1887
Volume 4(2023) Number 1
  • EISSN: 2708-0463

Abstract

لمضاد الهستامين-1 الدايفنهايدرامين صفات مواجهة المستقبلات الكولينية المسكرينية، مما يؤهله لأن يعمل مضاداً لتأثيرات مبيدات الحشرات الفوسفورية العضوية والكارباميتية المثبّطة لإنزيم الكولين إستيريز في الإنسان والحيوان. وفي ضوء المنشورات العلمية العديدة التي تُبين الفائدة النوعية للدايفنهايدرامين في علاج التسمم بهذه المبيدات، مع بعض الاختلاف في فاعلية الدواء الترياقي أو العلاجي، تهدف هذه المراجعة إلى حصر الدراسات التي تناولت تأثيرات الدايفنهايدرامين في السمّية الحادة للمبيدات، وعرض تحليل ميتا لبيان الدلالة الإحصائية من هذا الدواء الذي يُحسب مضاداً نوعياً إضافياً مع الترياق الأساس الأتروبين. استخدمنا طريقة بريسما بحسب عناصر التقارير المفضلة للمراجعات المنهجية، وتحليل ميتا لمؤشرات التسمم بالمبيدات الحشرية في الحيوانات التي شملت على حدوث الموت وعلامات التسمم ومرتبة التسمم. وجرى حصر الدراسات وبياناتها من قواعد المعلومات التي تُفهرِس المنشورات العلمية، فضلاً عن الفحص اليدوي للمنشورات من الجامعات. وفي تحليل ميتا، استخدمنا برنامج محلل ميتا الحر لمجموعتين، والذي شمل رسم الغابة وحجم التأثير وهو الخطورة النسبية، وتحليل التباين، فضلاً عن تحليل حجب مجموعة واحدة. كما طبَّقنا برنامج (Meta-Essentials) لرسم مخطط القمع الذي يشمل حجم التأثير والخطأ القياسي، واختبار إيغر لتقييم أيّ تحيز نشر ذي دلالة إحصائية، مع تحليل التقليم والملء للدراسات المفقودة. بلغ عدد الدراسات المختارة 13، واحتوت على 16 تقريراً مختلفاً لمؤشرات التسمم بالمبيدات وتأثير الدايفنهايدرامين فيها. وأظهرت نتائج تحليل ميتا لكل مؤشر من مؤشرات التسمم أن الدايفنهايدرامين قلّل معنوياً من الخطورة النسبية للمبيدات الفوسفورية العضوية أو الكارباميتية، حيث بلغت هذه النسبة مع 95% فاصل الثقة 0.375 (0.261، 0.54) لموت الحيوانات، و0.399 (0.283، 0.563) لعلامات التسمم، و0.466 (0.363، 0.597) لمرتبة التسمم. وتباينت النسب المئوية لأوزان التقارير الواردة في الدراسات ما بين 1.713 و20.245% لتحليل الموت، وبين 1.612 و23.062% لعلامات التسمم، وبين 4.566 و13% لمرتبة التسمم. وبيَّن تحليل حجب مجموعة واحدة عدم تأثر حجم التأثير لمؤشرات التسمم، إذ كانت القيم قريبة من حجم التأثير عند حذف قيمة أيّ تقرير من تقارير الدراسات المشمولة في التحليل. وقد ظهر اختلاف معنوي ذو دلالة إحصائية في تحليل التباين لبيانات مرتبة التسمم، في حين لم يكن التباين معنوياً لبيانات الموت وعلامات التسمم. وفي مخطط القمع، ظهر تحيّز النشر وبيَّن تحليل التقليم والملء احتمال وجود دراسات مفقودة. نستنتج من هذه المراجعة وتحليل ميتا أن للدايفنهايدرامين خاصية مضادة للتسمم بالمبيدات الحشرية المثبّطة لإنزيم الكولين إستيريز والتقليل من خطورتها النسبية ضمن مؤشرات التسمم، مع التأكيد أنه ليس بديلاً من الترياق الأساس الأتروبين.

