Administration Of Minoxidil Research Articles

Minoxidil in the treatment of refractory hypertension.

Minoxidil, a powerful vasodilator, is a very effective antihypertensive drug. Twenty-two patients, who were mostly refractory to conventional anti-hypertensive medication, were treated with this drug. There was a swift and definite drop of blood pressure in all cases. In 7 patients with renal disease, renal function did not deteriorate during the administration of minoxidil, and it improved dramatically in the eighth patient. Side effects of the drug were hirsutism, fluid retention, and in 1 patient a pruritic bullous erruption which disappeared when the drug was discontinued.

Metabolic assessment of exercise in chronic heart failure patients treated with short-term vasodilators.

Metabolic assessment of exercise in chronic heart failure patients treated with short-term vasodilators.

Minoxidil in the treatment of refractory hypertension.

Minoxidil, a powerful vasodilator, is a very effective antihypertensive drug. It was used to treat 22 patients, most of whom were refractory to conventional antihypertensive medication. There was a swift and definite drop of blood pressure in all cases. In 7 patients with renal disease, renal function did not deteriorate during the administration of Minoxidil, and it improved dramatically in the eighth patient. Side effects of the drug were hirsutism, fluid retention, and in 1 patients a pruritic bullous eruption which disappeared when the drug was discontinued.

Rapid reduction of severe hypertension with minoxidil.

Five patients presenting with severe hypertension who failed to exhibit diastolic blood pressures less than 120 mm Hg following the oral administration of propranolol (60--80 mg) and furosemide (40 mg) received minoxidil (20 mg, p.o.). Systemic blood pressure, heart rate, and cardiac output were measured prior to and hourly following the addition of minoxidil to the regimen of propranolol and furosemide. One hour following the addition of minoxidil, systemic blood pressure decreased from 204/126 to 186/114 mm Hg (mean systolic/mean diastolic blood pressure). Four hours after minoxidil administration, systemic blood pressure was 175/105 mm Hg. Four of the 5 subjects exhibited diastolic blood pressures greater than 100 mm Hg at 4 hr and were given a booster dose of minoxidil (5--20 mg). Systemic blood pressure subsequently decreased to 153/92 mm Hg at 8 hr and to 142/86 mm Hg at 12 hr following the initial dose of minoxidil. The reduction of systemic blood pressure was achieved without significant change in heart rate or cardiac output. These data indicate that stepped-care therapy utilizing a diuretic, a beta-blocking agent, and minoxidil produces prompt, significant, and sustained reduction of systemic blood pressure in patients with severe, potentially life-threatening hypertension.

Pharmacology and pharmacokinetics of minoxidil.

Minoxidil is a potent oral vasodilator acting on the arteriolar side of the circulation. Reflex tachycardia and sodium retention are consequences of increased sympathetic activity. Its biotransformation is 90% hepatic, with no evidence of accumulation of minoxidil when it is given chronically in patients with either normal renal function. The half-life is approximately 3 hr, regardless of whether the dose is given singly or on a multiple-dose basis. It is widely distributed throughout the body, and hence its volume of distribution is greater than 200 liters. There appears to be a dissociation between the peak plasma concentration and the antihypertensive response owing to the fact that minoxidil rapidly leaves the plasma on its way to the principal site of action, that is, the vascular smooth-muscle receptor site. No tolerance or refractoriness appears to develop with long-term minoxidil administration.

Pulmonary Hemodynamics in Systemic Hypertension: Long-Term Effect of Minoxidil

To assess the effect of minoxidil on pulmonary hemodynamics, we performed cardiac catheterization on ten patients, prior to the administration of minoxidil, at six months after its addition to their existing drug regimens, and on seven patients following 12 or more months of minoxidil therapy. Systemic blood pressure and systemic vascular resistance were significantly reduced at six months and following 12 or more months of minoxidil therapy. Before receiving minoxidil, nine of ten patients had elevated pulmonary vascular resistance. There were no significant changes in pulmonary vascular resistance following the initiation of minoxidil. The data suggest that pulmonary hypertension is common in patients with long-standing poorly controlled systemic hypertension, and that minoxidil, in doses sufficient to significantly reduce systemic blood pressure, does not cause or aggravate pulmonary hypertension.

