Skip to main content

Minoxidil: A Review of its Pharmacological Properties and Therapeutic Use

Summary

Synopsis: Minoxidil1is an orally effective vasodilator which is more potent than hydralazine. The drug induces reflex stimulation of the sympathetic nervous system and of plasma renin activity and produces fluid retention. For these reasons, minoxidil must usually be administered in combination with an antiadrenergic agent and with a diuretic. Its acceptability for use in females is limited by the frequent appearance of hypertrichosis. Minoxidil is particularly useful in the treatment of patients with severe refractory hypertension. However, its suitability in the management of male patients with moderate hypertension remains to be determined.

Pharmacodynamic Studies: Minoxidil is a potent direct vasodilator, which reduces both systolic and diastolic blood pressure by lowering peripheral resistance. The drug acts predominantly on the arterioles and has little effect on the venous capacitance vessels. Hence, minoxidil blood pressure reduction is associated with an increase in heart rate, stroke volume and cardiac index, and is usually not accompanied by orthostatic hypotension. Minoxidil produces reflex stimulation of the sympathetic nervous system, with increases in plasma noradrenaline (norepinephrine) levels and in plasma renin activity (PRA). Plasma aldosterone levels increase during acute administration of minoxidil but return to pretreatment levels during chronic treatment. The concomitant use of a β-blocker, such as propranolol or atenolol, or of a centrally acting inhibitor of sympathetic activity such as Clonidine or α-methyldopa, potentiate the antihypertensive action of minoxidil by inhibiting the reflex increase in cardiac output and in renin release. Diuretics also potentiate the antihypertensive activity of minoxidil, by antagonising the sodium-retaining effect of this drug.

As with many other antihypertensive agents, the administration of minoxidil in patients with malignant hypertension may be accompanied by a transitory continuing deterioration of renal function to a point where haemodialysis may be required. However, subsequent improvement of renal function may be observed in many patients, sometimes to a degree where haemodialysis is no longer needed. In patients with so-called ‘benign’ hypertension not responding well to ‘traditional’ therapy, better control of blood pressure with minoxidil may prevent the deterioration of renal function which occurs in the majority of such patients.

Pharmacokinetics: Peak plasma concentrations of minoxidil usually occur within 1 hour after ingestion. More than 95% of the drug is absorbed from the gastrointestinal tract. Minoxidil has a relatively large volume of distribution of approximately 200L, the drug preferentially concentrating in certain extravascular sites, such as vascular smooth muscle. Minoxidil is metabolised in the liver predominantly by conjugation with glucuronic acid. The drug and its metabolites are minimally protein bound, and are readily excreted from the kidneys or dialysed across the membranes used for haemodialysis. The drug reportedly has an elimination half-life of approximately 3 to 4 hours; however, the duration of its antihypertensive effect may exceed 72 hours. This prolonged activity may be related to the reported high affinity of this drug for vascular smooth muscles.

Therapeutic Trials: Most therapeutic trials with minoxidil have been of open design and limited to patients in whom a conventional ‘triple therapy’ regimen (a diuretic, an antiadrenergic drug and a vasodilator) had failed because of ineffectiveness or intolerable side effects. These limitations to use, imposed by the American Food and Drug Administration, were originally justified by experimental evidence of atrial haemorrhagic and degenerative lesions in the dog. These lesions have subsequently been shown to be specific for this animal species. A number of trials have shown that minoxidil can be effective in the management of the most severe and resistant forms of hypertension in adults as well as in children. Some therapeutic trials have shown that minoxidil is a more potent vasodilator and antihypertensive agent than hydralazine. In many instances, this drug has been used successfully in combination as a medical alternative to bilateral nephrectomy. A few studies have also demonstrated the efficacy of this drug in the management of patients with moderate hypertension. However, further clinical experience is needed before the risk-benefits of minoxidil in less severe forms of hypertension in male patients can be clearly ascertained; in females the occurence of hypertrichosis may preclude use of the drug in less severe forms of the disease.

