Use of Propranolol in Angina Pectoris

Abstract

Pronethalol, an adrenergic beta-receptor-blocking drug (Black and Stephenson, 1962), has been shown to relieve the pain of angina pectoris in a double-blind trial (Prichard, Dickinson, Alleyne, Hurst, Hill, Rosenheim, and Laurence, 1963). Its use in angina was, however, discontinued following a report of its tumour-producing activity in mice (Paget, 1963). A further disadvantage of pronethalol was that the therapeutic dose was close to that which produced side-effects.Black, Crowther, Shanks, Smith, and Dornhorst (1964) have described the pharmacology of propranolol (Inderal), a betareceptor-blocking agent in animals and man with about ten times the potency of pronethalol. It is non-carcinogenic in mice and other experimental animals. In view of the effectiveness of pronethalol it was thought that the closely related drug propranolol might be of value in angina. The present paper reports a double-blind trial in out-patients with angina pectoris. Design of TrialThe design of the trial closely followed that described by Prichard et ad. (1963). The original aim was to compare maximum tolerated doses of propranolol with placebo, but this was modified in that an upper dose limit of 100 mg. q.d.s. was later fixed ; this dose represented 40 tablets a day. During the " run-in period" the initial dosage was 10 mg. q.d.s. Increments of 10 mg. per dose per week were made up either to 100 mg. q.d.s. or to the maximum tolerated dose, when this was less. This variable dosage was selected because of the need to take into account individual variability, and also because benefit at a lower dosage might be largely a placebo effect, which may also result from increased frequency of out-patient visits. This latter factor was mitigated by having a long run-in period before the trial proper, three months or more, a period further extended owing to delay in obtaining identically tasting placebo tablets. During this time patients were seen every two weeks and the dosage was adjusted.The period of the actual trial was eight weeks. Patients were given placebo and propranolol each for two periods of two weeks' duration; they were identical in taste and appearance. Randomization of these four periods was made so that the six possible orders were achieved for every six patients admitted to the trial.Patients were considered suitable for admission to the trial if they were having at least two typical attacks of angina pectoris each week. The pain had to be of characteristic nature, site, and radiation, brought on by exertion, relieved by rest and glyceryl trinitrate, and usually lasting for one to three minutes. The purpose of the trial was explained to the patients, who were told that the new drug would be compared with identical dummy tablets in order to try to eliminate bias. Sixteen AssessmentPatients were asked to take glyceryl trinitrate for pain, but not prophylactically, and to record their attacks of angina and glyceryl trinitrate consumption on record sheets that were provided. The sheets were divided into four periods for ea...

Physiological and Psychological Effects of ±‐propranolol, +‐propranolol and Diazepam in Induced Anxiety

“…On balance, the beneficial effect of propranolol and other ,B-adrenoceptor blocking agents in anxiety would appear to be due to peripheral blockade rather than to central action. Thus, definite central effects of propranolol do occur in man (Gillam & Prichard, 1965;Stephen, 1966;Hinshelwood, 1969;Orzack, Branconnier & Gardos, 1973;Bryan, Efiong, Stewart-Jones & Turner, 1974) and in animals (Leszkovsky & Tardos, 1965; Bainbridge & Greenwood, 1971), but only in higher dosages than those used in the clinical studies of anxiety (Granville-Grossman & Turner, 1966;Wheatley, 1969). Practolol, a,-adrenoceptor blocking agent which does not enter the brain in appreciable amounts, is similar in effects to propranolol (Bonn, Turner & Hicks, 1972).…”

73. Coronare Herzkrankheit und Bypass- Chirurgie aus der Sicht des Internisten

“…Die internistische Therapie blieb im wesentlichen auf zwei Entwicklungsstufen beschr~inkt, auf die Einftihrung der Nitrok6rper Ende des letzten Jahrhunderts durch Brunton (1867) sowie Murrell (1879) und Mitte der 60er Jahre dieses Jahrhunderts auf die Einfiihrung der Substanzen mit betasympathicolytischer Eigenschaft dutch Prichard (1965), Chaimberlain (1966), Sowton (1966 und zahlreiche andere Kardiologen (Lichtlen, 1970). Obwohl der therapeutische Effekt der internistischen Therapie, n~imlich die Verbesserung der Symptomatik, ftir diese Substanzen eindeufigbelegt ist, so ist die internistische Behandlung doch weit enffernt davon geblieben, kurativ zu sein.…”

Mechanism of a Sympathomimetic Action of Propranolol in Dog

“…In more detailed studies it was found to be devoid of intrinsic sympathomimetic activity (Black, Duncan & Shanks, 1965;Shanks, 1966). Long term treatment with this agent was reported to cause reductions of blood pressure in hypertensive and normotensive patients (Prichard & Gillam, 1964;Gillam & Prichard, 1965). These authors attributed this effect of propranolol to interference with the function of the sympathetic nerves to the heart.…”