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Aconitum Alkaloid Poisoning

Aconitum Alkaloid Poisoning. Review of Cases. Aconitum L. ( 烏頭 ). 製川烏 毛茛科植物烏頭的母根的炮製品 1.5~3g 製草烏 毛茛科植物北烏頭的塊根的炮製品 1.5~3g 製附子 毛茛科植物烏頭的子根的炮製品 3~15g. 草烏. Wide variety in China market Source: Cultivated /Wild > 16 species. Aconitum alkaloids.

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Aconitum Alkaloid Poisoning

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  1. Aconitum Alkaloid Poisoning Review of Cases

  2. Aconitum L. (烏頭) • 製川烏 • 毛茛科植物烏頭的母根的炮製品 • 1.5~3g • 製草烏 • 毛茛科植物北烏頭的塊根的炮製品 • 1.5~3g • 製附子 • 毛茛科植物烏頭的子根的炮製品 • 3~15g

  3. 草烏 • Wide variety in China market • Source: Cultivated /Wild • > 16 species

  4. Aconitum alkaloids • Aconitine (乌头碱), Hypaconitine (次乌头碱), Mesaconitine (新乌头碱) • Effective ingredients • Analgesic and anti-inflammatory actions • Potent toxins • Cardio-toxic, neuro-toxic • voltage-gated Na(+) channel activators

  5. Processing (炮製) • Essential to reduce toxicity • As low as 0.3g of 生草烏 is toxic • Hydrolysis: • Aconitine Benzoylaconine Aconine 1/200 Toxic 1/2000 Toxic

  6. 生薑、甘草: decrease aconite toxicity •  pH of herbal broth  enhance hydrolysis • 十八反: 本草明言十八反,半蔞貝薟芨攻烏, 藻戟遂芫俱戰草,諸參辛芍叛藜蘆. • 烏頭反半夏: enhance aconite toxicity •  pH of herbal broth  inhibit hydrolysis

  7. Aconitum Poisoning • Taiwan • 17 cases from 1990-99 • H.K. PWH (1989-91): • 15 patients • DH (1/00 – 6/04): • 7 admissions with 3 requiring intensive care • All recovered • Overdose /improper decoction/ self-prescription

  8. Case 1 • Apr 2004 • M/20 • Taking TCM for back pain for 2 months • Formula did not contain aconite herbs • 牛膝, 杜仲,杞子, 知母, 川斷, 白芥子, 蒼朮, 白朮, 防風, 淫羊藿, 百花蛇, 枳殼, 白芍, 威靈仙, 茯苓, 狗脊, 春砂仁 • Bought 3 identical packs of herbs from herbal shop • Became unwell shortly after taking second pack • Vomiting • Drowsy

  9. ECG: polymorphic ventricular tachycardia • Arrhythmia resistant to treatment • Admitted to Cardiac care unit • Recovered eventually

  10. Lab Findings • Herbal broth remains: • Aconitum alkaloids (yunaconitine, crassicauline) detected by LCMS • Suggestive of 云南烏頭 • No herbal residue for inspection • 3rd pack of raw herbs: • No aconite herbs on inspection • No aconitum alkaloids detected by chemical analysis • Urine: • Aconitum alkaloids detected + drugs given after admission

  11. Cause of Poisoning: • Aconite contamination • Present in the 2nd pack but not the 1st /3rd pack

  12. Case 2 • June 2004 • F/50 • Inoperable kidney tumor • On TCM for pain control and tolerated • Double dosage by herself • 熟附子(五錢), 製川烏(六錢), 製草烏(六錢) • 生薑、甘草 二錢

  13. Presented with numbness, palpitation and dizziness • Uneventful recovery

  14. Lab Findings • Urine: Hypaconitine detected • No residue a/v

  15. Cause of Poisoning • Self prescription • Exceed the recommended dose

  16. Case 3 • July 2004 • M/30 • Low back pain • Took prescribed herbal broth • 制川烏, 制草烏 各三錢 • 甘草 二錢 • 40 minutes later • Numbness, weakness, vomit, chest discomfort

