Low-dose cyclopenthiazide in the treatment of hypertension: a one-year community-based study.

After an 8-week placebo period, 73 patients whose diastolic blood pressures were between 90 and 110 mmHg were randomly assigned to receive 125 micrograms (low dose) or 500 micrograms of cyclopenthiazide (standard dose) for a period of one year. Blood pressure was measured in the patient's home by the same observer at two-weekly intervals during an 8-week placebo run-in period, every 4 weeks for a further 12 weeks and at 24, 36 and 52 weeks thereafter. Serum potassium, urate, glucose, glycosylated haemoglobin, total and HDL cholesterol, and apolipoproteins were measured at the end of the placebo period and at 4, 8, 24 and 52 weeks of active treatment. Twelve of the 73 patients had an inadequate antihypertensive response--five on the higher dose and seven on the lower dose. One patient receiving 500 micrograms was withdrawn because of adverse effects. In the remaining 60 patients, systolic and diastolic blood pressures were significantly reduced when compared with pretreatment values in both treatment groups throughout the one year period. The decreases in blood pressure were not significantly different from each other (p greater than 0.65). Three patients on 500 micrograms required potassium supplements. Maximum decreases in the serum potassium of 0.52 mmol/l (500 micrograms dose) and 0.14 mmol/l (125 micrograms dose) were observed at 24 weeks of treatment in the remaining 57 patients. The differences between the two doses at this time were statistically significant (p less than 0.05), as were the increases in serum urate observed at 4, 8 and 24 weeks (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

An open, parallel group study comparing a frusemide/amiloride diuretic and a diuretic containing cyclopenthiazide with sustained release potassium in the treatment of congestive cardiac failure--a multicentre general practice study.

A total of 71 patients with cardiac failure requiring diuretic treatment were randomly allocated to receive either 20 mg frusemide/2.5 mg amiloride or 0.25 mg cyclopenthiazide/8.1 mmol sustained release potassium once daily for 12 weeks. Of the 35 patients treated with cyclopenthiazide/potassium, in 47% of patients the daily dose was doubled compared with in only 30% of the 36 patients treated with frusemide/amiloride. Both treatments significantly improved crepitations, oedema, orthopnoea and patient self-assessments of dyspnoea on effort; there were no significant differences between the two treatments. Plasma potassium concentrations were unaffected by either treatment and there were no clinically significant changes in laboratory data. Of the five patients receiving frusemide/amiloride and of the eight receiving cyclopenthiazide/potassium who withdrew from the trial, three and four, respectively, were due to possible drug-related effects. It is concluded that frusemide/amiloride is efficacious and acceptable for the treatment of congestive heart failure.

The case for low dose diuretics in hypertension: comparison of low and conventional doses of cyclopenthiazide.

In a double blind placebo controlled randomised parallel study the antihypertensive activity and adverse biochemical effects of three doses of cyclopenthiazide were evaluated in patients with mild essential hypertension that had been recently diagnosed or was being treated with a single drug. After a four week placebo washout period 53 patients with diastolic blood pressures between 90-110 mm Hg were randomly assigned to 50, 125, or 500 micrograms cyclopenthiazide or matching placebo for an eight week period of treatment. Blood pressure was measured in the patients' homes by the same observer every two weeks. Serum urea, electrolytes, urate, and creatinine concentrations and 24 hour urinary sodium excretion were monitored every four weeks and serum magnesium concentration and plasma renin activity at the end of the washout and treatment periods. After eight weeks of treatment systolic and diastolic blood pressures were significantly reduced in patients taking 125 and 500 micrograms cyclopenthiazide when compared with those taking placebo. The decrement in serum potassium concentration (0.6 mmol/l) and increase in serum urate concentration 0.06 mmol/l) were greatest with the 500 micrograms dose, the increase in serum urate concentration alone being significant. No change in serum magnesium concentration or 24 hour urinary sodium excretion was noted with any dose of cyclopenthiazide. Only the 500 micrograms dose of cyclopenthiazide significantly increased the mean plasma renin activity (1.8 (95% confidence interval 0.2 to 3.4)-5.4 (3.9 to 6.8) nmol angiotensin I/l/h); the other doses like the placebo had no effect. Cyclopenthiazide 125 micrograms, a dose lower than is currently marketed, produced a similar hypotensive response to 500 micrograms of the drug without upsetting the biochemical profile.

Arrhythmogenic potential of diuretic induced hypokalaemia in patients with mild hypertension and ischaemic heart disease.

