Search PubMed⌕ Search

Biomedical subjects

I H Stevenson

Publications and source records attributed to I H Stevenson.

At least 37 records · Page 2Linked to original sources

Nadolol in thyrotoxicosis.

1 Twenty outpatients with thyrotoxicosis received the non-selective beta-adrenoceptor antagonist nadolol as sole treatment for 3 weeks. 2 Clinical improvement as measured by reduction in thyrotoxicosis therapeutic index occurred during the first week of treatment and was continued thereafter, and was accompanied by a significant reduction in serum T3 and elevation of serum reverse T3. 3 As measured by reduction in exercise heart rate, during chronic dosing nadolol 160 mg once daily produced blockade of beta-adrenoceptors for 12 h in all patients and 24 h in all but 2. 4 Wide interindividual variability was noted in steady state plasma nadolol concentrations, in part related to age and renal function. 5 Steady state plasma nadolol concentrations were related to reduction in heart rate.

Adrenergic beta-Antagonists↗

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↗

Drug response in the elderly--sensitivity and pharmacokinetic considerations.

There is now a considerable body of evidence to indicate that response to many drugs changes as people ages. As a result, interest has increased in recent years in the investigation of mechanisms contributing to altered drug responsiveness with age. Significant changes in pharmacokinetics and/or tissue sensitivity have been shown to occur. In the former cases, decreased renal elimination is undoubtedly the most important factor but decreased plasma protein binding and rate of metabolism may also be of clinical significance. In the case of tissue sensitivity, there have been few opportunities so far to determine age-related changes in the number and sensitivity of drug receptors and studies have been largely confined to relating drug effect to plasma levels in patients of different age. Such studies in the elderly have been complicated by alteration in the normal homoeostatic mechanisms and by the presence of disease. Further work in both healthy volunteers and patients is necessary to provide a comprehensive data base from which drug regimens appropriate for elderly patients may be developed.

Aged↗

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↗

Plasma 8-methoxypsoralen concentrations in photochemotherapy of psoriasis.

A quantitative study of 8-methoxypsoralen plasma profiles in patients with psoriasis undergoing photochemotherapy shows that a poor response to the treatment may be explained in terms of abnormal pharmacokinetic behaviour. However, not all 'poor responders' exhibit an abnormal pattern and for these an alternative explanation is required.

Adult↗

Cardiovascular, sedative and anticholinergic effects of amitriptyline and zimelidine in young and elderly volunteers.

Single doses of amitriptyline (50 mg) and zimelidine (100 mg) were administered orally to 4 young and 4 elderly healthy volunteers (aged 21--26 and 68--75 respectively) in a comparative study of the two drugs. Systolic time intervals, supine and standing blood pressure, salivary flow and indices of sedation were measured at regular intervals up to 6 hours post dose. No conclusive changes in the QS2 interval, left ventricular ejection time (LVETc) LVET index, pre-ejection period (PEPc), resting heart rate, or blood pressures were observed with either drug. Salivary flow was reduced by about 40% at 3.5 hours and 50% at 5.5 hours after ingestion of amitriptyline. No change in salivary flow was observed after zimelidine (significant difference between treatments; P less than 0.01 at 3.5 and 5.5 hours). Subjective drowsiness as measured by visual analogue ratings was significantly greater for amitriptyline at 3.5 hours (P less than 0.01). Postural sway was also increased by amitriptyline but not zimelidine (difference between treatments significant at 3.5 and 5.5 hours; P less than 0.01 and 0.05 respectively). Auditory reaction time increased with amitriptyline, the difference between treatments achieving significance at 5.5 hours. No differences in response to either drug between young and elderly volunteers were demonstrable in these small groups, although variability was greater in the older group. Possible implications of these findings for the treatment of depression in the elderly are discussed.

Adult↗

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↗

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↗

Patterns of drug prescribing for children in hospital.

The drugs prescribed for children in Tayside hospitals in 1974 and 1975 were surveyed using the computer files of over 4000 children in each year. The results were compared with similar data on adult patients. Although similar proportions of both age groups received drugs, less than 3 drugs were prescribed for the great majority of the children (mean 2.5) compared with twice that number for adults. Seven classes of drugs accounted for almost four-fifths of the drugs prescribed for children but the same classes formed two-fifths only of the total drug use in adults. There was significantly greater use of antihistamine/sedative, anticonvulsant and decongestant/mucolytic drugs in children than in adults while the reverse was true for diuretics, KCL, cardio active agents, sedatives/hypnotics, and tranquillisers. Antimicrobial drugs accounted for approximately one-third of the total drugs used in children and one half of all patients received at least one drug from this class. Penicillin preparations alone accounted for 65.1 per cent of all antimicrobial drug use. The percentage of children given ampicillin fell by almost half from 1974 to 1975 with a corresponding increase in the proportion receiving amoxycillin.

Age Factors↗

Reduced induction of drug metabolism in the elderly.

Young and elderly subjects were given the hypnotic dichloralphenazone (Welldorm) in a dose of 20 mg/kg nightly for two weeks and the extent of induction of liver microsomal drug metabolism was assessed from alteration in the plasma elimination of quinine and antipyrine (phenazone). With both indices, there was a significant increase in plasma drug clearance in young subjects following dichloralphenazone treatment but no significant alterations occured in the elderly group. These results indicate that, in addition to being less able to metabolize some drugs, elderly patients show a reduced induction response. They may therefore be less likely to become tolerant to those drugs which are inactivated by metabolism.

Adult↗