Side Effects: Minoxidil therapy is frequently associated with significant side effects, some of which are particularly pronounced in patients with impaired renal function. The drug may cause renal sodium and fluid retention and stimulate thirst. This can lead to peripheral oedema and, in the most severe cases, to congestive heart failure and pulmonary oedema. When this problem becomes recurrent or refractory to diuretics or to dialysis, discontinuation of the drug may be necessary. Minoxidil administration has also been associated with pericardial effusion, particularly in patients with severe impairment in renal function. However, the real incidence of this side effect remains to be determined. The use of minoxidil may cause electrocardiographic T-wave changes during the first 2 weeks of therapy. This abnormality is usually not associated with symptoms or with cardiac enzyme elevation and reverts spontaneously. Pulmonary hypertension has been described in patients treated with minoxidil, but a cause-effect relationship is uncertain. Orthostatic hypotension is not likely to occur with minoxidil.

Reversible hypertrichosis is a common side effect which appears to some degree in nearly all patients treated with minoxidil for longer than 1 month, and constitutes a serious limitation to the use of this drug in females.

Dosage and Administration: The usual initial dose is 5 to 10mg daily in 2 divided doses. (Once-daily dosing can also be used, particularly with total daily doses of 20mg or less.) This dose can be increased slowly (5 to 10mg/day increments every 2 to 3 days) up to 100mg per day. However, the majority of patients with severe hypertension usually respond to a dose not exceeding 50mg/day. Accelerated regimens of dosage increase can be used in patients with the most severe forms of hypertension, to achieve a more rapid control of blood pressure. In patients on haemodialysis or peritoneal dialysis, minoxidil should be administered after the dialysis, since the drug is easily dialysible. Patients receiving minoxidil who are not on dialysis must also receive sufficient diuretic therapy to maintain salt and water balance. Most patients will also require a sympathetic nervous system suppressant, preferably a β, to limit reflex tachycardia.

This is a preview of subscription content, access via your institution.

References

  1. Alpert, M.A.; Bauer, J.H.; Parker, B.M.; Brooks, C.S. and Freeman, J.A.: Pulmonary hemodynamics in systemic hypertension. Long-term effect of minoxidil. Chest 76: 379–383 (1979).

    PubMed  CAS  Google Scholar 

  2. Andersson, O. and Sivertsson, R.: Minoxidil in refractory hypertension. Acta Medica Scandinavica 205: 213–219 (1979).

    PubMed  CAS  Google Scholar 

  3. Andersson, O. and Sivertsson, R.: Renal function and vascular resistance during long-term minoxidil treatment of severe hypertension. Journal of Cardiovascular Pharmacology 2:(Suppl. 2): 123–130 (1980).

    Google Scholar 

  4. Atkins, J.M.; Mitchell, H.C. and Pettinger, W.A.: Increased pulmonary vascular resistance with systemic hypertension. Effect of minoxidil and other antihypertensive agents. American Journal of Cardiology 39: 802–807 (1977).

    PubMed  CAS  Google Scholar 

  5. Baer, L.; Radichevich, I. and Williams, G.S.: Treatment of drug-resistant hypertension with minoxidil or angiotensin-converting enzyme inhibitor: Blood pressure, renin, aldosterone, and electrolyte responses. Journal of Cardiovascular Pharmacology 2(Suppl. 2): 206–216 (1980).

    Google Scholar 

  6. Balazs, T. and Payne, B.J.: Myocardial papillary muscle necrosis induced by hypotensive agents in dogs. Toxicology and Applied Pharmacology 20: 442–445 (1971).

    PubMed  CAS  Google Scholar 

  7. Bauer, J.H. and Alpert, M.A.: Rapid reduction of severe hypertension with minoxidil. Journal of Cardiovascular Pharmacology 2:(Suppl. 2) 189–199 (1980).

    Google Scholar 

  8. Bailey, G.L.; Hanapers, C.C.; Hager, E.G. and Merrill, J.P.: Uremic pericarditis: Clinical features and management. Circulation 38: 582–591 (1968).

    PubMed  CAS  Google Scholar 

  9. Bennett, W.M.; Golper, T.A.; Muther, R.S. and McCarron, D.A.: Efficacy of minoxidil in the treatment of severe hypertension in systemic disorders. Journal of Cardiovascular Pharmacology 2(Suppl. 2): 142–148 (1980).

    Google Scholar 

  10. Brunner, H.R.; Jaeger, P.; Ferguson, R.K.; Jequier, E.; Turini, G. and Gavras, H.: Need for beta-blockade in hypertension reduced with long-term minoxidil. British Medical Journal 2: 385–388 (1978).

