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A case report involving a 34-year-old white male who was found dead at home by his roommate is presented. At the time of his death, he was being treated with tramadol/acetaminophen, metaxalone, oxycodone, and amitriptyline. The decedent's mother stated that he had been taking increasing amounts of pain medication in order to sleep at night. There were no significant findings at autopsy; however, toxicology results supported a cause and manner of death resulting from suicidal mixed tramadol and amitriptyline toxicity. This case reports the tissue and fluid distribution of tramadol, amitriptyline, and their metabolites in an acutely fatal ingestion in an effort to document concentrations of these analytes in 12 matrices with respect to one another to assist toxicologists in difficult interpretations.

The clinical applications of plasmapheresis are rapidly increasing in number and scope. This trend is also observed in the application of plasmapheresis as a method of detoxification in clinical toxicology. Because of a lack of large controlled series, the rationale for using plasmapheresis must be confirmed in each type of intoxication by evidence of effective clearance, as well as by high plasma protein binding and a low volume of distribution of the toxic substance. Plasmapheresis is used mostly to treat phalloid mushroom intoxications. In this potentially fatal intoxication, for which there is no antidote, plasmapheresis is at least as effective as haemoperfusion in reducing mortality from as high as 30-50% with conventional therapy to <20%. In our series of 28 patients treated with plasmapheresis, mortality was 17.8%. In our experience, plasmaphe-resis is also very effective in the treatment of life-threatening intoxications with tricyclic (amitriptyline) and 4-cyclic (maprotyline) antidepressants. We confirmed a 63% reduction in the plasma level of amitriptyline in one patient after single plasmapheresis. Other drugs such as L-thyroxine, verapamil, diltiazem and carbamazepime are also removed effectively by plasmapheresis, as are theophylline and heavy metals (mercury and vanadate). Phosphoroorganic substances are not removed effectively. We measured the plasma concentrations of dimethoate in two patients with this intoxication and did not find clinically significant clearance with plasmapheresis.

A selective, sensitive, and reliable method was devised to determine concentrations of amitriptyline and its major metabolite, nortriptyline, in human plasma using high-performance liquid chromatography (HPLC) combined with UV and particle beam mass spectrometry (PBMS). Amitriptyline and nortriptyline were effectively extracted in a three-step solvent extraction procedure. Imipramine was used as the internal standard (IS). Amitriptyline, nortriptyline, and the IS were clearly separated by HPLC on a silica column with the mobile phase of acetonitrile-0.1 M ammonium acetate (94:6, v/v). The calibration curves were linear in the concentration range of 10-1000 ng/g for both compounds with UV and PBMS detections. The lower limits of detection were 5 ng/g for amitriptyline and 10 ng/g for nortriptyline with UV detection and 2 ng/g for amitriptyline and 5 ng/g for nortriptyline with PBMS detection. The absolute recoveries were 58% for amitriptyline and 47% for nortriptyline at a concentration of 50 ng/g. This method proved most useful in accurately identifying amitriptyline and nortriptyline in tissues from an autopsied individual.

I report a case of intestinal pseudo-obstruction, spontaneous caecal perforation and faecal peritonitis caused by an overdose of amitriptyline. This rare but serious complication should be borne in mind in patients who remain constipated while convalescing after self-poisoning with tricyclic antidepressants.

Thirty-two cases of fatal self-ingested overdose involving amitriptyline were studied over the two-year period 1978 to 1979. The average decedent was a 44-year-old woman who ingested amitriptyline and at least one other drug (usually ethanol, diazepam, propoxyphene, or codeine). The mean concentrations of amitriptyline and nortriptyline were significantly higher in liver than in myocardium, and they were significantly higher in myocardium than in blood. In addition, concentrations in these tissues showed significant correlation with each other. The mean tissue concentrations of amitriptyline and nortriptyline in this series of overdoses were significantly greater than those in fourteen other decedents whose deaths were not due to drug overdose but involved amitriptyline as an incidental finding. The mean ratio of amitriptyline to nortriptyline in each tissue was also significantly higher in overdose than those in the corresponding tissues of the non-overdose group, suggesting that the former ingestions were more acute. The estimated survival times showed no significant correlation with tissue concentrations of either amitriptyline or nortriptyline.

This paper describes the use of a Celite 560 column extraction technique in the initial separation of drugs from the contents of the skull of a severely decomposed body. Analysis of the extract obtained resulted in the determination of the presence of amitriptyline, and maprotiline and two of its metabolites. As a consequence, the laboratory was able to provide the medical examiner with information concerning an extremely difficult case.

In the year May 1976 to April 1977, 489 enquiries about the management of tricyclic antidepressant poisoning received at the London Centre of the National Poisons Information Service were followed-up. One hundred and sixty-four patients (33.5%) were unconscious, convulsions occurred in 62 (12.7%), hypotension in 31 (6.3%), respiratory depression in 28 (5.7%), tachydysrhythmias in 17 (3.5%) and cardiac arrest in 12 patients (2.5%). Sixteen patients died (3.3%). No statistically significant differences were found between individual antidepressants although poisoning with amitriptyline-like drugs resulted in a significantly higher proportion of unconscious patients than poisoning with imipramine-like drugs (P less than 0.01). There were more asymptomatic children than adults and more unconscious adults than children. Tricyclic antidepressant poisoning is a major clinical problem in general medical and paediatric practice.

We describe a gas-chromatographic procedure for the simultaneous determination of amitriptyline and its active metabolite, nortriptyline, in therapeutic concentrations in human plasma, with use of a nitrogen detector. Both drugs are extracted at pH 10.5 into hexane/isoamyl alcohol, back-extracted into dilute HCl, and re-extracted into hexane/isoamyl alcohol after alkalinization of the HCl. The solvent is evaporated and the residue gas-chromatographed. Protriptyline is used as the internal standard. As little as 5 mug of amitriptyline or nortriptyline can be detected per liter of plasma. The coefficients of variation, for a concentration of 200 mug/liter, are 4.6% and 4.3% within-day and 8.6% and 3.4% day-to-day for amitriptyline and nortriptyline, respectively. The procedure was applied to patients receiving therapeutic doses of both drugs and also to patients who had taken overdoses of amitriptyline.

A 22 year old woman was admitted with amitriptyline overdose. Twenty six hours later she developed acute myocardial infarction. Cardiotoxic effects of tricyclic antidepressants are discussed and the importance of considering myocardial infarction as a complication of tricyclic antidepressant overdose is emphasized.

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)