Second-generation antihistamines: a study of poisoning in children.

Background and objectives: The toxicity of second-generation antihistamines after an overdose by a child is still unknown. The objective of this study is to use data from Poisons Centres in France to describe the toxicity profile of second-generation antihistamines for children and to compare the severity of poisoning observed from these with a first-generation antihistamine.Method: This was a retrospective, multi-centre and observational study focusing on human cases of single-substance exposure to a second-generation antihistamine and to mequitazine, reported between 1 January 2001 and 31 December 2016 in Poisons Centres in France.Results: From a total of 9403 children included, 5980 were exposed to a second-generation antihistamine and 3423 were exposed to mequitazine. The severity of exposure to second-generation antihistamines in children is low: among the children followed until a known outcome, 9% of children were symptomatic and in 97% of cases, the symptoms shown were of a minor-level severity (primarily drowsiness or restlessness). Depending on the substance, children who ingested doses 16 to 69 times the maximum recommended therapeutic dose remained asymptomatic. No deaths or severe symptoms were observed. No cases of lengthening of the QT interval or arrhythmias were identified. Mequitazine led to more symptoms than other substances (14.8% symptomatic children vs. 7.5%, Odd ratio (OR): 2.3 (2.0-2.6), p < 0.0001), more symptoms of moderate intensity (1.4 vs. 0.2%, OR: 8.3 (4.1-18.5), p < 0.0001) and more hospitalisation (19.1 vs. 8.7%, OR: 2.5, 95% CI: (2.2-2.8), p < 0.0001).Conclusion: The severity of poisoning from second-generation antihistamines appears to be low among children and considerably lower than poisoning caused by mequitazine.

Laryngeal teflonoma identified by Fourier-transform infrared microspectroscopy after forensic autopsy: an interesting tool for foreign material identification in forensic cases.

Forensic pathologists are sometimes confronted with microscopic foreign bodies mixed in with soft tissues surrounding wounds and which are thus difficult to identify. This identification, however, could be primordial in investigating a crime and in determining the weapon used. A case of a fatal respiratory distress syndrome due to conjoining suicidal drug intoxication and laryngeal obstruction by a voluminous foreign body giant cell granuloma is presented. The classical histological examination showed exogenous particles in the vocal cord tumor with birefringent qualities. Their analysis with Fourier-Transform infrared (FTIR) spectrometry coupled with infrared microscope allows the determination of their chemical nature as polytetrafluoroethylene and to the diagnosis of teflonoma. This case report put the emphasis on the forensic interest of the FTIR imaging.

[Application of the clinoid dehydration method in forensic medical expert examination of poisoning with narcotic and strong medicine preparations].

The method of clinoid dehydration of biological fluids along with pH measurement is shown to be suitable for the diagnosis of narcotic intoxication and poisoning with narcotic and potent agents. The data obtained by this and conventional methods are compared. Diagnostically significant signs of narcotic intoxication are deduced from the hemogram of a dry blood droplet and serum pH values.

[Extended suicidal poisoning with carbamazepine and phenothiazine derivatives]. / Rozszerzone samobójcze zatrucie karbamazepina i fenotiazynami.

UNLABELLED: Two cases (woman and man) of the extended suicidal poisonings with carbamazepine and phenothiazine derivatives are presented. Drug's blood concentrations during poisoning were monitored. We examine correlation between patient's general status and the drug's blood concentrations, carbamazepine and phenothiazine derivatives interaction due to young, healthy people who received no earlier treatment. MATERIAL AND METHODS: blood samples for toxicological examinations were collected at 0, 12, 24 and 48 hours after admission. Carbamazepine was determined using FPIA method and phenothiazines derivatives by HPLC-DAD. The highest blood concentrations were for carbamazepine: 30.92 mg/l (woman) and 20.95 ng/ml (man); for phenothiazine derivatives: 927 ng/ml (woman) and 733 ng/ ml (man). CONCLUSIONS: In both cases severe central nervous depression was observed due to summed action of the drugs. Sex and individual differences in cytochromes activities should have influence to carbamazepine metabolism and faster elimination time in woman. In the case of phenothiazine derivatives faster elimination time in man was observed. The differences in elimination times between compared drugs confirm their different metabolic routes.

Are one or two dangerous? Phenothiazine exposure in toddlers.

Traditionally, pediatric phenothiazine exposures are considered dangerous even at low doses. The actual risk of exposure to 1-2 tablets is unclear. In an attempt to determine this risk, the authors performed a literature search, review of the American Association of Poison Control Center data, and evaluation of related resources (e.g., textbooks, bibliographies of relevant papers). This review reveals only sparse data from case reports regarding morbidity and mortality in the pediatric population despite years of clinical experience. Serious toxicity from exposure to low doses is rare and nearly always the result of chlorpromazine ingestion. Although the risk to the toddler ingesting 1-2 tablets seems to be extremely low, several factors should be considered when determining the need for triage to a health care facility.

Acute fatal poisoning with cyamemazine.

A case of fatal poisoning with cyamemazine is presented. The cyamemazine was identified in post-mortem blood using a specific gas chromatographic/mass spectrometry method. The autopsy blood concentration of cyamemazine was 1800 ng/ml. Chronic use of cyamemazine was demonstrated by the presence of the drug in hair. Two other drugs were also detected (bromazepam and trimeprazine). We think that this current blood concentration (1800 ng/ml) is a fatal blood concentration because of the negativity of the other parameters, but careful interpretation of analytical findings are important, the possibility that this death was a consequence of the toxicity of combined drugs could not be excluded. Not many therapeutics and toxic levels were previously reported in overdosage cases in which cyamemazine was involved. We consider that this concentration is only of guidance value for a fatal cyamemazine poisoning.

