Increased drug effect induced by surgery.

1 A thyrotoxic patient receiving a constant dose of propranolol and digoxin developed marked bradycardia postoperatively. 2 Compared to preoperative levels there was a considerable rise post-operatively in both plasma propranolol and serum digoxin steady-state concentrations. 3 Surgery by effecting drug disposition and disease processes may significantly alter drug handling in the perioperative period.

Effects of cimetidine on the elimination and actions of ethanol.

The influence of cimetidine hydrochloride (300 mg four times daily for seven days) on plasma ethanol concentrations and the subjective assessment of intoxication after a single oral dose of ethanol (0.8 g/kg) were investigated in a randomized double-blind placebo controlled study in six volunteers. Compared with the placebo, cimetidine produced a small increase in both the peak plasma ethanol level (from 146 +/- 5.

Increased toxicity and reduced clearance of lidocaine by cimetidine.

Cimetidine reduced liver blood flow and the systemic clearance of drugs, such as propranolol, that are highly extracted by the liver. In a randomized placebo-controlled study, we examined the influence of cimetidine, 300 mg four times daily for 1 d, on the disposition of lidocaine, 1 mg/kg body weight by a 10-minute intravenous infusion. Cimetidine reduced the systemic clearance of lidocaine from 766 +/- 50 mL/min to 576 +/- 47 mL/min (p less than 0.

The many faces of idiopathic oedema of women.

The variable presentation and paucity of physical signs in idiopathic oedema may commonly delay diagnosis. The resultant unnecessary investigations and hazardous treatment are described for six patients. The management of these patients is discussed in the light of the current controversy concerning the role of diuretics in the pathophysiology of this condition.

Propranolol in the surgical treatment of hyperthyroidism, including severely thyrotoxic patients.

The perioperative course of 44 hyperthyroid patients prepared for surgery with propranolol alone, including 11 with severe thyrotoxicosis was compared to that of 20 euthyroid patients prepared for surgery with carbimazole. Conventional propranolol at a dosage of 160 mg/day was frequently insufficient to produce a high degree of beta-adrenergic blockade, particularly in severely thyrotoxic patients. A greater than 25 per cent reduction in sitting pulse rate was associated with a high degree of beta-blockade.

Propranolol and the hypercalcaemia of thyrotoxicosis.

The effect of propranolol on serum calcium was studied in 25 patients with thyrotoxicosis including 5 with hypercalcemia. In patients with hypercalcaemia iv propranolol significantly reduced serum calcium. Oral therapy 160 mg/day reduced calcium non-significantly from 2.

Altered plasma protein binding of drugs in thyroid disease.

The plasma protein binding of propranolol and warfarin was studied in vitro by ultrafiltration in hyper- and hypothyroid patients both before and after treatment. The degree of binding of propranolol was significantly decreased in hyperthyroid patients and increased in hypothyroid patients, and was negatively correlated with serum thyroxine and the free thyroxine index. The plasma protein binding of warfarin was also decreased in hyperthyroid patients, but was unchanged in hypothyroid patients.

The influence of age, smoking and hyperthyroidism on plasma propranolol steady state concentration.

1 Plasma propranolol steady state concentration (Css) was determined during chronic dosage (160 mg/day) in 22 hyperthyroid patients (aged 16-75 years, 11 smokers, 11 non-smokers) and again following treatment when euthyroid. 2 There was a positive correlation between plasma propranolol Css and age in patients both when hyperthyroid (r = 0.74, P less than 0.

Altered endocrine response to partial thyroidectomy in propranolol-prepared hyperthyroid patients.

The endocrine response to partial thyroidectomy in a group of twenty hyperthyroid patients prepared with propranolol alone was compared to that of a matched control group of ten euthyroid patients. In propranolol-prepared patients the glucose response to surgery was reduced (P less than 0.05) for up to 4 h post-operatively and biochemical hypoglycaemia was noted in one patient.

