Entrez PubMed

1: Acad Emerg Med. 2004 Aug;11(8):820-6. Related Articles, Links: Effects of 4-methylpyrazole on ethanol neurobehavioral toxicity in CD-1 mice.

Paez AM, Shannon M, Maher T, Quang L.

Division of Emergency Medicine and the Program in Clinical Pharmacology/Toxicology, Children's Hospital Boston, Harvard Medical School, Boston, MA, USA. ana.paez@tch.harvard.edu

OBJECTIVES: 4-Methylpyrazole (4-MP), an alcohol dehydrogenase (ADH) antagonist, is used for the treatment of ethylene glycol and methanol ingestions. However, ethanol is frequently co-ingested by those who ingest these more toxic alcohols. Several in vitro and in vivo studies have shown a decrease in the elimination rate of ethanol after the administration of 4-MP, but none has evaluated the effects of 4-MP administration on the neurobehavioral toxicity of ethanol. This was a study to determine whether ADH blockade with 4-MP prolongs ethanol neurobehavioral toxicity in a murine model. METHODS: D-1 mice were pretreated with 4-MP, with observation of its effect on ethanol dose-response curves. 4-MP (25 mg/kg) or an equal volume of saline was administered intraperitoneally. Ten minutes later, incremental ethanol doses of 1-5 g/kg were administered intraperitoneally. Pretreated and control groups were composed of ten mice each for each dose of ethanol tested. Outcomes for assessing ethanol neurobehavioral toxicity were successful performance on the rotarod test and presence of the righting reflex, two established and validated outcome measures for ethanol-induced neurobehavioral toxicity in mice. RESULTS: The dose of ethanol at which 50% of the animals failed a particular outcome test (toxic dose 50 [TD(50)]) was decreased with 4-MP administration for both the rotarod test and the righting reflex. The TD(50) intergroup differences (control vs. 4-MP) were statistically significant at 60, 120, and 180 minutes (p < 0.05). CONCLUSIONS: Pretreatment with 4-MP significantly prolonged ethanol neurobehavioral toxicity in CD-1 mice, presumably by inhibiting its metabolism by ADH. Further investigation is warranted to evaluate this interaction.

PMID: 15289186 [PubMed - indexed for MEDLINE]

2: Ann Pharmacother. 2004 Dec;38(12):2005-11. Epub 2004 Nov 02. Related Articles, Links: Poisoning in Older Adults: A 5-Year Experience of US Poison Control Centers.

Crouch BI, Caravati EM, Mitchell A, Martin AC.

Utah Poison Control Center; Professor, College of Pharmacy, University of Utah, Salt Lake City, UT.

BACKGROUND: Poisoning in older adults has received relatively little attention. OBJECTIVE: To describe poison exposures in older adults reported to US poison centers and identify substances that pose a unique risk to this population. METHODS: A retrospective review of human exposures for patients aged >60 years reported to the American Association of Poison Control Center's Toxic Exposure Surveillance System from 1993 to 1997 was performed. Frequencies and cross-tabulations were used to describe the data. Hazard factor analysis was conducted to identify medications that pose risk in this population. Statistical analysis included chi(2) and Fisher's exact test for hazard factors. RESULTS: A total of 298 713 poison exposure cases were reported to US poison centers involving individuals aged >60 years between 1993 and 1997. The proportion of cases in this age group also steadily increased from 2.5% of all cases in 1993 to 3.4% of all cases in 1997. The mean age of the patients was 64.7 years, and 34.1% were males. Hazard factor analysis was conducted on unintentional exposures and adverse reactions to pharmaceutical agents to determine medications that posed increased risk to older adults. The substance categories that had the highest hazard factor were radiopharmaceuticals, asthma therapies, anti-coagulants, anesthetics, and antidepressants. CONCLUSIONS: Therapeutic errors and adverse reactions to medications are common reasons for major effects and fatal outcomes among older adults reported to poison centers. Understanding poisoning issues specific to this population may help direct future outreach education efforts.

PMID: 15522976 [PubMed - in process]

3: BMJ. 2004 Nov 6;329(7474):1076. Epub 2004 Oct 29. Related Articles, Links: UK legislation on analgesic packs: before and after study of long term effect on poisonings.

Hawton K, Simkin S, Deeks J, Cooper J, Johnston A, Waters K, Arundel M, Bernal W, Gunson B, Hudson M, Suri D, Simpson K.

Centre for Suicide Research, University of Oxford Department of Psychiatry, Warneford Hospital, Headington, Oxford OX3 7JX. keith.hawton@psych.ox.ac.uk

OBJECTIVE: To evaluate the long term effect of legislation limiting the size of packs of analgesics sold over the counter. DESIGN: Before and after study. SETTING: Suicides in England and Wales, data from six liver units in England and Scotland and five general hospitals in England, and UK data on sales of analgesics, between September 1993 and September 2002. DATA SOURCES: Office for National Statistics; six liver units in England and Scotland; monitoring systems in general hospitals in Oxford, Manchester, and Derby; and Intercontinental Medical Statistics Health UK. MAIN OUTCOME MEASURES: Deaths by suicidal overdose with paracetamol, salicylates, or ibuprofen; numbers of patients admitted to liver units, listed for liver transplant, and undergoing transplantations for paracetamol induced hepatotoxicity; non-fatal self poisonings with analgesics and numbers of tablets taken; and sales figures for analgesics. RESULTS: Suicidal deaths from paracetamol and salicylates were reduced by 22% (95% confidence interval 11% to 32%) in the year after the change in legislation on 16 September 1998, and this reduction persisted in the next two years. Liver unit admissions and liver transplants for paracetamol induced hepatotoxicity were reduced by around 30% in the four years after the legislation. Numbers of paracetamol and salicylate tablets in non-fatal overdoses were reduced in the three years after the legislation. Large overdoses were reduced by 20% (9% to 29%) for paracetamol and by 39% (14% to 57%) for salicylates in the second and third years after the legislation. Ibuprofen overdoses increased after the legislation, but with little or no effect on deaths. CONCLUSION: Legislation restricting pack sizes of analgesics in the United Kingdom has been beneficial. A further reduction in pack sizes could prevent more deaths.

PMID: 15516343 [PubMed - in process]