[Severe meprobamate poisoning: description of 146 cases in a French department]. / Intoxications graves au méprobamate : description d'une série de 146 cas dans le département de la Loire.

Meprobamate poisoning are serious and sometimes fatal. Faced with a potential stop of marketing, we conducted a multicenter retrospective study to assess the severity criteria presented by patients admitted to the ICU for severe meprobamate poisoning, whether with alone form or in combination with aceprometazine. One hundred fourty-six patients have been enrolled between January 2005 and June 2011: 38 had a single meprobamate poisoning, 104 to meprobamate and aceprometazine and 4 to both forms. At admission, 88% of patients exhibited coma (Glasgow ≤ 7) and half of them a systolic blood pressure ≤ 90 mmHg. Mortality rate was 3%. Our results did not find any significant between-group difference, either in regard of clinical or biological severity criteria. These data argue for a cessation of marketing of all meprobamate-based specialities.

Radiopacity of clomipramine conglomerations and unsuccessful endoscopy: report of 4 cases.

BACKGROUND: The radiopacity of ingested substances may serve as a clue to the presence of particular compounds, as this characteristic varies considerably among medications and household products. Tablet conglomerations are also variably radiopaque. We report 4 cases of clomipramine poisoning associated with formation of radiopaque masses, believed to be clomipramine, in the area of the stomach. CASE REPORTS: Four patients were admitted to the Toxicological Intensive Care Unit after ingestions of, respectively, 8.5 g (180 tablets of mixed strength), 7.5 g (100 tablets), 10.5 g (140 tablets), and 4.5 g (60 tablets) of clomipramine, along with other sedatives and antipsychotics. In each case, a rounded density was observed in the gastric area on plain chest radiograph. The hospital courses of each patient were marked by tachycardia, hypotension, QRS and QT prolongation, seizures, and decreased mental status. Three of 4 patients underwent unsuccessful endoscopy to remove tablet fragments and subsequently suffered gastrointestinal hemorrhage requiring transfusion. All patients were discharged recovered from the hospital. DISCUSSION: Clomipramine, a potent tricyclic antidepressant, has been previously reported to be nonradiopaque, and has not been reported to induce formation of concretions. These cases suggest that massive ingestions of clomipramine may form bezoars which are radiopaque and may be associated with serious toxicity. Careful consideration should be given prior to the use of gastric endoscopy for the retrieval of tablet fragments since significant hemorrhage, attributed to the procedure itself rather than to clomipramine toxicity, may ensue.

A previously unidentified acepromazine metabolite in humans: implications for the measurement of acepromazine in blood.

High-performance liquid chromatography-diode-array detection results obtained during the investigation of two cases involving acepromazine prompted us to study the stability of the drug in blood. It was found that acepromazine can undergo in vitro conversion by human red blood cells to 2-(1-hydroxyethyl)promazine, a product that has been reported as a minor urinary metabolite in horse urine but not previously identified in humans. Further, our analytical findings in the two cases examined suggest that 2-(1-hydroxyethyl)promazine may be the major unconjugated metabolite of acepromazine in humans. These findings have important implications for the analytical toxicology of acepromazine.

Risk of syncope in the elderly and consumption of drugs: a case-control study.

A multicenter case-control study (588 cases and 1807 controls) was performed to assess the risk of syncope in the elderly according to drug consumption within the three days before syncope, controlling the underlying cardiovascular diseases. Pair-matched and non-pair-matched analyses using logistic regression were performed, providing consistent results. After adjustment for age, sex, and cardiovascular disease, cases were shown to consume more often than non-cases drugs in classes of non-tricyclic antidepressants, neuroleptic drugs, and antiparkinsonians. A detailed analysis has shown that only four drugs were significantly associated with an excess risk of syncope: fluoxetine (OR = 2.6; 95% CI: [1.8-3.5]), aceprometazine (OR = 2.0; [1.5-2.5]), haloperidol (OR = 2.8; [2.0-3.6]), and L-dopa (OR = 2.8; [2.2-3.7]). This analysis shows that these drugs should be prescribed with special caution in the elderly.

The metabolism of promazine and acetylpromazine in the horse.

Promazine hydrochloride and acetylpromazine maleate were administered intravenously at clinical dose levels to horses. In urine from horses given promazine hydrochloride, the parent drug and four metabolites were detected. The two major metabolites, present as conjugates were identified after hydrolysis by beta-glucuronidase/arylsulfatase as 3-hydroxypromazine and 3-hydroxydesmonomethyl-promazine. Conjugated 3-hydroxypromazine has been previously identified as a major metabolite in the horse. Two minor metabolites isolated in this study were primaizine N-oxide and promazine N-oxide sulfoxide. At the administered dosage, promazine sulfoxide was not found to be the major nonconjugated metabolite, as had been reported elsewhere. In urine from horses given acetylpromazine maleate, only three metabolites were found. Two were identified after hydrolysis by beta-glucuronidase/arylsulfatase as 7-hydroxyacetylpromazine and 2-(1-hydroxyethyl)-7-hydroxypromazine. The third, nonconjugated metabolite was 2-(1-hydroxyethyl)promazine sulfoxide.