Tuesday, September 21, 2010

TOPIC DISCUSSION: MINOXIDIL for Hypertension? what is the evidence?

Many nephrologists and internists use Minoxidil for resistant hypertension. What is the evidence of this medication in this current era of hypertensive management?

Minoxidil is a direct acting vasodilator. The usual dose is 5mg once a day and can be given as high as 100mg/day in divided dose. It was first used in early 19790s. Minoxidil's effect can be limited because of an increase in pulse rate and/or sodium (and water) retention. The latter may prove quite debilitating in some patients. Thus, minoxidil is generally administered with both a diuretic and an agent that can keep pulse rate in check, such as a ß blocker or a combined -ß blocker. The prominent tachycardia with minoxidil can aggravate myocardial ischemia and, if long-standing, leads to left ventricular hypertrophy. Minoxidil has a particularly annoying side effect of hypertrichosis that may limit its use, particularly among women. But someone with severe renal diseases, this drug can be quite effective.

In large measure, minoxidil acts by opening adenosine triphosphate-sensitive potassium channels in vascular smooth muscle cells.  The major site of minoxidil action is arterial. Venodilation does not occur with minoxidil; thus, postural hypotension is unusual with its administration. The arterial vasodilatation leads to increased sympathetic activity.  In conjunction with activation of the sympathetic system, both pulse rate and cardiac output increase with minoxidil; however, cardiac output and heart rate will tend to revert to pretreatment values with long-term treatment. And that’s the reason they get very tachycardic and should be on a beta blocker as well.

Another major problem is fluid retention. Why is that? The use of an arterial vasodilator will activate the renin system leading to ultimate activation of aldosterone and salt absorption. Hence it works well with Diuretic in place. Most patients who have been started on minoxidil are probably already on an ACEI, ARB and a diuretic and there is resistant hypertension.
Data on these drugs dates back to 1970s and very few studies.  Look below for the references. No recent data exists on this medication. No data clearly for CKD patients.
But, even with this scant data,  as a last resort, the drug is used frequently in patients with chronic kidney disease (CKD) who have been unresponsive to other antihypertensive medications. Most forms of hypertension, independent of severity and/or the degree of renal insufficiency, are at least partially responsive to minoxidil. In this regard, shortly after minoxidil was made available, it quickly replaced bilateral nephrectomies as the treatment of choice in advanced CKD patients with otherwise uncontrollable hypertension. 
Minoxidil does not adversely affect renal function in the majority of patients with hypertension and a normal glomerular filtration rate (GFR). Basically, you get good control of their blood pressure and perhaps might even improve their GFR.

How many think that this medication works? And have used it a lot?
Any thoughts? Here are some old references. Not many articles recently on the use of this agent since 1980s.  Only review articles recently


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