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Biomedical subjects

R L Talbert

Publications and source records attributed to R L Talbert.

At least 37 records · Page 2Linked to original sources
PubMed1988

Biological mechanisms and cardiovascular effects of omega-3 fatty acids.

The mechanisms and cardiovascular effects of omega-3 fatty acids are reviewed. Omega-3 polyunsaturated fatty acids are the major ingredient found in commercially available fish oil products. The incidence of many diseases, including coronary heart disease, diabetes mellitus, and psoriasis, is lower in Eskimos, who ingest diets rich in omega-3 fatty acids, compared with European controls. Potential mechanisms by which these fatty acids cause their many physiologic effects include competing with omega-6 fatty acids for prostaglandin and leukotriene pathways and enhancing cell membrane fluidity by virtue of the high degree of unsaturation. Numerous studies have documented longer bleeding times and decreased platelet aggregation in subjects ingesting omega-3 fatty acids. Omega-3 fatty acids may reduce serum cholesterol concentrations by decreasing the synthesis of very low density lipoprotein and, therefore, low-density lipoprotein. Blood viscosity is significantly and uniformly lower in subjects receiving omega-3 fatty acids compared with controls. Potential risks of supplementation with fish oils include hypervitaminosis A and D, vitamin E deficiency, increased bleeding times, decreased platelets, and ingestion of contaminated fish. Supplementation with moderate amounts of omega-3 fatty acids appears to be relatively safe. Possible adverse effects include nausea, diarrhea, and a "fishy" taste. Properly controlled, long-term clinical trials are needed to determine whether supplementation with omega-3 fatty acids would be therapeutically beneficial in various patient populations and disease states.

Fatty Acids, Unsaturated↗
PubMed1988

Respiratory effects of high-dose butorphanol.

The effect of butorphanol on respiratory drive was assessed using a carbon dioxide response test (CRT). Eight male volunteers received 3 mg/70 kg of intravenous butorphanol every 30 min to a cumulative dose of 15 mg/70 kg (5 doses). Thirty minutes before the first butorphanol dose, each subject received normal saline to establish a baseline CRT. After each butorphanol dose, a CRT was repeated at 15 min to assess respiratory depression. Minute ventilation was plotted against PaCO2 to generate a regression line for saline and each dose. Slopes and intercepts for each line were calculated by least squares linear regression, and CRT displacement from saline was determined at each dose. The mean slope for each dose was not significantly different from the saline slope (p = 0.23-0.91). The mean displacement (+/- SEM) of the CRT from saline was greatest after the second dose (7.29 +/- 1.94 mm Hg) but not significantly different from the first or subsequent doses (p greater than 0.05). Butorphanol in doses of up to 15 mg/70 kg may have a 'ceiling effect' in respiratory depression.

Adult↗
PubMed1987

Lovastatin: a new cholesterol-lowering agent.

Lovastatin is a potent new drug for lowering serum cholesterol through inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, the rate-limiting enzyme for cholesterol biosynthesis. Metabolic studies with lovastatin in healthy volunteers and patients with hypercholesterolemia suggest reduced synthesis of low-density lipoprotein cholesterol (LDL-C) as well as enhanced catabolism LDL-C mediated through LDL receptors as the principal mechanisms for lipid-lowering effects. Total cholesterol and LDL-C are reduced by 30% or more on average when added to baseline therapy, with the effects being more pronounced in nonfamilial than in familial hypercholesterolemia. Optimal dosing appears to be 20 mg given twice a day. The most common adverse effects are gastrointestinal, while the most serious are elevated transaminase levels and the potential for lens opacities. Lovastatin is the first of a new class of lipid-lowering agents, and is effective when added to diet therapy or in combination with other drugs.

Cholesterol↗
PubMed1987

Current concepts in clinical therapeutics: ischemic cerebrovascular disease.

