Abstract
The current drugs and strategy for treating hypertension are the result of truly remarkable advances during the past 20 years. The pathways to discovery of new antihypertensive drugs have been varied. The vasodilators were developed largely as a result of systematic searches for compounds that lower blood pressure in experimental animals. By contrast, there was no evidence from investigations in animals that the beta-adrenergic blockers, methyldopa, Clonidine, or the oral diuretics could lower blood pressure. Importantly, each of these drugs had been developed for the purpose of affecting a biological system of sufficient importance to merit their investigation in man. Only after they were introduced into clinical investigation was their antihypertensive action discovered.
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References
Section II. The Guanidinium Adrenergic Neuron Blocking Drugs
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Section III. Methyldopa
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Henning, M.: Studies on the mode of action of α-methyldopa. Acta physiol. scand. Suppl. 322
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Hoyumpa, A.M., Connell, A.M.: Methyldopa hepatitis: report of 3 cases. Amer. J. dig. Dis. 18, 213–224 (1973).
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Mason, D.T., Braunwald, E.: Effect of guanethidine, reserpine and methyldopa on reflex venous and arterial constriction in man. J. clin. Invest. 43, 1449–1463 (1964).
Mohammed, S., Fasola, A.F., Privitera, P.J., Lipicky, R.J., Martz, B.L., Gaffney, T. E.: Effects of methyldopa on plasma renin activity in man. Circulat. Res. 25, 543–548 (1969).
Mohammed, S., Hanenson, I.B., Magenheim, H.G., Gaffney, T.E.: Effects of alpha-methyldopa on renal function in hypertensive patients. Amer. Heart. J. 76, 21–27 (1968).
Mroczek, W.J., Leibel, B.A., Finnerty, F. A.: Comparison of Clonidine and methyldopa in hypertensive patients receiving a diuretic - a double-blind crossover study. Amer. J. Cardiol. 29, 712–717 (1972).
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Porter, C.C., Titus, B.C.: Distribution and metabolism of methyldopa in the rat. J. Pharmacol, exp. Ther. 139, 77–87 (1963).
Prescott, L.F., Buhs, R.P., Beattie, J.O., Speth, O.C., Trenner, N.R., Lasagna, L.: Combined clinical and metabolic study of the effects of alpha-methyldopa on hypertensive patients. Circulation 34, 308–321 (1966).
Prichard, B.N.C., Gillam, P.M.S.: Treatment of hypertension with propranolol. Brit. med. J. 1969 I, 7–16.
Rand, M. J., Rush, M., Wilson, J.: Some observations on the inhibition of salivation by St 155 (2-(2, 6-dichlorophenylamine)-2-imidazoline hydrochloride, Catapres, Catapresan. Europ. J. Pharmacol. 5, 168–172 (1969).
Rehman, O.U., Keith, T.A., Gall, E.A.: Methyldopa induced submassive hepatic necrosis. J. Amer. med. Ass. 224, 1390–1392 (1973).
Saavedra, J.A., Reid, J.L., Jordan, W., Rawlins, M.D., Dollery, C.T.: Plasma concentration of α-methyldopa and sulphate conjugate after oral and intravenous administration. Europ. J. clin. Pharmacol, (in press) 1974.
Sannerstedt, R., Bojs, G., Varnauskas, E., Werkö, L.: Alpha-methyldopa in arterial hypertension. Acta med. scand. 174, 53–67 (1963).
Sannerstedt, R., Varnauskas, E., Werko, L.: Hemodynamic effects of methyldopa (Aldomet) at rest and during exercise in patients with arterial hypertension. Acta med. scand. 171, 75–82 (1962).
Schweitzer, I. L., Peters, R.L.: Acute submassive hepatic necrosis due to methyldopa. Gastroenterology 66, 1203–1211 (1974).
Sherman, J.D., Lover, D.E., Harrington, J.F.: Anemia, positive lupus and rheumatoid factors with methyldopa. Arch, intern. Med. 120, 321–326 (1967).
Sjoerdsma, A., Vendsalu, A., Engelman, K.: Studies on the metabolism and mechanism of action of methyldopa. Circulation 28, 492–502 (1963).
Stone, C.A., Porter, C.C.: Methyldopa and adrenergic nerve function. Pharmacol. Rev. 18, 569–575 (1966).
Toghill, P.J., Smith, P. G., Benton, P., Brown, R.C., Matthews, H. L.: Methyldopa liver damage. Brit. med. J. 1974 III, 545–548.
Trinker, F. R.: The significance of the relative potencies of noradrenaline and α-methyl-noradrenaline for the mode of action of α-methyldopa. J. Pharm. (Lond.) 23, 306–308 (1971).
Wilson, W.R., Fisher, F.D., Kjrkendall, W.M.: The acute hemodynamic effects of α-methyldopa in man. J. chron. Dis. 15, 907–913 (1961).
Worlledge, S. M., Carstairs, K. C., Dacie, J. V.: Autoimmune haemolytic anaemia associated with α-methyldopa therapy. Lancet 1966 II, 135–139.
Section IV. Clonidine
Ajmery, A., Verstraete, M., Bossaert, H., Verstreken, G.: Hypotensive action and side effects of clonidine-chlorthalidone and methyldopa-chlorthalidone in treatment of hypertension. Brit. med. J. 1970 II, 392–395.