Among fatal poisonings dextropropoxyphene predominates in younger people, antidepressants in the middle aged and sedatives in the elderly.

To compare the characteristics of dextropropoxyphene (DXP) poisoning victims with those of victims of poisonings by antidepressants and sedatives, we examined all fatal poisonings due to DXP, antidepressants or sedatives among autopsies performed at one department of forensic medicine in Sweden during the six-year period from 1992 to 1997. In 202 cases, death was classified as fatal poisonings by DXP, antidepressants or sedatives. DXP caused death in 78 cases (39%), antidepressants in 49 (24%), and sedatives in 75 (37%). DXP as a single preparation was predominant in causing death. The second compound, flunitrazepam, caused death in 30 cases (15%). The victims of poisonings by DXP, antidepressants, or sedatives shared a similar history of alcohol/drug abuse, depression and somatic illness. They were mostly living alone at the time of death (>60%), the majority died at home (81%), and suicide was the most frequent manner of death (73%). Age seemed to be an important characteristic regarding the choice of drug. Younger people predominantly died of DXP (mean age 43 years, 95% confidence interval, CI 39-47), and elderly people of sedatives (mean age 59 years, CI 55-63). Antidepressants were found mainly in middle-aged victims (mean age 51 years, CI 48-54). The predominance of sedatives among the elderly might be explained by a very high prescription rate of such drugs in older age groups, but prescription rate could not explain the DXP predominance among younger people. We hypothesize that younger people are more prone to abuse therapeutic drugs for euphoric reasons than elderly people, and that because of its high toxicity, DXP leads to accidental deaths more often than sedatives.

Cyamamezine-induced acute hepatitis after unique massive intake: a case report.

Hepatotoxicity of cyamamezine, a phenothiazine structurally related to chlorpromazine, has been rarely documented. We report here a case of acute symptomatic hepatitis following a unique massive intake of cyamamezine in a suicide attempt and discuss the mechanisms of such injury.

[Use of dobutrex in critical states in patients with acute poisoning of chemical etiology]. / Primenenie dobutreksa pri kriticheskikh sostoianiiakh u bol'nykh s ostrymi otravleniiami khimicheskoi étiologii.

Efficacy of dobutrex was assessed in 75 patients with grave poisonings. In 45 of these poisoning with cardiotoxic agents was complicated by acute heart failure and in 30 poisoning with psychopharmacological agents involved secondary disorders of cardiac contractile function. A sharp reduction of cardiac contractile function and output were observed in all the cases. Treatment efficacy was assessed by monitoring the parameters of central hemodynamics and by phase analysis of left-ventricular systole by rheopolycardiography with recording by mingograf-82. The results indicated a rapid and effective correction of decreased cardiac contractility and increase of cardiac output. The dose-effective concentration of dobutrex in the blood needed for the treatment of acute heart failure was from 10 to 17.5 micrograms/kg/min. Arterial pressure, cardiac contractility, and cardiac output stabilized within 4 to 6 h. After poisoning with psychopharmacological agents cardiac contractility recovered in 3-3.5 h. The dose-effective concentration of dobutrex in the blood was 5 micrograms/kg/min. Dobutrex is a highly active cardiotonic agent for the treatment of critical states developing in the aforesaid poisonings.

[The determination of etatsizin in cadaveric material]. / Opredelenie étatsizina v trupnom materiale.

Ethacizin and its principal metabolite 2-carbethoxyaminophenothiazine may be isolated from cadaveric material by acetonitrile and subsequent ether extraction at pH 13.0. Detection of ethacizin from the hydrolysis product improves the sensitivity of detection.

Toxicological data in a fatality involving cyamemazine.

A fatality involving cyamemazine, a phenothiazine derivative, is presented. Cyamemazine was formally identified in postmortem blood using an HPLC-DAD screening procedure, and then quantified in some postmortem samples by means of a specific HPLC method. The blood concentration of cyamemazine was 9.8 micrograms/mL. Tissue distribution of cyamemazine is discussed in light of the existing literature.

[Therapy of the anticholinergic syndrome in poisonings]. / Die Therapie des anticholinergen Syndroms bei Intoxikationen.

Underlying literature and taking into consideration own experiences in the anticholinergic syndrome the following view is taken: Physostigmine salicylate is the remedy of choice for the treatment of the anticholinergic syndrome and altogether causes only slight side effects. While for differential-diagnostic reasons the application is recommended under hospital conditions, the pre-hospital application is to be estimated as problematical. The improvement of the clinical symptoms under the influence of physostigmine salicylate must not lead to the neglect of the control of the patient. A differentiated use of physostigmine salicylate is necessary, and it cannot be regarded as "universal antidote" in intoxications caused by central-nervous effective substances.

[Failure of gastric lavage in severe drug poisoning. Value of esophagogastric fibroscopy]. / Echec du lavage gastrique dans une intoxication médicamenteuse grave. Intérêt de la fibroscopie oeso-gastrique.

A case is reported of massive drug self-poisoning (more than 200 pills associated with slices of oranges) in which repeated gastric lavage failed to empty the stomach. An attempt to split up the amalgamated pills, adherent to the gastric mucosa, by fibre-optic gastroscopy failed and a gastrotomy was required. Endoscopy together with gastric lavage is indicated in certain situations to quickly empty the stomach and so shorten the course of the poisoning. Indications are the large number of pills swallowed, a poor result of the treatment, a worsening of the clinical condition despite treatment, and three positive gastric toxicological assays within the first 24 h.