Abrupt withdrawal of atenolol in patients with severe angina. Comparison with the effects of treatment.

The effects of abrupt withdrawal of atenolol, a long acting cardioselective beta blocker, were studied in 20 patients with severe stable angina pectoris admitted to hospital for coronary arteriography. During the 144 hour postwithdrawal period no serious coronary events occurred. Mean and maximal daily heart rates rose steadily for at least 120 hours. No important arrhythmias were noted on ambulatory electrocardiographic monitoring. Treadmill exercise testing at 120 hours showed little reduction in the times to angina, ST depression, and maximal exercise when compared with those recorded at 24 hours. This deterioration was small when contrasted with the improvements in these indices produced by atenolol treatment in a similar group of patients not admitted to hospital. No change in catecholamine concentrations or acceleration of the heart rate response to exercise occurred after atenolol withdrawal, suggesting that rebound adrenergic stimulation or hypersensitivity was absent or insignificant. Catastrophic coronary events after beta blockade withdrawal (the beta blockade withdrawal syndrome) have occurred almost exclusively in patients taking propranolol, many of whom had unstable angina at the time of withdrawal. This study showed that in patients with stable angina, even when severe, the abrupt withdrawal of atenolol can be expected to result in only minor clinical consequences. The risk to any patient of so called rebound events after withdrawal of beta blockade seems to be related to both the clinical setting and the agent being used.

Prophylaxis against ventricular arrhythmias in suspected acute myocardial infarction: a comparison of tocainide and disopyramide.

Five hundred and seventy one patients admitted to a coronary care unit with suspected acute myocardial infarction were considered for entry into a double-blind study. Two hundred and eighty-three patients were excluded, mainly because of recent treatment with beta-adrenoceptor blocking agents, life threatening arrhythmias requiring specific treatment and left ventricular failure presenting with hypotension or pulmonary oedema. Two hundred and eighty-eight entered the trial of whom 202 were subsequently confirmed to have had myocardial infarction. The effects of tocainide and disopyramide on ventricular arrhythmias were compared with placebo over the first 48 h period. The three treatments were given by a combination of intravenous infusion and oral administration. The doses used were tocainide 500 mg intravenously over 30 min plus 2800 mg orally over 48 h and disopyramide 150 mg intravenously over 30 min plus 1050 mg orally over 48 h. As judged by counts of ventricular premature beats, tocainide and disopyramide exerted a similar and significant antiarrhythmic effect. The median number of ventricular premature beats over the first 24 h of treatment was 58 on placebo compared with 30 on tocainide (P less than 0.05) and 19 on disopyramide (P less than 0.05). The corresponding figures for the second 24 h were 9, 6 and 2, respectively. There were eight deaths and three episodes of ventricular fibrillation with no significant differences between the three treatment groups. Sustained ventricular tachycardia was observed in one patient in the tocainide group.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of indoramin added to oxprenolol and bendrofluazide as a third agent in severe hypertension.

1 Indoramin, an alpha-adrenoreceptor blocking agent has been given as a third agent to patients with severe hypertension treated with adequate doses of a beta-adrenoceptor blocking drug and a thiazide diuretic. 2 A further fall in blood pressure followed the addition of indoramin. With 75 mg twice daily this was on average a fall of 12% of mean arterial pressure in the supine position, 16% standing an 17% after exercise. 3 The rise in blood pressure caused by isometric exercise was not altered by indoramin. 4 Indoramin slowed the heart rate. On 75 mg twice daily the reduction was 14% at rest and 19% after exercise. 5 Side effects of indoramin were sedation, sleep disturbance and vivid dreams.

Dose response for blood pressure and degree of cardiac beta-blockade with atenolol.

The hypotensive effect of 25 mg, 50 mg, 75 mg, 100 mg and 0 mg of atenolol daily were compared in a double-blind within-patient study. The fall in blood pressure with 25 mg daily was not significantly different than with 100 mg. The dose response curve lies between 0 and 25 mg daily. Cardiac beta-blockade (measured by suppression of exercise tachycardia) was not maximal with 25 mg of atenolol daily. The dose response curves for beta-blockade and the hypotensive effect are not parallel.

