Pharmacist involvement in Norwegian clinical drug trials: a questionnaire study.

In order to survey the involvement of pharmacists in clinical drug trials (CDTs) in Norway, a questionnaire was submitted to all community pharmacies (288), pharmacy departments in hospitals (98), and pharmaceutical companies (52). The response rate was 81, 73, and 64 percent, respectively. Community pharmacies had minimal involvement, while 34 percent of the pharmacy departments had taken part in one or more CDTs annually 1980-1982. During the same three-year period, 393 trials had been started by the responding companies. Within the pharmaceutical industry 41 percent of the CDT staff were pharmacists. Pharmacists in 48 percent of community pharmacies and 96 percent of pharmacy departments in hospitals considered CDTs a pharmaceutical task. However, none of the community pharmacists and less than half of the hospital pharmacists said they had knowledge of CDT methodology. We recommend that pharmacists should be more extensively engaged in CDTs. Their participation should not be limited to traditional pharmaceutical work, but should include CDT planning and monitoring. This in turn requires education in CDT methodology, which should be included in the compulsary pharmaceutical curriculum.

Comparative effects of long-acting and conventional propranolol on stress-induced angina pectoris and on frequency of ventricular premature beats.

Ten male patients with chronic stable angina pectoris completed a randomized, double-blind cross-over study, with matched placebo run-in period (P), to compare the effects of a long-acting preparation of propranolol (LA, 160 mg once a day) with that of conventional propranolol (CP, 40 mg four times a day) each given for 14 days. Response was assessed by symptom-limited bicycle ergometry, degree of ST segment depression, daily anginal attack rate and glyceryl trinitrin consumption (GTN). Heart rate and ventricular extra-systolic frequency (VES) were recorded by 24 h Holter monitor. Bicycle ergometry was performed and a trough blood sample taken for propranolol estimation on day 14 prior to the morning dose. Both formulations increased total work capacity (P 3412, LA 4095, CP 3697 kpm/min), reduced rate-pressure product (P 21896, LA 16011, CP 15609 mm Hg beats/min), and degree of ST segment depression (P 4.53, LA 2.48, CP 2.43), but without differences between the formulations. Daily anginal attack rate was reduced from 30 (placebo) to 7.5 (CP) and 14.5 (LA) (P less than 0.05 between treatment groups). There was a reduction in daily GTN consumption by both treatments. The heart rate and total number of VESs during 24 h was similar in the two treatment groups and was reduced in comparison with placebo. Both formulations were well tolerated. Long-acting propranolol is an effective and well-tolerated alternative to conventional propranolol in the treatment of chronic stable and stress-induced angina, and in reducing VES frequency.

Increased plasma free dopamine after treatment with atenolol and oxprenolol in essential hypertension.

In 19 men aged 50 with essential hypertension, 18 weeks' treatment with atenolol (n = 9) or oxprenolol (n = 10) increased supine plasma free dopamine concentrations by 78% (p less than 0.05) and 121% (p less than 0.001) respectively. Increments in plasma dopamine were observed in all patients except for one treated with atenolol. Supine peripheral venous adrenaline and noradrenaline concentrations were not influenced by beta-blockade. The mechanism and significance of the present elevation of plasma free dopamine by beta-blockade are unknown. However, increased plasma free dopamine may be involved in the hypotensive effect of chronic beta-adrenergic blockade, both beta-1 selective and non-selective, and may lend further support to decreased dopaminergic activity in essential hypertension.

The effect on HDL cholesterol of oxprenolol and atenolol.

In 19 healthy men aged 50 with untreated mild essential hypertension (WHO group I classification) randomized into two groups, treatment (18 weeks) with oxprenolol (n = 10) lowered HDL cholesterol by 11.4% (P less than 0.02) and cholesterol ratio (HDL cholesterol X 100/LDL + VLDL cholesterol) by 13.7% (P less than 0.05) whereas atenolol (n = 9) lowered HDL cholesterol by 16.5% (P less than 0.02) and cholesterol ratio by 19.2% (P less than 0.01). In the total material (n = 19) the reduction of HDL cholesterol correlated positively with initial concentration of HDL (r = 0.48, P less than 0.05). Increments of total triglycerides by 20.0 and 17.9%, respectively, for the two drugs and small changes in total cholesterol, LDL + VLDL cholesterol and uric acid were not significant. The HDL cholesterol lowering effect of oxprenolol and atenolol observed in the present study may have clinical importance since such metabolic side effects have been postulated to counteract the beneficial effect of blood pressure reduction on development of atherosclerosis and coronary heart disease in mild essential hypertension.