Potassium shift in thyrotoxic periodic paralysis.

A thyrotoxic patient who initially presented with periodic paralysis is described. Precipitation of an attack by a high carbohydrate diet was associated with only a modest fall in plasma potassium but with a marked rise in total blood cell potassium.

Increased clearance of propranolol in thyrotoxicosis.

The pharmacokinetics of oral propranolol were studied during chronic treatment in six patients when thyrotoxic and again when euthyroid. The mean total plasma propranolol steady-state concentration was 42% lower when the patients were thyrotoxic. After treatment of thyrotoxicosis there was a fall (P less than 0.

Reduction of liver blood flow and propranolol metabolism by cimetidine.

We studied the influence of cimetidine on liver blood flow in eight normal subjects. Cimetidine acutely reduced liver blood flow during fasting by almost 25 per cent, as measured by indocyanine green clearance. Chronic cimetidine therapy (300 mg four times daily for seven days) reduced the flow by 33 per cent, as measured over eight hours by calculating the relative disposition of oral and intravenous propranolol.

Plasma propranolol steady state concentrations in thyroid disorders.

Plasma propranolol steady-state concentrations (Css) were measured in 24 hyperthyroid and 6 hypothyroid patients before and after correction of the thyroid disorder. Following treatment of hyperthyroidism by surgery, antithyroid drugs or radioiodine, there was a significant rise in the plasma propranolol Css in patients receiving propranolol either 160 mg/day, 240 mg/day, or 480 mg/day. In addition, in five patients the area under the plasma propranolol concentration versus time curve during a dosing interval increased significantly from 405 ng/ml/h when hyperthyroid to 778 ng/ml/h when euthyroid.

Influence of surgery on plasma propranolol levels and protein binding.

The influence of surgery and anesthesia on perioperative plasma propranolol levels was studied in 25 hyperthyroid and five euthyroid patients undergoing thyroidectomy. Propranolol levels fell markedly after surgery as a consequence of poor drug administration in the immediate postoperative period due largely to patients' nausea and inability to swallow. Propranolol was not detectable in the plasma of three hyperthyroid patients 8 hr after surgery.

Propranolol dosage in thyrotoxicosis.

Eighteen thyrotoxic patients receiving chronic treatment with propranolol (160 mg/day) were studied to determine the relationship between plasma propranolol concentration and drug effect. There was a considerable interindividual variability in both the plasma propranolol steady state concentration and the degree of beta-adrenergic blockade. The plasma propranolol steady state concentration correlated significantly with both beta-adrenergic blockage and weight change but not with the degree of subjective improvement.

Propranolol dynamics in thyrotoxicosis.

Twenty-five thyrotoxic patients were treated with propranolol (160 mg/day) for 1 to 2 wk. Although the response to therapy varied there was a reduction (p less than 0.001) in supine and exercise heart rates and in sitting pulse rate.

Beta-adrenoceptor-blocking drugs, growth hormone and acromegaly.

Chronic treatment with oxprenolol or propranolol in active hypertensive patients was associated with elevation of serum growth hormone (GH). Propranolol, 80 mg orally, caused a marked rise in GH in 3 of 4 acromegalic patients.

Hyperthyroidism in the land of Graves: results of treatment by surgery, radio-iodine and carbimazole in 837 cases.

A review of the outcome of treatment by subtotal thyroidectomy, radio-iodine and carbimazole of 837 patients with hyperthyroidism seen consecutively over the period 1954--78 inclusive is presented. The age and sex distribution, the male to female ratio, the ABO blood group distribution and the prevalence of pernicious anaemia and diabetes mellitus in these patients was also analysed. Life-table data showed that the five-year and ten-year cumulative relapse rates following a two-year course of carbimazole (n = 162) were 56 per cent and 62 per cent; following surgery (n = 266), 6 per cent and 10 per cent and following radio-iodine (n = 43), 3 per cent and 14 per cent.