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Biomedical subjects

M Chauvin

Publications and source records attributed to M Chauvin.

At least 163 records · Page 9Linked to original sources

[Pharmacology of narcotics administered by the epidural or intrathecal route (author's transl)].

Owing to the presence of specific opiate receptors in the spinal cord, analgesia can be obtained with epidural or intrathecal injections of morphine derivatives. The duration of analgesia depends upon the degree of water solubility of the compound. Compounds with low coefficient of distribution in lipids (e.g. morphine) do not readily cross the blood-brain barrier and have a prolonged action, whereas the duration of analgesia induced by highly lipid-soluble compounds, such as dextromoramide and phenoperidine, is not very different from that obtained with more conventional routes of administration. The fact that large amounts of narcotics are taken up by the spinal cord explains that central effects are relatively rare. However, side-effects may be observed, and their frequency mainly depends upon the quantity of narcotic injected. These side-effects reduce the number of indications, which cannot yet be precisely determined. Epidural and intrathecal analgesia appears to be particularly useful during the post-operative period in patients liable to respiratory complications.

Analgesia↗

Plasma pharmacokinetics of morphine after i.m., extradural and intrathecal administration.

Eighteen patients received morphine 0.2 mg kg-1 in 0.9% saline i.m. (n = 6), extradurally (n = 6), or in a 10% dextrose solution intrathecally (n = 6) for pain relief operation. Plasma unmetabolized morphine was isolated by extraction using liquid-solid chromatography and measured by radioimmunoassay. Conjugated morphine was calculated from the difference between total immunoreactive morphine and unmetabolized morphine. Initial vascular absorption was significantly less in the intrathecal group than in the i.m. and extradural groups. This accounts for persistence of plasma unmetabolized morphine at 24 h and for more prolonged analgesia in the intrathecal group. Prolonged analgesia observed following extradural and intrathecal administration was caused by a small quantity of unmetabolized morphine. Extradural and i.m. groups showed the same pharmacokinetic patterns although extradural analgesia is much more prolonged. Morphine glucuronide appeared later in blood in the intrathecal group than in the two other groups.

Epidural Space↗

Plasma morphine concentration after intrathecal administration of low doses of morphine.

Plasma morphine concentration was measured in eight patients who received morphine 0.02 mg kg-1 intrathecally. The concentration was less than 0.5 ng ml-1 at 2 min and 10 min, 2 +/- 1 ng ml-1 at 30 min, 3 +/- 2 ng ml-1 at 1 h, 6 +/- 4 ng ml-1 at 3 h, 5 +/- 3 ng ml-1 at 12 h, 0.8 +/- 0.2 ng ml-1 at 24 h and less than 0.5 ng ml-1 at 36 h. The small plasma morphine concentrations we observed after intrathecal administration of morphine indicated that analgesia is a result of an action of morphine on opiate receptors, either spinal or cerebral.

Humans↗

Postoperative spinal analgesia with morphine.

Patients with pain after operation received morphine hydrochloride intrathecally in doses of 0.02 mg kg-1 (n = 30) and 0.2 mg kg-1 (n = 30). The high-dose group showed slightly longer-lasting and more potent analgesia than the low-dose group. Sedation, decreases in heart rate and systolic arterial pressure, oliguria, nausea and urinary retention were more frequent in the high-dose group. Two patients of the high-dose group showed evidence of respiratory depression which appeared after a late change in posture (7 and 11 h). We conclude that postoperative analgesia with intrathecal morphine 0.02 mg kg-1 must be followed by a prolonged head-up posture and be performed in hospital units where the treatment of respiratory depression is competent.

Clinical Trials as Topic↗

Plasma concentration of morphine after i.m., extradural and intrathecal administration.

Seventeen patients received morphine 0.2 mgkg-1 in a 10% dextrose solution i.m. (n = 5), extradurally (n = 6) and intrathecally (n = 6) for pain after operation. Morphine was measured in plasma by radioimmunoassay. Plasma immunoreactive morphine concentration was significantly less after intrathecal administration after i.m. and extradural administration (P less than 0.05) at 2, 10, 15 and 30 min. We conclude that morphine given extradurally has a greater initial rate of vascular absorption than morphine given intrathecally and is similar to that observed after i.m. administration.

Absorption↗

Beta-adrenoceptor blocking effects and pharmacokinetics of betaxolol (SL 75212) in man.

1 The pharmacological effects and the pharmacokinetics of betaxolol (SL 75212), a new beta-adrenoceptor blocking agent, were compared with those of propranolol and a placebo in a double-blind trial involving six healthy volunteers. 2 Heart rate (HR), myocardial contractile force (MCF), systolic blood pressure (SBP) and peak expiratory flow rate (PEFR) were measured at rest and during vigorous exercise before and at intervals up to 25 h after oral administration of the drugs. In addition, plasma renin activity (PRA) at rest and blood levels of betaxolol and propranolol were determined. 3. Betaxolol proved to be a potent and long-lasting beta-adrenoceptor blocking drug, devoid of intrinsic beta-sympathomimetic activity. Its beta-adrenoceptor blocking action was shown to four-fold that of propranolol at the cardiac and renal levels and to last at least 25 h after drug intake. 4 The peak blood level of betaxolol was reached 2 to 4 hr after its administration, the first-pass loss is likely to be low and the half-life is 12.3 h. These pharmacokinetic data are perfectly consistent with the long duration of the pharmacological effects of betaxolol in man.

