PubMed Health⌕ Search

Biomedical subjects

S G Carruthers

Publications and source records attributed to S G Carruthers.

At least 73 records · Page 4Linked to original sources
PubMed1983

Simplified liquid-chromotographic analysis for cyclosporin A, and comparison with radioimmunoassay.

We describe a simplified isocratic "high-performance" liquid-chromatographic method for measuring a new immunosuppressive drug, cyclosporin A, in biological fluids with use of its analogs cyclosporin C and cyclosporin D as internal standards. The method is reproducible and accurate and appears to be specific for cyclosporin A; the detection limit is 31 micrograms/L. The chromatographic measurements of the concentration of cyclosporin A in serum of patients receiving the drug were invariably lower than those by radioimmunoassay and the difference became more pronounced the greater the period of time after dosing. Because measurements of cyclosporin A in serum standards were almost identical with both techniques, the differences between the two sets of results for patients' samples suggests that the radioimmunoassay is nonspecific and measures metabolites of cyclosporin A.

Adult↗
PubMed1982

Comparison of the electrophysiologic effects of intravenous and oral verapamil in patients with paroxysmal supraventricular tachycardia.

The electrophysiologic effects of intravenous verapamil (a bolus dose of 0.15 mg/kg body weight followed by infusion of 0.005 mg/kg per min) were compared with those of oral verapamil (80 mg every 6 hours for 48 hours) in eight patients who had paroxysmal supraventricular tachycardia. The mechanism of tachycardia was atrioventricular (A-V) nodal reentry in four patients and A-V reentry utilizing an accessory pathway for retrograde conduction in the remaining four. The electrophysiologic effects of oral and intravenous verapamil were similar. Both preparations significantly prolonged anterograde effective and functional refractory periods of the A-V node (p less than 0.001). Both significantly increased the shortest pacing cycle length maintaining 1:1 anterograde conduction over the A-V node (p less than 0.001). Retrograde conduction over the A-V node was greatly prolonged with verapamil in one patient but was unaffected in the others. There was no significant effect on sinoatrial conduction time, sinus nodal recovery time or atrial or ventricular refractoriness. Both preparations prevented induction of tachycardia in six patients none of whom had recurrence of sustained tachycardia while receiving long-term oral therapy (5 to 10 months). Neither preparation had a significant effect in two patients and this predicted failure of long-term oral therapy in one of these patients. The results of acute drug testing with intravenous verapamil can be extrapolated to predict the electrophysiologic results and response to long-term therapy with oral verapamil.

Administration, Oral↗
PubMed1982

Ineffectiveness of beta-adrenergic blockers on ventilatory response to carbon dioxide.

The effects of the beta-adrenoceptor blockers atenolol, metoprolol, pindolol, and propranolol on the ventilatory response to carbon dioxide rebreathing have been determined in a double-blind randomized manner. Eight healthy, male, nonsmoking subjects received cumulative doses of each drug over a 10-hr period. The effects of each drug on heart rate and carbon dioxide sensitivity were determined at intervals of 2 hr and were related to plasma concentrations of each drug. Maximum reduction of exercise heart rate was achieved with all four beta blockers and plasma concentrations were in the usual therapeutic range for these drugs. There was considerable intersubject and within-subject variability in ventilatory responsiveness to inhaled carbon dioxide, but we were not able to discern any alteration in central sensitivity to increasing carbon dioxide concentrations.

Adrenergic beta-Antagonists↗
PubMed1982

Acceleration of the ventricular response during atrial fibrillation in the Wolff-Parkinson-White syndrome after verapamil.

We examined the electrophysiologic effects of verapamil in eight patients with the Wolff-Parkinson-White syndrome. Verapamil shortened the antegrade effective refractory period of the accessory pathway in three patients and abbreviated the shortest cycle length with 1:1 conduction over the accessory pathway in two patients. More significantly, verapamil decreased the shortest RR interval between preexcited ventricular complexes during atrial fibrillation (279 +/- 20 msec vs 236 +/- 18 msec, mean +/- SEM; p less than 0.01). After verapamil, two patients required cardioversion for hemodynamic deterioration after acceleration of the ventricular response during atrial fibrillation. In the four patients with predominantly preexcited ventricular complexes during atrial fibrillation the ventricular rate accelerated after verapamil, whereas in patients with predominantly normal ventricular complexes, the average ventricular rate decreased or did not change after verapamil. Verapamil may result in significant acceleration of ventricular response during atrial fibrillation in the Wolff-Parkinson-White syndrome. The safety of verapamil in individual patients with the Wolff-Parkinson-White syndrome should be established by electrophysiologic testing before its use.

Adult↗
PubMed1981

Measurement of partial agonist activity of pindolol.

