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Biomedical subjects

S Langlois

Publications and source records attributed to S Langlois.

At least 91 records · Page 5Linked to original sources
PubMed1987

Midazolam: kinetics and effects on memory, sensorium, and haemodynamics.

This study aimed not only to compare the pharmacokinetics of oral and intravenous doses of the new water-soluble benzodiazepine, midazolam, but also to study the effects on haemodynamics, sensorium, and memory performance. Eight normal human volunteers each received a single 15 mg dose of midazolam base orally and intravenously in randomized sequence 2 weeks apart. Serial venous samples were obtained for 12 h after dosing. Vital signs, sensorium testing and memory testing using word lists were also performed. Computerized non-linear least squares curve-fitting of the two-compartment open model to the oral and intravenous data simultaneously yielded the following estimates: V1, 0.33 1 kg-1, VdSS, 1.08 1 kg-1, t1/2,lambda, 0.10 h, t1/2,Z, 1.89 h, ka 1.17 h-1 and bioavailability, 49%. The intravenous dose decreased the systolic pressure 22 mm Hg during the first half-hour and the oral dose had 50% less effect. Most subjects became drowsy halfway through the infusion and were only rousable to voice by its end. The sensorium was clear by 2-3 h. After oral dosing the peak sensorium effects of ataxia-dysarthria were seen at 30 min and had cleared by 2 h. Memory testing showed that memory acquisition was markedly impaired for at least 90 min after the intravenous dose and slight recovery was apparent at this time after the oral dose. Memory performance was proportionately more impaired than the sensorium score. We conclude that: midazolam kinetics are characterized by rapid absorption, but incomplete bioavailability and rapid elimination, midazolam intravenously may lower blood pressure significantly, and the level of consciousness correlates poorly with the degree of memory impairment.

Absorption↗
PubMed1986

Pharmacokinetic study of ioxaglate, a low osmolality contrast medium, in patients with renal failure.

Determination of changes in plasma concentration of ioxaglate in patients with renal failure made it possible to demonstrate that distribution and clearance of this contrast medium, as in the case of classic uroangiographic products, conform to an open two-compartment model with clearance from the central compartment. Various pharmacokinetic parameters were calculated. The metabolic clearance of ioxaglate was lower for all 6 patients studied, as compared with results for 3 normal subjects tested, but less marked than with iodamide, a contrast medium involving tubular secretion.

Adult↗
PubMed1985

Labetalol infusion in hypertensive emergencies.

The antihypertensive effects of labetalol infusion (2 mg/min; maximal dose 150 mg) were evaluated in 22 subjects requiring rapid lowering of blood pressure because of severe hypertension, a hypertensive crisis after surgery, or before angiographic examination. Overall systolic and diastolic blood pressures were reduced from 201 +/- 4 to 164 +/- 4 mm Hg and from 123 +/- 3 to 107 +/- 3 mm Hg, respectively. By the end of the infusion, diastolic blood pressure in 16 (73%) subjects was lowered to less than or equal to 110 mm Hg. No adverse effects were encountered, but one subject had a transitory hypotensive episode that did not require treatment. Intravenous labetalol appears effective and well tolerated in the control of blood pressure in hypertensive emergencies.

Adult↗
PubMed1983

Antihypertensive effect of indapamide with special emphasis on renal prostaglandin production.

A study was undertaken in 19 patients with benign to moderate essential hypertension to verify the effect of indapamide alone or combined with a beta-blocker on plasma renin activity, plasma aldosterone, serum potassium and urinary prostaglandins PGE2 and PGF2a. Blood pressure was normalized in 11 (58%) patients with 2.5 mg indapamide/day. In the remaining 8 patients, the addition of pindolol resulted in blood pressure control. Under indapamide, a 70% increase in plasma renin activity and 81% (p less than 0.01) in plasma aldosterone was observed, whereas there was an 18% (p less than 0.001) decrease in potassium. Simultaneously, an increase in urinary PGE2 and PGF2a was observed; these values were significant for PGE2 (p less than 0.025). The addition of pindolol did not produce significant change in the biochemical parameters measured. The increase in the excretion rate of primary prostaglandins could play a role in the mode of action of indapamide.