The H1-antihistamine diphenhydramine possesses antimuscarinic-cholinoceptors properties, which enable it to act against cholinesterase inhibiting organophosphate and carbamate pesticides in humans and animals. Several reports on the use of diphenhydramine, in spite of some variations in its antidotal or therapeutic efficacy, specify beneficial effects of the drug in treating poisoning induced by these pesticides. Therefore, the purpose of the present review was to identify studies that encompass effects of diphenhydramine on the acute toxicity of pesticides with meta-analysis to demonstrate statistically the benefit of the drug which is considered as an additional antidote besides the standard one atropine. We used PRISMA and meta-analysis on the toxicity indices of pesticides in animals which were the occurrence of death, signs of poisoning and toxicity score. The studies were identified and then included in the review after searching data bases in addition to the manual search of publications at the universities. Two-group meta-analysis was conducted using software tools. Open-Meta Analyst was used for the forest plot, effect size of the relative risk, heterogeneity test and leave-one-group assessment, whereas Meta-Essentials Version 1.5 was used for the funnel plot that included effect size and standard error, with Egger’s test for the statistical publication bias and trim-and-fill analysis for missing points. Studies selected for analysis were 13, which comprised 16 reports on the effects of diphenhydramine on toxicity indices of the pesticides. Diphenhydramine statistically significantly reduced the relative risks of the organophosphate and carbamate pesticides, which were with their 95% confidence intervals: 0.375 (0.261, 0.54) for animal death, 0.399 (0.283, 0.563) for the signs of poisoning and 0.466 (0.363, 0.597) for the toxicity score. The % weight of the reports varied between 1.713% to 20.245% for death analysis, 1.612% to 23.062% for signs of poisoning and 4.566% to 13% for the toxicity score. The leave-one-group assessment of the reports indicated the effect size was not affected, as the values were close to the original one. A significant statistical heterogeneity was found related to the data of toxicity score but not related to the death and signs of poisoning data. Publication bias was identified by the funnel plot and the trim-and-fill assessment identified the missing points. We conclude from the present review and meta-analysis that diphenhydramine characteristically possesses effects against poisoning with cholinesterase inhibiting pesticides with a reduction of their relative risks within the toxicity indices. It is stressed that diphenhydramine should not be considered a substitute for the standard antidote atropine.

Loading

Article metrics loading...

/content/journals/10.5339/ajsr.2023.1
2023-04-30
2024-05-04
Loading full text...

Full text loading...

/deliver/fulltext/ajsr/2023/1/ajsr.2023.1.html?itemId=/content/journals/10.5339/ajsr.2023.1&mimeType=html&fmt=ahah

