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1 A preliminary survey showed that many outpatients with partially controlled epilepsy had serum concentrations of phenytoin below the recommended therapeutic range (10-20 μg/ml). A phenytoin tolerance test was devised with the intention of predicting a more adequate daily dose for such a patient. 2 Fifteen patients were each given an oral test dose of 600 mg phenytoin sodium and the serum concentration of phenytoin was measured at intervals over 48 h; the concentration rose during the first 4 h and decayed between 12-48 h as an almost linear function of time. 3 The serum concentration/time curves were fitted by an interative computer program based on the Michaelis-Menten equation. The mean saturated rate of elimination of phenytoin was 435 mg/day and the serum concentration (K(m)) corresponding with 50% saturation was 3.8 μg/ml. The mean calculated dose of phenytoin sodium required for a steady state serum concentration of 10-20 μg/ml was 345-400 mg/day. 4 The Michaelis-Menten principle was used to predict steady state serum phenytoin concentrations in individual patients receiving daily doses of phenytoin sodium adjusted by steps of 100 mg. The serum concentrations tended to be either too low or too high. The steep relationship between phenytoin concentration and dose indicates that when the concentration reaches 5-10 μg/ml it is then appropriate to adjust dose by small steps of about 25 mg.

1 Fifteen patients with diastolic blood pressures between 90 and 120 mmHg were admitted to a trial comparing placebo with practolol at doses up to 500 mg 12 hourly. 2 The trial was a double blind cross over study. Treatments were allocated at random and each treatment block lasted 12 weeks. 3 Ten patients completed the trial, and none of those who withdrew experienced serious unwanted effects. 4 Practolol caused significant falls in standing systolic and diastolic pressures and the supine diastolic pressure.

1 Intravenous propranolol and practolol both reduced resting supine heart rate in patients with hyperthyroidism. Propranolol produced a significantly greater reduction than practolol, which did not have a dose-dependent effect. 2 The effect of these drugs on resting heart rate was much less than their effect on the tachycardias produced both by severe exercise and by standing upright in hyperthyroid patients. Propranolol again produced a significantly greater reduction than practolol in each situation, but practolol did have a dose dependent effect on exercise heart rate. 3 The percentage reduction of standing tachycardia produced by the two drugs appeared to parallel closely the reduction in exercise tachycardia. 4 It is concluded that a simple and convenient way of assessing the activity of β-adrenoceptor blocking drugs in hyperthyroid patients would be to measure their effect on the tachycardia induced by standing. Their effect on resting heart rate should not be used. 5 Practolol may be useful in the management of hyperthyroidism in patients in whom propranolol and similar non-selective β-adrenoceptor blocking drugs are contraindicated.

1 Δ(1)-trans-tetrahydrocannabinol (Δ(1)-THC; 10 mg) or a placebo was given orally on 7 days to two groups of six patients on a cross-over pattern with 7 days rest between. 2 The patients were hospitalized, suffering from inoperable bronchogenic carcinoma, subjected to radiation therapy, and anxious. 3 Self-rating mood scales were filled in before, and 2 and 6 h after ingestion on the first and seventh day of medication. 4 Records of sleep, pain, general well-being, temperature, cardiovascular and gastrointestinal parameters were kept. 5 Δ(1)-THC caused drowsiness and improved night sleep, reduced pain, increased fatigue and confusion and reduced elation and vigour; it caused slight tachycardia and hypotension as also did placebo. 6 The effects of Δ(1)-THC were stronger after 2 h than 6 h and no tolerance had developed at 7 days. 7 The management of stressful patients was considered to have been improved by the drug.

1 ST-91, 2-(2,6-diethylphenylamino)-2-imidazoline hydrochloride produces in animal experiments bradycardia, and in larger doses, also hypertension, due to α-sympathomimetic activity and probable central sympathetic inhibition. 2 The effects of ST-91, after oral administration, were studied in 10 healthy volunteers. A dose-dependent, significant decrease of the heart rate was observed. On average the resting heart rate was reduced by 11-19 beats/min (15-29%). During exercise the decrease of the heart rate was less pronounced. After the largest dose there was a fall of the systolic blood pressure during exercise averaging at 14-15 mmHg (11-12%). Otherwise the blood pressure remained unchanged. 3 Eight out of the 10 test-subjects complained of hair-raising and goose-flesh after all doses, due to the α-sympathomimetic effect of the drug. No toxic effects were observed.

1 Ko 1313 competitively inhibited the increases in heart rate produced by isoprenaline in anaesthetized dogs. 2 Ko 1313 was 35 times more active than propranolol in blocking an isoprenaline induced tachycardia in anaesthetized dogs but only three times more active in blocking the increase in femoral blood flow produced by the injection of isoprenaline into the femoral artery. These observations suggest that Ko 1313 may have some cardio-selective activity. 3 When a series of doses of Ko 1313 was injected intravenously into anaesthetized dogs, the lower doses decreased heart rate while the larger doses increased heart rate. The same doses of propranolol reduced heart rate. 4 In lightly anaesthetized dogs, a series of doses of Ko 1313 progressively increased heart rate while propranolol produced little change. These observations indicate that Ko 1313 has slight intrinsic sympathomimetic activity. 5 The oral administration of Ko 1313 and propranolol had no effect on resting heart rate in man but reduced the increases produced by head-up tilt, standing and exercise.

1 The effect of propranolol 2 h following doses of 10, 30, or 100 mg upon the blood oxygen-haemoglobin dissociation curves has been studied in four normal subjects. 2 The pO2 at 50% saturation (p50) was not changed significantly under control conditions or after 10 and 100 mg doses. There was a just significant increase of 2 mmHg in the p50 value after the 30 mg dose. 3 There was no significant change in red cell adenosine triphosphate or 2, 3-diphospho-glycerate nor in plasma phosphate. 4 There was no correlation between plasma propranolol concentration and changes in blood p50.