Lidocaine and pentobarbital: a potentially lethal drug-drug interaction.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
J LeLorier
Publications and source records attributed to J LeLorier.
Pharmacokinetics of lidocaine after prolonged intravenous infusions in uncomplicated myocardial infarction.
The kinetics of the elimination of lidocaine upon discontinuation of lidocaine infusions lasting more than 24 h were studied in 12 patients with uncomplicated myocardial infarctions. In this group of patients the mean half-life of the elimination phase was found to be 3.22 h. This is significantly different from the half-life of 100 min that has been reported after bolus injections or infusions lasting less than 12 h. This longer half-life should be taken into consideration in estimating the duration of toxicity and the rate of administration of the drug during and after intravenous infusions lasting 24 h or more.
Female↗
Diet and probucol in lowering cholesterol concentrations. Additive effects on plasma cholesterol concentrations in patients with familial type ii hyperlipoproteinemia.
Probucol [4,4-(isopropylidendithio bis)(2,6-di-t-butylphenol)], as as an adjunct to diet, was evaluated for its effect on lowering the plasma cholesterol level in patients with familial hypercholesterolemia (type II). The trial had a double-blind, placebo-controlled, crossover design. About half of the 30 patients responded to a low-cholesterol modified-fat diet with a decrease in the plasma cholesterol level of approximately 13%. When probucol was added to the diet of the responders, their plasma cholesterol level was lowered a further 13%. Patients who did not respond to the diet did show reduced plasma cholesterol concentrations when receiving probucol plus the diet. Analysis of the cholesterol content of the various lipoprotein fractions showed that the low-density lipoproteins accounted for most of the total plasma cholesterol level decrease. There was, as expected, no effect on plasma triglyceride concentrations. Neither the 7-dehydrocholesterol nor the desmosterol level was increased in the plasma of patients treated with probucol for three months. Probucol is useful as an adjunct to diet in lowering plasma cholesterol levels in patients with familial hypercholesterolemia. The drug was well tolerated by all patients.
Adult↗
Effects of sotalol in twenty patients with cardiac arrhythmias.
Sotalol was given intravenously at doses of 20 to 60 mg to 20 selected patients with various cardiac arrhythmias. Ten of these patients subsequently received oral sotalol at doses of 80 to 160 mg twice a day. The drug was beneficial in 2 out of 2 patients with sinus tachycardia and in 4 out of 7 patients with other supraventricular tachycardias. The drug was particularly effective in lidocaineresistant ventricular arrhythmias since it was effective in 9 out of 11 patients. The blood pressure of the 4 patients who were hypertensive was significantly lowered while that of the normotensive patients was not affected. Three patients who suffered from severe myocardial disease developed sinus bradycardia, which was life-threatening in 2 of them.
Administration, Oral↗
Effect of the duration of infusion on the disposition of lidocaine in dogs.
Lidocaine is a commonly used and efficacious antiarrhythmic agent whose pharmacokinetics after a rapid intravenous bolus injection have been extensively studied. Due to its short half-life, a continuous infusion of lidocaine is necessary whenever therapeutic blood levels need to be maintained for prolonged periods of time. Recent work in man has shown that the elimination of lidocaine is much slower after a prolonged infusion than after a bolus. We present the results of a pharmacokinetic study of the disposition of lidocaine after the discontinuation of short (90 minutes) and long (24 hours) intravenous infusions which demonstrate that in both cases the elimination of lidocaine is best explained by a two-compartment open model with elimination from the central compartment and that the longer half-life of lidocaine after a prolonged infusion is due to an impairment of its hepatic extraction. Lidocaine hepatic elimination data obtained at the end of short- and long-term infusions confirmed the inferences drawn from the pharmacokinetic analysis by demonstrating that a long-term infusion produces an important decrease in the arterial clearance and hepatic extraction rate of lidocaine.
Animals↗
Uptake of and response to norepinephrine by certain tissues of hypertensive rats.
