[The chemical toxicological determination of isoniazid and metoclopramide in the objects used for animals poisoning and in biological fluids]. / Khimiko-toksikologicheskoe opredelenie izoniazida i metoklopramida v ob''ektakh, ispol'zuemykh dlia otravleniia zhivotnykh, i v biologicheskikh zhidkostiakh.

The number of mass casualty incidents among the dogs has significantly increased during a few recent years in the cities of this country; they are most frequently attributed to the activities of the so-called dog hunters. The dog hunters make use of a variety of chemical compounds for poisoning the dogs. Most of them are the multi-component substances, with their chemical composition being highly variable and continuously modified. The objective of the present study was to develop the method for the isolation and identification of isoniazid and metoclopramide introduced into the baits that are distributed by the dog hunters for the poisoning of the animals. The proposed method was tested with the use of biological fluids obtained from the laboratory animals. The effectiveness of isolation of the compounds of interest from these materials with the use of the liquid-liquid and fractional freezing extraction techniques was evaluated. In addition, the method for solid phase extraction with the use of the 'Oasis HLB' cartridges was developed.

Overdose in young children treated with anti-reflux medications: Poisons enquiry evidence of excess 10-fold dosing errors with ranitidine.

BACKGROUND: Accidental drug overdose is a common problem in young children. We examined the influence of formulation and dose in enquiries for different gastro-oesophageal reflux disease treatments in children under 5 years to the UK's National Poisons Information Service. METHODS: Overdose characteristics with ranitidine, omeprazole or domperidone were compared with those of metoclopramide and the H-1 antagonist chlorphenamine, for the period 1 July 2007 to 30 June 2015. RESULTS: There were a total of 1092 ranitidine, 618 domperidone and 1193 omeprazole cases; 669, 281 and 424, respectively, were single agent enquiries; of these 77% (517) of ranitidine, 52% (145) domperidone and 32% (135) omeprazole cases occurred in children <5 years. In comparison, 17% (34/424) of metoclopramide and 53% (533/1013) of chlorphenamine were <5 years; 79% (410/517) of ranitidine overdose enquiries in children <5 years were under 6 months of age, higher than domperidone (68/145, 47%; p < 0.05), omeprazole (8/135, 6%), chlorphenamine (13/553, 2%) or metoclopramide (1/34, 3%) (all p < 0.01). In children aged <6 months, 101 were 10-fold overdoses, 86 with ranitidine. CONCLUSIONS: Tenfold overdoses in children (<5 years) were a feature of ranitidine enquiries, likely due to the high concentration of the syrup. This has relevance to other liquid formulations used for non-licenced indications in young children. Such therapeutic errors cause significant carer anxiety and healthcare utilization. Assistance is needed from manufacturers and legislators in modifying formulation so that drugs can be safely used in young children. Education of prescribers and carers is also needed to reduce the incidence of such errors that cause significant carer anxiety and healthcare utilization.

Metoclopramide-induced methemoglobinemia.

The case of a 3-week-old male infant is described. After receiving an iatrogenic overdose of metoclopramide (1.0 mg/kg every six hours) throughout a 36-hour period for the treatment of suspected gastroesophageal reflux, he became cyanotic, lethargic, and irritable, he fed poorly, and he had diarrhea and respiratory distress. Methemoglobinemia (20.5%) and reduced oxyhemoglobin saturation (79%) were identified. The patient had an excellent clinical response following a single IV dose of methylene blue. Subsequently, methemoglobin reductase activity was normal and there was no measurable hemoglobin M. The diagnosis of methemoglobinemia should be considered in any infant receiving large doses of metoclopramide who has clinical findings of cyanosis, ashen color, or a history of lethargy and/or motor restlessness.

Metoclopramide. An updated review of its pharmacological properties and clinical use.

Since previously reviewed in the Journal (Vol. 12, No. 2), metoclopramide has been confirmed as an effective drug in treating and preventing various types of vomiting and as a useful agent in oesophageal reflux disease, gastroparesis, dyspepsia, and in a variety of functional gastrointestinal disorders. Of considerable importance is the recent evidence of its efficacy when administered intravenously in high dosages in preventing severe vomiting associated with cisplatin. Good results have been achieved in patients not previously treated with cisplatin, but further studies are needed to determine its level of efficacy in patients who have experienced severe vomiting during earlier courses of cytotoxic therapy. Side effects consisting of mild sedation, diarrhoea and reversible extrapyramidal reactions have occurred, but are tolerated by many patients.

Diltiazem and metoclopramide overdose.

