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Biomedical subjects

J Feely

Publications and source records attributed to J Feely.

At least 145 records · Page 8Linked to original sources
PubMed1982

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 +/- 5.2 to 163 +/- 7.6 mg/dL, mean +/- SEM) and th area under the ethanol concentration time curve (from 717 +/- 17 to 771 +/- 44 mg/dLXhr). In addition, using a visual analogue scale, subjects rated themselves more intoxicated at their peak of intoxication while receiving cimetidine. These results suggest that cimetidine has a small effect on the handling of ethanol in humans.

Adult↗
PubMed1982

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.

Bradycardia↗
PubMed1982

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 0.05); the apparent volume of distribution at steady-state and the degree of plasma protein binding of lidocaine also were decreased. Five of the six subjects noted lidocaine toxicity during the cimetidine infusion in contrast to one subject on the placebo day. The peak lidocaine concentration (mean +/- SE) was 50% +/- 10% higher when subjects received cimetidine. This study provides additional evidence that the effect of cimetidine on the elimination of other drugs has multiple factors, and shows a previously unrecognized mechanism, involving altered initial drug distribution, whereby the interaction of cimetidine with other drugs may cause toxicity.

Adult↗
PubMed1981

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. In addition to reducing the clearance of intravenous propranolol by decreasing live blood flow, cimetidine also inhibited the metabolism of oral propranolol and thereby further reduced elimination. The reduction in clearance of oral propranolol correlated positively (r = 0.87, P less than 0.05) with the average steady-state concentration of plasma cimetidine, suggesting that the inhibition of drug metabolism by cimetidine is dose related. Pulse rates at rest were markedly lower after propranolol plus cimetidine than after propranolol alone. The reduction in liver blood flow produced by cimetidine has important therapeutic implications for patients with alterations in liver and gastrointestinal blood flow and when drugs are used whose hepatic elimination depends on liver blood flow.

Administration, Oral↗
PubMed1981

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. The clinical course of patients with mild or moderate thyrotoxicosis was similar to that of the patients prepared with carbimazole. In contrast, the course of severely thyrotoxic patients was complicated and, in addition to a higher preoperative propranolol dosage, these patients commonly required supplemental propranolol after operation. Although thyroid crisis did not occur in any patient, we cannot recommend the use of propranolol alone for the severely thyrotoxic patient.

Adult↗
PubMed1981

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. In the hypothyroid patients given propranolol 160 mg/day concomitantly with 1-thyroxine therapy the plasma propranolol Css fell significantly when euthyroid. There was a small but significant increase in the degree of plasma protein binding of propranolol, following treatment of hyperthyroidism and a significant decrease following correction of hypothyroidism. It is concluded that thyroid disorders markedly influence propranolol handling.

Adolescent↗
PubMed1981

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 0.01) and when euthyroid (r = 0.58, P less than 0.05). 3 Plasma propranolol Css in hyperthyroid patients were lower (P less than 0.05) in smokers than in non-smokers. 4 Following correction of hyperthyroidism there was a significant increase (P less than 0.01) in both the plasma propranolol Css and degree of plasma protein binding of propranolol. 5 Hyperthyroidism and smoking are known to increase the rate of drug metabolism and it is suggested that these variables may give rise to or accentuate an age related reduction in propranolol clearance.

Adolescent↗
PubMed1981

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. Both thyroxine and triiodothyronine (T3) fell significantly, associated with a marked rise in reverse T3. Growth hormone levels were higher (P less than 0.05) both pre- and post-operatively in propranolol-prepared patients, whereas prolactin levels, although similar pre-operatively, were lower (P less than 0.05) in these patients post-operatively. Cortisol and ACTH levels were lower (P less than 0.05) both before and following thyroidectomy in propranolol-prepared patients. These results suggest that the endocrine response to surgical stress is markedly altered in propranolol-prepared hyperthyroid patients.

Adrenocorticotropic Hormone↗
PubMed1981

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.

Adult↗
PubMed1981

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 2.72 +/- 0.09 (mean +/- SD) to 2.59 +/- 0.13 mmol/l, however on 320 mg/day the reduction (to 2.5 +/- 0.15 mmol/l) was significant. In normocalcaemic patients oral propranolol did not influence serum calcium. Both in hyper- and normocalcemic thyrotoxic patients propranolol increased (P less than 0.01) serum phosphate.

Adolescent↗
PubMed1981

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 0.05) in the oral clearance of both total (4.2 +/- 0.6 to 2.7 +/- 0.4 L/min, mean +/- SEM) and free (30.5 +/- 4.7 to 25.5 +/- 4.1 L/min) propranolol although the half-life of propranolol did not change significantly. The free fraction of propranolol was higher (p less than 0.05) in the thyrotoxic (14.2% +/- 1.3%) than in the euthyroid (11.4% +/- 0.8%) state. These results suggest that the pharmacokinetics of propranolol are significantly altered in thyrotoxicosis.

Administration, Oral↗
PubMed1980

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. Serum triiodothyronine (T3) fell (p less than 0.001) and serum thyroxine did not change during propranolol therapy. Plasma propranolol levels before assessment varied from 5 to 121 ng/ml, and there were positive correlations between them and percentage reduction in exercise (r = 0.78, p less than 0.001) and resting (r = 0.61, n = 14, p less than 0.05) heart rates, percentage reduction in sitting pulse rate (r = 0.73, p less than 0.001), and the percentage reduction in serum T3 (r = 0.59, n = 23, p less than 0.01). Although weight loss ceased in the group as a whole the degree of continued weight loss or weight gain in individual patients was also related to plasma propranolol concentration (r = 0.61, p less than 0.01). The plasma propranolol level correlated (r = 0.62, p less than 0.01) with thyrotoxicosis therapeutic index. There was no correlation between degress of subjective improvement and plasma propranolol level.

Adolescent↗