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1.
Clin Pharmacol Ther ; 30(5): 581-6, 1981 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-7297017

RESUMO

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.


Assuntos
Pindolol/farmacologia , Simpatomiméticos/farmacologia , Adulto , Frequência Cardíaca/efeitos dos fármacos , Humanos , Masculino , Metoprolol/farmacologia , Esforço Físico , Postura
2.
Clin Pharmacol Ther ; 32(3): 289-94, 1982 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-6125288

RESUMO

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.


Assuntos
Antagonistas Adrenérgicos beta/farmacologia , Dióxido de Carbono/farmacologia , Respiração/efeitos dos fármacos , Adulto , Atenolol/farmacologia , Ensaios Clínicos como Assunto , Método Duplo-Cego , Frequência Cardíaca/efeitos dos fármacos , Humanos , Masculino , Metoprolol/farmacologia , Pindolol/farmacologia , Propranolol/farmacologia , Distribuição Aleatória
3.
Clin Cardiol ; 7(9): 474-83, 1984 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-6529866

RESUMO

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.


Assuntos
Fibrilação Atrial/tratamento farmacológico , Verapamil/uso terapêutico , Adulto , Idoso , Fibrilação Atrial/fisiopatologia , Eletrocardiografia , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Cinética , Masculino , Pessoa de Meia-Idade , Verapamil/metabolismo
4.
J Endocrinol Invest ; 10(2): 107-9, 1987 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-3584851

RESUMO

A 44-year-old female with Cushing's disease associated with a pituitary macroadenoma was treated with cyproheptadine, 24 mg per day, after partial surgical resection of the tumor. A large residual tumor remained. There was no clear suppression of serum and urinary cortisol during therapy, but both levels rose markedly to beyond pre cyproheptadine levels, on withdrawal of the drug. This is the first report on the use of cyproheptadine in Cushing's disease associated with a pituitary macroadenoma. The response in this patient indicates an influence of cyproheptadine on ACTH secretion by the macroadenoma.


Assuntos
Adenoma/complicações , Síndrome de Cushing/metabolismo , Ciproeptadina/uso terapêutico , Hidrocortisona/metabolismo , Neoplasias Hipofisárias/complicações , Síndrome de Abstinência a Substâncias/metabolismo , Adenoma/metabolismo , Adulto , Síndrome de Cushing/tratamento farmacológico , Síndrome de Cushing/etiologia , Feminino , Humanos , Neoplasias Hipofisárias/metabolismo
5.
Ther Drug Monit ; 5(3): 249-54, 1983.
Artigo em Inglês | MEDLINE | ID: mdl-6636251

RESUMO

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.


Assuntos
Digoxina/sangue , Adulto , Idoso , Doenças Cardiovasculares/tratamento farmacológico , Digoxina/uso terapêutico , Prescrições de Medicamentos , Feminino , Humanos , Masculino , Auditoria Médica , Pessoa de Meia-Idade , Ontário
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