Minoxidil: An Underused Vasodilator for Resistant or Severe Hypertension

Domenic A. Sica, MD

Disclosures
In This Article

Clinical Use

The effectiveness of minoxidil in patients with resistant hypertension is well established. In one report, 11 patients with hypertension given minoxidil alone saw their mean BP fall from 188/124 mm Hg to 159/108 mm Hg. With the addition of the ß blocker propranolol, BP fell to 134/86 mm Hg. In these patients there were no signs of orthostatic hypotension and fluid retention was easily controlled with diuretics.[15]

Minoxidil is frequently a therapy of last resort in patients with chronic kidney disease (CKD) who have been unresponsive to other antihypertensive medications.[9,16,17,18] Most forms of hypertension, independent of severity and/or the degree of renal insufficiency, are at least partially responsive to minoxidil.[5,19,20] 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.[9,21] Minoxidil does not adversely affect renal function in the majority of patients with hypertension and a normal glomerular filtration rate (GFR).[22] In patients with established CKD, minoxidil can stabilize GFR -- if not improve renal function -- when BP is properly controlled.[16,22,23] On occasion, patients with CKD with malignant hypertension and sudden BP control with minoxidil experience an acute further deterioration in renal function. This fall in GFR can be of sufficient magnitude to call for dialysis; however, GFR is often recoverable and discontinuation of dialysis possible if normal BP is established with minoxidil therapy.[17,22,23]

In persons with advanced stage 2 hypertension, minoxidil is almost always given as one of several antihypertensive medications. If so, the coadministered antihypertensive medications should include a diuretic (usually a loop diuretic) and a ß blocker or a combined -ß blocker such as labetalol or carvedilol. It is not appropriate to simply give these medications without having established goals for their use. In the case of concomitant diuretic therapy, the potency of the chosen diuretic and its frequency of dosing should be sufficient to keep the patient free of edema. This can prove challenging, and occasionally, the volume expansion (edema) with minoxidil can be of sufficient severity to require combination therapy with a loop diuretic and metolazone. (In many cases, large doses of a loop diuretic [i.e, furosemide >100mg/d] may be necessary to control edema.)

Concomitant ß-blocker or combined -ß-blocker therapy should be directed to the problem of pulse rate control. The vasodilation induced by minoxidil can provoke a significant tachycardic response, particularly at peak medication effect; thus, ß blockade or combined -ß blockade should be timed to coincide with the presumed (or determined) time of maximal pulse rate response with minoxidil. This is often easier said than done, particularly if sustained-release compounds are being used for ß blockade. In the case of tachycardia with minoxidil, which proves difficult to control, it is reasonable to empirically split-dose the total required amount of minoxidil on a two-or three-times daily basis. In theory, this will attenuate the peak pulse rate response because lower individual doses are being given.

In a patient treated with minoxidil who is ß-blocker intolerant it simply may not be possible to use this drug if the pulse rate response is too extreme; however, patients treated with minoxidil usually receive several other medications, including drugs such as the central -agonist clonidine and/ or a pulse rate reducing calcium channel blocker such as verapamil or diltiazem.[9,24] Physicians should be mindful of the fact that both of these drug classes are known to reduce heart rate and may be used to support (or occasionally substitute) for ß blockade. When this triple-drug regimen is correctly constituted, more than 75% of patients with hypertension who were previously resistant to multidrug therapy can achieve control.[25,26]

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