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Biomedical subjects

D G McDevitt

Publications and source records attributed to D G McDevitt.

At least 199 records · Page 11Linked to original sources
PubMed1976

Clinical pharmacologic observations on atenolol, a beta-adrenoceptor blocker.

The effects of oral and intravenous administration of atenolol were studied in healthy volunteers. The oral administration of a series of single doses of atenolol reduced an exercise tachycardia. After a 200-mg dose, the effect on an exercise tachycardia was maximal at 3 hr and declined linearly with time at a rate of approximately 10% per 24 hr. The peak plasma atenolol concentration occurred at 3 hr and thereafter declined exponentially with time with an elimination half-life of 6.36 +/- 0.55 hr: 43 +/- 3.9% of the dose was excreted in the urine within 72 hr. There was a correlation between the reduction in an exercise tachycardia and the logarithm of the corresponding plasma concentration. The intravenous administration of atenolol reduced exercise tachycardia with a significant correlation between effect and plasma concentration. After 50 mg intravenously, 100% of the dose was recovered from the urine, and the clearance was 97.3 ml/min. Comparison of AUC O leads to chi after oral and intravenous administration of 50 mg showed the bioavailability to be 63% after oral drug. Repeated oral administration of atenolol 200 mg daily either as a single dose or in divided 12 hourly doses for 8 days maintained reduction of an exercise tachycardia of at least 24% during the period of drug administration. The plasma elimination half-life, area under the plasma concentration-time curve, and peak plasma concentration after 200 mg atenolol were not changed by chronic dosing for 8 days.

Administration, Oral↗
PubMed1976

Simultaneous measurement of cardiac output and its distribution with microspheres in the rat.

The radioactive microsphere method was used to estimate simultaneoulsy the cardiac output and its distribution in the same rat by the use of an arterial reference sample obtained during microsphere distribution. Sufficient microspheres were injected so that all counted samples contained more than 400 spheres. No haemodynamic changes occurred during microsphere injection. The results for cardiac output of 253 +/- 11 ml/min per kg body weight agree with published estimates utilizing other techniques. The distribution of cardiac output also agrees with most published reports. This method should allow the rat to be conveniently used for certain haemodynamic studies when cardiac output and organ blood flow are necessary.

Animals↗
PubMed1976

Propranolol in the treatment of thyrotoxicosis: a review.

The clinical manifestations of hyperthyroidism have suggested to physicians for many years that the sympathetic nervous system may be involved in their production. Despite this, the precise interrelationship between the thyroid gland and the sympathetic nervous system has never been defined but controlled investigations have shown that hypersensitivity to catcholamines does not occur in animals or man with artificially produced thyrotoxicosis. In recent years beta-adrenoceptor blocking drugs, and in particular propranolol, have been used in patients with hyperthyroidism. Evidence exists that they control some of the peripheral manifestations of the disease, including nervousness, palpitations, tachycardia, increased cardiac output and tremor, but they do not appear to affect the underlying thyrotoxic process itself. Propranolol has been used with sucess in the treatment of acute hyperthyroid crisis, in pre-operative preparations for thyroidectomy, for the control of symptoms and signs following the administration of radioactive iodine therapy and antithyroid drugs, during the period of diagnostic thyroid investigations and occasionally as the sole therapy. The supportive role of propranolol in the management of hyperthyroidism is now established and in some instances such as radioactive iodine therapy, it has enabled improvements in the existing methods of treatment to be achieved.

Antithyroid Agents↗
PubMed1975

Plasma concentrations and the time-course of beta blockade due to propranolol.

The effectiveness of intravenously administered propranolol in antagonizing the chronotropic effect of isoproterenol and exercise has been investigated, and has been found at all times to be a predictable function of its plasma concentrations according to the classical drug-receptor theory for competitive antagonism. The data show further that the relationship between effectiveness and time depends on the way in which antagonism is measured. If the dose ratio to isoproterenol (DR) is measured, then (DR-1) declines with time in parallel with drug concentration. On the other hand, if propranolol's effects are measured as percentage reduction in a given response, then this declines linearly with time, even though plasma concentrations decline exponentially. This fact explains why confusion has in the past arisen concerning the relationship of the duration of beta blockade and pharmacokinetic half-life.

Adrenergic beta-Antagonists↗
PubMed1975

Comparative trial of propranolol and practolol in hyperthyroidism.

The possible role of practolol in the management of hyperthyroidism has been studied by comparing it with propranolol. 2. In a double-blind cross-over trial, propranolol (40 mg), practolol (120 mg) and a placebo four times daily for one week were compared in twenty-one hyperthyroid patients by sequential analysis. 3. Judged by their effect on the symptoms and signs of thyrotoxicosis, both propranolol and practolol were significantly better than the placebo but no clear distinction could be made between the two active compounds. 4. Propranolol and practolol reduced heart rate by 24 and 17% respectively compared with placebo. 5. Patients generally preferred propranolol or practolol to placebo but this preference did not achieve significance with either drug. 6. Only in its effect on heart rate was practolol significantly inferior to propranolol, and it would appear to be a useful alternative to propranolol in the management of the peripheral manifestations of hyperthyroidism.