Barnett, A.J., Cantor, S.: Observations on the hypotensive action of Catapres (St-155) in man. Med. J. Aust. 1, 87–91 (1968).
Bock, K.D., Heimsoth, V.V., Merguet, P, et al: Klinische und klinische-experimentelle Untersuchungen mit einer neuen blutdrucksenkenden Substanz: Dichlorophenylaminoimidazolin. Dtsch. med. Wschr. 91, 1761–1770 (1966).
Bolme, P., Fuxe, K.: Pharmacological studies on the hypotensive effects of Clonidine. Europ. J. Pharmacol. 13, 168–174 (1971).
Conolly, M.E., Briant, R.H., George, C.F., Dollery, C. T.: A cross over comparison of Clonidine and methyldopa in hypertension. Europ. J. clin. Pharmacol. 4, 222–227 (1972).
Constantine, J. W., McShane, W. K.: Analysis of the cardiovascular effects of 2-(2, 6-Dichlorophenylamino)-2-imidazoline hydrochloride (Catapres). Europ. J. Pharmacol. 4, 109–123 (1968).
Davies, D.S., Wing, L.M.H., Reid, J.L., Neill, E., Tippett, P, Dollery, C.T.: Pharmacokinetics and concentration-effect relationships of intravenous and oral Clonidine. Clin. Pharmacol. Ther. 21 (1977).
Dollery, C.T., Reid, J. L.: Central noradrenergic neurons and the cardiovascular actions of Clonidine in the rabbit. Brit. J. Pharmacol. 47, 206–216 (1973).
Dollery, C.T., Davies, D.S., Draffan, G.H., Dargie, H.J., Dean, C.R., Reid, J.L., Clare, R. A., Murray, S.: Clinical pharmacology and pharmacokinetics of Clonidine. Clin. Pharmacol. Ther. 19, 11–17 (1976).
Draffan, G.H., Clare, R.A., Murray, S., Bellward, G.D., Davies, D.S., Dollery, C.T.: The determination of Clonidine in human plasma. Proceedings of the Third International Symposium on Mass Spectrometry in Biochemistry and Medicine, Sardinia, Italy, June 1975.
Ehringer, H.: Die Wirkung von 2-(2, 6-Dichlorophenylamino)-2-imidazolin-hydrochlorid auf die Extremitatendurchblutung, den Blutdruck und die Venenkapazität bei Normotonikern. Arzneimittel-Forsch. 16, 1165–1169 (1966).
Gratjbner, W., Wolf, M.: Kritische Betrachtungen zum Wirkungsmechanismus des 2-(2, 6-dichlorophenyl-amino)-2-imidazolin-hydrochlorid. Arzneimittel-Forsch. 16, 1055–1058 (1966).
Hannington, E.: Clonidine hydrochloride (Dixarit) for migraine. Prescriber’s J. 12, 21–22 (1972).
Heilmann, K.: Untersuchungen über die Wirkung von Catapresan auf den intraokularen Drucker. 1. Mitteilung. Klin. Mbl. Augenheilk. 157, 182–192 (1970).
Hökfelt, B., Hedeland, H., Dymling, J. F.: Studies on catecholamines, renin and aldosterone following Catapresan (2-(2, 6-dichloro-phenyl-amine)-2-imidazoline hydrochlori de) in hypertensive patients. Europ. J. Pharmacol. 10, 389–397 (1970).
Hoobler, S.W., Sagastume, E.: Long term clinical experience with Catapres: Comparison with guanethidine. In: Conolly, M.E. (Ed.): Catapres in hypertension-an international symposium, pp. 207–226. London: Butterworths 1970.
Hunyor, S.N., Hansson, L., Harrison, T.S., Hoobler, S.W.: Effects of Clonidine withdrawal: possible mechanisms and suggestions for management. Brit. med. J. 1973 II, 209–211.
Kobinger, W.: Über den Wirkungsmeehanismus einer neuen antihypertensiven Substanz mit Imidazolinstruktur. Naunyn-Schmiedebergs Arch. Pharmak. exp. Path. 258, 48–58 (1967).
Mathew, J.Y., Parker, M.L.: The use of Clonidine (Catapres) in the treatment of hypertension. Med. J. Aust. 2, 1120–1122 (1971).
McRaven, D.R., Kroetz, F.W., Kioschos, J.M., Kirkendall, W.M.: The effect of Clonidin on hemodynamics in hypertensive patients. Amer. Heart J. 81, 482–489 (1971).
Mroczek, W.J., Leibel, B.A., Finnerty, F.A.: Comparison of Clonidine and methyldopa in hypertensive patients receiving a diuretic. Amer. J. Cardiol. 29, 712–717 (1972).
Mtjtr, A.L., Burton, J.L., Lawrie, D.M.: Circulatory effects at rest and exercise of Clonidine, an imidazoline derivative with hypotensive properties. Lancet 1969 II, 181–185.
Nayler, W.G., Price, J.M., Swann, J.B., McInnes, L, Race, D., Lowe, T.E.: Effect of hypotensive drug St-155 (Catapres) on the heart and peripheral circulation. J. Pharmacol, exp. Ther. 164, 45–59 (1968).
Onesti, G., Schwartz, A.B., Kim, K.E., Paz-Martinez, V., Swartz, C.: Antihypertensive effect of Clonidine. Circulat. Res. 28 (Suppl. II), 53–69 (1971).