  17. ECG: sinus bradycardia (40bpm), VEB • Under Cardiac care unit • Recovery

  18. Lab Findings • Yunaconitine detected in urine • No herbal residue

  19. Cause of Poisoning • ?Improper decoction • No “先煎” instruction in the prescription • Exceed recommended dose

  20. Case 4 • Sep 2004 • F/83 • DM, IHD, HT, AF • Chronic kidney disease • GFR: 12.3 mL/min/1.73m2 • Admit with general malaise, decrease general condition • Found slow AF (~30bpm) on admission • To Cardiac care unit for observation • Took prescribed herbal broth • 附子 三錢, 甘草 二錢,川貝母三錢

  21. Lab Findings • Urine: hypaconitine detected • No herbal residue

  22. Cause of Poisoning • ?Improper decoction • No “先煎” instruction in the prescription • ?Underlying renal impairment

  23. Case 5 • Dec 2004 • F/44 • Knee pain • Took prescribed herbal broth • 制草烏 (二錢) • 生薑、甘草 not added • Prepared at herbal shop

  24. Numbness, weakness • Hypotension BP 89/49 • ECG: bradycardia(48bpm), frequent VEBs • Admitted to CCU

  25. Lab Findings • Urine: Aconitine, deoxyaconitine detected

  26. Cause of Poisoning • Exceed recommended dose

  27. Case 6 • Jan 2005 • M/52 • Took prescribed herbal broth for LBP • 川烏, 草烏(製) and 附子 (各三錢 先煎) • 甘草 二錢 • Numbness and weakness • Full Recovery

  28. Lab Findings • Urine: yunaconitine, hypaconitine, deoxyaconitine • Herbs sent to Govt Lab for quantitation: • Aconitum Alkaloids content <0.15%

  29. Cause of Poisoning • Exceed recommended dose

  30. Case 7 • Mar 2005 • M/62 • Headache • Self prescribed herbal broth • 川烏 二兩 • 生薑、甘草 not added • 五味子 added • Numbness, weakness, dizziness, chest discomfort

  31. Shock on admission (BP 75/54, P105) • ECG: multiple premature ventricular contractions • Admitted to ICU • Patient survived

  32. Lab Findings • Urine: Mesaconitine, Hypaconitine detected • No herbal residue

  33. Cause of Poisoning • Self prescription • Overdose • Improper decoction

  34. Case 8 • Apr 2005 • F/27 • URTI symptoms • Prescribed 2 packs of TCM by herbalist • No aconite herbs • Took 1st pack  numbness, weakness, chest discomfort • Subside afterwards

  35. Reboil the herbal residue the next morning • Re-develop symptoms • Seen at A&E • BP 104/66 P62 • ECG normal • Discharged directly

  36. Lab Findings • Urine: yunaconitine • 1st pack (herbal residue): yunaconitine • 2nd pack (raw herb): no aconitum alkaloids • Small piece of herb remnant that looked different from the rest was isolated and identified by microscopy to be 草烏

  37. Cause of Poisoning • Aconite contamination

  38. Summary • 4 males and 4 females • Age range from 20-83 • 5 admitted to intensive/ cardiac care unit • All recovered • Aconite contamination: 2 cases • Self prescription: 2 cases • Improper decoction: 3 cases • Exceed recommended dose: 5 cases • 生薑、甘草 not added: 2 cases

  39. Safe Practice • Follow safety dosage • Proper processing and decoction • BE careful with high dosage/combined use

  40. Other herbs reported to cause Arrhythmia

  41. Other herbs reported to cause Arrhythmia • 山豆根 • 鴉胆子 • 石榴樹皮 • 藜芦

  42. Lab investigations • Blood/urine for toxicology screening • Herbal broth/ remnants • Formulas • Raw herbs

  43. Management • No specific antidote • Treatment is supportive • Decontamination • Lavage, activated charcoal • Arrhythmia refractory to drug Rx • Atropine for bradycardia • No single anti-arrhythmic agent was uniformly effective for arrhythmia control

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