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Biomedical subjects

S G Carruthers

Publications and source records attributed to S G Carruthers.

At least 55 records · Page 3Linked to original sources
PubMed1986

Evaluation of once daily endralazine in hypertension.

Endralazine, a novel vasodilator related to hydralazine, exhibits a longer half-life and is only minimally influenced by acetylator status. The antihypertensive action of once daily endralazine has been studied in 17 patients previously controlled with an antihypertensive regimen which included hydralazine and a beta-blocker. Hydralazine was discontinued but other medications were unchanged. Pre-study dosage of hydralazine ranged from 25 mg b.i.d. to 50 mg g.i.d., mean daily dose 126.5 mg. Endralazine was started at a dose of 10 mg o.d. and increased by 10 mg to a maximum of 40 mg o.d. until seated DBP was controlled below 95 mmHg. All 17 patients completed the study. Seated BP significantly decreased from 147.5/99.7 to 133.8/83.9 and standing BP from 145.8/99.2 to 133.6/87.3 mmHg. Ten patients (59%) were successfully controlled with endralazine once daily but 7 patients required twice daily dosage schedules because of lack of BP control at 24 h after dosing or excessive hypotension shortly after dosing. Other adverse effects were headache, palpitations and fatigue. There was a statistically insignificant average weight gain of 1 kg but pedal edema was not observed. Endralazine is an effective antihypertensive agent with adverse symptoms similar to those experienced with hydralazine.

Acetylation↗
PubMed1986

The influence of age on dorsal hand vein responsiveness to norepinephrine.

The influence of age on the responsiveness of dorsal hand vein alpha-receptors to local infusions of norepinephrine was investigated by the use of a novel technique, the linear variable differential transformer. Studies were conducted in two groups of healthy subjects, 26 elderly individuals (14 men and 12 women) 60 to 78 years old and 32 young individuals (24 men and eight women) 16 to 29 years old. There was wide interindividual variation in responsiveness to norepinephrine within both groups of subjects. The dose of norepinephrine required to produce 50% venoconstriction in the elderly ranged from 1.5 to 300 ng/min (geometric mean 24.0 ng/min). The dose required to produce 50% venoconstriction in younger individuals ranged from 1.6 to 360 ng/min (geometric mean 23.8 ng/min). These results suggest that there is no systematic influence of age on dorsal hand vein alpha-receptor responsiveness. A power calculation demonstrates a very small likelihood of a type II error.

Adolescent↗
PubMed1986

Respiratory and cardiac effects of metoprolol and bevantolol in patients with asthma.

The effects on standing heart rate and respiratory function of two relatively selective beta 1-adrenoceptor antagonists, metoprolol and bevantolol, were compared in a double-blind, randomized, crossover study of 16 patients with asthma. After control observations on 2 separate days, the patients received approximately equivalent cardiac beta-adrenoceptor antagonist doses of metoprolol, 12.5, 25, 50, and 100 mg, and bevantolol, 18.75, 37.5, 75 and 150 mg, at intervals of 2 hours. Dosing was stopped if symptoms warranted or if there was a fall of greater than or equal to 20% in the forced expiratory volume in 1 second. In general, the cumulative dosing regimen proved a safe and effective means of assessing bronchial responsiveness to these beta-blockers in asthma, but one patient had to be dropped from the study because of severe bronchoconstriction after the first dose. Of the 15 patients studied who were taking both drugs, seven patients were withdrawn prematurely. In these seven patients, the average maximum tolerated cumulative doses were 45.5 mg bevantolol and 26.8 mg metoprolol, doses that are much lower than those usually required for therapeutic activity. The respiratory response to either drug could not be predicted.

Administration, Oral↗
PubMed1986

Gastric emptying before and after transverse gastroplasty for morbid obesity.

Twenty-three morbidly obese patients underwent gastric emptying studies (Tc-99m egg salad sandwich--a semisolid meal) preoperatively, and at three months and 12 months postoperatively to evaluate the effect of transverse gastroplasty on gastric emptying and to determine the predictive value of this study for weight loss. At three months pouch emptying was variable with nine of 23 patients having prolonged half-times, and 14 shortened half-times compared with preoperative values, despite both groups having identical weight loss. At 12 months pouch half-times returned to baseline. The data suggests that this type of gastroplasty causes weight loss solely by reducing the gastric volume resulting in reduced meal volume. Weight loss is not related to impaired pouch emptying, which might result in a prolonged feeling of fullness. Gastric emptying studies neither preoperatively nor postoperatively have weight loss predictive value for this particular operation.