The classification, epidemiology, pathophysiology, diagnosis, and treatment of ischemic cerebrovascular disease (ischemic stroke) are reviewed, and the major drugs used in the prevention of this disease are discussed. Ischemic stroke is a major problem in terms of morbidity and mortality because of the high prevalence of atherosclerosis in the United States population. The pathogenesis of cerebral ischemia is multifactorial, beginning with an atherosclerotic plaque on the arterial wall that may result in stenosis or ulceration with subsequent thrombosis or embolization. Platelets may adhere to the exposed arterial wall endothelium, stimulating further platelet aggregation and accumulation of leukocytes and fibrin. Consequences of cerebral ischemia include transient ischemic attacks and brain infarcts. Diagnosis is based mainly on patient history and ancillary radiologic studies. Treatment of ischemic cerebrovascular disease is primarily preventive, since the brain has limited capacity to recover neurologic function after an infarction. Transient ischemic attacks are treated with either antiplatelet agents, anticoagulants, or surgery. Treatment of stroke is also preventive, although anticoagulation is sometimes used to prevent stroke progression. Agents that may reverse neurologic impairment following an acute stroke, such as prostacyclin, calcium-channel blockers, and opiate antagonists, are being investigated. Antiplatelet therapy is indicated in subsets of patients with cerebral vascular insufficiency. Anticoagulation therapy, if needed, should be given for only three to four months.

Brain Ischemia↗
PubMed1986

Sexual dysfunction with antihypertensive and antipsychotic agents.

The physiology of the normal sexual response, epidemiology of sexual dysfunction, and the pharmacologic mechanisms involved in antihypertensive- and antipsychotic-induced problems with sexual function are discussed, with recommendations for patient management. The physiologic mechanisms involved in the normal sexual response include neurogenic, psychogenic, vascular, and hormonal factors that are coordinated by centers in the hypothalamus, limbic system, and cerebral cortex. Sexual dysfunction is frequently attributed to antihypertensive and antipsychotic agents and is a cause of noncompliance. Drug-induced effects include diminished libido, delayed orgasm, ejaculatory disturbances, gynecomastia, impotence, and priapism. The pharmacologic mechanisms proposed to account for these adverse effects include adrenergic inhibition, adrenergic-receptor blockade, anticholinergic properties, and endocrine and sedative effects. The most frequently reported adverse effect on sexual function with the antihypertensive agents is impotence. It is seen most often with methyldopa, guanethidine, clonidine, and propranolol. In contrast, the most common adverse effect on sexual function with the antipsychotic agents involves ejaculatory disturbances. Thioridazine, with its potent anticholinergic and alpha-blocking properties, is cited most often. Drug-induced sexual dysfunction may be alleviated by switching to agents with dissimilar mechanisms to alter the observed adverse effect while maintaining adequate control of the patient's disease state.

Adrenergic beta-Antagonists↗
PubMed1985

Population pharmacokinetics of racemic warfarin in adult patients.

The population pharmacokinetics of racemic warfarin was evaluated using 613 measured warfarin plasma concentrations from 32 adult hospitalized patients and 131 adult outpatients. Warfarin concentrations were measured in duplicate using a high-performance liquid chromatographic procedure. The pharmacokinetic model used was a one-compartment open model with first-order absorption (absorption rate constant set equal to 47 day-1) and first-order elimination. The extent of availability was assumed to be one. A linear regression model was used to evaluate the influence of various demographic factors on warfarin oral clearance. Age appeared to be an important determinant of warfarin clearance in this adult population. There was about a 1%/year decrease in oral clearance over the age range of 20-70 years. Smoking appeared to result in a 10% increase in warfarin clearance, while coadministration of the inducers phenytoin or phenobarbital yielded about a 30% increase in clearance. This study has yielded a predictive model that, when combined with appropriate pharmacological response data, may be useful in the design and adjustment of warfarin regimens.

Adolescent↗
PubMed1984

Plasma protein binding of warfarin: methodological considerations.