The partial agonist activity of pindolol was assessed by examining the action of cumulative doses on the heart rate of resting, standing, and exercising healthy men and by studying the interaction of pindolol with metoprolol, a beta blocker devoid of partial agonist activity. Pindolol did not affect resting or standing heart rates (RHR, SHR) but reduced the heart rate after vigorous exercise by approximately 25%. The flatter dose-response curve of pindolol for exercise heart rate (EHR) has been reported from practolol and oxprenolol, which also exert partial agonist activity. After extremely large doses of pindolol there was no evidence of enhancement of agonist activity on RHR, nor was there any evidence of dominance of agonist activity over antagonist activity on EHR. Metoprolol did not alter RHR but reduced SHR by approximately 20% and EHR by approximately 31%. The effects of pindolol on SHRs and EHRs were not enhanced by metoprolol, even though the drug itself induced greater reductions of both. The reduction of SHR by metoprolol was reversed by pindolol. Pindolol appears to have greater affinity than metoprolol for atrial beta adrenoceptors in man.

Adult↗
PubMed1980

Cholestyramine and spironolactone and their combination in digitoxin elimination.

The effects of oral cholestyramine 4 gm 8 times daily and spironolactone 300 mg daily, given independently and in combination, on the elimination rate of digitoxin were studied in 6 healthy subjects pretreated with 0.1 or 0.15 mg oral digitoxin daily for 30 days before each intervention. The mean pretreatment digitoxin concentrations for the group ranged from 21 +/- 2.9 (SD) ng/ml to 28.5 +/- 6.9 ng/ml. The mean control digitoxin half-life (t 1/2) was reduced from 141.6 to 84.4 by treatment with cholestyramine alone. Treatment with spironolactone alone prolonged the mean digitoxin t 1/2 to 192.2 hr. The mean digitoxin t 1/2 after both active drugs was intermediate at 102.9 hr. Spironolactone did not fulfill the expectation from animal studies that it would enhance the clearance of digitoxin by cholestyramine. The prolongation of digitoxin elimination after spironolactone may contraindicate this drug in digitoxin intoxication.

Canrenone↗
PubMed1980

Duration of drug action.

Duration of drug action depends on several factors: the absolute amount of drug given; the pharmaceutical preparation; the reversibility of drug action; the half-life of the drug; the slope of the concentration-response curve; the activity of metabolites, and the influence of disease on drug elimination. The duration of action of a drug with more than one effect may differ, depending on which effect is followed. Drugs with a prolonged therapeutic effect should be given once or twice daily. Drugs with a short duration of therapeutic effect are best given at regular intervals rather than by t.i.d. or q.i.d. regimens.

Adult↗
PubMed1979

Kinetics of pamatolol, a cardioselective beta adrenoreceptor blocker.

The systemic bioavailability, elimination half-life (t1/2), and plasma concentration--response relationships of pamatolol, a relatively cardioselective beta adrenoceptor blocker, have been measured in healthy subjects. Pamatolol is rapidly and completely absorbed after oral dosing. Elimination t1/2 ranged from 2.9 to 4.6 hr after oral doses and from 2.2 to 5.6 hr after intravenous doses. There was a clear relationship between log plasma pamatolol concentration and sympathetic blockade assessed by reduction of exercise heart rate. Concentration-response curves were essentially identical after oral and intravenous doses. There is no evidence of a first-pass effect, nor is there any evidence of metabolite activity.

Administration, Oral↗
PubMed1978

Correlation between plasma diphenhydramine level and sedative and antihistamine effects.

The sedative and antihistamine effects of diphenhydramine were assessed in relation to plasma concentration after placebo, diphenhydramine 50 mg intravenously, and diphenhydramine 50 mg orally to each of 6 healthy volunteers on three separate occasions. Diphenhydramine plasma elimination t1/2 was 3.0 to 4.3 hr, volume of distribution was 188 to 336 L, and clearance was 637 to 1,014 ml/min. Systemic bioavailability of the oral preparation ranged from 0.26 to 0.60. The sedative effect of intravenous diphenhydramine differed from that of placebo only during the first 3 hr. Antihistamine effect, as measured by reduction of histamine provoked skin wheal diameter, was significantly different from that of placebo for at least 8 hr. There was a positive correlation between plasma diphenhydramine level and sedative and antihistamine effects, but wide variation in the extent and rate of change of these effects were observed between the subject. There appears to be a concentration range of 25 to 50 ng/ml, within which there is significant antihistamine effect without significant sedation.

Administration, Oral↗
PubMed1978

Pamatolol: phase I evaluation of the pharmacodynamics of a cardioselective beta adrenoceptor blocking drug.

A Phase I evaluation of a new adrenoceptor blocker, pamatolol, was performed in 10 healthy male volunteers. Minor reductions in standing and exercise and isoproterenol-induced increases in heart rate were observed with the 10-mg oral dose and appeared maximal with the 400-600 mg dose. The rate of decline of effect averaged 1.5% of the exercise heart rate/hr. Neither resting systolic time intervals nor post-exercise pulmonary function was affected by this dose range of pamatolol. Based on the latter responses and the isoproterenol dose response curve, we tentatively conclude that pamatolol is relatively cardioselective in man.

Adolescent↗
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↗