Putzeys, M.R., Hoobler, S. W.: Comparison of Clonidine and methyldopa on blood pressure and side effects in hypertensive patients. Amer. Heart. J. 83, 464–468 (1972).
Rehbinder, D.: The metabolism of Clonidine (Catapres, St 155). In: Conolly, M.E. (Ed.): Catapres in hypertension-an international symposium, pp. 227–236. London: Butterworths 1970.
Schmitt, H.: Centrally mediated decrease in sympathetic tone induced by 2-(2, 6-dichlorophenylamino)-2-imidazoline (St 155, Catapres). In: Conolly, M.E. (Ed.): Catapres in hypertension-an international symposium, pp. 23–42. London: Butterworths 1970.
Schmitt, H., Schmitt, H., Fenard, S.: Evidence for an a sympathomimetic component in the effects of Catapresan on vasomotor centres: antagonism by piperoxan. Europ. J. Pharmacol. 14, 98–100 (1971).
Schneider, K. W.: Cardial-Hämodynamik im akuten Versuch, nach chronischer Behandlung und im Belastungstest mit St 155. In: Heilmeyer, L., Holtmeier, H. J., Pfeiffer, E.F. (Eds.): Hochdrucktherapie: Symposion über 2-(2, 6-dichlorophenylamino)-2-imidazolin-hydrochlorid, pp. 78–83. Stuttgart: Thieme 1968.
Shafar, J., Tallett, E.R., Knowlson, P.A.: Evaluation of Clonidine in prophylaxis of migraine. Lancet 1972 I, 403–407.
Shaw, J., Hunyor, S.N., Korner, P.I.: The peripheral circulatory effects of Clonidine and their role in the production of arterial hypotension. Europ. J. Pharmacol. 14, 101–111 (1971).
Sherman, G.P., Grega, G.L, Woods, R. J., Buckley, J.R.: Evidence for a central hypotensive mechanism of 2-(2, 6-dichlorophenylamino)-2-imidazoIine (Catapresan, St 155). Europ. J. Pharmacol. 2, 326–328 (1968).
Smet, G., Hoobler, S.W., Sanbar, S., Julius, S.: Clinical observations on a new anti-hypertensive drug, 2-(2, 6-dichlorophenylamine)-2-imidazoline hydrochloride. Amer. Heart. J. 77, 473–478 (1969).
Stenberg, J., Holmberg, S., Naets, E., et al: Hemodynamic effects of Catapresan: Central circulation at rest; circulation at rest and under exercise. In: Hellmeyer, L., Holtmeier, H. J., Pfeiffer, E.F. (Eds.): Hochdrucktherapie: Symposion über 2-(2, 6-Dichloro-phenyíamino)-2-imidazolin-hydrochlorid, S. 68–75. Stuttgart: Thieme 1968.
Vorburger, C., Butikofer, E., Reubi, F.: Die akute Wirkung von St 155 auf die cardiale und renale Hämodynamik. In: Heilmeyer, L., Holtmeier, H. J., Pfeiffer, E.F. (Eds.): Hochdrucktherapie: Symposion über 2-(2, 6-Dichlorophenylamino)-2-imidazolin-hydrochlorid, S. 86–94. Stuttgart: Thieme 1968.
Werner, U., Starke, K., Schuman, H. J.: Actions of Clonidine and 2-(2-methyl-6-ethyl-cyclo-hexylamino)-2-oxazoline on postganglionic autonomic nerves. Arch. int. Pharmacodyn. 195, 282–290 (1972).
Zaimis, E.: On the pharmacology of catapres (St 155). In: Conolly, M.E. (Ed.): Catapres in hypertension-an international symposium, pp. 9–22. London: Butterworths 1970.
Section V. Beta-Adrenoreceptor Blocking Drugs
Åblad, B., Ervik, M., Hallgren, J., Johnsson, G., Solvell, L.: Pharmacological effects and serum levels of orally administered alprenolol in man. Europ. J. clin. Pharmacol. 5, 44–52 (1972).
Aellig, W.H., Prichard, B.N.C., Scales, B.A.: Blood levels of practolol following intravenous administration. Brit. J. Pharmacol. 40, 572P (1970).
Aellig, W.H., Sameli, K.: Prolonged action of pindolol. Brit. med. J. 1973 II, 365.
Amery, A., Billiet, L., Fagard, R.: Beta receptors and renin release. New Engl. J. Med. 290, 284 (1974).
Barrett, A.M., Carter, J., Fitzgerald, J.D., Hull, R., Le Count, D.: A new type of cardioselective adrenoceptive blocking drug. Brit. J. Pharmacol. 48, 340 (1973).
Beilin, L. J., Juel-Jensen, B.E.: Alpha and beta adrenergic blockade in hypertension. Lancet 1972 I, 979.
Berglund, G., Andersson, O., Hansson, L., Ocander, R.: Propranolol given twice daily in hypertension. Acta med. scand. 194, 513 (1973).
Bett, J. H.: Hypotension after oral propranolol. Lancet 1968 I, 302.
Boakes, A. J., Boeree, B. H., Prichard, B. N. C.: Dose response studies to Oxprenolol, pindolol, practolol, propranolol and Sotalol on tilt, valsalva and exercise tachycardia. Naunyn-Schmiedeberg’s Arch. Pharmacol. 279, R. 42 (1973).