    PubMed  CAS  Google Scholar 

  11. Bryan, A.K.; Hoobler, S.W.; Rosenzweig, J.; Weller, J.M. and Purdy, J.M.: Effect of minoxidil on blood pressure and hemodynamics in severe hypertension. American Journal of Cardiology 39: 796–801 (1977).

    PubMed  CAS  Google Scholar 

  12. Burton, J.L. and Marshall, A.: Hypertrichosis due to minoxidil. British Journal of Dermatology 101: 593–595 (1979).

    PubMed  CAS  Google Scholar 

  13. Camel, G.H.; Carmody, S.E. and Perry, H.M.: Use of minoxidil in the azotemic patient. Journal of Cardiovascular Pharmacology 2(Suppl. 2): 173–180 (1980).

    Google Scholar 

  14. Campbell, W.B.; Pettinger, W.A.; Keeton, K. and Brooks, S.N.: Vasodilating antihypertensive drug-induced aldosterone. A study of endogenous angiotensin-mediated aldosterone release in the rat. Journal of Pharmacology and Experimental Therapeutics 193: 166–175 (1975).

    PubMed  CAS  Google Scholar 

  15. Campese, V.M.; Stein, D. and DeQuattro, V.: Treatment of severe hypertension with minoxidil: Advantages and limitations. Journal of Clinical Pharmacology 19: 231–241 (1979).

    PubMed  CAS  Google Scholar 

  16. Campese, V.M.; Romoff, M.; Telfer, N.; Weidmann, P. and Massry, S.G.: Role of sympathetic nerve inhibition and body sodium-volume state in the antihypertensive action of Clonidine in essential hypertension. Kidney International 18: 351–357 (1980).

    PubMed  CAS  Google Scholar 

  17. Campese, V.M.; Romoff, M.S.; Levitan, D.; Lane, K. and Massry, S.G.: Mechanisms of autonomic nervous system dysfunction in uremia. Kidney International. In Press (1981).

    Google Scholar 

  18. Carlson, R.G. and Feenstra, E.S.: Toxicology studies with the hypertensive agent minoxidil. Toxicology and Applied Pharmacology 39: 1–11 (1977).

    CAS  Google Scholar 

  19. Chidsey, C.A. and Gottlieb, T.B.: The pharmacologic basis of antihypertensive therapy: The role of vasodilator drugs. Progress in Cardiovascular Diseases 27: 99–113 (1974).

    Google Scholar 

  20. Connor, G.; Wilburn, R.L. and Bennett, C.M.: Double-blind comparison of minoxidil and hydralazine in severe hypertension. Clinical Science and Molecular Medicine 51: 593–595 (1976).

    Google Scholar 

  21. Devine, B.L.; Fife, R. and Trust, P.M.: Minoxidil in severe hypertension after failure of other hypotensive drugs. British Medical Journal 2: 667–669 (1977).

    PubMed  CAS  Google Scholar 

  22. Dormois, J.C.; Young, J.L. and Nies, A.S.: Minoxidil in severe hypertension: Value when conventional drugs have failed. American Heart Journal 90: 360–368 (1975).

    PubMed  CAS  Google Scholar 

  23. DuCharme, D.W.; Freyburger, W.A.; Graham, B.E. and Carlson, R.B.: Pharmacologic properties of minoxidil: A new hypotensive agent. Journal of Pharmacology and Experimental Therapeutics 184: 662–670 (1973).

    PubMed  CAS  Google Scholar 

  24. Dunea, G.; Mamdani, B. and Muhurkar, S.D.: Treatment of severe and moderate hypertension with minoxidil. Experience in twenty-eight patients. Clinical Science and Molecular Medicine 51 (Suppl.): 583–585 (1976).

    Google Scholar 

  25. Earhart, R.N.; Ball, J.; Nuss, D.D. and Aeling, J.L.: Minoxidil-in-duced hypertrichosis: Treatment with calcium thioglycolate depilatory. Southern Medical Journal 70: 442–445 (1977).

    PubMed  CAS  Google Scholar 

  26. Epstein, A.N.; Fitzsimons, J.T. and Rolls, B.J.: Drinking induced by injection of angiotensin into the brain of the rat. Journal of Physiology (London) 210: 457–474 (1970).