References

  1. Rashid S, Rashid W, Tulcan RXS, Huang H. Use, exposure, and environmental impacts of pesticides in Pakistan: A critical review. Environmental Science and Pollution Research. 2022;29:43675–43689. https://doi.org/10.1007/s11356-022-20164-7.
    [Google Scholar]
  2. Dereumeaux C, Fillol C, Quenel P, Denys S. Pesticide exposures for residents living close to agricultural lands: A review. Environment International. 2020;134:114. https://doi.org/10.1016/j.envint.2019.105210
    [Google Scholar]
  3. Bhattu M, Verma M, Kathuria D. Recent advancements in the detection of organophosphate pesticides: A review. Analytical Methods. 2021; 13:(38):4390-4428. https://doi.org/10.1039/d1ay01186c
    [Google Scholar]
  4. U.S. EPA. Insecticides. Sources, stressors and responses. Causal Analysis/Diagnosis Decision Information System [CADDIS]. Vol. 2 [Internet] Washington, DC: Office of Research and Development, EPA; 2017. Accessed 5 April 2022. https://www.epa.gov/caddis-vol2/insecticides
  5. Tudi M, Daniel Rua. H, Wang L, Lyu J, Sadler R, Connell D, et al. Agriculture development, pesticide application and its impact on the environment. International Journal of Environmental Research and Public Health. 2021; 18:(3):1112. https://doi.org/10.3390/ijerph18031112
  6. Baynes RE. Ectoparasiticides. In: Riviere JE, Papich MG, editors. Veterinary pharmacology and therapeutics. 10th ed. Hoboken, NJ: Wiley Blackwell; 2018. pp. 1166–1187
    [Google Scholar]
  7. Wilson BW. Cholinesterase inhibition. In: Wexler P, editor. Encyclopedia of toxicology. 3rd ed. Amsterdam: Elsevier; 2014. pp. 942–951
    [Google Scholar]
  8. Vale A, Lotti M. Organophosphorus and carbamate insecticide poisoning. Handbook of Clinical Neurology. 2015;131:149–168. https://doi.org/10.1016/B978-0-444-62627-1.00010-X
    [Google Scholar]
  9. Samareh A, Asadikaram G, Abbasi-Jorjandi M, Abdollahdokht D, Abolhassani M, Khanjani N, et al. Occupational exposure to pesticides in farmworkers and the oxidative markers. Toxicology and Industrial Health. 2022; 38:(8):455–469. https://doi.org/10.1177/07482337221106754.
    [Google Scholar]
  10. Eddleston M, Buckley NA, Eyer P, Dawson AH. Management of acute organophosphorus pesticide poisoning. Lancet. 2008; 371:(9612):597-607. https://doi.org/10.1016/S0140-6736(07)61202-1
    [Google Scholar]
  11. Mukherjee S, Gupta RD. Organophosphorus nerve agents: Types, toxicity, and treatments. Journal of Toxicology. 2020;2020:3007984. https://doi.org/10.1155/2020/3007984
    [Google Scholar]
  12. Gupta RC. Toxicology of organophosphate and carbamate compounds. Amsterdam, Netherlands: Elsevier; 2006.
    [Google Scholar]
  13. Aman S, Paul S, Chowdhury FR. Management of organophosphorus poisoning: Standard treatment and beyond. Critical Care Clinics. 2021; 37:(3):673-686. https://doi.org/10.1016/j.ccc.2021.03.011
    [Google Scholar]
  14. Fikes JD. Organophosphorus and carbamate insecticides. Veterinary Clinics of North America: Small Animal Practice. 1990; 20:(2):353-367. https://doi.org/10.1016/s0195-5616(90)50029-7
    [Google Scholar]
  15. Ojha S, Sharma C, Nurulain SM. Antihistamines: Promising antidotes of organophosphorus poisoning. Military Medical Science Letters. 2014; 83:(3):97-103. https://doi.org/10.31482/mmsl.2014.019
    [Google Scholar]
  16. محمد، فؤاد قاسم. علاج التسمم بالمبيدات الفسفورية العضوية: مراجعة علمية. المجلة العراقية للعلوم البيطرية، 1995، المجلد 8، العدد 2: 73-77.
  17. Panula P. Histamine receptors, agonists, and antagonists in health and disease. Handbook of Clinical Neurology. 2021;180:377–387. https://doi.org/10.1016/B978-0-12-820107-7.00023-9
    [Google Scholar]
  18. Kawauchi H, Yanai K, Wang DY, Itahashi K, Okubo K. Antihistamines for allergic rhinitis treatment from the viewpoint of nonsedative properties. International Journal of Molecular Sciences. 2019; 20:(1):213. https://doi.org/10.3390/ijms20010213
    [Google Scholar]
  19. Moody SB, Terp DK. Dystonic reaction possibly induced by cholinesterase inhibitor insecticides. Drug Intelligence & Clinical Pharmacy. 1988; 22:(4):311-312. https://doi.org/10.1177/106002808802200408
    [Google Scholar]
  20. Montoya-Cabrera MA, Escalante-Galindo P, Rivera-Rebolledo JC, Higuera-Romero F, Hernandez-Gutiérrez V. Intoxicación aguda por paratión-metílico con manifestaciones extrapiramidales antes no informadas [Acute methyl parathion poisoning with extrapyramidal manifestations not previously reported]. Gaceta Médica de México. 1999; 135:(1):79–82. Spanish. PMID: 10204315.
