Drugs online research references
J Anal Toxicol. 1988 Jul-Aug;12(4):216-24.
Application of expert systems analysis to interpretation of fatal cases involving amitriptyline.
Spiehler V, Spiehler E, Osselton MD.
Central Research Establishment, Home Office Forensic Science Service, Aldermaston, Reading, Berkshire, United Kingdom.
Part I. Expert 4: The object of this study was to investigate the applicability of commercially available expert system shells to interpretation in forensic toxicology. Amitriptyline toxicology was selected as a pilot trial. Blood and tissue concentrations of amitriptyline and nortriptyline in fatal and nonfatal amitriptyline cases from the literature and from the Registry of Human Toxicology databank were entered into the expert system shell Expert 4 (Rivers, Elsevier). The statistical evaluation routines of the shell were used to search for patterns in the data. Successive changes in the data base were made to test for the influence of the data base on the conclusions. Finally the data base was refined, based on the evaluations, to strengthen the probabilities of the conclusions. The refined database was coupled with the Expert 4 inference engine to infer unknown parameters in the cases. The results of the expert system analysis were compared to known values and published expert opinions. The ratio of amitriptyline/nortriptyline and tissue levels of nortriptyline were found to be the most significant measures for interpretation of effect and time since ingestion. Part II. Computer Induction of Rules: Blood and tissue concentrations of amitriptyline and nortriptyline in fatal and nonfatal amitriptyline cases from the literature and from the Registry of Human Toxicology databank were entered into the expert system shell BEAGLE, (Forsyth, Machine Learning Research, Ltd.). The automatic rule induction routines of the shell were used to search for patterns in the data. The program expressed these patterns as numerical predictions or Boolean logic rules. The results were compared to those obtained with the Expert 4 (Rivers, Elsevier) using the same case knowledge base.(ABSTRACT TRUNCATED AT 250 WORDS)
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3184890&dopt=Abstract
JAMA. 1979 Jun 8;241(23):2530-3.
Monitoring tricyclic antidepressant plasma concentrations.
Hollister LE.
Plasma concentrations of tricyclic antidepressants were monitored during treatment of 126 patients. Noncompliance in taking medication was suspected in 19 patients because of unusually low plasma concentrations in relation to the presumed dose. Determinations of plasma concentrations may also be useful for detecting inadequate treatment as judged by levels below the presumed therapeutic range. Attempts to correlate plasma concentrations with clinical response to amitriptyline hydrochloride and nortriptyline hydrochloride failed, probably because of the heterogeneity of depressive syndromes being treated. Plasma concentrations were correlated highly with dose in the case of amitriptyline, less so in the case of other drugs. Amitriptyline and imipramine hydrochloride generally produced plasma concentrations of the parent drug and metabolite higher in nanograms per milliliter than was the daily dose in milligrams; nortriptyline and desipramine hydrochloride did the opposite.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=439339&dopt=Abstract
Aliment Pharmacol Ther. 1987 Apr;1(2):141-51.
The gastric proton pump, a target for neuroleptics and antidepressant drugs?
Beil W, Stunkel P, Pieper A, Sewing KF.
Abteilung Allgemeine Pharmakologie, Medizinische Hochschule Hannover, F.R.G.
The antisecretory action of the antidepressant drugs trimipramine, doxepin and nortriptyline was studied in two different in-vitro test systems; the isolated and enriched guinea-pig parietal cell and the purified H+/K(+)-ATPase preparation. The effect of the antidepressants was compared with that of the neuroleptic agents chlorpromazine, triflupromazine, trifluperazine, haloperidol, fluspirilene and with that of the tricyclic anticholinergic agent pirenzepine. All neuroleptics and antidepressants inhibited acid formation in intact parietal cells with IC50 values in the nanomolar range. The inhibitory potency for each compound was identical regardless of whether histamine or db-cAMP was used as stimulant. Isolated H+/K(+)-ATPase, measured in the presence of 5 mmol litre-1 KCl, was inhibited by all psychotropic drugs with IC50 values in the micromolar range. EGTA did not affect the inhibitory potency at the H+/K(+)-ATPase, indicating that the action of the drugs does not depend on their calmodulin blocking activity. Pirenzepine was ineffective in both test systems. Kinetic studies done with nortriptyline, chlorpromazine and haloperidol showed a competitive type of inhibition with respect to K+ at low inhibitor concentrations. This competitive type was changed to a mixed type of inhibition with increasing inhibitor concentrations, demonstrating cooperative effects between drug binding and K+ activation of the enzyme. From these data it is suggested that antidepressants and neuroleptics act by an allosteric mechanism of action, and that the lipid solubility is a significant factor to establish enzyme inhibition.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2908748&dopt=Abstract
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