    CAS  Google Scholar 

  27. Fitzsimons, J.T.: The physiological basis of thirst. Kidney International 10: 3–11 (1976).

    PubMed  CAS  Google Scholar 

  28. Gilmore, E.; Weil, J. and Chidsey, C.: Treatment of essential hypertension with a new vasodilator in combination with beta-adrenergic blockade. New England Journal of Medicine 282: 521–527 (1970).

    PubMed  CAS  Google Scholar 

  29. Gottlieb, T.B.; Katz, F.H. and Chidsey, C.A.: Combined therapy with vasodilator drugs and beta-adrenergic blockade in hypertension. Circulation 45: 571–582 (1972a).

    PubMed  CAS  Google Scholar 

  30. Gottlieb, T.B.; Thomas, R.C and Chidsey, C.A.: Pharmacokinetic studies of minoxidil. Clinical Pharmacology and Therapeutics 13: 436–441 (1972b).

    PubMed  CAS  Google Scholar 

  31. Grim, C.E.; Luft, F.C.; Grim, C.M.; Klotman, P.E.; Van Huysse, J.W. and Weinberger, M.H.: Rapid blood pressure control with minoxidil: Acute and chronic effects on blood pressure, sodium excretion, and the renin-aldosterone system. Archives of Internal Medicine 139: 529–533 (1979).

    PubMed  CAS  Google Scholar 

  32. Hall, D.; Froer, K.L. and Loracher, C.: Treatment of severe hypertension with minoxidil and its effects on systemic and pulmonary haemodynamics. Clinical Science and Molecular Medicine 51 (Suppl.): 587–589 (1976).

    Google Scholar 

  33. Hall, P.M.; Magsini, F. and Tarazi, R.C.: Paradoxical renal blood flow response to minoxidil (Abstract). American Society of Nephrology 7: 35 (1974).

    Google Scholar 

  34. Hall, D.; Froer, K.L. and Rudolph, W.: Serial electrocardiographic changes during long-term treatment of severe hypertension with minoxidil. Journal of Cardiovascular Pharmacology 2(Suppl. 2): 200–205 (1980).

    Google Scholar 

  35. Hammond, J.J. and Kirkendall, W.M.: Minoxidil therapy for refractory hypertension and chronic renal failure. Southern Medical Journal 72: 1429–1432 (1979).

    PubMed  CAS  Google Scholar 

  36. Heel, R.C.; Brogden, R.N.; Speight, T.M. and Avery, G.S.: Captopril: A preliminary review of its pharmacological properties and therapeutic efficacy. Drugs 20: 409–452 (1980).

    PubMed  CAS  Google Scholar 

  37. Herman, E.H.; Balazs, T.; Young, R.; Earl, F.L.; Krop, S. and Ferrans, V.J.: Acute cardiomyopathy induced by the vasodilating antihypertensive agent minoxidil. Toxicology and Applied Pharmacology 47: 493–503 (1979).

    PubMed  CAS  Google Scholar 

  38. Hostetter, T.H.; Olson, J.L.; Rennke, H.G.; Venkatachalam, M.A. and Brenner, B.M.: Increased glomerular pressure and flow: A potentially adverse adaptation to reduced renal mass. Clinical Research 27: 498A (1979).

    Google Scholar 

  39. Hull, A.R.; Long, D.L.; Prati, R.C.; Pettinger, W.A. and Parker, T.F. III: The control of hypertension in patients undergoing regular maintenance hemodialysis. Kidney International 7(Suppl. 2): 184–187 (1975).

    Google Scholar 

  40. Humphrey, S.J.; Wilson, E.; and Zins, G.R.: Whole body tissue blood flow in conscious dogs treated with minoxidil (Abstract). Federation Proceedings 33: 583 (1974).

    Google Scholar 

  41. Jacomb, R.G. and Brunnberg, F.J.: The use of minoxidil in the treatment of severe essential hypertension: A report on 100 patients. Clinical Science and Molecular Medicine 51 (Suppl): 577–581 (1976).

    Google Scholar 

  42. Javier, R.; Dumler, F.; Park, J.H.; Bok, D.V.; Riley, R.W. and Levin, N.W.: Long-term treatment with minoxidil in patients with severe renal failure. Journal of Cardiovascular Pharmacology 2(Suppl. 2): 149–155 (1980).

    Google Scholar 

  43. Jeatzer, J.H. and Kirk, E.S.: Myocardial infarction with normal blood flow: Failure of vasodilation in border zone to enhance survival. Circulation 62(Suppl. 3): 314 (1980).