Boakes, A.J., Knight, E. J., Prichard, B.N.C.: Preliminary studies of the pharmacological effects of 5(l-Hydroxy-2(l-Methyl-3-phenylpropyl)amino-ethyl)Sylicylamide (AH 5158) in man. Clin. Sci. 40, 18 (1971).
Bodem, G., Brammell, H.L., Weil, J. V., Chidsey, C.A.: Pharmacodynamic studies of beta adrenergic antagonism induced in man by propranolol and practolol. J. clin. Invest. 52, 747–754 (1973).
Bodem, G., Chidsey, C.A.: Pharmacokinetic studies of practolol, a β-adrenergic antagonist, in man. Clin. Pharmacol. Ther. 14, 26–29 (1973).
Bond, P.A.: Metabolism of propranolol (Inderal); a potent, specific β-adrenergic receptor blocking agent. Nature (Lond.) 213, 721–723 (1967).
Branch, R. A., Nies, A. S., Shand, D.G.: The disposition of propranolol VIII. General implications of the effect of liver blood flow on elimination from the perfused rat liver. Drug Metab. Disp. 1, 687–690 (1973).
Breckenridge, A.M., Buranapong, P., Dollery, C.T., George, CF., Macerlean, D., Orme, M.L.E.: Hepatic clearance of propranolol in dogs. Brit. J. Pharmacol. 48, 336P (1973).
Brick, I., Hutchinson, K.J., McDevitt, D. G.: Comparison of the effects of ICI 50172 and. propranolol on the cardiovascular responses to alrenaline, isoprenline and exercise. Brit. J. Pharmacol. 34, 127–140 (1968).
Brown, J. J., Davies, D.L., Ferriss, J.B., Fraser, R., Haywood, E., Lever, A. F., Robertson, J. I. S.: Comparison of surgery and prolonged spironolactone therapy in patients with hypertension, aldosterone excess and low plasma renin. Brit. J. Pharmacol. 2, 729–734 (1972).
Brown, P., Baddeley, H., Read, A.E., Davies, J.D., McGarry, J.: Sclerosing peritonitis, an unusual reaction to a β-adrenergic blocking drug (Practolol). Lancet 1974 II, 1477–1481.
Brtjnner, H.R., Gavras, H., Laragh, J.H., Keenan, R.: Angiotensin II blockase in man by Sar 1–8 angiotensin II for understanding and treatment of high blood pressure. Lancet 1973 II, 1045–1047.
Buhler, F.R., Laragh, J.H., Baer, L., Darracott Vaughan, E., Brunner, H.R.: Propranolol inhibition of renin secretion. New Engl. J. Med. 287, 1209–1214 (1972).
Btjhler, F.R., Laragh, J.H., Darracott Vaughan, E., Brunner, H.R., Gavras, H., Baer, L.: Antihypertensive action of propranolol. Amer. J. Cardiol. 32, 511–522 (1973).
Ca Stenfors, J., Johnsson, H., Oro, L.: Effect of alprenolol on blood pressure and plasma renin activity in hypertensive patients. Acta med. scand. 193, 189–195 (1973).
Cleaveland, C. R., Shand, D. G.: Effect of route of administration on the relationship between β-adrenergic blockase and plasma propranolol level. Clin. Pharmacol. Ther. 13, 181–195 (1972).
Collins, I.S., King, I.W.: Pindolol (Visken, LB 46). A new treatment for hypertension: Report of a multicentre open study. Curr. ther. Res. 14, 185 (1972).
Coltart, D. J., Gibson, D. G., Shand, D. G.: Plasma propranolol levels associated with suppression of ventricular ectopic beats. Brit. med. J. 1971 I, 490–491.
Coltart, D. J., Shand, D.G.: Plasma propranolol levels in the quantitative assessment of β- adrenergic blockade in man. Brit. med. J. 1970 III, 731–734.
Day, Gillian, M., Prichard, B.N.C.: Hypotensive action from combination of propranolol and other hypotensive drugs. Brit. J. Pharmacol. 41, 408 (1971).
Day, M.D., Owen, A. A., Warren, P. R.: An adrenergic neuron blocking action of propranolol in isolated tissues. J. Pharm. (Lond.) 20, 1305–1345 (1968).
Dollery, C.T., Patterson, J. W., Conolly, M.E.: Clinical pharmacology of β-receptor-blocking drugs. Clin. Pharmacol. Ther. 10, 765–799 (1969).
Dollery, C.T., Lewis, P. J., Myers, M.G., Reid, J. L.: Central hypotensive effect of propranolol in the rabbit. Brit. J. Pharmacol. 48, 343P (1973).
Dorph, S., Binder, C.: Evaluation of the hypotensive effect of beta-adrenergic blockade in hypertension. Acta med. scand. 185, 443–448 (1969).
Dunlop, D., Shanks, R.G.: Inhibition of the carotid sinus reflex by the chronic administration of propranolol. Brit. J. Pharmacol. 36, 132–143 (1969).
Epstein, S.E., Braunwald, E.: The effect of beta adrenergic blockade on patterns of urinary sodium excretion. Ann. intern. Med. 65, 20–27 (1966).
Epstein, S.E., Robinson, B. F., Kahler, R.L., Braunwald, E.: Effects of beta adrenergic blockade on the cardiac response to maximal and submaximal exercise in man. J. clin. Invest. 44, 1745–1753 (1965).