A decrease in the capacity of the sympathetic nervous system of hypertensive rats to take up norepinephrine (NE) has been previously described. In the present study, rats were made hypertensive by one of the following technics: "adrenal regeneration," figure-of-eight knot around one kidney, ingestion of a 10% NaCl solution. After 2 mo, the adrenal regeneration rats were hypertensive, and there was a significant decrease in the capacity of their hearts to take up NE as well as a significant increase in the inotropic response to the amine. Similar results were obtained with hearts and aortic strips of renal hypertensive rats, as well as of rats made hypertensive by drinking a 10% NaCl solution. In renal hypertensive rats, there was no appreciable difference in the time of appearance of hypertension, the decrease in NE uptake by the heart or aorta, or the increase of the inotropic response. Previous work showing a decrease of NE uptake in rats made hypertensive by administration of deoxycorticosterone has been confirmed utilizing three other models of the disease.
Animals↗
The effects of propranolol, practolol, and placebo on the clinical manifestations of thyrotoxicosis.
Thirty patients with thyrotoxicosis were randomly divided into 3 groups of ten which were treated for 8 weeks with either practolol, propranolol or placebo. The pills were administered in a double blind manner and the investigator had the option of doubling the dose at each visit. Propranolol and practolol were equally effective, and better than placebo, at relieving the patients general well-being as well as the tachycardia, subjective and objective tremor, skin warmness and moistness and the intensity of the thyroid bruit.
Auscultation↗
Uptake of norepinephrine as a determinant of the magnitude of the inotropic response.
Explore the source record for details and available documents.
Animals↗
Autoinhibition in rabbit aortic strips after epinephrine.
Explore the source record for details and available documents.
Animals↗
3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors and the risk of cancer: a nested case-control study.
BACKGROUND: During the past 15 years there has been an exponential increase in the number of prescriptions for lipid-lowering drugs. Uncertainties remain about the long-term impact of these medications on cancer, which is particularly bothersome given that the duration of these treatments may extend for several decades. OBJECTIVE: To explore the association between 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors and cancer incidence. METHODS: Using the administrative health databases of the Régie de l'Assurance-Maladie du Québec we performed a nested case-control study. We selected a cohort of 6721 beneficiaries of the health care plan of Quebec who were free of cancer for at least 1 year at cohort entry, 65 years and older, and treated with lipid-modifying agents. Cohort members were selected between 1988 and 1994 and were followed up for a median period of 2.7 years. From the cohort, 542 cases of first malignant neoplasm were identified, and 5420 controls were randomly selected. Users of HMG-CoA reductase inhibitors were compared with users of bile acid-binding resins as to their risk of cancer. Specific cancer sites were also considered. RESULTS: Users of HMG-CoA reductase inhibitors were found to be 28% less likely than users of bile acid-binding resins to be diagnosed as having any cancer (rate ratio, 0.72; 95% confidence interval, 0.57-0.92). All specific cancer sites under study were found to be not or inversely associated with the use of HMG-CoA reductase inhibitors. CONCLUSION: The results of our study provide some degree of reassurance about the safety of HMG-CoA reductase inhibitors.
Adverse Drug Reaction Reporting Systems↗
Incontinence drug utilization patterns in Québec, Canada.