    Google Scholar 

  44. Keeton, T.K. and Pettinger, W.A.: The dominance of adrenergic mechanisms in mediating hypotensive drug-induced renin release in the conscious rat. Journal of Pharmacology and Experimental Therapeutics 208: 303–309 (1979).

    PubMed  CAS  Google Scholar 

  45. Kern, T.; DeQuattro, V.; Bornheimer, J.F.; DeQuattro, E. and Kolloch, R.E.: Long-term effects of minoxidil therapy on renal function on patients with refractory hypertension: The significance of albuminuria. Journal of Cardiovascular Pharmacology. 2(Suppl. 2): 156–162 (1980).

    Google Scholar 

  46. Keusch, G.W.; Weidmann, P.; Campese, V.; Lee, D.B.N.; Upham, A.T. and Massry, S.G.: Minoxidil therapy in refractory hypertension. Analysis of 155 patients. Nephron 21: 1–15 (1978).

    PubMed  CAS  Google Scholar 

  47. Klotman, P.E.; Grim, C.E.; Weinberger, M.Y. and Judson, W.E.: The effects of minoxidil on pulmonary and systemic hemodynamics in hypertensive man. Circulation 55: 394–400 (1977).

    PubMed  CAS  Google Scholar 

  48. Kolbenzer, P.J. and Baber, L.: Hypertrichosis lanuginosa associated with diazoxide therapy in prepubertal children: A clinicopathological study. Annals of the New York Academy of Sciences 150: 373–382 (1968).

    Google Scholar 

  49. Larochelle, P.; Hamet, P.; Beroniade, V. and Kuchel, O.: Minoxidil in severe hypertension. European Journal of Clinical Pharmacology 14: 1–5 (1978).

    PubMed  CAS  Google Scholar 

  50. Larochelle, P.; Beroniade, V.; Hamet, P. and Kuchel, O.: Treatment of refractory hypertension with minoxidil. Journal of Cardiovascular Pharmacology 2(Suppl. 2): 107–113 (1980).

    Google Scholar 

  51. Lazarus, J.M.; Hampers, C.L.; Bennett, A.H.; Vandam, L.D. and Merrill, J.P.: Urgent bilateral nephrectomy for severe hypertension. Annals of Internal Medicine 76: 733–739 (1972).

    PubMed  CAS  Google Scholar 

  52. Liebau, G.; Hayduk, K. and Bundschu, H.D.: Klinische erfahrungen mit minoxidil, einen neuen antihypertonikum. Verhandlungen Der Deutschen Gesells. Chaft Für Innere Medizin 80: 277–279 (1974).

    CAS  Google Scholar 

  53. Limas, C.J. and Freis, E.D.: Minoxidil in severe hypertension with renal failure: Effect of its addition to conventional antihypertensive drugs. American Journal of Cardiology 31: 355–361 (1973).

    PubMed  CAS  Google Scholar 

  54. Lowenthal, D.T. and Affrime, M.B.: Pharmacology and pharmacokinetics of minoxidil. Journal of Cardiovascular Pharmacology. 2(Suppl. 2): 93–106 (1980).

    Google Scholar 

  55. Lowenthal, D.T.; Onesti, G.; Mutterperl, R.; Affrime, M.; Martinez, E.W.; Kim, K.E.; Busby, P.; Shirk, J. and Swartz, C.: Long-term clinical effects, bioavailability and kinetics of minoxidil in relation to renal function. Journal of Clinical Pharmacology 18: 500–508 (1978).

    PubMed  CAS  Google Scholar 

  56. Mahony, J.F.; Gibson, G.R.; Sheil, A.G.R.; Storey, B.G.; Stokes, G.S. and Stewart, J.H.: Bilateral nephrectomy for malignant hypertension. Lancet 1: 1036–1038 (1972).

    PubMed  CAS  Google Scholar 

  57. Makker, S.P. and Moorthy, B.: Rebound hypertension following minoxidil withdrawal. Journal of Pediatrics 96: 762–766 (1980).

    PubMed  CAS  Google Scholar 

  58. Martin, W.B.; Spodick, D.H. and Zins, G.R.: Pericardial disorders occurring during open-label study of 1,869 severely hypertensive patients treated with minoxidil. Journal of Cardiovascular Pharmacology. 2(Suppl. 2): 217–227 (1980).

