Minoxidil: An Underused Vasodilator for Resistant or Severe Hypertension

Domenic A. Sica, MD

In This Article

Side Effects

Fluid retention and tachycardia are dose-dependent side effects that occur with minoxidil.[31] The mechanism of the sodium and water retention with minoxidil is a varying combination of renal hemodynamic and/or neurohumoral changes as well as direct tubular effects.[15] The latter may relate to minoxidil's action as a potassium channel opener. Activation of the potassium channel in the thick ascending limb increases Na+/2Cl-/K+ co-transporter activity and thereby increases sodium and chloride reabsorption. This occurs without major changes in potassium or calcium excretion.[32]

Fluid retention can be extreme enough to require discontinuation of the medication. Daily monitoring of a patient's weight as therapy progresses can pinpoint those experiencing the most marked fluid retention. The earlier fluid retention is identified in a patient treated with minoxidil the easier it is to manage this side effect. Pericardial effusions have also been reported in as many as 3% of patients treated with minoxidil.[33,34] Such effusions can spontaneously resolve, obviating the need for catheter drainage in some patients.[35] The true incidence of pericardial effusion with minoxidil is difficult to estimate because many such patients have CKD (pericardial effusions can occur in advanced CKD in and of itself) and no pretreatment echocardiogram. In many cases a minoxidil-related pericardial effusion is simply an extension of the generalized volume overload that can accompany therapy; however, in some instances it is idiopathic (and volume-independent) and recurs with minoxidil rechallenge.[35] Under these circumstances further therapy with minoxidil is ill advised.

During the first 2 weeks of treatment with minoxidil, ST-segment depression and T-wave flattening or inversion can be seen in up to 90% of patients.[4,11,36] These electrocardiogram abnormalities often resolve during long-term therapy; on the other hand, their persistence can be a sign of myocardial ischemia or the onset of progressive left ventricular hypertrophy (LVH). Moreover, it has been observed that despite good control of hypertension with minoxidil, the ß blocker betaxolol, and furosemide, left ventricular size often continues to increase.[37] Minoxidil-associated LVH has been further investigated in a cohort of hypertensive patients with LVH (echocardiographically determined) treated with the ß blocker bopindolol and guanfacine and either cilazapril, cilazapril and minoxidil, or minoxidil alone.[38] Minoxidil-associated LVH was significantly attenuated by the coadministration of the angiotensin-converting enzyme inhibitor cilazapril in these studies suggesting that an angiotensin-converting enzyme inhibitor should be viewed as important adjunctive therapy in patients treated with minoxidil.

The reflex tachycardia that occurs with minoxidil can precipitate myocardial ischemia.[4,19,20] If symptoms of myocardial ischemia occur in a patient treated with minoxidil and the severity of the patient's hypertension requires therapy to be continued, aggressive ß-blocker therapy becomes imperative. Elevated pulmonary artery pressures have been observed in patients receiving chronic minoxidil therapy, an effect less likely to occur in patients concurrently receiving ß-blocker therapy. When pulmonary hypertension is detected in patients treated with minoxidil it is not a direct medication effect; rather, it is more likely to be a sign of a pretherapy abnormality.[39]

Hypertrichosis is quite common with minoxidil and can be cosmetically disfiguring, particularly in women (Figure 1).[40] Hair growth begins within 3-6 weeks of starting therapy, occurring over the temples and eyebrows initially, spreading to areas between the eyebrows and hairline or sideburn regions, to finally involve the trunk, extremities, and scalp. Hair growth can be extensive, even having occurred in the ear canal with resultant hearing loss. [41] Although increased cutaneous blood flow to affected areas is one possible explanation for the increased hair growth with minoxidil; several lines of evidence, from clinical observations, animal studies and in vitro experiments, suggest that the promotion of hair growth by minoxidil is related in some way to its action as a potassium channel opener.[42]

Facial hair growth in a woman receiving minoxidil therapy. Reprinted with permission from White G, Cox N, eds. Diseases of the Skin. Philadelphia, PA: WB Saunders; 2000.

Hypertrichosis disappears within a few weeks of discontinuing minoxidil, although in some cases there is less hair than before the drug was started.[43] Generalized hair growth in areas that are not bald can also occur with any of the topical minoxidil solutions that are currently available in both 2% and 5% solutions. For this to occur it generally requires application of the topical solution in amounts exceeding current recommendations.[44]

In women, hypertrichosis can be treated in a number of ways. Shaving the affected areas has the fewest side effects but is usually psychologically objectionable to the patient. Women should be reassured that shaving will not cause the hair to grow faster or become darker. Other treatment options include bleaching, waxing, electrolysis, depilatories, and plucking. Finally, topical minoxidil (and oral minoxidil) should be used with care during pregnancy because topically applied minoxidil has been associated with fetal malformations.[45] Thus, although minoxidil is a potent vasodilator and will lower blood pressure, there are significant problems that limit its use to resistant hypertension or patients with definite renal disease.