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Acute fatal poisoning with pilsicainide and atenolol

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Abstract

A fatal case of intentional poisoning with two antiarrhythmic agents, pilsicainide, a pure sodium channel blocker, and atenolol, a selective β1 blocker, is presented. A woman in her twenties was found dead at home and empty pill packages of pilsicainide, atenolol, and aspirin were found near by. Hesitation marks were found on the wrist, and strong fibrous degeneration was observed in the cardiomyocytes of the sinoatrial node. The blood concentrations of pilsicainide and atenolol were 7.83 and 4.94 μg/ml, respectively, both far above the reported therapeutic levels. According to these results, we concluded that death was due to cardiac arrhythmia caused by poisoning with pilsicainide and atenolol. This is the first report of fatal poisoning attributable to an overdose of the combination of these two antiarrhythmic drugs.

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References

  1. Kumagai K, Nakashima H, Tojo H et al (2006) Pilsicainide for atrial fibrillation. Drugs 66:2067–2073

    Article  PubMed  CAS  Google Scholar 

  2. Hoffman BB, Lefkowitz RJ (1996) Catecholamines, sympathomimetic drugs, and adrenergic receptor antagonists. In: Goodman LS, Gilman A, Hardman JG, Limbird LE (eds) Goodman & Gilman’s the pharmacological basis of therapeutics, 9th edn. McGraw Hill, New York, pp 199–248

    Google Scholar 

  3. Nakata K, Moriwaki R, Yamaguchi A, Takenouchi S, Mato T, Tsutsumi H (2006) Case in which magnesium sulfate effectively treated ventricular tachycardia due to overdose of pilsicainide hydrochloride. Chudoku Kenkyu 19:49–53

    PubMed  Google Scholar 

  4. Horita Y, Kanaya H, Uno Y et al (2004) A case of the toxicity of pilsicainide hydrochloride with comparison of the serial serum pilsicainide levels and electrocardiographic findings. Jpn Heart J 45:1049–1056

    Article  PubMed  Google Scholar 

  5. Ozeki S, Utsunomiya T, Matsuo S, Yano K (1999) Pilsicainide intoxication in a patient with dehydration. Jpn Circ J 63:219–222

    Article  PubMed  CAS  Google Scholar 

  6. Petrov D, Sardowski S, Geshava M (2007) ‘Silent’ Prinzmetal’s ST elevation related to atenolol overdose. J Emerg Med 33:123–126

    Article  PubMed  Google Scholar 

  7. Love JN, Elshami J (2002) Cardiovascular depression resulting from atenolol intoxication. Eur J Emerg Med 9:111–114

    Article  PubMed  CAS  Google Scholar 

  8. Snook CP, Sigvaldason K, Kristinsson J (2000) Severe atenolol and diltiazem overdose. J Toxicol Clin Toxicol 38:661–665

    Article  PubMed  CAS  Google Scholar 

  9. Pertoldi F, D’Orlando L, Mercante WP (1998) Electromechanical dissociation 48 hours after atenolol overdose; usefulness of calcium chloride. Ann Emerg Med 31:777–781

    Article  PubMed  CAS  Google Scholar 

  10. Delima LG, Kharasch ED, Butler S (1995) Successful pharmacologic treatment of massive atenolol overdose: sequential hemodynamics and plasma atenolol concentrations. Anesthesiology 83:204–207

    Article  PubMed  CAS  Google Scholar 

  11. Stinson J, Walsh M, Feely J (1992) Ventricular asystole and overdose with atenolol. BMJ 305:693

    PubMed  CAS  Google Scholar 

  12. Saitz R, Williams BW, Farber HW (1991) Atenolol-induced cardiovascular collapse treated with hemodialysis. Crit Care Med 19:116–118

    Article  PubMed  CAS  Google Scholar 

  13. Abbasi IA, Sorsby S (1986) Prolonged toxicity from atenolol overdose in an adolescent. Clin Pharm 5:836–837

    PubMed  CAS  Google Scholar 

  14. Freestone S, Thomas HM, Bhamra RK, Dyson EH (1986) Severe atenolol poisoning: treatment with prenalterol. Hum Toxicol 5:343–345

    Article  PubMed  CAS  Google Scholar 

  15. Weinstein RS, Cole S, Knaster HB, Dalbert T (1985) Beta blocker overdose with propranolol and with atenolol. Ann Emerg Med 14:161–163

    Article  PubMed  CAS  Google Scholar 

  16. Montgomery AB, Stager MA, Schoene RB (1985) Marked suppression of ventilation while awake following massive ingestion of atenolol. Chest 88:920–921