    Google Scholar 

  59. McChesney, J.A. and Amend, W.J.C.; Jr.: Minoxidil in the treatment of refractory hypertension due to a spectrum of causes. Journal of Cardiovascular Pharmacology 2(Suppl. 2): 131–141 (1980).

    Google Scholar 

  60. McMahon, F.G.: Management of Essential Hypertension, pp. 163–166 (Futura Publishing Co.; New York 1978).

    Google Scholar 

  61. Mehta, P.K.; Mamdani, B.; Shansky, R.M.; Mahurkar, S.D. and Dunea, G.: Treatment of minoxidil. Journal of the American Medical Association 233: 249–252 (1975).

    PubMed  CAS  Google Scholar 

  62. Mitchell, H.C. and Pettinger, W.A.: Long-term treatment of refractory hypertensive patients with minoxidil. Journal of the American Medical Association 239: 2131–2138 (1978).

    PubMed  CAS  Google Scholar 

  63. Mitchell, H.C.; Graham, R.M. and Pettinger, W.A.: Renal function during long-term treatment of hypertension with minoxidil. Comparison of benign and malignant hypertension. Annals of Internal Medicine 93: 676–681 (1980).

    PubMed  CAS  Google Scholar 

  64. Mitchell, H.C. and Pettinger, W.A.: Renal function in long-term minoxidil treated patients. Journal of Cardiovascular Pharmacology. 2(Suppl. 2): 163–197 (1980).

    Google Scholar 

  65. Montgomery, R.G. and DuCharme, D.W.: Hemodynamic effects of chronic and acute changes in blood pressure. Federation Proceedings 27: 758 (1968).

    Google Scholar 

  66. Muller, S.A.: Hirsutism. American Journal of Medicine 46: 803–817 (1969).

    PubMed  CAS  Google Scholar 

  67. Mutterperl, R.E.; Diamond, F.B. and Lowenthal, D.T.: Long-term effects of minoxidil in the treatment of malignant hypertension in chronic renal failure. Journal of Clinical Pharmacology 16: 498–509 (1976).

    PubMed  CAS  Google Scholar 

  68. Nawar, T.; Nolin, L.; Plante, G.E.; Caron, C. and Montambault, P.: Long-term treatment of severe hypertension with minoxidil. Canadian Medical Association Journal 19: 1178–1182 (1977).

    Google Scholar 

  69. Nicholson, G.D.; Alleyne, G.A.O.; Valdes, G. and Westerman, R.L.: Minoxidil in the management of moderate hypertension. Journal of Cardiovascular Pharmacology 2(Suppl. 2): 242–246 (1980).

    Google Scholar 

  70. Nickerson, M.: Antihypertensive agents and the drug therapy of hypertension; in Goodman and Gilman (Eds) The Pharmacological Basis of Therapeutics, 4th ed.; p.728 (Macmillan, New York 1971).

    Google Scholar 

  71. Oka, M. and Makela, M.: Minoxidil in severe hypertension. Acta Medica Scandinavica 203: 43–47 (1978).

    PubMed  CAS  Google Scholar 

  72. O’Malley, K. and McNay, J.L.: A method for achieving blood pressure control expeditiously with oral minoxidil. Clinical Pharmacology and Therapeutics 18: 39–44 (1975).

    PubMed  Google Scholar 

  73. O’Malley, K.; Velasco, M.; Wells, J. and McNay, J.L.: Control plasma renin activity and changes in sympathetic tone as determinants of minoxidil-induced increase in plasma renin activity. Journal of Clinical Investigation 55: 230–235 (1975).

    PubMed  Google Scholar 

  74. Onesti, G.; Swartz, C.; Ramirez, O. and Brest, A.N.: Biilateral nephrectomy for control of hypertension in uremia. Transaction of the American Society for Artificial Internal Organs 144: 361 (1968).

    Google Scholar 

  75. Pedersen, O.L.: Long-term experiences with minoxidil in combination treatment of severe arterial hypertension. Acta Cardiologica 32: 283–293 (1977).

    Google Scholar 

  76. Pennisis, A.J.; Takahashi, M.; Bernstein, B.H.; Singsen, B.H.; Uittenbogaart, C.; Ettenger, R.B.; Malekzadeh, M.H.; Hanson, V. and Fine, R.N.: Minoxidil therapy in children with severe hypertension. Paediatric Pharmacology and Therapeuticss 90: 813 (1977).

