N.A. Jaffer ( Sughrabai Millwalla Hospital, Karachi. )
Fifty six patients suffering from moderate essential hypertension (with supine diastolic blood pressure values between 106-120mm Hg), whose current treatment produced inadequate control, troublesome side-effects, or a combination of both were included in the study. Newly detected cases and patients who had discontinued treatment were also included in the study.
The regimen consisted of 160mg of Oxprenolol in sustained release formulation (Trasicor l60 SR.) and 25mg of Chlorthalidone (Hygroton) administered once daily in the morning, for eight weeks.
The mean duration of hypertension was five years and the mean heart rate and blood pressure on admission to the study was 93 & 177/112 mm of Hg respectively.
On conclusion of the study, the mean heart rate and blood pressure were 77 & 145/89mm of Hg respectively., a supine diastolic blood pressure equal to or less than 95mm Hg was reached in 45 of 56 patients (80%). Side effects were observed in 10 patients (17.9%) and were of mild nature; in no case did the treatment have to be prematurely withdrawn because of the side effects.
This study has shown that a combination of Oxprenolol. slow release (Trasicor 160 SR.) & Chlorthalidone 25mg (Hygroton) given once daily induces normalization.of blood pressure in approximately 80% of patients and a single morning dose of sustained release formulation of Oxprenolol improves patient compliance in moderate essential hypertension (JPMA 32.206, 1982).
Beta-receptor antagonists are widely used in the treatment of essential hypertension. To produce a satisfactory therapeutic response they are commonly prescribed twice or thrice daily and may be combined with diuretics, vasodilators, adrenergic neurone blockers and methyldopa. Several reports (Ayd, 1974; Blackwell," 1973; Galley, 1968) indicate that compliance with therapy falls as the frequency of dosage increases.
Oxprenolol is a beta-blocking drug which possesses effective antihypertensive properties. Its duration of action is longer than its plasma concentration would suggest, but probably does not exceed 8-12 hours (Brunner et al., 1975). Oxprenolol is usually administered twice or thrice daily to achieve a therapeutic anti-hypertensive effect. The inconvenience associated with multiple daily doses is of concern when long term treatment is required, as is the case in essential hypertension. West et al. (1976) showed that 160 mg sustained-release oxprenolol produces maximum blood levels similar to those with 80 mg of con-ventional oxprenolol and almost, as quickly. Moreover, high concentrations of the compound persist much longer and are associated with a prolonged beta blocking effect that lasts up to 24 hours. Thus, with the development of a sustained-release formulation the goal of prolonging the half-life of the drug has been reached. An added advantage is the reduction of the peak concentra-tion thereby minimizing the marked reduction in heart rate and possibly\' tiredness on exercise which might occur when plasma levels are high (Owens, 1978).
Chlorthalidone is a diuretic widely used for the treatment of hypertension. Since it possesses a prolonged duration of action, once daily administration seems appropriate.
Beta-blockers have been shown to reduce cardiac output whereas diuretics lower peripheral resistance, at least on long term administration (Lund-Johansen, 1970; Simpson, 1974). Moreover beta-blockers may blunt the renin stimulating effect of diuretics and attenuate their hypokalemic effect (Hettiarachchi et al., 1977).
Most authorities agree that beta-blockers and diursties, are groups of drugs with different modes of actions, useful in the treatment of moderate hypertension. Although it is possible to use a wide variety of dose levels, it appears that in practice 160 mg oxprenolol combined with 25 mg chlorthalidone is an effective ratio (Raftery, 1978; Elsdon Dew et al., 1978).
Hence this study was designed to examine the feasibility of substituting once-daily treatment with sustained release oxprenolol hydrochloride and chlorthalidone in group of hypertensive patients whose current treatment was giving inadequate blood pressure control, troublesome side-effects or a combination of both. This study was an open assessment under general practice conditions with individual doctors, each contributing a maximum of five patients.
Patients and Methods
Patients with moderate essential hypertension (with supine diastolic blood pressure values between 106-120 mm Hg), whose current treatment produced inadequate control, troublesome side-effects or a combination of both were included in this study. Newly detected cases and patients who had discontinued treatment were also included The regimen consisted of 160 mg of oxprenolol in sustained -release formulation (TRASI-COR 160 SR) and 25 mg of chlorthalidon: (HY-GROTON) administered once daily in the morning for eight weeks. All patients were seen regularly at intervals of two weeks. At each visit supin. and standing blood pressure and pulse rate were recorded and an assessment of tolerability was made recording the nature, duration and severity of any side-effects.
It is well known that the prognosis of hypertension can be improved by appropriate treatment, provided that patients take the prescribed drugs regularly (Dollery and Bulpitt, 1977). In tact, in anti-hypertensive therapy, the patient\'s cooperation is one of the most important factors in obtaining satisfactory blood pressure control. The percentage of patients who stop taking anti-, hypertensive drugs has been shown to increase to 50% during the first year of therapy and to about: 70% over a 4 year period (Cladwell et al., 1970; Haynes and Sackctt, 1976). The need to take a number of tablets daily tor a long period very often leads to poor compliance (Havnes and Sackctt, 1976).
Our results confirm recent findings that a combination of Oxprenolol + Chlorthalidone, given daily, is well tolerated and permits normalization of diastolic blood pressure (less than 95 mm Hg) in 70% of hypertensive patients (Zan-chetti et al., 1976). This study has shown that a combination of oxprenolol slow-release and chlorthalidone, given once daily, induces normalization of blood pressure in approximately 80% of patients with moderate hypertension.
We are thankful to the following hospital physicians and general practitioners in Pakistan who took part in this study: Dr. S.U. Siddiqui, Karachi; Dr. Ahmed Padhiar, Karachi; Dr. Inamul Haq Qureshi, Karachi; Dr. A. Karim Abassi, Hyderabad; Dr. Akhtar Memon, Hyderabad; Prof. Mumtaz Hassan, Lahore; Dr. Rashid Ahmed, Lahore; Dr. Mohd. Fazil, Multan; Dr. Saced Ahmed, Multan; Dr. Rashid Seyal, Multan; Dr. Saifur Rehman, Dera Ismail Khan; Dr. M. Bashir, Kohat & Dr. Roshan Hilal, Saidu Sharif.
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