A fatality resulting from the suicidal ingestion of diltiazem and metoclopramide is described. The decedent was a 25-year-old female with a history of alcoholism and cocaine abuse who overdosed on her mother's medications. On admission she was bradycardiac with severe hypotension and third-degree heart block which progressed to asystole. She was resuscitated but remained comatose until her death four days later. Serum samples from the first 15 h of hospitalization were analyzed for diltiazem and metoclopramide by gas chromatography with nitrogen-phosphorus detection. Diltiazem levels 1 hour post admission were 8.49 mg/L. Diltiazem elimination followed zero-order kinetics with an elimination rate of 0.68 mg/L/h. Metoclopramide levels 1 hour post admission were 4.4 mg/L. Data indicated a biphasic elimination curve for metoclopramide with an initial half-life of 1.3 h and a terminal half-life of 20 h.

[Acute dystonia from metoclopramide in children]. / Dystonies aiguës au métoclopramide chez l'enfant.

A retrospective study (1995-2000) of reports of cases of metoclopramide poisoning collected at the Lille poison control centre (184 phone calls) shows the frequent occurrence of acute dystonia in children (81 cases). These spectacular extrapyramidal symptoms consist of abnormal movements (31 cases), local hypertonia (30 cases), acute dyskinesia (17 cases), general hypertonia (16 cases) and oculogyric crisis (13 cases). There is no dose-effect correlation and sex has no influence on the occurrence of neurological symptoms. Medical management is simple surveillance or symptomatic therapy (a sedative drug and/or anti-parkinsonian therapy and/or a gastrointestinal adsorbent). Hospitalisation was needed in only 9.1% of cases. Providing better information to physicians about metoclopramide adverse effects and their medical management should allow a reduction in the number of unnecessary hospitalizations.

[Poisoning caused by neuroleptics and other related drugs]. / Intoxicaciones causadas por neurolépticos y otros fármacos afines.

Neuroleptics (phenothiazines) and related medicaments such as haloperidol and metoclopramide, are frequent cause of intoxication. The main manifestations are extrapyramidal symptoms. In most cases the intoxications have an acute evolution and the large doses may be complicated with shock, coma and ventricular fibrillation; persistent hyperthermia brings poor prognosis. Their chronic use, even at therapeutic doses, may produce late dyskinesia, difficult to manage. Diphenhydramine is particularly useful to treat the acute intoxication; this could be started with slowly intravenous injected 1 mg/kg until symptoms disappear, and then continue per os for a minimum of these drugs. Its improper use and abuse are due to therapeutic mode.

Metoclopramide poisoning in children.

15 children with metoclopramide (Maxolon) poisoning are reported. One of the 5 children accidentally poisoned developed slight extrapyramidal signs. All 10 children who experienced extrapyramidal side effects while being treated with metoclopramide had received a dose greater than that recommended by the manufacturer of 0.5 mg/kg per day. Dystonic reactions are likely to occur if the recommended dose is exceeded, but individual susceptibility to metoclopramide and the cumulative effect of repeated doses of the drug may also be important.

[Tetanus: problems of differential diagnosis in the presence of contemporaneous administration of metoclopramide]. / Tetano: problemi di diagnosi differenziale in presenza di contemporanea assunzione di metoclopramide.

Here we report a clinical case concerning differential diagnosis between tetanus and metoclopramide intoxication. A 67 year old woman was admitted to our intensive care unit complaining of both trisma and four limbs hypertone soon after a massive metoclopramide bolus administration. The patient was affected by a chronicle renal insufficiency and a diagnosis of metoclopramide intoxication was made. The long lasting dystonic symptomatology together with respiratory insufficiency ruled out the hypothesis of drug overdose. The intensive care physicians would take into account that at least a 24 hours clinical observation is mandatory in order to perform a correct diagnosis.

Metoclopramide toxicity in an infant.

Metoclopramide (4-amino-5-chloro-N-2-methoxybenzamide) is a central and peripheral acting dopamine antagonist. It also stimulates motility in the upper gastrointestinal tract and increases lower esophageal sphincter pressure. In the pediatric population, it is used extensively as an antiemetic and in the treatment of gastroesophageal reflux disease. The case of a six-month-old infant who was accidentally overdosed with 24 mg (3 mg/kg) of metoclopramide within a nine-hour period is presented. The patient demonstrated toxic extrapyramidal effects. There have been multiple early reports in the European literature of acute extrapyramidal reactions in the pediatric population, but no reports of toxicity exist in the current emergency medicine literature.