    Google Scholar 

  77. Pettinger, W.A. and Mitchell, H.C.: Minoxidil — An alternative to nephrectomy for refractory hypertension. New England Journal of Medicine 289: 167–173 (1973).

    PubMed  CAS  Google Scholar 

  78. Pettinger, W.A. and Keeton, K.: Altered renin release and propranolol potentiation of vasodilatory drug hypotension. Journal of Clinical Investigation 55: 236–243 (1975).

    PubMed  CAS  Google Scholar 

  79. Pettinger, W.A.; Mitchell, H.C. and Gullner, H.G.: Clonidine and the vasodilating beta blocker antihypertensive drug interaction. Clinical Pharmacology and Therapeutics 22: 164–171 (1977).

    PubMed  CAS  Google Scholar 

  80. Pettinger, W.A.: Minoxidil and the treatment of severe hypertension. New England Journal of Medicine 303: 922–926 (1980).

    PubMed  CAS  Google Scholar 

  81. Pluss, R.G.; Orcutt, J. and Chidsey, C.A.: Tissue distribution and hypotensive effects of minoxidil in normotensive rats. Journal of Laboratory and Clinical Medicine 79: 639–647 (1972).

    PubMed  CAS  Google Scholar 

  82. Pratt, J.H.; Grim, C.E. and Parkinson, C.A.: Minoxidil increases aldosterone metabolic clearance in hypertensive patients. Journal of Clinical Endocrinology and Metabolism 49: 834–837 (1979).

    PubMed  CAS  Google Scholar 

  83. Radvany, P.; Davis, M.A.; Muller, J.E. and Maroko, P.R.: Effects of minoxidil on coronary collateral flow and acute myocardial injury following experimental coronary artery occlusion. Cardiovascular Research 12: 120–126 (1978).

    PubMed  CAS  Google Scholar 

  84. Robie, N.W. and McNay, J.L.: Comparative splanchnic blood flow effects of various vasodilator compounds. Circulatory Shock 4: 69–78 (1977).

    PubMed  CAS  Google Scholar 

  85. Rogers, P.W. and Kurtzman, N.A.: Renal failure, uncontrollable thirst, and hyperreninemia. Cessation of thirst with bilateral nephrectomy. Journal of the American Medical Association 225: 1236–1238 (1973).

    PubMed  CAS  Google Scholar 

  86. Rosello, S.; O’Malley, K.; Boles, M.; Robie, N. and McNay, J.L.: Impairment of renal autoregulation in hypertension with nephrosclerosis. Clinical Research 22: 301A (1974).

    Google Scholar 

  87. Ryan, J.R.; Jain, A.K. and McMahon, F.G.: Minoxidil treatment of severe hypertension. Current Therapeutic Research 17: 55–66 (1975).

    PubMed  CAS  Google Scholar 

  88. Sannerstedt, R.; Brorson, L.; Berglund, G. and Werko, L.: Minoxidil. Haemodynamic and clinical experiences with a new peripheral vasodilator. Acta Medica Scandinavica 197: 409–414 (1975).

    PubMed  CAS  Google Scholar 

  89. Severs, W.B.; Summy-Long, J.; Taylor, J.S. and Connor, J.D.: A central effect of angiotensin: Release of pituitary pressor material. Journal of Pharmacology and Experimental Therapeutics 174: 27–34 (1970).

    PubMed  CAS  Google Scholar 

  90. Sinaiko, A.R. and Mirkin, B.L.: Management of severe childhood hypertension with minoxidil: A controlled clinical study. Journal of Pediatrics 91: 138–142 (1977).

    PubMed  CAS  Google Scholar 

  91. Sinaiko, A.R.; O’Dea, R.F. and Mirkin, B.L.: Clinical response of hypertensive children to long-term minoxidil therapy. Journal of Cardiovascular Pharmacology 2(Suppl. 2): 181–188 (1980).

    Google Scholar 

  92. Sobota, J.T.; Martin, W.B.; Carlson, R.G. and Feenstra, E.S.: Minoxidil: Right atrial cardiac pathology in animals and man. Circulation 62: 376–387 (1980).

    PubMed  CAS  Google Scholar 

  93. Tarazi, R.C.; Dustan, H.P.; Bravo, E.L. and Niarchos, A.P.: Vasodilating drugs: Contrasting haemodynamic effects. Clinical Sciences and Molecular Medicine 51 (Suppl.): 575–578 (1976).