Adult↗
PubMed1986

Simplified liquid-chromatographic assay of amiodarone and desethylamiodarone after solid-phase extraction.

We describe a rapid, simplified isocratic "high-performance" liquid-chromatographic method for simultaneous measurement of the antiarrhythmic drug amiodarone and its major metabolite, desethylamiodarone, in small volumes of sera (100 microL). Compared with liquid-liquid extraction, the solid-phase method of extraction saves time and glassware and improves reproducibility for small sample volumes. Amiodarone and desethylamiodarone could be measured at concentrations as low as 250 micrograms/L. Standard curves for the drug and metabolite are linear over the range of concentrations found in our patients. Within-run CVs (n = 6) ranged from 2.7% to 4.5% for amiodarone and from 4.0% to 5.7% for desethylamiodarone over the range of 250 to 4000 micrograms/L. Between-run CVs (n = 12) were 8.3% and 5.7% for amiodarone and desethylamiodarone, respectively. Commonly used cardiovascular medications do not interfere with the assay.

Amiodarone↗
PubMed1985

Evaluation and application of the linear variable differential transformer technique for the assessment of human dorsal hand vein alpha-receptor activity.

Diurnal, day-to-day, intrasubject, and intersubject variability of responsiveness of dorsal hand veins to norepinephrine has been investigated in healthy young subjects through the use of a novel technique in which a linear variable differential transformer (LVDT) is placed directly over the vein. Under constant operating conditions, control vein diameter remained consistent. There is a log dose responsiveness to norepinephrine infused directly into the hand vein. There was little diurnal, day-to-day, or intrasubject variability in the dose of norepinephrine required to induce 50% constriction of hand vein diameter. The responsiveness to norepinephrine of different veins in either hand was also consistent. However, there was wide intersubject variability, apparently unrelated to age, gender, or other subject characteristics. We conclude that the LVDT method is reproducible and reliable and offers a relatively noninvasive means of assessing the effects of disease and drugs on the human dorsal hand vein in vivo. The LVDT technique has been applied to study the rate of onset, magnitude of effect, dose responsiveness, and duration of action of intravenous dihydroergotamine, 0.1, 0.2, and 0.4 mg, on human dorsal hand veins. Despite systemic intravenous administration, there was an average delay in maximum response of 30 minutes to 1 hour. Venoconstriction was incomplete, with a maximum reduction of approximately 50% of vein diameter after each of the larger doses. There was no significant difference between the effects produced by 0.2 or 0.4 mg, which persisted for 6 hours after dosing.

Adult↗
PubMed1985

Contrasts between pindolol and propranolol concentration-response relationships.

The plasma concentration-response relationships of oral and intravenous pindolol and propranolol have been studied in a group of eight healthy male subjects who received each dosage form in a randomized single-blind cross-over manner. Despite similar elimination half-lives, the duration of action of pindolol was longer than that of propranolol. This longer duration of action was associated with a flatter concentration-response curve for pindolol and may be related to the partial agonist activity of pindolol. Propranolol concentration-response curves were dependent on the route of drug administration whereas pindolol curves were similar following oral and intravenous routes of administration.

Adult↗
PubMed1984

Verapamil in chronic atrial fibrillation: variable patterns of response in ventricular rate.

