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Biomedical subjects

R G Shanks

Publications and source records attributed to R G Shanks.

At least 109 records · Page 6Linked to original sources
PubMed1978

Effect of catecholamines on gastrin release.

In vivo and in vitro techniques have been used to study the effect of catecholamines on gastrin release. The i.v. infusion of epinephrine in dogs produced a significant rise in plasma gastrin concentration. This response was prevented by the administration of propranolol to block beta-adrenergic receptors. The infusion of isoproterenol, a beta-adrenergic agonist, produced a significant rise in gastrin levels, while phenylephrine, an alpha-adrenergic agonist, had no effect. In in vitro studies using isolated pieces of rat antrum, isoproterenol stimulated acute phase release of gastrin, whereas phenylephrine was again without effect. The studies indicate that catecholamines directly influence G cell function.

Animals↗
PubMed1978

The clinical pharmacology of mexiletine.

1. Mexiletine was given to 156 patients by intravenous or oral routes of administration. 2. There was great interpatient variation in kinetics and plasma concentrations with both routes of administration. 3. The mean volume of distribution was 6.63 l/kg. The mean plasma elimination haf-life after chronic oral therapy was 11.31 h. 4. Plasma concentrations between 0.75 and 2.00 microgram/ml were usually effective. Within this therapeutic range severe side effects were uncommon. 5. Plasma concentrations within this range were achieved in 72% of patients when doses of 10--14 mg-1 kg-1 day were given orally.

Administration, Oral↗
PubMed1977

Influence of intrinsic sympathomimetic activity and cardioselectivity on beta adrenoceptor blockade.

Dose-response curves for propranolol and oxprenolol were studied in healthy volunteers, with a standardized excercise test and percentage reduction in excercise heart rate (EHR) as the index of drug effect. The dose-response curves obtained were compared with similar curves previously reported for sotalol, practolol, and atenolol with identical experimental methods. Two distinct types of response were identified: in the first, shown by propranolol and sotalol, increasing doses of the beta adrenoceptor-blocking drug continued to produce increasing effects to the limits of the dose levels examined; with the second (oxprenolol and practolol), increasing the dose initially resulted in substantial increase in effect but subsequently larger doses produced almost no increase in effect. Consideration of the additional properties of these beta adrenoceptor-blocking drugs revealed that both practolol and oxprenolol have intrinsic sympathomimetric activity (ISA), whereas propranolol and sotalol do not. In addition, practolol is cardioselective. Further investigation of the possible influence of ISA or cardioselectivity on beta adrenoceptor-blocking activity was undertaken by studying the effects of combinations of drugs on EHR. Sotalol produced greater effect when given 2 hr after sotalol, oxprenolol, practolol, or atenolol. When oxprenolol was given after sotalol or oxprenolol, or practolol was given after sotalol or practolol, there was no further increase in percentage reduction in EHR. When atenolol was given, the combinations of sotalol and atenolol together with two doses either of sotalol or atenolol all induced increases and similar final percentage reductions in EHR. Thus atenolol induces effects like those of sotalol, which are quite different from those of oxprenolol or practolol. The presence or absence of ISA would appear to be the important difference between these two groups of drugs: ISA would, therefore, appear to be demonstrated in man by flattening of the dose-response curves with exercise.

Adrenergic beta-Antagonists↗
PubMed1977

The effects of heart rate, myocardial ischemia and vagal stimulation on the threshold for ventricular fibrillation.

The minimum current required to cause ventricular fibrillation was determined by electrical stimulation of the normal or ischemic canine left ventricle. The threshold for ventricular fibrillation in the normal heart decreased when the heart rate was rapid. Strong vagal stimulation did not affect the ventricular fibrillation threshold when the heart rate was fixed. The fall in the ventricular fibrillation threshold in the presence of acute myocardial ischemia was greater and more prolonged when the heart rate was rapid. These findings indicate the importance of the immediate correction of tachycardia in patients suffering from acute myocardial infarction.

Animals↗
PubMed1976

Observations on the efficacy and pharmacokinetics of sotalol after oral administration.

The effects of sotalol after oral administration were measured on the tachycardia induced by strenuous exercise in normal subjects. Plasma sotalol levels were also determined. The oral administration of sotalol (50, 100, 200 and 400 mg) to 6 subjects produced a progressive reduction in the tachycardia induced by severe exercise. This was similar to the effects of 25, 50, 100, 200, 400 and 800 mg given to different subjects. Each increase in sotalol dose produced a successively greater reduction in exercise tachycardia. This did not appear to be maximum even with 800 mg. Oral sotalol was rapidly absorbed and produced peak blood levels in 2 - 3 hours. The plasma levels of sotalol measured 2 hours after the oral administration of 25 to 800 mg showed never more than a six-fold variation between different subject. The half-life of sotalol in plasma was 12.7 +/- SE 1.6 hours. There was a significant correlation between the logarithm of the plasma sotalol concentration and the percentage reduction of exercise heart rate. It is concluded that the oral administration of sotalol either once or twice daily (depending on dose level) will provide satisfactory 24-hour blockade of beta-adrenoceptors.

Administration, Oral↗
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↗