Adult↗
PubMed1982

Ouabain-insensitive net sodium influx in erythrocytes of normotensive and essential hypertensive humans.

The Na+ content of erythrocytes is elevated in people with essential hypertension. There is conflicting evidence about its cause. The present study was designed to investigate whether the increase in content is due to a defect in a ouabain-resistant Na+ flux. Net Na+ influx was determined from the increase in Na+ content of erythrocytes during incubation in the presence of ouabain. Na+ content of erythrocytes from 24 normotensive Caucasian subjects with no known family history of hypertension was 6.9 +/- 1.3 mmol per litre of cells. It was 7.9 +/- 2.0 mmol per litre of cells in 18 subjects with essential hypertension. The difference was less and not significant when the two non-Caucasian subjects of the hypertensive group were excluded. Net Na+ influx was 1.83 mmol/h per litre of cells in the normotensive group. In eight subjects it was measured on a second occasion after an interval of several months. The coefficient of a variation of the duplicate tests was 2.4%. Net Na+ influx was significantly higher in the hypertensive group, the value was 2.18 +/- 0.15 mmol/h per litre of cells. In 11 of these subjects, Na+ influx was measured on a second occasion. The coefficient of variation was 6.2%, significantly greater than in the control group. In some of these subjects Na+ influx was within the normal range on one of the two occasions. When the groups were compared with use of the mean values from the duplicate tests, net Na+ influx was elevated in 17 of the 18 hypertensive subjects. The findings are discussed with reference to previous work and in relation to the established facilitatory effects of an increased intracellular Na+ concentration on excitable cells that influence blood pressure.

Biological Transport, Active↗
PubMed1982

Comparison of withdrawal phenomena after propranolol, metoprolol, and pindolol.

Three groups of hypertensive patients were studied after they had received one of the three pharmacologically different beta blockers for at least 1 month: pindolol, 10 mg twice a day (n = 7), propranolol median dose, 80 mg three times a day (n = 9), or metoprolol, 150 mg (twice a day (n = 8). After abrupt withdrawal of drug and replacement with placebo, we measured the following on day 0 and approximately every 2 days up to 3 weeks; beta-adrenergic sensitivity (BAS) by the chronotropic dose of isoproterenol to increase heart rate by 25 bpm (CD25), resting heart rate and blood pressure, and symptoms. All values are medians. On day 0, beta blockade was evident by increased CD25 values of 618 micrograms for pindolol, 57 micrograms for propranolol, and 10 micrograms for metoprolol as compared to 2.8, 2.4, and 3.0 microgram, respectively, at days 14 to 21, which were considered the ultimate baseline. After pindolol on day 0, the CD25 slowly decreased to, but never below, baseline by days 8 to 21. In contrast, after propranolol on day 0, the CD25 decreased significantly two- to fivefold below baseline from days 4 to 14 (BAS) and after metoprolol two- to threefold below baseline from days 2 to 8. After pindolol, heart rate and blood pressure gradually returned to, but not above, ultimate baseline. In contrast, during the period of BAS there was a significant overshoot of heart rate in eight patients after metoprolol (day 0 = 61, peak = 88, baseline = 74) but not after propranolol, while a significant overshoot of blood pressure occurred in six of nine patients after propranolol (day 0 = 140/87, peak = 157/95, baseline = 140/89) but not after metoprolol. Withdrawal symptoms of headache, palpitations, and tremor occurred in one of seven patients after pindolol, six of nine after propranolol, and three of eight after metoprolol. The degree and duration of beta blockade appeared related to drug potency. Withdrawal phenomena occurred after propranolol and metoprolol but not after pindolol.