Clinical Trials as Topic↗
PubMed1975

The uterine and cardiovascular effects of salbutamol and practolol during labour.

Intravenous salbutamol, a beta-adrenoceptor stimulant, given to nine patients in normal labour, with continous monitoring of uterine activity and of the maternal and fetal cardiovascular systems, was shown to decrease uterine activity significantly; maternal and fetal heart rates were significantly increased, and maternal systolic and diastolic arterial pressures were significantly decreased during the infusion, although no treatment had to be discontinued because of these effects. Apart from worsening of low back pain during the infusion in one patients, subjective side-effects were trival. With the salbutamol infusion continued at an effective maintenance rate, the carioselective beta-adrenoceptor blocking drug, practolol, given intravenously, reduced the maternal heart rate (although not significantly) but it did not alter the fetal heart rate; it also appeared to interfere transiently with the inhibiting action of salbutamol on uterine activity, but cerevical dilatation was arrested until the salbutamol infusion was discontinued. At least in five patients, labour remained suppressed until oxytoxin was infused intravenously.

Albuterol↗
PubMed1975

Plasma and tissue digoxin concentrations in patients undergoing cardiopulmonary bypass.

Plasma myocardial, and skeletal muscle digoxin concentrations were measured in 32 patients undergoing cardiopulmonary bypass who were on long-term treatment with digoxin. The patients were divided into 4 groups according to the daily digoxin dose and the interval between discontinuation of the drug and operation. Before bypass, the mean digoxin concentrations were 1.58 nmol/l (1.24 ng/ml) in plasma 65.2 nmol/kg (50.9 ng/g) in the atria, 121.4 nmol/kg (94.98 ng/g) in 11 papillary muscles, and 16.6 nmol/kg (13.0 ng/g) in skeletal muscle. Mean atrial digoxin concentrations were significantly lower tham mean papillary muscle concentrations in 11 patients. Ratios of plasma of myocardial or skeletal muscle digoxin concentrations were very variable. Generally digoxin concentrations were higher in patients on the larger digoxin dose and with the shorter discontinuation time before surgery. These differences attained significance only with plasma digoxin concentrations. There was a slight fall in plasma digoxin concentration during cardiopulmonary bypass but no significant differences were observed between plasma, atrial, or skeletal muscle digoxin concentrations before and at the end of bypass. No clear relation was seen between plasma or atrial digoxin concentrations and postoperative cardiotoxicity. Stopping digoxin 48 hours before operation appeared to account for pre- or post-bypass plasma digoxin concentrations of less than 1.0 nmol/l (0.8 ng/ml) in most of the instances encountered, whereas the 3 patients who developed pulsus bigeminus postoperatively had received 0.5 mg digoxin only 24 hours before operation.

Adult↗
PubMed1974

Environmental stress and thyrotoxicosis. Absence of association.

The incidence of treated thyrotoxicosis in Northern Ireland has been estimated by the technique of "therapeutic auditing" for the periods (a) three years preceeding the start of the present civil unrest and (b) the ensuing three years. No change in incidence was found, which supports the concept that environmental stress is not important in the pathogenesis of this disease.

Carbimazole↗
PubMed1974

Further observations on the cardiotoxicity of isoprenaline during hypoxia.

1 In dogs respired with 10% oxygen: 90% nitrogen, only five out of 16 dogs survived repeated intravenous doses of isoprenaline (either 0.5 or 1.0 mug/kg) and only one out of six dogs survived repeated isoprenaline inhalations from a pressurized aerosol.2 In dogs respired with 15% oxygen: 85% nitrogen, five out of six dogs survived repeated intravenous doses of isoprenaline (2.5 mug/kg).3 The fatal response in these animals consisted of a fall in heart rate, arterial and pulse pressures. Sinus rhythm persisted even after the arterial pressure had fallen, though occasionally a slow A-V nodal rhythm or irregular ventricular ectopic beats occurred. Ventricular fibrillation did not occur.4 Eight out of 10 dogs brought to the verge of a fatal response with 10% oxygen: 90% nitrogen and repeated doses of isoprenaline (2.5 mug/kg) were resuscitated by the administration of 100% oxygen and, when necessary, cardiac massage.5 A group of five dogs survived the combined effects of repeated doses of isoprenaline (2.5 mug/kg) and respiration with 10% oxygen: 90% nitrogen when the time interval between doses was 11 min, instead of the usual 5 minutes.6 Control of pH by infusion of sodium bicarbonate did not protect the dogs from the combined effects of hypoxia and repeated isoprenaline challenge.7 After a 60 min period of continuous isoprenaline infusion in dogs breathing room air, only one of 10 dogs survived artificial respiration with 10% oxygen: 90% nitrogen and repeated challenge with intravenous isoprenaline (1.0 mug/kg) at 5 min intervals. At the higher infusion levels of isoprenaline (0.1 and 1.0 mug kg(-1) min(-1)), two dogs out of four died after the hypoxic mixture was started but before any isoprenaline challenge was given.8 The possible relevance of these findings in dogs to the recently observed increase in mortality in young asthmatics is discussed.

Animals↗