Drugs online research references
Toxicology. 1999 Aug 13;136(1):1-13.
Amitriptyline-induced loss of tight junction integrity in a human endothelial--smooth muscle cell bi-layer model.
Dahlin KL, Bohlin K, Strindlund J, Ryrfeldt A, Cotgreave IA.
Division of Inhalation Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Tricyclic antidepressants can, when taken in overdose, cause serious pulmonary failure such as the adult respiratory distress syndrome (ARDS). In this study we have examined the effects of some tricyclic antidepressants (amitriptyline, imipramine, nortriptyline and desipramine) on the viability and morphology of human endothelial and smooth muscle cells derived from umbilical cord. Effects of amitriptyline on endothelial cell fluidity, as well as permeability changes to an endothelial-smooth muscle cell bi-layer, were also studied. The tricyclic antidepressants induced acute, sub-lethal toxicity in both cell types above 100 microM as assessed by the MTT reduction assay. Morphological changes were also observed at these concentrations. Such changes were, however, absent at 33 microM and below. Amitriptyline did, however, cause a concentration-dependent fall in the electrical resistance of an endothelial-smooth muscle cell bi-layer, with significant effects already evident at 33 microM. All of these observed effects were fairly rapid and appeared within 5-15 min of exposure. The rapidity of these permeabilisation effects suggests potential membrane perturbations, since tricyclic antidepressants are lipophilic molecules with affinity for cell membranes. However, fluorescence anisotropy measurements showed no significant difference in membrane fluidity between amitriptyline-treated and control endothelial cells. Collectively, these data point to specific mechanisms of action of amitriptyline, and probably also the other tricyclic antidepressants studied, on endothelial permeability, which is a hallmark of ARDS. The data suggest that increased endothelial permeability could be due to impaired tight junction function.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10499846&dopt=Abstract
J Pharmacokinet Biopharm. 1999 Feb;27(1):85-101.
Optimal sampling times for Bayesian estimation of the pharmacokinetic parameters of nortriptyline during therapeutic drug monitoring.
Merle Y, Mentre F.
INSERM U436, CHU Pitie-Salpetriere, Paris, France.
Sampling times for Bayesian estimation of the pharmacokinetic parameters of an antidepressant drug, nortriptyline, during its therapeutic drug monitoring were optimized. Our attention was focused on designs including a limited number of measurements: one, two, and three sample designs in which sampling times had to be chosen between 0 and 24 hr after the last intake of a test-dose study. The optimization was conducted in four groups of patients defined by their gender and the administration or not of concomitant drugs inhibiting the metabolism of nortriptyline. The Bayesian design criterion was defined as the expected information provided by an experiment. A stochastic approximation algorithm, the Kiefer-Wolfowitz algorithm, was used for the criterion maximization under experimental constraints. Results showed that optimal Bayesian sampling times differ between patients in monotherapy and polytherapy. For one-sample designs the measurements have to be performed either at the lower (0 hr) or at the upper (24 hr) bound of the admissible interval. Replications were often found for 2- and 3-point designs. Other sampling designs can lead to criterion close to the optimum and can therefore be performed without great loss of information. In contrast, we found that several designs lead to low values of the information criterion, which justifies the approach.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10533699&dopt=Abstract
Aust N Z J Med. 1975 Feb;5(1):7-11.
Assessment of cardiovascular side effects of therapeutic doses of tricyclic anti-depressant drugs.
Vohra J, Burrows GD, Sloman G.
An assessment of the side effects of therapeutic doses of tricyclic anti-depressant drugs was attempted in 32 patients with depressive illness. The patients studied had no evidence of clinical heart disease or hypertension and were not receiving any other drugs. Moderate increase in heart rate and mild prolongation of atrioventricular conduction occurred. No significant effect on the corrected QT interval or blood pressure was found. There was no correlation between the increased heart rate, prolongation of the atrioventricular conduction time (PR interval) and plasma nortriptyline levels measured in 20 out of 32 patients.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1057916&dopt=Abstract
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