Recent theoretical work has suggested that radiochemical impurities can significantly alter the binding results for highly protein-bound drugs. We compared protein binding of warfarin by ultrafiltration and equilibrium dialysis with 98% radiochemically pure [14C]warfarin. Ultrafiltration and equilibrium dialysis were performed at 37 degrees C and pH 7.45 on the plasma of patients receiving chronic warfarin therapy. Binding to plasma from seven patients were measured in duplicate by both a nonspecific radioisotopic technique and a specific HPLC technique. The nonspecific technique gave percentage of free warfarin values of 1.84 +/- 0.11 (mean +/- SD) and 1.59 +/- 0.14 for ultrafiltration and equilibrium dialysis, respectively. The HPLC procedure yielded a percentage of free warfarin by ultrafiltration of 0.969 +/- 0.203 and a value of 0.690 +/- 0.095 by equilibrium dialysis (p less than 0.05). The HPLC procedure for protein binding was performed on plasma samples from 12 additional patients and yielded a percentage of free warfarin of 1.01 +/- 0.69 by ultrafiltration and 0.44 +/- 0.34 by equilibrium dialysis (p less than 0.05). It can be concluded that radiochemical impurities may lead to significant overestimation of the percentage of free warfarin. Ultrafiltration yielded a higher percentage of free warfarin than did equilibrium dialysis, but the ability to distinguish binding differences among patients was similar.

Blood Proteins↗
PubMed1982

Clodronate kinetics and bioavailability.

Carbon 13-labeled clodronate disodium was given to healthy adult men by intravenous infusion and orally in a crossover design. Serum and urine levels were determined as a function of time by isotope-ratio mass spectrometry. Clodronate disodium (Cl2/MDP) is primarily excreted unchanged by the kidney; more than 80% of the intravenous dose was recovered within 48 hr. The serum concentrations-time curve over the first 8 hr after intravenous dosing appears biexponential with the disposition phase having a harmonic mean half-life (t 1/2) of 2 hr. The mean serum clearance was found to be 1.4 ml min-1 kg-1 and the apparent volume of distribution was approximately 25% of body weight. Simulations and computer fitting of the cumulative urinary excretion and urinary excretion rates based on the biexponential serum decay curve demonstrated the presence of a slow disposition component with a t 1/2 of 12.8 hr. Thus, the disposition kinetics of Cl2MDP appear to be triexponentials, although the slowest component is not of major significance after a single dose and could not be verified because of a lack of serum data after 8 hr. Cl2MDP is poorly absorbed with an absolute bioavailability of only 1% to 2%.

Administration, Oral↗
PubMed1981

Propranolol plasma concentrations and plasmapheresis.

Propranolol plasma concentrations were determined in a patient with hemolytic-uremic syndrome undergoing plasmapheresis before and after the procedure on three occasions. The mean half-life and elimination rate constant during plasmapheresis were estimated to be 25.6 percent of the values obtained without plasmapheresis. These changes suggest that plasmapheresis may influence propranolol disposition.

Adult↗
PubMedDate not supplied

Rapid establishment of therapeutic serum concentrations of salicylates.

A minimum serum salicylate concentration of 150 microgram/ml is required to control certain inflammatory disease processes. A loading regimen designed to rapidly achieve this minimal level was evaluated in six normal volunteers (age 22 to 27 years, weight 70.5 to 84.1 kg) using a randomized crossover design. The control group received 650 mg aspirin (ASA) every 4 hours for 48 hours. The loading regimen was 2600 mg ASA divided into two equal doses 4 hours apart. Maintenance dosing of 650 mg ASA every 4 hours was then started 4 hours after the completion of the loading regimen and continued for 40 hours. Serum samples were drawn at 0, 2, 4, 6, 8, 12, 24, 36, and 48 hours after initiation of the study and were assayed for salicylate concentration by UV spectrophotometry. Loading with aspirin produced serum concentrations which were significantly higher (P less than 0.01) for the first 24 hours and reduced the time to reach 150 microgram/ml (15.3 +/- 5.9 hours versus 30.4 +/- 8.65 hours, P less than 0.001) for five of six subjects when compared to a conventional regimen. One subject did not achieve 150 microgram/ml at 48 hours with either regimen. Considerable intersubject variation in serum concentration was noted at 48 hours for both regimens. We suggest that a loading regimen for aspirin may have utility for patients in whom rapid attainment of a therapeutic antiinflammatory serum concentration is desirable.

Adult↗