Comparison of natriuretic, uricosuric, and antihypertensive properties of tienilic acid, bendrofluazide, and spironolactone.

The antihypertensive properties of the new diuretic tienilic acid were investigated. Thirteen previously untreated hypertensive patients took part in a double-blind crossover study in which 30 days' treatment with tienilic acid 250 mg, bendrofluazide 5 mg, and spironolactone 100 mg were compared. Bendrofluazide caused the greatest natriuresis on the first treatment day and the most rapid fall in blood pressure. The ultimate antihypertensive effect of all three drugs was similar. Tienilic acid caused a noticeable reduction in serum urate concentrations and a rise in urate clearance, in contrast to the other two agents, which caused slight urate retention. Tienilic acid and bendrofluazide caused falls and spironolactone a rise in plasma potassium concentrations. No untoward effects were seen from any of the drugs. It is concluded that tienilic acid is a moderately potent diuretic that lowers plasma urate concentrations. It may be the drug of first choice for hypertensive patients who already have gout or are likely to develop it when taking thiazide diuretics.

Respiratory disease associated with practolol therapy.

Six patients who had surgical treatment for sclerosing peritonitis caused by practolol now have a respiratory disorder characterised by dyspnoea, extensive fibrotic pleural thickening, and lesions in the lung parenchyma. Respiratory disease appears to be a further feature of the practolol syndrome.

Beta blockade in essential hypertension: an analysis of response to oxprenolol.

The data from 40 patients with essential hypertension treated with oxprenolol alone have been used to analyse the falls of blood pressure and heart rate. Blood pressure and heart rate did not fall further as the daily dose was increased above 160 mg. The range of fall in mean pressure was from 0 to 40 mmHg and there was no clear separation into response groups. Pressure falls were unrelated to sex, age, initial heart rate, increase in heart rate on standing, the fall of heart rate with the drug, or the initial height of blood pressure. In the absence of predicting factors the use of oxprenolol, and, by deduction, other beta blocking agents, in hypertension remains empirical, but the simplification of the dose range allows the response to oxprenolol to be determined quickly.

Evaluation of beta blockade bendrofluazide, and prazosin in severe hypertension.

20 patients with severe essential hypertension (average blood-pressure 211/123 mm Hg) had an inadequate fall in blood-pressure with beta blockade alone. They were given in random order either 5 and then 10 mg of bendrofluazide a day or prazosin 2 mg three times daily rising to 5 mg if required. The trial was a within-patient comparison of the two drug regimens. 10 patients who did not achieve a satisfactory fall in pressure with either agent were then given all three drugs together. When bendrofluazide 5 or 10 mg was added to beta blockade there was an average fall in mean blood-pressure, standing, of 13%. When prazosin was added to beta blockade the average fall in mean blood-pressure, standing, was 16%. 18 patients who completed the trial had an average final blood-pressure, standing, of 139/93 mm Hg. In the prazosin period 8 patients continued to complain of dizziness after the first 24 h. With bendrofluazide serum-potassium levels fell below 3-6 mmol/l in half the patients within the first two weeks of treatment. It is concluded that patients with essential hypertension already treated with beta blockade who need an additional agent will get a further fall in blood-pressure with 5 mg of bendrofluazide. Prazosin appears to be a potent and appropriate third agent.

Practolol peritonitis. A study of 16 cases and a survey of small bowel function in patients taking beta adrenergic blockers.

Sixteen patients with practolol peritonitis are described. Dense peritoneal thickening and adhesions caused small bowel stasis and obstruction with characteristic radiology and histology. The disease was best treated by surgery though complications were frequent and three of 16 patients died. Ocular and skin involvement were common. Fifty four asymptomatic patients who had taken a beta adrenoceptor blocking drug for more than 12 months were studied. Seven were found to have radiological abnormalities of the small bowel. These changes were associated with propranolol, oxprenolol and practolol therapy. It is not known whether they are related to practolol peritonitis.