Potassium+Channel+Openers

__General Pharmacology__ Potassium-channel openers are drugs that activate (open) ATP-sensitive K+-channels in vascular smooth muscle. Opening these channels hyperpolarizes the smooth muscle, which closes voltage-gated calcium channels and decreases intracellular calcium. With less calcium available to combine with calmodulin, there is less activation of myosin light chain kinase and phosphorylation of myosin light chains ([|click here for details]). This leads to relaxation and vasodilation. Because small arteries and arterioles normally have a high degree of [|smooth muscle tone], these drugs are particular effective in dilating these resistance vessels, decreasing systemic vascular resistance, and lowering arterial pressure. The fall in arterial pressure leads to reflex cardiac stimulation ([|baroreceptor]-mediated tachycardia). __Therapeutic Indications__ Being effective arterial dilators, potassium-channel openers are used in the treatment of **hypertension**. These drugs are not first-line therapy for hypertension because of their side effects, and therefore they are relegated to treating refractory, severe hypertension. They are generally used in conjunction with a [|beta-blocker] and [|diuretic] to attenuate the reflex tachycardia and retention of sodium and fluid, respectively. __Specific Drugs__ Although several potassium-channel openers have been used in research for many years, only one, **minoxidil**, is approved for use in humans for treating hypertension. __Side Effects and Contraindications__ Common side effects to minoxidil include headaches, flushing and reflex tachycardia. The potent vasodilator actions of minoxidil can lead to fluid retention and edema formation. Reflex cardiac stimulation can precipitate angina in patients with coronary artery disease. Minoxidil produces [|T wave] changes in a high percentage (~60%) of patients under chronic treatment. One of the most noted side effects of minoxidil is hypertrichosis, a thickening and enhanced pigmentation of body hair, and therefore this drug is more commonly used for treating baldness.
 * Potassium-Channel Openers**