In view of evidence suggesting an association of mild hypokalaemia with cardiac arrhythmia, the arrhythmogenic potentials of potassium losing and potassium sparing diuretic treatments were compared in a controlled prospective crossover study of 10 patients with mild hypertension and ischaemic heart disease. Mean (SEM) plasma potassium was 4.3(0.06) mmol/l and 3.3(0.07) mmol/l after potassium sparing and potassium losing treatments respectively. Blood pressure and volume depletion as assessed by weight change, plasma renin activity, and noradrenaline concentrations did not differ significantly in the two treatment periods. The potassium losing treatment phase was associated with an increased frequency of ventricular extrasystoles, a higher Lown grading during ambulatory electrocardiographic monitoring, prolonged duration and decreased phase 0 velocity of the monophasic action potential, a prolonged ventricular effective refractory period, and increased myocardial electrical instability as assessed by programmed ventricular stimulation. It is concluded that minor changes in plasma potassium concentration are associated with increased ventricular electrical instability in patients with ischaemic heart disease. Mild hypokalaemia in such patients may predispose to life threatening arrhythmias and should be avoided.

An open comparison between free and a fixed combination of diuretic and beta-blocker in the management of essential hypertension.

A total of 1,117 patients with inadequately controlled hypertension in spite of treatment with a combination of diuretic and beta-adrenergic blocker were studied. Treatment was changed to one or two tablets daily of Trasidrex (160 mg oxprenolol hydrochloride in a sustained release formulation and 0.25 mg cyclopenthiazide) with a subsequent improvement, 4 weeks later, in blood pressure control. Side-effects of treatment were uncommon and treatment was approved by the majority of patients. The majority of doctors participating thought a fixed combination would improve patient compliance with therapy.

Use of a sustained-release formulation of oxprenolol and cyclopenthiazide ('Trasidrex') in the management of hypertension: a general practice study.

An open study was carried out in general practice on 678 hypertensive patients being treated with a beta-blocker but who still had resting diastolic blood pressures greater than 100 mmHg. Previous treatment was stopped and substituted with 1 or 2 tablets daily of a fixed combination product containing 160 mg oxprenolol hydrochloride in a sustained-release formulation plus 0.25 mg cyclopenthiazide per tablet. After 4-weeks' treatment on this regimen, blood pressure levels fell significantly, from 179/108 mmHg to 155/93 mmHg, without any increase in the reporting of unpleasant side-effects.

Drug-associated primary acute pancreatitis.

Drug histories were taken from 100 patients in their first attack of acute pancreatitis, and each was matched with a control subject of the same sex who was admitted to hospital as an emergency with acute abdominal pain, whose serum-amylase was within the normal range, and whose age was within three years of the pancreatitis patient's. The major differences between the patient groups was in the use of cardiovascular agents, and this was primarily due to a statistically significant excess of diuretic takers among the pancreatitis patients. There was an associated excess of intake of digoxin and antihypertensive and anti-anginal agents, but neither difference was statistically significant. Other categories of drugs showed no substantial differences. The difference between the pancreatitic patients and controls is almost entirely accounted for by takers of cyclopenthiazide with potassium chloride and of frusemide, especially the former. Further clinical and experimental evidence is required before the role of diuretics and/or potassium chloride in causing acute pancreatitis can be determined.

Trasidrex (a fixed combination of slow Trasicor 16o mg and Navidrex 0.25mg) in the treatment of hypertension: a multicentre clinical trial in general practice.

Sixty-two patients with hypertension who were treated with a free combination of Slow Trasicor or Trasicor and Navidrex K were transferred to a fixed combination tablet, Trasidrex (slow oxprenolol 160 mg + cyclopenthiazide 0.25 mg). Blood pressure control was marginally improved and there was no increase in side-effects.

Inappropriate antihypertensive therapy in the elderly.

Six symptomless patients aged 64-84 (mean 72) years received antihypertensive therapy from their family doctors. Pretreatment systolic pressures ranged from 160 to 220 mm Hg and disastolic pressures from 80 to 120 mm Hg. Within one week of starting therapy all six patients were admitted as emergencies with epidoses of unconsciousness. Admission systolic pressures ranged from 80 to 150 mm Hg and diastolic pressures from 50 to 90 mm Hg. Before admission each patient had experiences symptoms of postural hypotension and had become housebound. After antihypertensive therapy was stopped, one patient had a residual left homonymous hemianopia but the others recovered completely. A raised systolic and distolic pressure is common in the elderly; potent antihypertensive treatment may seriously impair the quality of life and is often unecessary.

Effect of long-term diuretic treatment on body-potassium in heart-disease.

Plasma and total body potassium have been measured in 151 patients with chronic heart-disease, 83 of whom were taking diuretics and potassium supplements. After allowance for age and body-size, the deficit in total body-potassium was only 3-5% (100-150 mmol) in the diuretic group. 13 of the 83 patients taking diuretic had hypokalaemia (less than 3-5 mmol/1) but the potassium deficit was no greater than in the patients with normal plasma-potassium. There was no relation between the dose of potassium supplements and either the plasma-potassium or the total body-potasium. It is suggested that potassium depletion is not a major problem in patients with heart-failure treated with diuretics. The dose of potassium supplements should therefore be determined entirely by the plasma-potassium.