    [Google Scholar]
  21. Clemmons RM, Meyer DJ, Sundlof SF, Rappaport JJ, Fossler ME, Hubbell J, et al. Correction of organophosphate-induced neuromuscular blockade by diphenhydramine. American Journal of Veterinary Research. 1984; 45:(10):2167–2169. PMID: 6497117.
    [Google Scholar]
  22. Mohammad FK, Al-Kassim NA, Abdul-Latif AR. Effect of diphenhydramine on organophosphorus insecticide toxicity in mice. Toxicology. 1989; 58:(1):91–95. https://doi.org/10.1016/0300-483x(89)90107-8
    [Google Scholar]
  23. Faris GA-M, Mohammad FK. Reduction of some organophosphate insecticides toxicity in mice by diphenhydramine. Dirasat (University of Jordan). 1996; 23::95–97
    [Google Scholar]
  24. Faris GA, Mohammad FK. Prevention and treatment of dichlorvos-induced toxicosis in mice by diphenhydramine. Veterinary and Human Toxicology. 1997; 39:(1):22–25. PMID: 9004462.
    [Google Scholar]
  25. Al-Baggou’ BK, Mohammad FK. Antagonism of methomyl-induced toxicosis by diphenhydramine in rats. Environmental Toxicology and Pharmacology. 1999; 7:(2):119–125. https://doi.org/10.1016/s1382-6689(99)00002-2
    [Google Scholar]
  26. Mohammad FK, Faris GA-M, Shindala MK. Comparative antidotal effects of diphenhydramine and atropine against dichlorvos-induced acute toxicosis in rats. Veterinary Archives. 2002; 72:(1):19–28. Available from: https://hrcak.srce.hr/en/78390
    [Google Scholar]
  27. Bird SB, Gaspari RJ, Lee WJ, Dickson EW. Diphenhydramine as a protective agent in a rat model of acute, lethal organophosphate poisoning. Academic Emergency Medicine. 2002; 9:(12):1369-1372. https://doi.org/10.1111/j.1553-2712.2002.tb01604.x. PMID: 12460839.
    [Google Scholar]
  28. Bird SB, Gaspari RJ, Dickson EW. Early death due to severe organophosphate poisoning is a centrally mediated process. Academic Emergency Medicine. 2003 Apr; 10:(4):295–298. https://onlinelibrary.wiley.com/doi/epdf/10.1111/j.1553-2712.2003.tb01338.x
    [Google Scholar]
  29. Yürümez Y, Yavuz Y, Şahin Ö, Çiftçi İ H, Özkan S, Büyükokuroğlu ME. Can diphenhydramine prevent organophosphate-induced acute pancreatitis? An experimental study in rats. Pesticide Biochemistry and Physiology. 2007; 87:(3):271–275.
    [Google Scholar]
  30. Yavuz Y, Yurumez Y, Ciftci IH, Sahin O, Saglam H, Buyukokuroglu M. Effect of diphenhydramine on myocardial injury caused by organophosphate poisoning. Clinical Toxicology (Philadelphia). 2008; 46:(1):67-70. https://doi.org/10.1080/15563650701261470. PMID: 18167037
    [Google Scholar]
  31. الشمري، يعرب جعفر موسى. استعمال مضاد الهستامين للوقاية والعلاج في نموذج التسمم الحاد بالمبيدات الحشرية الفسفورية العضوية في أفراخ الدجاج. رسالة ماجستير. الموصل، العراق: جامعة الموصل، 2008.
  32. Mohammad FK, Mousa YJ, Al-Zubaidy MHI, Alias AS. Assessment of diphenhydramine effects against acute poisoning induced by the organophosphate insecticide dichlorvos in chicks. Human & Veterinary Medicine. 2012; 4:(1):6–13. http://www.hvm.bioflux.com.ro/docs/HVM_4.1.2.pdf.
    [Google Scholar]
  33. Mohammed AA, Mohammad FK. Recognition and assessment of antidotal effects of diphenhydramine against acute carbaryl insecticide poisoning in a chick model. Toxicology International. 2022; 29:(3):339-352. https://doi.org/10.18311/ti/2022/v29i3/29732
    [Google Scholar]
  34. Klainbart S, Grabernik M, Kelmer E, Chai O, Cuneah O, Segev G, et al. Clinical manifestations, laboratory findings, treatment and outcome of acute organophosphate or carbamate intoxication in 102 dogs: A retrospective study. Veterinary Journal. 2019 Sep;251:105349. https://doi.org/10.1016/j.tvjl.2019.105349
    [Google Scholar]
  35. Klainbart S, Grabarnik M, Kelmer E, Chai O, Cuneah O, Segev G, et al. Clinical manifestations, laboratory findings, treatment and outcome of acute organophosphate or carbamate intoxication in 39 cats. Veterinary Record. 2022; 191:(1):e1633. https://doi.org/10.1002/vetr.1633
    [Google Scholar]
  36. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. British Medical Journal. 2021;372:n71. https://doi.org/10.1136/bmj.n71
    [Google Scholar]
  37. Mohammad FK, Basher HA. Treatment of organophosphorus insecticide (fenamiphos) poisoning in a chicken by diphenhydramine: A case report. Iraqi Journal of Veterinary Sciences. 1995;8:167–168.
    [Google Scholar]
