Clinical pharmacology and therapeutics
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Clin. Pharmacol. Ther. · Sep 1986
Arterial isoflurane concentration and EEG burst suppression during cardiopulmonary bypass.
Isoflurane (1.5 to 3.0 vol% in oxygen) was used to control intraoperative hypertension in 10 patients undergoing hypothermic cardiopulmonary bypass surgery. Isoflurane was administered through the membrane oxygenator of the bypass pump and yielded plateau concentrations in arterial blood ranging from 36.6 to 84.4 micrograms/ml (0.5 and 1.16 vol%, respectively). Isoflurane dosing resulted in prolonged periods (21 to 63 minutes) of EEG burst suppression and isoelectric activity in nine patients. ⋯ There was a close temporal relationship between isoflurane concentration and the onset of burst suppression (mean onset time: 27.3 +/- 4.56 minutes after isoflurane begun). The mean arterial isoflurane concentration at the onset of burst suppression was 46.5 +/- 10.7 micrograms/ml; the nasopharyngeal temperature was 26.0 degrees +/- 0.61 degrees C. Isoflurane was eliminated rapidly from blood with a mean apparent t1/2 of 18.8 +/- 5.46 minutes.
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Clin. Pharmacol. Ther. · Mar 1986
Oral contraceptives and other risk factors for gallbladder disease.
Prior studies of the association between oral contraceptives (OCs) and gallbladder disease (GBD) have yielded conflicting results. To clarify this association, a retrospective (historical) cohort study was performed on a very large data base including 1980 and 1981 Medicaid billing data from the states of Michigan and Minnesota in which 138,943 users of OCs were compared with 341,478 nonusers. The crude relative risk (RR) and 95% confidence interval (CI) for symptomatic GBD resulting in medical care was 1.14 (CI 1.09 to 1.20), with a clear dose-response (P less than 0.001). ⋯ The effects of a number of other risk factors on GBD, some which have been controversial, were also confirmed. Adjustment for these did not change the results. In conclusion, OCs are risk factors for GBD, although the risk is of sufficient magnitude to be of potential clinical importance only in young women.
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Clin. Pharmacol. Ther. · Jan 1986
Comparative Study Clinical Trial Controlled Clinical TrialComparative effects of metoprolol and celiprolol on cardiac hemodynamics and left ventricular volume at rest and during exercise-induced angina.
Celiprolol is a cardioselective beta-adrenoceptor antagonist with attributed cardiostimulant properties. Its hemodynamic profile was compared in a dose-response study with that of metoprolol, which is also cardioselective but lacks cardiostimulatory activity. In 24 patients with angiographically proved coronary artery disease, simultaneous hemodynamic and left ventricular ejection fraction (EF) values were determined at rest in the control (drug-free) state and repeated 3 to 5 minutes after each of four intravenous boluses of celiprolol, 1, 1, 2, and 4 mg, or equivalent beta-blocking doses of metoprolol, 1.25, 1.25, 2.5, and 5.0 mg. ⋯ At exercise both drugs reduced cardiac index and heart rate, but neither altered the EF. The cardiac function curve demonstrated greater depression at rest after metoprolol than after celiprolol; these differences were attenuated during dynamic exercise. The lesser adverse impact of celiprolol on cardiac function may be attributable to ancillary cardiac stimulatory properties offsetting the cardiac depression after beta-adrenoceptor blockade.
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Clin. Pharmacol. Ther. · Dec 1985
Comparative StudyEpidural and intrathecal opiates: cerebrospinal fluid and plasma profiles in patients with chronic cancer pain.
We studied the cerebrospinal fluid (CSF) and plasma concentration-time profiles of morphine, methadone, and beta-endorphin after lumbar epidural or intrathecal injection in 17 patients with cancer. After epidural injection, all three drugs reached peak levels in lumbar CSF within 34 minutes that were 50 to 1300 times higher than free drug concentrations in plasma. The rate of decline of CSF levels correlated with drug lipid solubility (methadone [t1/2 = 73 minutes] greater than morphine [126 minutes] greater than beta-endorphin [317 minutes]). ⋯ Three of 17 patients reported improved analgesia initially, but none were improved at 2 weeks after chronic therapy. We conclude that analgesia induced by intrathecal or epidural morphine injections is caused by drug acting at both spinal and supraspinal sites. The use of spinal opiates such as morphine is of limited value in patients whose pain is not adequately managed by high systemic doses of morphine-like drugs.