We determined the effects of single intravenous (10 mg) and oral (80, 160 mg) doses of verapamil in 8 digitalized patients with chronic atrial fibrillation. The time course of drug effect was analyzed with computer assistance by considering several measures in atrial fibrillation, including average R-R interval (ARR), shortest R-R interval (SRR), longest R-R interval (LRR), and variability of R-R intervals. Peak plasma concentrations of verapamil were observed immediately after intravenous verapamil (mean elimination half-life of 3.3 h) and 1 hour after oral verapamil (mean elimination half-life 3.4 h, 80 mg; 3.1 h, 160 mg). In contrast to previous studies, we observed the maximum bradycardic effect of intravenous verapamil to occur at one-half to 1 h, and this effect lasted for 2-4 h. Following oral verapamil the peak effect occurred at 3-4 h and lasted for 5-8 h. Analysis of the time course of changes in APR, SRR, LRR, and variability of R-R revealed two distinct "patterns" of ventricular response. In one group (4 of 8 patients), verapamil caused an increase in SRR but a decrease in LRR. R-R intervals "regularized" in this group. In the remaining patients, verapamil increased the SRR but did not change or increase the LRR. This enhanced the observed increase in ARR intervals. We postulate that the decrease in LRR intervals after verapamil is due to reflex adrenergic discharge as a result of the vasodilator effect of the drug while the increase in SRR is a direct effect. These two opposing effects result in regularization of R-R intervals in many patients. Patients demonstrating an increase in LRR intervals after verapamil may not get reflex adrenergic discharge or may be incapable of responding to the latter due to conduction disease; these patients may experience bradycardic complications after verapamil.

Adult↗
PubMed1984

Influence of cardioselectivity and respiratory disease on pulmonary responsiveness to beta-blockade.

The effects on ventilation of the non-selective beta-blocker propranolol, and the relatively cardioselective beta-blocker, metoprolol, were compared in a randomized single-blind crossover study in 16 patients with asthma, bronchitis and emphysema (American Thoracic Society criteria). Group I had "fixed" airways disease with less than 20% improvement in FEV1 following inhaled salbutamol 5 mg by nebuliser. Group II had "reversible" obstruction, greater than 20% improvement. Bronchodilator therapy was withheld for 24 h with the exception of aerosols which were permitted until 12 h before study. After control observations on each of 2 study days, each patient received cumulative doses of propranolol (maximum 170 mg) and metoprolol (maximum 187.5 mg). Ventilatory function (FEV1, FVC, FEV1%) was assessed at 0, 2, 4, 6 and 8 h. In Group I, 2 patients were unable to complete the study. One patient became dizzy with propranolol 70 mg but tolerated metoprolol 187.5 mg. One patient developed wheeze with propranolol 15 mg but tolerated metoprolol 187.5 mg. Metoprolol was tolerated in all 8 patients with "fixed" disease, although FEV1 was reduced by more than 30% in 1 patient. Three patients in Group II did not complete the study because of wheezing following propranolol 10 mg, metoprolol 37.5 mg; propranolol 17.5 mg, metoprolol 37.5 mg; propranolol 45 mg, tolerated metoprolol 187.5 mg respectively. Wheezing responded in all cases to inhaled isoprenaline. The response to either propranolol or metoprolol was unpredictable in patients with "reversible" disease. When wheezing occurred in this group, it developed following small, potentially subtherapeutic doses of each drug. Although metoprolol was better tolerated, the practical benefit of cardioselectivity in those patients with reversible airways disease was negligible.

Adrenergic beta-Antagonists↗
PubMed1984

Evaluation of cyclosporin-phenytoin interaction with observations on cyclosporin metabolites.

We have observed that patients on concurrent cyclosporin and phenytoin therapy required increased doses of cyclosporin to maintain therapeutic concentrations of this novel immunosuppressive drug. We have, therefore, studied the influence of phenytoin on the pharmacokinetics of oral cyclosporin in six healthy male subjects. Cyclosporin concentrations in serum and whole blood were measured by high pressure liquid chromatography (h.p.l.c.) and radioimmunoassay (RIA). Concentrations of cyclosporin in whole blood were consistently higher than corresponding values in serum. Concentrations of cyclosporin determined by RIA were also consistently higher than those determined by h.p.l.c. Irrespective of the biological fluid (serum or whole blood) or the type of drug analysis (h.p.l.c. or RIA), changes in cyclosporin kinetics following phenytoin administration exhibited similar patterns. Phenytoin significantly reduced the maximum concentration and the area under the concentration-time curve and significantly increased total body clearance of cyclosporin. There was a statistically significant reduction of cyclosporin half-life (t 1/2) in whole blood using h.p.l.c. analysis. However, there was no significant change in cyclosporin t 1/2 in serum following phenytoin administration, using either form of drug analysis. Cyclosporin metabolites 17 and 18 were measured by h.p.l.c. in whole blood samples only, since these metabolites were found almost entirely in red blood cells. Phenytoin significantly reduced the Cmax and AUC of both metabolites, but no significant change was observed in the t 1/2 of either. Phenytoin enhanced the metabolism of antipyrine which was co-administered with cyclosporin to assess oxidative enzyme activity. We conclude that patients undergoing organ transplantation should be carefully monitored if they require phenytoin or other drugs known to accelerate oxidative metabolism.