  38. Faris GA-M, Mohammad FK. Cholinesterase inhibition by dichlorvos and diphenhydramine in mice. Iraqi Journal of Veterinary Sciences. 1996;9:7–13.
    [Google Scholar]
  39. Faris GA-M, Mohammad FK. Reduction of dichlorvos-induced increase in small intestinal transit in mice. Iraqi Journal of Veterinary Sciences. 1998;11:11–15.
    [Google Scholar]
  40. Anastasio JD, Sharp CR. Acute aldicarb toxicity in dogs: 15 cases (2001–2009). Journal of Veterinary Emergency and Critical Care (San Antonio). 2011; 21:(3):253-260. https://doi.org/10.1111/j.1476-4431.2011.00613.x
    [Google Scholar]
  41. Arnot LF, Veale DJ, Steyl JC, Myburgh JG. Treatment rationale for dogs poisoned with aldicarb (carbamate pesticide). Journal of the South African Veterinary Association. 2011; 82:(4):232-238. https://doi.org/10.4102/jsava.v82i4.80
    [Google Scholar]
  42. Kristofco LA, Du B, Chambliss CK, Berninger JP, Brooks BW. Comparative pharmacology and toxicology of pharmaceuticals in the environment: Diphenhydramine protection of diazinon toxicity in Danio rerio but not Daphnia magna. The AAPS Journal. 2015; 17:(1):175-183. https://doi.org/10.1208/s12248-014-9677-5
    [Google Scholar]
  43. Mohammed AA, Mohammad FK. Monitoring blood cholinesterase activity of farmworkers: In vitro inhibition by diphenhydramine and carbaryl. Malaysian Applied Biology. 2022; 51:(2):23–32. Available from: https://jms.mabjournal.com/index.php/mab/article/view/2204
    [Google Scholar]
  44. Wallace BC, Dahabreh IJ, Trikalinos TA, Lau J, Trow P, Schmid CH. Closing the gap between methodologists and end-users: R as a computational back-end. Journal of Statistical Software [Internet]. 2012 Jun 30 [cited 2022 May 9]; 49:(5):1–15. Available from: https://www.jstatsoft.org/index.php/jss/article/view/v049i05
    [Google Scholar]
  45. Suurmond R, van Rhe H, Hak T. Introduction, comparison, and validation of Meta-Essentials: A free and simple tool for meta-analysis. Research Synthesis Methods. 2017; 8:(4):537–553. https://doi.org/10.1002/jrsm.1260
  46. Nakagawa S, Noble DW, Senior AM, Lagisz M. Meta-evaluation of meta-analysis: Ten appraisal questions for biologists. BMC Biology. 2017; 15:(1):18. https://doi.org/10.1186/s12915-017-0357-7
    [Google Scholar]
  47. Vesterinen HM, Sena ES, Egan KJ, Hirst TC, Churolov L, Currie GL, et al. Meta-analysis of data from animal studies: A practical guide. Journal of Neuroscience Methods. 2014;221:92–102. https://doi.org/10.1016/j.jneumeth.2013.09.010
    [Google Scholar]
  48. Lee YH. An overview of meta-analysis for clinicians. Korean Journal of Internal Medicine. 2018; 33:(2):277-283. https://doi.org/10.3904/kjim.2016.195
    [Google Scholar]
  49. Kossmeier M, Tran US, Voracek M. Visual inference for the funnel plot in meta-analysis. Zeitschrift für Psychologie. 2019; 227:(1):83–89. https://doi.org/10.1027/2151-2604/a000358
    [Google Scholar]
  50. Mohammad FK, Abdul-Latif AR, Al-Kassim NA. Interaction of diphenhydramine with cholinesterase inhibitors in mice. Toxicology Letters. 1987; 37:(3):235–240. https://doi:10.1016/0378-4274(87)90137-8
    [Google Scholar]
  51. Peter JV, Moran JL, Graham P. Oxime therapy and outcomes in human organophosphate poisoning: An evaluation using meta-analytic techniques. Critical Care Medicine. 2006; 34:(2):502-510. https://doi.org/10.1097/01.ccm.0000198325.46538.ad
    [Google Scholar]
  52. Faiz Norrrahi MN, Idayu Abdul Razak MA, Ahmad Shah NA, Kasim H, Wan Yusoff WY, Halim NA, et al.. Recent developments on oximes to improve the blood brain barrier penetration for the treatment of organophosphorus poisoning: A review. RSC Advances. 2020; 10:(8):4465–4489. https://doi.org/10.1039/c9ra08599h
    [Google Scholar]
  53. Mohammad FK, Mousa YJ, Hasan MM. Acute toxicity and neurobehavioral effects of diphenhydramine in chicks. Journal of Poultry Science. 2012; 49:(1):51-56. https://doi.org/10.2141/jpsa.011050
    [Google Scholar]
  54. Mohammad FK, Garmavy HMS, Mohammed AA, Rashid HM. First meta-analysis study of cholinesterase inhibition in experimental animals by organophosphate or carbamate insecticides under the influence of diphenhydramine. Veterinary World. 2023; 16:(1):118–125. Available from: http://www.veterinaryworld.org/Vol.16/January-2023/14.pdf
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journals/10.5339/ajsr.2023.1
Loading
/content/journals/10.5339/ajsr.2023.1
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error