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HYPERTENSION: FIXED COMBINATIONS OF ~·BLOCKERS AND DIURETIC

Oxprenolol + chlorthalidone ('Trasitensin') improves on prior therapy ... 56 hypertensive patients on a ~-blocker and a diuretic in free combination, were switched over to a flXed combination of ox­prenolol 80mg + chlorthalidone I Omg ('Trasitensin') for 12 weeks. Dosage ranged from }-4 tablets once daily, the dosage being equipotent to that of the ~-blocker take~ previously. During treatment supine BP dropped from 170/99mm Hg to 158/95mm Hg and standing BP dropped from 1621100mm Hg to 148/96mm Hg.Heart rate remained unchanged, serum potassium was somewhat lower and serum uric acid so~ewhat higher than before. Seven patients dropped out due mainly to dizziness, headache and palpitations, and 16 of the 49 who completed the trial complained of side effects. Bergstrom. M. et aI.: Current Therapeutic R~ch 27: 80S (Jun 1980)

. . . and is better than chlorthalidone alone 92 hypertensive patients (BP:> 160/1 OOmm Hg during 2-week placebo washout) were randomly assigned to 'Trasitensin' 1-2 tablets bid or chlorthalidone IO-20mg bid for 6 weeks. Five patients dropped out. BP decreased significantly on both treatments but significantly more in the 44 patients on Trasitensin' than in the 43 on chlorthalidone. BP normalized in 73% on'Trasitensin' and 49% on chlorthalidone. Side effects occurredin 14 patient"; in each group. Motolese. M. et al.: International Journal of Clinical Pharmacology, Therapy and ToxicolQ8Y 18: 332 (Aug 1980)

Oxprenol + cyclopenthiazide ('Trasidrex') may be better than diuretic alone 1080 hypertensive patients inadequately controlled on diuretics (diastolic BP :> 100mm Hg) were switched to the fixed combination of oxprenolol 160mg + cyclopenthiazide O.25mg (Trasidrex'), 1-2 tablets daily for 4 weeks. During their diuretic treatment the mean BP was 1801108mm Hg. This fell to 154/93mm Hg in the 985 patients who completed the study. Heart rate dropped from 81 to 71 beats/min. Subjective assessment indicated 65.5 % of the patients felt better, 23.5 % . felt the same and 1.5 % felt worse than on the diuretic. 82.5 % felt the fixed combination assisted in compliance. Tiredness, headache and dizziness were the main side effects during both diuretic and combination phases of the study. Forrest, W.A.: British Journal of Qinica1 Practice 34: 140 (May 1980>

A three-way combination: timolol + hydrochlorothiazide + amiloride 220 hypertensive patients entered a 10·week open, uncontrolled trial consisting of 2 weeks on placebo and 8 weeks on a 3-way fixed combination of timolol 10mg + hydrochlorothiazide 25mg + amiloride 2.5mg. 212 patients completed this first phase, 3 withdrawing due to side effects (skin rash, bronchospasm, fatigue and hypotension). 159 of these patients then entered 'phase 2' which continued for a further 40 weeks (making 50 weeks total). 141 completed this phase, none dropping out due to side effects. Supine BP at 3 weeks (phase J) was 1721105mm Hg and at 10 weeks (end of phase n was 141/87mm Hg. At 50 weeks (end of phase 2) it was 143/87mm Hg.- Standing BP was 168/106inm Hg atl'weeks, 135/87mm Hg.at 3 weeks, 135/87mm Hg at 10 weeks and I 37/87mm Hg at 50 weeks. Mean pulse rate was 80.7/min at 3 weeks, 64.8/min at 10 weeks and 66.2!min at 50 weeks. 18 patients (\2,6%) had bradycardia below 60/min at 50 weeks. There were no significant changes in serum potassium or urate. Three patients discontinued treatment at the end oftbe 50 weeks due to skin rash. During phase I, 72 (of 220) patients experienced a total of 89 side effects (IO in the placebo period) consisting mainly of hypotension, bradycardia « SO/min) and bronchospasm. Throughout both phases, drowsiness, nausea or headache also occurred in 27 patients, 4 patients complained of impotence and others suffered vague symptoms of tight chest, tiredness, cramps, fatigue, dry mouth and itching. Pittaway. D.: South African Medical Journal 58: 231 (Aug 9,1980)

And acebutolol vs hydrochlorothiazide + amiloride 24 patients with essential hypertension, after a pretreatment study, were randomly allocated to acebutolol 500mg in a single daily dose or to a fixed combination diuretic tablet of hydrochlorothiazide 50mg + amiloride 5mg, with a crossover change after 6 weeks. Both acebutolol and the diuretic combination produced a significant but almost identical drop in BP at rest from 164.4/I06.2mm Hg to 148.9/94.6mm Hg on acebutolol and to 152.0/98.lmm Hg on the diuretics. Heart rate dropped from 74.0 to 61.7 on acebutolol and remained the same (75.3) on the diuretics. However during exercise there was a significantly greater reduction in BP on acebutolol (from 221.71124.4mmHg to 188.51109.3mmHg on 80 watt workload) than there wa<; on the diuretics (dropping to 21 O.9/116.6mm Hg). Heart rate dropped from 125.8 to 101.6 on acebutolol but only to 122.4 on the diuretics. Twelve patients who responded inadequately to the single 500mg acebutolol dose continued for a further 6 weeks on a combination of the acebutolol and the 2 diuretics. There was a further significant

reduction in systolic and diastolic BP at rest and after work. Hypertensive patients may be at particular risk from high increases in BP during work. Because of the superior effect of acebutolol during exercise, a ~-blocker would be the first choice of treatment for mild-moderate hypertension. However in those who fail to respond adequately to a ~-blocker, the addition of a diuretic may potentiate the antihypertensive effect. Franz. E.-W.: American Journal of Cardiology 46: 301 (Aug 1980)

10 INPHARMA 25 Oct 1980 0156-2703/80/1025-0010 $00.50/0 ©ADIS Press