    Article  PubMed  CAS  Google Scholar 

  17. Ishida T, Kudo K, Inoue H, Tsuji A, Kojima T, Ikeda N (2006) Rapid screening for and simultaneous semiquantitative analysis of thirty abused drugs in human urine samples using gas chromatography–mass spectrometry. J Anal Tox 30:468–477

    CAS  Google Scholar 

  18. Venkatesh G, Ramanathan S, Mansor SM et al (2007) Development and validation of RP-HPLC-UV method for simultaneous determination of buparvaquone, atenolol, propranolol, quinidine and verapamil: a tool for the standardization of rat in situ intestinal permeability studies. J Pharm Biomed Anal 43:1546–1551

    Article  PubMed  CAS  Google Scholar 

  19. Drasch G, Dahlmann F, von Meyer L, Roider G, Eisenmenger W (2008) Frequency of different anti-depressants associated with suicides drug deaths. Int J Legal Med 122:115–121

    Article  PubMed  Google Scholar 

  20. Watson WA, Litovitz TL, Rodgers GC Jr et al (2005) 2004 Annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg Med 23:589–666

    Article  PubMed  Google Scholar 

  21. Miyano S, Sumoto K, Satoh F et al (1985) New antiarrhythmic agents. N-aryl-8-pyrrolizidinealkamides. J Med Chem 28:714–717

    Article  PubMed  CAS  Google Scholar 

  22. Hattori Y, Hidaka T, Aisaka K, Satoh F, Ishihara T (1988) Effects of SUN 1165, a new potent antiarrhythmic agent, on the kinetics of rate-dependent block of Na channels and ventricular conduction of extrasystoles. J Cardiovasc Pharmacol 11:407–412

    Article  PubMed  CAS  Google Scholar 

  23. Kanki H, Mitamura H, Takatsuki S et al (1998) Postrepolarization refractoriness as a potential anti-atrial fibrillation mechanism of pilsicainide, a pure sodium channel blocker with slow recovery kinetics. Cardiovascular Drugs and Therapy 12:475–482

    Article  PubMed  CAS  Google Scholar 

  24. Satoh S, Watanabe J, Keitoku M et al (1989) Effects of N-(2,6-dimethylphenyl)-8-pyrrolizine acetamide hydrochloride hemihydrate on the ventriculo-atrial conductivity of accessory pathways. Arzneimittel-Forschung Drug Res 39:908–911

    CAS  Google Scholar 

  25. Holstege CP, Eldridge DL, Rowden AK (2006) ECG manifestations: the poisoned patient. Emerg Med Clin North Am 24:159–177

    Article  PubMed  Google Scholar 

  26. Reith DM, Dawson AH, Epid D, Whyte IM, Buckley NA, Sayer GP (1996) Relative toxicity of beta blockers in overdose. J Toxicol Clin Toxicol 34:273–278

    PubMed  CAS  Google Scholar 

  27. Delk C, Holstege CP, Brady WJ (2007) Electrocardiographic abnormalities associated with poisoning. Am J Emerg Med 25:672–687

    Article  PubMed  Google Scholar 

  28. Moriya F, Hashimoto Y (1999) Redistribution of basic drugs into cardiac blood from surrounding tissues during early-stages post-mortem. J Forensic Sci 44:10–16

    PubMed  CAS  Google Scholar 

  29. Pelissier-Alicot AL, Gaulier JM, Dupuis C et al (2006) Post-mortem redistribution of three beta-blockers in the rabbit. Int J Legal Med 120:226–232

    Article  PubMed  Google Scholar 

  30. https://www.daiichisankyo.co.jp/med/contents/di/sr1/if/pdf/if_sr_cap_0801_06.pdf

  31. Ishizaki T, Oyama Y, Suganuma T et al (1983) A dose ranging study of atenolol in hypertension: fall in blood pressure and plasma renin activity, beta-blockade and steady state pharmacokinetics. Br J Clin Pharmacol 16:17–25

    PubMed  CAS  Google Scholar 

  32. Maeno K, Ikeda T, Takada S, Kobayashi K, Bunko H, Hisada K (1990) The effect of oral SUN-1165 on hemodynamics at rest and during exercise in patients with ischemic heart disease. Jpn Pharmacol Ther 18:4051–4057

    Google Scholar 

  33. Baselt RC (ed.) (2002) Disposition of toxic drugs and chemicals in man, 7th ed. Biomedical Publications, Foster City, CA, pp 87–88

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Correspondence to N. Ikeda.

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Hikiji, W., Kudo, K., Nishida, N. et al. Acute fatal poisoning with pilsicainide and atenolol. Int J Legal Med 122, 503–506 (2008). https://doi.org/10.1007/s00414-008-0269-8

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