Esler, M.D., Nestel, P.J.: Evaluation of practolol in hypertension. Effects on sympathetic nervous system and renin responsiveness. Brit. Heart. J. 35, 469–474 (1973).
Evans, G.H., Nies, A. S., Shand, D.G.: The disposition of propranolol III, decreased half life and volume of distribution as a result of plasma binding in man, monkey, dog and rat. J. Pharmacol, exp. Ther. 186, 114–122 (1973).
Evans, G. H., Shand, D.G.: Disposition of propranolol V. Drug accumulation and steady-state concentrations during chronic oral administration in man. Clin. Pharmacol. Ther. 14, 487–493 (1973a).
Evans, G.H., Shand, D.G.: Disposition of propranolol V. Independent variation in steady state circulating drug concentration and half-life as a result of plasma drug binding in man. Clin. Pharmacol. Ther. 14, 494–500 (1973b).
Felix, R. H., Ive, F. A., Dahl, M. G. C.: Cutaneous and ocular reactions to practolol. Brit. med. J. 1974 IV, 321–324.
Feltham, P.M., Watson, O.F., Peel, J.S., Dunlop, D.J., Turner, A.S.: Pindolol in hypertension: A double blind trial. N. Z. Med. 76, 167 (1972).
Finegan, R.E., Marlon, A.M., Harrison, D.C.: Circulatory effects of practolol. Amer. J. Cardiol. 29, 315–322 (1972).
Fitzgerald, J. D.: Beta adrenergic blocking drugs. Present position and future. Acta cardiol. (Brux.) XV, 199 (1972).
Fitzgerald, J. D., Scales, B.: Effect of a new adrenergic beta-blocking agent (ICI 50172) on heart rate in relation to its blood levels. Int. J. clin. Pharmacol. 1, 467–474 (1968).
Fitzgerald, J. D., O’Donnell, S.R.: Pharmacology of 4-hydroxy-propranolol, a metabolite of propranolol. Brit. J. Pharmacol. 43, 222–235 (1971).
Forsberg, S.A., Johnsson, G.: Hemodynamic effects of propranolol and H 56/28 in man. A comparative study of two beta adrenergic receptor antagonists Life Sci. 6, 1147–1154 (1967).
Furberg, C., Michaelson, G.: Effect of Aptin, a /? adrenergic blocking agent, in arterial hypertension. Acta med. scand. 186, 447–450 (1969).
George, CF., Fenyvesi, T., Conolly, M.E., Dollery, C.T.: Pharmacokinetics of dextro-laevo- and racemic propranolol in man. Europ. J. clin. Pharmacol. 4, 74–76 (1972).
George, C.F., Fenyvest, T., Dollery, C.T.: Pharmacoligical effects of propranolol in relation to plasma levels. In: Davies, D.S., Prichard, B.N.C (Eds.): Biological effects of drugs in relation to their plasma concentrations, p. 123: University Park Press 1973.
Gibson, D.G., Coltart, D.J.: Haemodynamic effects of practolol. Brit. Heart. J. 34, 95–99 (1972).
Gibson, D., Sowton, E.: Effects of ICI 50172 in man during erect exercise. Brit. med. J. 1968 I, 213–215.
Gllmore, E., Weil, J., Chidsey, C.: Treatment of essential hypertension with a new vasodilator in combination with beta-adrenergic blockade. New Engl. J. Med. 282, 521–527 (1970).
Graham, B.R., Littlejohns, D.W., Prichard, B.N.C., Scales, B., Southorn, P.: Preliminary observations on the human pharmacology of I.C.I. 66082 in normal volunteers. Brit. J. Pharmacol. 49, 154 (1973).
Grandjean, T., Rivier, J.L.: Cardio-circulatory effects of beta-adrenergic blockade in organic heart disease. Brit. Heart J. 30, 50–59 (1968).
Greenblatt, D. J., Koch-Weser, J.: Adverse reactions to propranolol in hospitalized medical patients. Amer. Heart J. 86, 478–484 (1973).
Gtjgler, R., Herold, W., Dengler, H.J.: Pharmacokinetics of pindolol in man. Europ. J. clin. Pharmacol. 7, 17 (1974).
Gugler, R., Hobel, W., Boden, G., Dengler, H.J.: The effects of pindolol on exercise induced cardiac acceleration in relation to plasma levels in man. Clin. Pharmacol. Ther. 17, 127 (1975).
Guyton, A.C.: Regulation of cardiac output. Anesthesiology 29, 314–326 (1968).
Hollander, W.: Hypertension, antihypertensive drugs and atherosclerosis. Circulation 48, 1112–1127 (1973).
Hansson, L.: Beta-adrenergic blockade in essential hypertension. Acta med. scand. (Suppl.) 550 (1973).
Hayes, A., Cooper, R.G.: Studies on the absorption, distribution and excretion of propranolol in rat, dog and monkey. J. Pharm, exp. Ther. 176, 302–311 (1971).
Heffernan, A., Carty, A., O’Malley, K., Bugler, J.: A within-patient comparision of debrisoquine and methyldopa in hypertension. Brit. med. J. 1971 I, 75.
Hicks, D.C., Arbab, A.G., Turner, P., Mills, M.: A comparison of intravenous pindolol and propranolol in normal man. J. clin. Pharmacol. 12, 212 (1972).
Hollifield, J.W., Sherman, K., Vander Zwaggr, Shand, D.G.: Proposed mechanisms of propranol’s antihypertensive effect in essential hypertension. New Engl. J. Med. 295, 68–73 (1976).