Adult↗
PubMed1984

A study of efficacy, tolerance and compliance of once-daily versus twice-daily metoprolol (Betaloc) in hypertension. Betaloc Compliance Canadian Cooperative Study Group.

The effects of metoprolol (Betaloc tablets) in a group of 193 hypertensives were compared with the effects of a slow-release formulation (Betaloc Durules) in a further group of 196 patients. Patients were selected at random for treatment. There were no differences between the groups in terms of age, weight, sex, blood pressure, concurrent illness or concomitant therapy. Blood pressure control and apparent adverse effects were similar for both groups; the overall withdrawal rate from each group was similar. Compliance, assessed by tablet counts, was significantly improved in the group receiving once-daily therapy. Simplification of the dosage regimen to once-daily therapy appears to improve the patient's willingness to comply with the physician's instructions.

Clinical Trials as Topic↗
PubMed1983

Pindolol and propranolol in patients with angina pectoris and normal or near-normal ventricular function. Lack of influence of intrinsic sympathomimetic activity on global and segmental left ventricular function assessed by radionuclide ventriculography.

To investigate the role of intrinsic sympathomimetic activity on left ventricular (LV) function during antianginal therapy with beta-adrenoreceptor antagonists, 23 patients with chronic, exercise-induced angina pectoris and normal or near normal LV function underwent radionuclide ventriculography at rest and during exercise, during 3 randomly allocated periods: (a) treatment with oral propranolol, a drug without intrinsic sympathomimetic activity, 40 to 80 mg 4 times a day; (2) treatment with pindolol, a drug with marked intrinsic sympathomimetic activity, 5 to 10 mg 2 times a day; and (3) a control period. During the control period, the LV ejection fraction decreased from rest (58.9 +/- 8.2%) to exercise (54.3 +/- 10.7%), and the wall motion score decreased from 0.57 +/- 1.08 at rest to 2.39 +/- 2.10 during exercise, p less than 0.001. After propranolol, the ejection fraction did not change significantly at rest (57.2 +/- 8.1%) but improved during exercise (56.8 +/- 11.8%), compared with control values. After pindolol, the ejection fraction did not change at rest (57.9 +/- 8.6%) but improved during exercise (56.9 +/- 8.1%), compared with control values. Similarly, the wall motion score after administration of both agents did not change significantly at rest, but improved during exercise (p less than 0.001). The number of anginal episodes, nitroglycerin tablets consumed, and magnitude of S-T segment depression decreased significantly with both pindolol and propranolol. With both drugs, a similar improvement in exercise tolerance and a similar decrease in exercise heart rate and blood pressure were obtained. It is concluded that pindolol and propranolol, beta-adrenoreceptor antagonists with and without intrinsic sympathomimetic activity, respectively, have similar effects on global and regional LV function in patients with angina pectoris, at doses producing equal suppression of exercise heart rate and similar antianginal effect.

Adult↗
PubMed1983

An audit of requests for therapeutic drug monitoring of digoxin: problems and pitfalls.

The use of serum digoxin measurements in a teaching hospital was audited. The reason for test requisition, the timing of blood samples, the recognition of results, and the action taken by house staff were assessed using formal criteria. In 200 consecutive requests for serum digoxin measurements, the reason for requesting the test could not be determined in 165 (82.5%). The timing of plasma samples with respect to duration of therapy and time since last dose was usually satisfactory. However, only 73 (36.5%) of results appear to have been adequately recognized, and approximately 1 result in 4 was followed by an inappropriate decision. High plasma concentrations were usually dealt with more promptly and more appropriately than low plasma concentrations, possibly because the biochemistry laboratory informed physicians directly of the high results. There is a clear need for physicians to better identify the reasons for measuring plasma concentrations of digoxin and to request serum digoxin measurements only when there is a pertinent problem. Indiscriminate requests for serum digoxin measurements are associated with apparent disregard for the results and a high likelihood of making an inappropriate decision regarding further digoxin prescription.

Adult↗