    Google Scholar 

  94. Taylor, S.H.; Donald, K.W. and Bishop, J.M.: Circulatory studies in hypertensive patients at rest and during exercise. Clinical Science 16: 351–376 (1957).

    PubMed  CAS  Google Scholar 

  95. Thomas, R.C. and Harpootlian, H.: Metabolism of minoxidil, a new hypotensive agent. II. Biotransformation following oral administration to rats, dogs, and monkeys. Journal of Pharmacological Sciences 64: 1366–1371 (1975).

    CAS  Google Scholar 

  96. Traub, Y.M.; Redmond, D.P.; Rosenfeld, J.B.; McDonald, R.H. and Shapiro, A.P.: Treatment of severe hypertension with minoxidil. Israel Journal of Medical Science 11: 991–998 (1975).

    CAS  Google Scholar 

  97. Traub, Y.M.; Aygen, M.M. and Rosenfeld, J.B.: Hazards in treatment of systolic hypertension. American Heart Journal 97: 174–177 (1979).

    PubMed  CAS  Google Scholar 

  98. Velasco, M.; O’Malley, K.; Robie, N.W.; Wells, J.; Israeli, Z.H. and McNay, J.L.: Differential effects of propranolol on heart rate and plasma renin activity in patients treated with minoxidil. Clinical Pharmacology and Therapeutics 16: 1031–1038 (1974).

    PubMed  CAS  Google Scholar 

  99. Weidmann, P.; Maxwell, M.H.; Lupu, A.N.; Lewin, A.J. and Massry, S.G.: Plasma renin activity and blood pressure in terminal renal failure. New England Journal of Medicine 285: 757–762 (1971).

    PubMed  CAS  Google Scholar 

  100. Weir, E.K.; Chidsey, C.A.; Weil, J.V. and Grover, R.F.: Minoxidil reduces pulmonary vascular resistance in dogs and cattle. Journal of Laboratory and Clinical Medicine 88: 885–894 (1976).

    PubMed  CAS  Google Scholar 

  101. Wells, J.O.: Unusual cases of resistance to minoxidil therapy. Journal of Cardiovascular Pharmacology. 2(Suppl. 2): 228–235 (1980).

    Google Scholar 

  102. Wilburn, R.L.; Blaufuss, A. and Bennett, C.M.: Long-term treatment of severe hypertension with minoxidil, propranolol and furosemide. Circulation 52: 706–713 (1975).

    PubMed  CAS  Google Scholar 

  103. Zacest, R.; Frewin, D.B.; Robinson, M.A.; Wilson, L.L.; Lawrence, J.R.; Clarkson, A.R. and Jackson, B.: Clinical and haemodynamic effects of minoxidil in refractory hypertension. Drugs 11(Suppl. 1): 177–184 (1976).

    PubMed  Google Scholar 

  104. Zins, G.R.: Alterations in renal function during vasodilator therapy; in Fanelli and We (Eds) Recent Advances in Renal Physiology and Pharmacology, pp. 165–186 (University Park Press, Baltimore 1974).

    Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Vito M. Campese.

Additional information

Various sections of the manuscript reviewed by: R.W. Gifford, Jr., Cleveland Clinic, Department of Hypertension and Nephrology, Cleveland, Ohio, USA; R.C. Heel, Australasian Drug Information Services, Auckland, New Zealand; F.H. Sheehan, Mercer Island, Washington, USA; H.R. Brunner, Centre Hospitalier, Universitaire Vaudois, Départment de Médecine Interne, Lausanne, Switzerland; H.C. Mitchell, Department of Pharmacology and Internal Medicine, University of Texas Health Science Center, Dallas, Texas, USA; B.N.C. Prichard, Department of Medicine, University College Hospital Medical School, University of London, London, England; H J. Waal-Manning, Wellcome Medical Research Institute, University of Otago, Dunedin, New Zealand

‘Loniten’ (Upjohn).

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Campese, V.M. Minoxidil: A Review of its Pharmacological Properties and Therapeutic Use. Drugs 22, 257–278 (1981). https://doi.org/10.2165/00003495-198122040-00001

Download citation

Keywords

  • Propranolol
  • Pulmonary Artery Pressure
  • Plasma Renin Activity
  • Pericardial Effusion
  • Hydralazine