Humphreys, G.S.,Delvin, D.G.: Ineffectiveness of propranolol in hypertensive Jamaicans-Brit, med. J. 1968 II, 601–603.
Johansson, B., Regardh, C G., Sjogren, J.: Absorption of alprenolol in man from tablets with different rates of release. Acta pharm, suec. 8, 59–70 (1971).
Julius, S., Pascual, P.H., London, R.: Effect of beta-adrenergic blockade on plasma volume in human subjects. Proc. Soc. exp. Biol. (N. Y.) 140, 982 (1972).
Kelliher, G.J., Buckley, J.P.: Central hypotensive activity of dl and 1-propranolol. J. pharm. Sci. 59, 1276 (1970).
Kerber, R. E., Goldman, R. H., Alderman, E. L., Harrison, D. C.: Circulatory responses to beta adrenergic blockade with alprenolol. Amer. J. Cardiol. 29, 26–32 (1972).
Laver, M.C., Fand, P., Kincaid Smith, P.: Double blind comparison of two beta-blocking drugs with previous therapy in the treatment of hypertension. Med. J. Aust. 61, 174 (1974).
Leishman, A.W.D., Thirkettle, J.L., Allen, B.R., Dixon, R.A.: Controlled trial of Oxprenolol and practolol in hypertension. Brit. med. J. 1970 IV, 342–344.
Lydtin, H., Kusus, T., Daniel, W., Schierl, W., Ackenheil, M., Kempter, H., Lohmoller, G., Niklas, M., Inge, W.: Propranolol therapy in essential hypertension. Amer. Heart J. 83, 589–595 (1972).
McNeill, R.S.: Effect of a beta-adrenergic blocking agent, propranolol, on asthmatics. Lancet 1964 II, 1101.
Michelakis, A.M., Caudle, J., Liddle, G.W.: In vitro stimulation of renin production by epinephrine, norepinephrine and cyclic AMP. Proc. Soc. exp. Biol. (N. Y.) 130, 748–753 (1969).
Michelakis, A.M., McAllister, R.G.: The effect of chronic adrenergic receptor blockade on plasma renin activity in man. J. clin. Endocr. 34, 386–394 (1972).
Morgan, T. O., Louis, W. J., Dawborn, J. K., Doyle, A. E.: The use of pindolol (Visken) in the treatment of hypertension. Med. J. Aust. 2, 309 (1972).
Nies, A. S., McNell, J. S., Schrier, R. W.: Mechanism of increased sodium reabsorption during propranolol administration. Circulation 44, 596–604 (1971).
Nies, A. S., Evans, G.H., Shand, D.G.: Regional hemodynamic effects of beta-adrenergic blockade with propranolol in the unanesthetized primate. Amer. Heart J. 85, 97–102 (1973a).
Nies, A. S., Evans, G.H., Shand, D.G.: The hemodynamic effects of beta-adrenergic blockade on the flow-dependent hepatic clearance of propranolol. J. Pharmacol, exp. Ther. 184, 716–720 (1973b).
Oates, J.A., Seligmann, A.W., Clarke, M.A., Rousseau, P., Lee, R.E.: The relative efficiency of guanethidine, methyldopa and pargyline as antihypertensive agents. New Engl. J. Med. 273, 729 (1965).
Ohnhaus, E.E., Nuesch, E., Meier, J., Kalberer, F.: Pharmacokinetics of unlabelled and 14C-labelled pindolol in uraemia. Europ. J. clin. Pharmacol. 7, 25 (1974).
Ollson, S.B., Varnatjskas, E.: Duration of beta-receptor blockade after oral administration of LB 46. Europ. J. clin. Pharmacol. 5, 214 (1973).
Parker, J. O., West, R. O., Digiorgi, S.: Hemodynamic effects of propranolol in coronary heart disease. Amer. J. Cardiol. 21, 11–19 (1968).
Passo, S.S., Assaykeen, T.A., Otsuka, K., Wise, B.L., Goldfien, A., Ganong, W.F.: Effects of stimulation of the medulla oblongata on renin secretion in dogs. Neuroendocrinology 7, 1–10 (1971).
Paterson, J.W., Conolly, M.E., Dollery, C.T., Hayes, A., Cooper, R.G.: The pharmacodynamics and metabolism of propranolol in man. Pharmacol. Clin. 2, 127–133 (1970).
Patterson, J. W., Dollery, C.T.: Effect of propranolol in mild hypertension. Lancet 1966 II, 1148–1150.
Pettinger, W.A., Mitchell, H. C.: Minoxidil-an alternative to nephrectomy for refractory hypertension. New Engl. J. Med. 289, 167–171 (1973).
Podolsky, S., Pattavina, C.G.: Hyperosmolar non-ketotic diabetic coma: a complication of propranolol therapy. Metabolism 22, 685–693 (1973).
Prichard, B.N.C.: Aspects of the evaluation of antihypertensive drugs. In: Proceedings of the International Symposium on Clinical Pharmacology, p. 193. Brussels: Royal Academies of Medicine of Belgium, 1970.
Prichard, B.N.C.: Hypotensive action of pronethalol. Brit. med. J. 1964 I, 1227–1228.
Prichard, B.N.C.: Communication-5th International Congress on Pharmacology, San Francisco (1972).
