distinct sub-set of the vasodilators. The endothelin receptor antagonists bosentan, ambrisentan, and macitentan block the endothelin-1 ET-A and ET-B receptors that drive pulmonary-vascular constriction and remodelling in pulmonary arterial hypertension; the soluble guanylate cyclase stimulator riociguat acts on the same pathway as the nitrates but is direct rather than nitric-oxide-dependent and is approved for both pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. The prostacyclin analogues epoprostenol (intravenous continuous infusion), iloprost (inhaled), treprostinil (subcutaneous, intravenous, inhaled, oral), and the IP-receptor agonist selexipag (oral) target the prostacyclin pathway in pulmonary vascular smooth muscle.

The clinical use of a vasodilator is constrained by the limitations of the chosen mechanism. Reflex tachycardia, common with the short-acting dihydropyridines, hydralazine, and minoxidil, is moderated by concurrent beta-blockade in chronic use. Postural hypotension, common with alpha blockers (the well-known "first-dose phenomenon" of prazosin) and with the nitrates, requires patient education and careful titration. Tachyphylaxis (the development of pharmacological tolerance on continuous exposure) limits the chronic use of the organic nitrates and is managed by a nitrate-free interval each day. The interaction between PDE5 inhibitors and any nitrate produces severe and prolonged hypotension and is an absolute contraindication; the same caution applies to the soluble guanylate cyclase stimulator riociguat with nitrates and with PDE5 inhibitors. Cyanide accumulation on prolonged or high-dose sodium nitroprusside infusion is monitored by serum thiocyanate level in extended ICU use.

By mechanism:

• Direct vasodilators (smooth-muscle-direct, non-receptor mechanisms):
  • Hydralazine (preferential arteriolar)
  • Minoxidil (potassium channel opener; also topical for hair growth)
  • Sodium nitroprusside (intravenous infusion, hypertensive emergencies, afterload reduction)
• Nitric oxide donors (cross-indexed under antianginals):
  • Nitroglycerin, isosorbide dinitrate and mononitrate
  • Molsidomine (in Europe)
• Alpha-adrenergic antagonists (cross-indexed under alpha-1 blockers and antihypertensives):
  • Doxazosin, terazosin, prazosin, alfuzosin, silodosin, tamsulosin
  • Non-selective: phentolamine (intravenous), phenoxybenzamine (oral, irreversible, for pheochromocytoma)
• Calcium channel blockers (cross-indexed):
  • Dihydropyridines: amlodipine, nifedipine, felodipine, nicardipine, clevidipine
  • Non-dihydropyridines: verapamil, diltiazem
• Renin-angiotensin blockers (cross-indexed under antihypertensives):
  • ACE inhibitors, ARBs, sacubitril-valsartan (ARNI)
• Phosphodiesterase inhibitors:
  • PDE5 inhibitors (erectile dysfunction, pulmonary arterial hypertension): sildenafil, tadalafil, vardenafil, avanafil
  • PDE3 inhibitors: milrinone (intravenous, acute heart failure), cilostazol (oral, peripheral arterial disease)
• Pulmonary arterial hypertension specific:
  • Endothelin receptor antagonists: bosentan, ambrisentan, macitentan
  • Soluble guanylate cyclase stimulator: riociguat
  • Prostacyclin pathway: epoprostenol, iloprost, treprostinil, selexipag (IP-receptor agonist)

The boundary of this category is "medicine whose principal mechanism is relaxation of vascular smooth muscle." Medicines that produce vasodilation as a secondary effect of their primary mechanism (the beta-blockers, the diuretics) are not collected here. The vasoconstrictor medicines (the alpha-adrenergic agonists phenylephrine, the catecholamines norepinephrine and epinephrine in their vasopressor doses, vasopressin, angiotensin II) are the opposite of vasodilators and are collected under vasopressors or under sympathomimetics depending on mechanism. The medicines used in Raynaud's phenomenon (calcium channel blockers, PDE5 inhibitors, topical nitroglycerin, alpha-blockers) are cross-indexed here. The intravenous medicines used in hypertensive emergency (sodium nitroprusside, nicardipine, clevidipine, fenoldopam, labetalol, hydralazine, phentolamine) are collected here for the indication.

This category page is an encyclopedia article about its subject. The actual index of medicines belonging to the category is generated automatically by the wiki engine, from category-membership declarations on the individual medicine pages, and appears at the foot of the page below the references.