OBJECTIVE: To assess prescription renewal and switch rates in an elderly population receiving oxybutynin or flavoxate for treatment of urinary incontinence in Quebec. METHODS: Sociodemographic, clinical, and drug claim data for patients > or = 65 years of age, with at least one claim for oxybutynin or flavoxate between January 1, 1994 and December 31, 1997, were randomly extracted from a database maintained by the Régie de l'assurance maladie du Québec (RAMQ). Rates of renewal of the first drug claim and the number of patients switching from one incontinence drug to the other were determined. In addition, survival curves defining the time until cessation of initial treatment were constructed. RESULTS: The oxybutynin (n = 5718) and flavoxate (n = 972) treatment groups were similar in terms of gender (62.1% female) and age (mean age 77). For oxybutynin, 56.8% of the claims were written by general practitioners and 36.6% by urologists compared to 40.5% by general practitioners and 51.4% by urologists for flavoxate. Only 39.3% of the oxybutynin patients renewed their first claims, compared to 36.6% of the flavoxate group. Switch rates were higher for flavoxate patients with more than twice as many patients switching from this drug to oxybutynin than vice versa. Survival curves indicated that there was only an 11.4% probability of a patient taking oxybutynin for 6 months compared to 5.7% for flavoxate patients. CONCLUSIONS: Drug claim renewal rates were low for both oxybutynin and flavoxate, suggesting that money spent on these therapies provides an inadequate clinical return on investment since the majority of patients discontinue treatment prematurely.
Journal Article↗
Predictors of long-term persistence on statins in a subsidized clinical population.
OBJECTIVES: The use of statins in primary prevention of cardiovascular disease is currently under debate. This study characterizes and identifies predictors of the persistence of use of statins in a clinical cohort of subsidized new users of similar age to the WOSCOPS trial subjects. METHODS: Medical, pharmaceutical, and demographic records for the period January 1, 1987 through December 31, 1994 were extracted from the databases of Québec's provincial health plan for a 10% random sample of social assistance recipients. Patients remained eligible for inclusion if they had received a first dispensation of a statin between January 1, 1987 and July 31, 1994. Persistence was defined as the number of days on treatment with a statin while continuing to renew dispensations within a defined time limit. RESULTS: New users of statins included 983 social assistance recipients who were observed for a total of 2,439,153 person-days. Median persistence on statin treatment was 173 (95% CI = 155, 204) days. Only 13% of patients persisted for 5 years of treatment. A higher index of chronic morbidity, pre-existing cardiovascular disease, and previous use of nicotinic acid were predictive of longer persistence on statin medication. Those patients whose first statin dispensation was for lovastatin discontinued treatment earlier than those whose first dispensation was for pravastatin or simvastatin. CONCLUSIONS: New users showed low persistence on statins in a cohort of socially assisted persons aged 45-64, in spite of the minimal financial cost of the drug for such beneficiaries of Québec's provincial health plan.
Journal Article↗
Management of new symptoms of dyspepsia in the elderly in Quebec.
OBJECTIVE: To use the Régie de l'assurance-maladie du Québec (RAMQ) database to study the clinical strategies used by Quebec physicians in the management of dyspepsia in the elderly. DESIGN: A 20% random sample of the RAMQ database for Quebec residents aged 65 years and older for the three years from July 1, 1991 to June 30, 1992 was used. Patients were placed in three cohorts according to the following treatment strategies: endoscopy, x-ray examination or drug therapy. Patients in each cohort were then categorized as either nonsteroidal anti-inflammatory drug (NSAID) users or non-NSAID users. The choice of drug treatment used to manage the dyspepsia in each cohort was recorded. Drug treatments were divided into the following six antidyspeptic categories: H2 blockers, omeprazole, sucralphate, misoprostol, prokinetic drugs or no drugs. The number of duodenal, oesophageal and stomach cancers diagnosed in each cohort was also counted. RESULTS: Drug therapy was the most frequently used strategy in all patients, and was used more frequently in NSAID users (87%) than in non-NSAID users (69%). A total of 22% of NSAID users in each group, and 46% of NSAID users in the drug therapy group, underwent investigation. H2 blockers were the most prescribed drug in all three treatment strategies, and omeprazole was the second most prescribed drug in the endoscopy and x-ray cohorts. Overall omeprazole was the least prescribed drug. There was a higher rate of cancer detection in the endoscopy and x-ray cohorts than in the drug therapy group. CONCLUSIONS: Previous NSAID use greatly influences the way in which physicians treat patients with dyspepsia.
Aged↗