Prichard, B.N.C., Gillam, P.M.S.: The use of propranolol in the treatment of hypertension. Brit. med. J. 1964 II, 725–727.
Prichard, B.N.C., Gillam, P.M.S.: Treatment of hypertension with propranolol. Brit. med. J. 1969 I, 7–16.
Prichard, B.N.C., Johnston, A. W., Hill, I.L., Rosenheim, M.L.: Bethanidine, guanethidine and methyldopa in the treatment of hypertension: a within patient comparison. Brit. med. J. 1968 I, 135.
Prichard, E. N. C., Gillam, P. M. S., Graham, B. R.: Beta receptor antagonism in hypertension; comparison with the effect of adrenergic neurone inhibition on cardiovascular responses. Int. J. clin. Pharmacol. 4–1, p. 135 (1970a).
Prichard, B.N.C., Shinebourne, E., Fleming, J., Hamer, J.: Haemodynamic studies in hypertensive patients treated by oral propranolol. Brit. Heart J. 32, 236–240 (1970).
Prichard, B.N.C., Boakes, A. J., Day, G.: Practolol in the treatment of hypertension. Postgrad, med. J. Suppl. 47, 84–92 (1971).
Raftery, E. B., Denman, A. M.: Systemic lupus erythematosus syndrome induced by practolol. Brit. med. J. 1973 II, 452–455.
Richardson, D.W., Freund, J., Gear, A.S., Matjck, H.P.,Preston, L.W.: Effect of propranolol on elevated arterial pressure. Circulation 37, 534–542 (1968).
Riess, W., Rajagopalan, T.G., Inhof, P., Schmid, K., Keberle, H.: Metabolic studies on Oxprenolol in animals and man by means of radiotracer techniques and GLC analysis. Postgrad, med. J. 46, (Suppl.) 32–39 (1970).
Robin, E., Cowan, Puri, P., Gangly, S., Deboyrie, E., Martinez, M., Stock, T., Bing, R.J.: A comparative study of nitroglycerine and propranolol. Circulation 36, 175–186 (1967).
Rowland, M.: Influence of route of administration on drug availability. J. pharm. Sci. 61, 70–74 (1972).
Saelens, D. A., Walle, T., Prwitga, P. J., Knapp, D. R., Gaffney, T.: Central nervous system effects and metabolic disposition of a glycol metabolite of propranolol. J. Pharmacol, exp. Ther. 188, 86–92 (1974).
Scales, B., Cosgrove, M.B.: The metabolism and distribution of the selective adrenergic beta blocking agent, practolol. J. Pharmacol, exp. Ther. 175, 338–347 (1970).
Schaffalitzky DeMuckadell, O.B., Gyntelberg, F.: The antihypertensive effect of a new beta-blocking agent pindolol compared with chlorthalidone. Europ. J. clin. Pharmacol. 5, 210 (1973).
Schneck, D. W., Aoki, V.S., Kroetz, F. W., Wilson, W.R.: Correlation of beta blockade with serum practolol levels after oral administration. Clin. Pharmacol. Ther. 13, 685–693 (1972).
Sederberg-Olsen, P., Ibsen, H.: Plasma volume and extracellular fluid volume during lorgterm treatment with propranolol in essential hypertension. Clin. Sci. 43, 165–170 (1972).
Seedat, Y.K., Stewart-Wynne, E.G., Reddy, J., Randeree, M.: Experiences with beta-adrenergic blockade drugs in hypertension. S. Afr. med. J. 47, 259 (1973).
Shand, D.G.: Proprandol. Disease-a-Month. October, 1974.
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Shand, D.G., Nuckolls, E.M., Oates, J.A.: Plasma propranolol levels in adults with observations in four children. Clin. Pharmacol. Ther. 11, 112–120 (1970).
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Shinebourne, E., Fleming, J., Hamer, J.: Haemodynamic responses to exercise in hypertension. Place of the sympathetic nervous system evaluated by a new selective beta adrenergic blocking agent ICI 50, 172. Cardiovasc. Res. 2, 379–383 (1968).
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Sleight, P., Golbbin, B., Pickering, T.G.: Baroreflex sensitivity in normal and hypertensive man: The effect of β-adrenergic blockade on reflex sensitivity. Postgrad, med. (Suppl.) 47, 79–81 (1971).
Sonnenblick, E.H., Ross, J., Braunwald, E.: Oxygen consumption of the heart. Newer concepts of its multifactorial determination. Amer. J. Cardiol. 22, 328–336 (1968).
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Sowton, E., Hamer, J.: Hemodynamic changes after beta adrenergic blockade. Amer. J. Cardiol. 18, 317–320 (1966).
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Stern, S., Hoffman, M., Braun, K.: Cardiovascular responses to carotid and vertebral artery infusions of propranolol. Cardiovasc. Res. 5, 425–430 (1971).
Stokes, G.S., Weber, M. A., Thornell, I.R.: β-blockers and plasma renin activity in hypertension. Brit. med. J. 1974 I, 60–62.
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Taylor, S. H., Majid, P.A., Saxton, C., Stoker, J.B.: Comparison of the circulatory effects of Oxprenolol and propranolol in hypertensive patients. In: Simpson, F.O. (Ed.): Beta adrenergic receptor blocking durgs-an international symposium. Auckland 1970.
Tewari, S.N., Grant, R. H. E.: Propranolol in hypertension. Postgrad, med. J. 44, 509–512 (1968).