Rapid blood pressure control with minoxidil: acute and chronic effects on blood pressure, sodium excretion, and the renin-aldosterone system

Changes in blood pressure, heart rate, electrolyte excretion, and the renin-angiotensin-aldosterone system were monitored before and after minoxidil was added to a regimen of a diuretic and propranolol hydrochloride in 12 severely hypertensive patients. None required more than 40 mg of minoxidil daily for control. On a constant intake, urinary sodium excretion decreased, while urinary potassium excretion remained stable. Heart rate, body weight, and plasma volume increased, while creatinine clearance did not change. Although plasma renin activity increased fourfold, the plasma aldosterone concentration did not increase. Six subjects were restudied after two months of minoxidil treatment. Although blood pressure control continued to be excellent in these subjects, plasma renin values and plasma volume had returned to pretreatment levels. These studies suggest that minoxidil rapidly and effectively lowers blood pressure. Although sodium retention accompanies minoxidil administration acutely, the effect is independent of aldosterone and may be transient.

Rapid Blood Pressure Control With Minoxidil

Changes in blood pressure, heart rate, electrolyte excretion, and the renin-angiotensin-aldosterone system were monitored before and after minoxidil was added to a regimen of a diuretic and propranolol hydrochloride in 12 severely hypertensive patients. None required more than 40 mg of minoxidil daily for control. On a constant intake, urinary sodium excretion decreased, while urinary potassium excretion remained stable. Heart rate, body weight, and plasma volume increased, while creatinine clearance did not change. Although plasma renin activity increased fourfold, the plasma aldosterone concentration did not increase. Six subjects were restudied after two months of minoxidil treatment. Although blood pressure control continued to be excellent in these subjects, plasma renin values and plasma volume had returned to pretreatment levels. These studies suggest that minoxidil rapidly and effectively lowers blood pressure. Although sodium retention accompanies minoxidil administration acutely, the effect is independent of aldosterone and may be transient. (<i>Arch Intern Med</i>139:529-533, 1979)

Oral Minoxidil in the Treatment of Hypertensive Crisis

WITH the advent of aggressive antihypertensive therapy, the mortality of patients with malignant hypertension has been drastically reduced. Because of new forms of drug therapy, bilateral nephrectomy, once recommended for severe and controlled hypertension, is no longer indicated.1In fact, studies often indicate improvement in renal function once control of blood pressure (BP) is obtained.2 Parenteral drugs such as diazoxide and sodium nitroprusside have replaced slower, less predictably acting antihypertensives for the rapid lowering of BP. However, if the patient fails to respond to these drugs, he still faces nephrectomy as a therapeutic choice. We report the case of a patient who failed to respond to high doses of sodium nitroprusside but had a rapid lowering of BP following oral administration of minoxidil, an experimental vasodilator used principally for the control of chronic refractory hypertension.3 Report of a Case A 15-year-old girl was referred to a neurosurgeon

The Effects of Sympatholytics, Angiotensin and Vasopressin on the Cardiovascular Response to Minoxidil or Hydralazine in Conscious Dogs

Oral administration of minoxidil, 1 mg/kg, or hydralazine, 12 mg/kg, decreased arterial blood pressure and peripheral vascular resistance, while cardiac output and rate increased in conscious dogs. These responses were not significantly altered by treatment with propranolol or phenoxybenzamine. Angiotensin infusions sufficient to increase arterial blood pressure to levels observed before treatment with the vasodilators did not obtund the heightened cardiac activity. In contrast, vasopressin infusions sufficient to normalize blood pressure markedly attenuated the increased cardiac output and rate associated with minoxidil or bydralazine. The results suggest that the increased cardiac output and tachycardia associated with administration of minoxidil or hydralazine are not dependent upon sympathetic nervous reflexes or cardiac afterload. The compensatory bradycardia normally associated with blood pressure increases appeared to be inhibited in the presence of minoxidil or hydralazine. In these experiments, v...

Severe hypertension in chronic renal failure treated with minoxidil.

Twenty patients suffering from severe hypertension associated with renal failure have been treated with Minoxidil. Ten patients, not on RDT, had a residual Creatinine clearance between 7-71 ml/min; 10 were on hemo-dialytic treatment. Before starting on Minoxidil, all patients had been unsuccessfully treated with an association of traditional anti-hypertensive drugs (blood pressure 200.24/125.6 mmHg). Minoxidil administration dramatically lowered the blood pressure in all cases. After 1 week of treatment the mean decrease in DBP was 22.7%; after 1 month 28.1%, and after 3 months 32.9%. At 6, 12, and 18 months the results were substantially unaltered. Minoxidil dosage ranged from 5 to 50 mg/day over the initial phase; by the third month the daily dose was between 5 and 25 mg/day. Previous anti-hypertensive drugs were suspended in all cases and not subsequently resumed. Furosemide and Propranolol were the only exceptions to counteract the Minoxidil induced fluid retention and tachycardia. The main side effec...

