1. 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. (Go to www.rxlist.com
for detailed information on minoxidil)
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.