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Tibblin, G., Ablad, B.: Antihypertensive therapy with alprenolol a β-adrenergic receptor antagonist. Acta med. scand. 186, 451–457 (1969).
Tuckman, J., Martin, R., Hodler, J.: Hypertensiebehandlung mit hohen Dosen von Oxprenolol, allein oder in Kombination mit dem Vasodilatator Dihydralazin. Helv. med. Acta 36, 243–244 (1972).
Turner, A. S., Peel, J. S.: An evaluation of hypotensive agents. Med. J. Aust. (Suppl. Sept. 16) p. 48 (1972).
Turner, A.S., Peel, J.S.: Comparative studies with beta-adrenergic receptor blockade. In: Simpson, F.O. (Ed.): Beta adrenergic receptor blocking durgs-an international symposium. Auckland 1970.
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Verniory, A., Staroukine, M., Telerman, M., Delwiche, F.: Effect of Sotalol on arterial blood pressure and renin-angiotensin system in hypertensive patients. Experta Medica Symposium on Clinical Advances in beta blocking therapy, in press (1974).
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Zacharias, F. J.,Cowen, K.J.: Controlled trial of propranolol in hypertension. Brit. med. J. 1970 I, 471.
Zacharias, F. J., Cowen, K.J., Presst, J., Vickers, J., Wall, B.G.: Propranolol in hypertension. A study of long-term therapy, 1964–1970. Amer. Heart J. 83, 755–761 (1972).
Section VI. The Direct Peripheral Vasodilators
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Ahearn, D.J., Grim, C.E.: Treatment of malignant hypertension with sodium nitroprusside. Arch, intern. Med. 133, 187–191 (1974).
Alarcon-Segovia, D.: Clinical and experimental studies on the hydralazine syndrome and its relationship to systemic lupus erythematosus. Medicine 46, 1–33 (1967).
Andersson, K.: Cyclic AMP as a mediator of the relaxing action of papaverine, nitroglycerine, diazoxide and hydralazine in intestinal and vascular smooth muscle. Acta pharmacol. (Kbh.) 32, 321–336 (1973).
Baeb, L., Goodwin, F. J., Labagh, J.H.: Diazoxide-induced renin release in man: Dissociation from plasma and extracellular fluid volume changes. J. clin. Endocr. 29, 1107–1109 (1969).
Bhatia, S.K., Frohlich, E. D.: Hemodynamic comparison of agents useful in hypertensive emergencies. Amer. Heart J. 85, 367–373 (1973).
Blackard, W.G., Aprill, C.N.: Mechanism of action of diazoxide. J. Lab. clin. Med. 69, 960–967 (1967).
Berglund, G.: A homogenously investigated, highly selected hypertensive population. Acta med. scand. 194, 87–91 (1973).
Boerth, R.: Personal communication.
Boxer, G.E., Rickards, J.C.: Studies on the metabolism of the carbon of cyanide and thiocyanate. Arch. Biochem. 39, 7–26 (1952).
Campbell, W.B., Pettinger, W.A., Keeton, K., Bbooks, S.N.: Vasodilating antihypertensive drug-induced aldosterone releasei a study of endogenous angiotensin-mediated aldosterone release in the rat. J. Pharmacol, exp. Ther. 193, 166–175 (1975).
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Chables, M.A., Danfobth, E., Jr.: Nonketoacidotic hyperglycemia and coma during intravenous diazoxide therapy in uremia. Diabetes 20, 501–503 (1971).
Chattebjee, K., Paemley, W.M., Ganz, W., Foerester, J., Walinsky, P., Crexells, C., Swan, H.J.C.: Hemodynamic and metabolic responses to vasodilator therapy in acute myocardial infarction. Circulation 48, 1183–1193 (1973).
Chidsey, C.A.: Clinical and pharmacokinetic studies of minoxidil a new antihypertensive agent. Clin. Sci. molec. Med. 45, Suppl. 1, 171–173 (1973).
Comerford, M.B., Pringle, A.: A long-term study of the antihypertensive effect of alprenolol. Acta med. scand. Suppl. 554, 15–22 (1974).
Crotjt, J.R., Andeeasen, F.V.V., Parks, R.I., Heimbach, D.M.: Intravenous diazoxide in hypertension. Clin. Res. 18, 337 (1970).
Danzig, L. E., Kringel, A. J.: Use of the artificial kidney in treatment of thiocyanate psychosis. J. Amer. med. Ass. 158, 560–563 (1955).
Domzalski, C.A., Kolb, L.C., Hines, E.A.: Delirious reactions secondary to thiocyanate therapy of hypertension. Mayo Clin. Proc. 28, 272–280 (1953).
Dormois, J.C., Young, J.L., Nies, A.S.: Minoxidil in severe hypertension: Value when conventional drugs have failed. Amer. Heart J. (in press).
Drug Ther. Bull. Emergency reduction of blood pressure. Drug Ther. Bull. 9, 80 (1971).
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Section VII. Diuretic Drugs
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Oates, J.A., Conolly, M.E., Prichard, B.N.C., Shand, D.G., Schapel, G. (1977). The Clinical Pharmacology of Antihypertensive Drugs. In: Gross, F. (eds) Antihypertensive Agents. Handbuch der experimentellen Pharmakologie / Handbook of Experimental Pharmacology, vol 39. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-66309-3_13
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