Adult↗
PubMed1982

Metoprolol withdrawal phenomena: mechanism and prevention.

Eight patients taking metoprolol (300 mg/day) for essential hypertension were studied after abrupt withdrawal and placebo replacement of the drug. A 52% average rebound increase in cardiac chronotropic sensitivity to isoproterenol and 15% rebound rise in resting heart rate occurred in all patients between 2 to 8 days after metoprolol withdrawal (P less than 0.05). Holter monitoring showed no associated arrhythmia. A transient increase in blood pressure occurred in one patient and withdrawal-like symptoms were noted in three patients. There were no meaningful changes in plasma norepinephrine, epinephrine, thyroxine, or triiodothyronine. Seven of the eight patients were again studied serially after the same metoprolol dosing, during a prolonged low-dose withdrawal schedule (50 mg/day for 10 days) and during placebo. Prolonged low dose before complete metoprolol withdrawal decreased but did not completely prevent the changes observed after abrupt withdrawal. The observed rebound of cardiac beta-adrenergic sensitivity may have application to the mechanism and prevention of the beta-blocker syndrome in patients with angina.

Adult↗
PubMed1982

Cardiac hyper- and hyporesponsiveness after pindolol withdrawal.

Abrupt withdrawal of some beta-adrenergic blockers has resulted in clinical syndromes suggestive of adrenergic hypersensitivity that may be due to an adaptive increase in cardiac beta-receptor responsiveness. it was postulated that the partial agonist activity of pindolol might limit enhanced responsiveness of cardiac beta receptors and prevent or diminish withdrawal manifestations. Pindolol was given to 10 hypertensive patients in doses of 10 mg b.i.d. for at least 4 wk, then abruptly replaced with placebo for 20 days. Cardiac chronotropic responsiveness to isoproterenol was decreased on pindolol and gradually returned to normal over 10 to 20 days with no evidence of enhanced responsiveness. In contrast, both resting and exercise heart rate showed rebound increase in responsiveness between the second to sixth day after pindolol (P less than 0.05). Resting and exercise blood pressures gradually rose to stable values without rebound. Plasma norepinephrine and epinephrine and serum thyroxine and triiodothyronine did not change. These data show that abrupt withdrawal of pindolol after long-term dosing leads to transient cardiac hyperresponsiveness of resting and exercise heart rate at the same time as persistent cardiac hyporesponsiveness to isoproterenol. These opposite effects of pindolol on subsets of cardiac beta-adrenergic chronotropic receptors.

Adult↗
PubMed1982

Comparison of withdrawal phenomena after propranolol, metoprolol and pindolol.

1 After abrupt propranolol withdrawal a rebound increase in cardiac sensitivity to isoprenaline occurred in 9/9 patients and persisted up to 14 days. A mild brief rebound in resting heart rate occurred in 4/9 patients and a rebound in blood pressure occurred in 6/9 patients. These withdrawal phenomena were prevented by gradual withdrawal on a prolonged small dose of propranolol. 2 After abrupt metoprolol withdrawal a rebound increase in cardiac sensitivity to isoprenaline occurred in 8/8 patients but had resolved by 8 days. A marked persistent rebound in resting heart rate occurred in 8/8 patients while a small brief rebound in blood pressure occurred in only one patient. These withdrawal phenomena were largely prevented by gradual withdrawal on a prolonged small dose of metoprolol. 3 After abrupt pindolol withdrawal there was no rebound in isoprenaline sensitivity but a mild brief rebound in resting heart rate occurred in 9/10 patients. There was no rebound in blood pressure. 4 The type, magnitude and frequency of withdrawal phenomena after various beta-adrenergic receptor blockers probably reflects substantial differences in their basic pharmacological characteristics. 5 Caution must be exercised when withdrawing any patient from any beta-adrenoceptor blocker since an adverse cardiac event is unpredictable.

Adrenergic beta-Antagonists↗