Adrenergic beta-Antagonists↗

Comparative beta-adrenoceptor blocking effects and pharmacokinetics of penbutolol and propranolol in man.

1 The beta-adrenoceptor blocking effects of penbutolol were compared with those of propranolol and a placebo in a double-blind trial involving six healthy volunteers. 2 Heart rate (HR), systolic blood pressure (SBP) and peak expiratory flow rate (PEFR) were measured at rest and during vigorous exercise before and at intervals up to 7 h after oral administration of the drugs. In addition, plasma renin activity (PRA) at rest and plasma levels of penbutolol and propranolol were determined. 3 Penbutolol proved to be a non-cardioselective beta-adrenoceptor blocking drug, antagonizing exercise-induced tachycardia, reducing exercise-induced increase in PEFR and decreasing PRA. The beta-adrenolytic potency of penbutolol was shown to be four-fold that of propranolol but the duration of its effect was similar. 4 The peak plasma level of penbutolol was reached 1 h after administration and its half-life was 4.5 h. 5 Comparison of plasma levels and biological activity of penbutolol revealed that after oral administration this drug is transformed into an active metabolite in man.

Adrenergic beta-Antagonists↗

Acute digitoxin intoxication treated by intracardiac pacemaker: experience in sixty-eight patients.

Out of 124 patients who had taken massive doses of digitoxin in attempted suicide, emergency endocardial pacing was performed in the 68 with the worst prognosis. The mortality (13%) in the 124 patients compared favorably with the mortality (20%) in a previous series of 70 similar patients none of whom were paced. Sixteen (23%) of the 68 paced patients died. The causes of death were: asystole (two); cardiogenic shock (two); septicemia (one); and ventricular fibrillation (eleven). Ventricular fibrillation occurred during introduction of the pacing catheter in two patients, as a result of electrode displacement in these patients, because of premature withdrawal of the catheter in one patient, and for no detectable reason, during normally proceeding pacing, in five patients. Endocardial pacing has a place in the emergency treatment of massive digitoxin poisoning. Its chief hazards are mechanical, and one of the commonest is electrode displacement.

Adolescent↗

[Pharmacokinetics of ofloxacin administered orally in elderly subjects with bronchial or urinary tract infections].

The pharmacokinetics of ofloxacin orally administered were investigated at the steady-state in sixteen elderly patients older than 65 years. Patients with either urinary tract of respiratory tract mild infectious were divided into two age-dependent groups A and B. Group A: eight patients (65-80 years) received 200 mg of ofloxacin by the oral route every 12 hours and group B: eight patients older than 80 years, received 200 mg of ofloxacin by the oral route every 24 hours. The pharmacokinetic study was performed on treatment day 5. Plasmatic levels and urinary excretion of ofloxacin during 12 or 24 hours were assayed by means of high pressure liquid chromatography. Wide variations in plasma ofloxacin concentrations were observed within each group (Cmax range, group A: 1.9-9.2 mg/l, group B: 1.6-10.0 mg/l). Similar variability was observed for ofloxacin elimination parameters (CI/F, renal CI(R)/F) and half-life. In contrast, within-group and between-group differences in the volume of distribution adjusted for weight were not significant (group A: 1.22 +/- 0.44 l.kg; group B: 1.49 +/- 0.53 l.kg), but these values were approximately half those observed in the young adult. Plasmatic [CI/F] and renal clearance [CI(R)/F] of ofloxacin were correlated with creatinine clearance in both groups and in the overall population studied. Then the overall population was classified in terms of creatinine clearance [group 1: greater than 50 ml/min; group 2: less than or equal to 50 (minimum 20) ml/min]. The pharmacokinetics of ofloxacin in the elderly are characterized by a decrease in the volume of distribution and in plasmatic and renal clearances.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

[Dense bone metastases and hypophosphatemic osteomalacia during the course of prostatic cancer (author's transl)].

In patient bearing an advenced prostatic carcinoma with bony metastases, a major hypophosphoremia had led to the detection of an osteomalacia. As far as we know, three observations of the same syndrome have been published previously. As a pathogenic hypothesis, we propose that this tumor secret a substance which inhibit the action of vitamine D. Hypophosphoremia could result from an hyperparathyroid due to hypocalcemia.

Aged↗

[Steinert's disease and conduction disorders. Apropos of a familial study].

The authors reported a new family case of Steinert with twelve years follow-up. The study of potentials in the bundle of his was performed in all patients, showed an intra- and infra-hisian blocks. This study showed a discrepancy between muscular and myocardial evolutive injury, a very important knowledge for follow-up. Conduction disturbances were found in two cases and pacemaker insertion was performed in one patient. The authors specified the indication of electrophysiological studies during the onset and pacemaker implantation in all patient with a typical or suggestive history of syncope.

Adult↗