Long‐Term Clinical Effects, Bioavailability, and Kinetics of Minoxidil in Relation to Renal Function

Minoxidil was used to treat 26 patients (17 to 67 years old) with severe hypertension and varying degrees of renal function. Our object was to assess long-term clinical efficacy, kinetics (acute and chronic), and bioavailability of minoxidil in chronic renal insufficiency. Minoxidil, 27 to 30 mg per day, decreased systolic and diastolic blood pressure during the first three months of therapy. Between the third and 24th months (30 months in one patient) there was no further change. Propranolol or clonidine was needed to control heart rate, and furosemide or dialysis was needed to control edema induced by minoxidil. Renal function improved in some of the mildy azotemic patients. Minoxidil kinetics after the customary dose did not differ whether the drug was taken as tablet or solution. Kinetic parameters during chronic administration of minoxidil did not differ from those after acute administration. The kinetics in chronic renal insufficiency do not differ from these in subjects with normal renal function.

Management of severe childhood hypertension with minoxidil: A controlled clinical study

The therapeutic efficacy of four antihypertensive regimens (minoxidil, propranolol, and hydrochlorothiazide; propranolol and hydrochlorothiazide; methyldopa and hydroch-orothiazide; and hydrochlorothiazide alone) was evaluated in one child with systolic hypertension and in eight children with systolic and diastolic hypertension. The mean blood pressure of 148/98+/-8/4 mm Hg observed during the hydrochlorothiazide control period fell to 142/88+/-8/4 mm Hg following methyldopa and hydrochlorothiazide, 141/85+/-6/2 mm Hg following propranolol and hydrochlorothiazide, and 128/74+/-4/2 mm Hg following minoxidil, propranolol, and hydrochlorothiazide. The only side effect directly associated with administration of minoxidil was hypertrichosis. The effectiveness of minoxidil in the present study suggests that this drug offers an important adjunct to current antihypertensive therapy in children.

Treatment of severe hypertension with minoxidil and its effects on systemic and pulmonary haemodynamics.

1. The chronic administration of minoxidil, 0-024-0-212 mmol (5-40 mg) daily, to fifty-two severely hypertensive patients resulted in an average reduction of mean arterial pressure from 170 to 111 mmHg. 2. Haemodynamic studies in twelve of these patients indicated that the rise in pulmonary arterial pressure in patients without heart failure appears to be a direct result of a disproportionately large increase in cardiac output with respect to a relatively small decrease in pulmonary vascular resistance. Anti-hypertensive treatment of patients with congestive heart failure resulted in a decrease in mean pulmonary arterial pressure.

Clinical Use of Renin Determinations

To the Editor.— The recent COMMENTARY by Vertes, Clinical Use of Renin Determinations (230:1279, 1974), was quite informative. However, one statement on page 1280 implied that minoxidil is a drug that produces renin inhibition. There is now ample evidence to demonstrate that minoxidil will produce definite increases in plasma renin activity. 1,2 Velasco found that minoxidil administration increased plasma renin activity from about 1.21±0.28 to 8.58±2.83 ng/ ml/hr. When propranolol was given concomitantly with minoxidil, plasma renin activity still increased in comparison with control values, but the activity on combined treatment, 3.63±1.05 ng/ml/hr, was much lower than that seen with minoxidil alone. Thus, it appears that minoxidil produces an increase in plasma renin activity similar to that seen with other vasodilator antihypertensive agents including hydralazine (Apresoline), 3,4 diazoxide (Hyperstat), 5,6 sodium nitroprusside (Nipride), 7 and thiazide diuretics. 8 Spironolactone (Aldactone) also appears to produce an increase in plasma renin activity.

Minoxidil in severe hypertension with renal failure: Effect of its addition to conventional antihypertensive drugs

Minoxidil, a new vasodilator antihypertensive compound, was given to 9 uremic patients with severe hypertension uncontrollable with currently available drugs. Addition of minoxidil in doses of 5 to 10 mg twice daily to their prior therapy, resulted in satisfactory control of blood pressure in all patients. Supine blood pressure fell from a control value of 200 ± 6/124 ± 3 to 164 ± 5/91 ± 2 mm Hg (mean and standard error) after administration of minoxidil, and no patient experienced orthostatic hypotension. Tachyphylaxis has not been seen during a follow-up period averaging 26 weeks. Side effects resulting from minoxidil have been limited to mild hypertrichosis in 2 patients, nausea in another 2 and fluid retention, which was readily controlled by either hemodialysis or furosemide. Minoxidil appears, therefore, to provide a means for controlling blood pressure in patients with severe hypertension resistant to all other antihypertensive drugs.