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Toxicology Meeting

Toxicology Meeting. Dr. V. Ng UCH. Chinese Herbs. 雷公滕. Case. M/56 PH : HT / gout / psoriasis Took 雷公滕片 1-10 /Dec/04 Presented on 17 / Dec/ 04 for facial rash & epigastric pain & frequency of urine P/E showed pigmentation and telegectasia over face, also oral mucositis was noted.

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Toxicology Meeting

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  1. Toxicology Meeting Dr. V. Ng UCH

  2. Chinese Herbs 雷公滕

  3. Case • M/56 • PH : HT / gout / psoriasis • Took 雷公滕片 1-10 /Dec/04 • Presented on 17 / Dec/ 04 for facial rash & epigastric pain & frequency of urine • P/E showed pigmentation and telegectasia over face, also oral mucositis was noted

  4. Other vitals : Normal • ECG : SR • CBP, APTT/PT/INR , L/RFT – Normal

  5. Management • Symptomatic treatment • Look for / Warn for other adverse effect • Advice to stop the herbs • Follow up

  6. 雷公滕 ( Lei Gong Teng) • Comes from the roots, leaves & flowers of Tripterygium Wilfordii Hook • Literal Name : thunder vine • English Name : Tripterygium, common broad lily root • Folk Name : ‘walk seven steps and die’

  7. Climbing vine that grow up to 12m. The root is the medicinal part of the plant & is generally collected in autumn

  8. Properties : bitter ,acrid and cool • Channels entered : liver • Safety index : Toxic • Chemical composition: • Alkaloids (wilfordine, wilforine, wilforidine, wilforgine, wilfortrine, wilforzine, wilformine, wilfornine, euonine, celacinnine, celafurine, celabenzine, neowilforine, regilidine), terpenoids (triptolide T13, tripdiolide, tripterolide, triptonide, triptolidenol T9, hypolide, triptonoterpenol, triptophenolide methylether, neotriptophenolide, isotriptophenolide, isoneotriptophenolide, triptonoterpene, triptonoterpene methylether, tripdioltonide, tripdiolide T8, triptriolide T11, triptolide T10, wilforlide AT1, triptotriterpenoidal lactone A, wilforlide B, triptotriterpenic acid AT3, triptotriterpenic acid BT2, triptoterpenic acid CT28, selaspermic acid, wilfornide, triptofordin A,B,C-1,C-2, D).10

  9. Epidemiology • Tripterygium wilfordii Hook f. is the second most frequent herb associated with poisoning in China • (Most common – Aconite roots) • R.J.Ko A US Perspective on the adverse reactions from traditional chinese medicine. J Clin Med Assoc 2004;67:109-116 • Lei Gong Teng is now being actively investigated with multiple clinical studies & research . Results showed that there are therapeutic benefits. • J.K.Chen. Herbal Safety. Acupuncture Today. 2004, Vol 05, Issue 01

  10. Medical Functions • Effect on immune system • Immunosuppression (Inhibition of PG E2 secretion & inhibited IL1, IL6,IL8, TNF) • Effect on antiinflammatory • Effect on arthritis • Effect on anti-cancer –leukemia (mice) • Triptolide and tripdiolide • Effect on contraception • Effect on urinary system • Others: anti-rejection on transplant (mice)

  11. Modern Clinical Application • Inflammatory of spinal cord- AS • Proliferative arthritis – RA • Lupus – SLE • Purpura • Kidney inflammation- focal segmental Gs • Asthma / Bronchitis • TB lung • Psoriasis • Dermatitis • Reiter’s syndrome

  12. Clinical Studies and Research • Using alcohol extract of lei gong teng (LGT), triptolide(雷公滕甲素) or tridiolide(雷公滕乙素) on mice with leukemia, showed the the therapy was highly effective • One study suggested that triptolide in LGT could inhibit the acute phase of transplant rejection

  13. Many studies published on the potential use of LGT for treatment of arthritis. These in vitro & in vivo studies confirm the therapeutic benefits of this herb • Extract of lei gong teng (LGT) exhibited marked effect to suppress the development of arthritis, antiB production & delayed type hypersensitivity to type II collagen • University of Texas and the National Institute of Health showed that the LGT has anti-inflammatory & immunosuppressive effect comparable to prednisone • On RCT reported that ~90% of sampled patient with RA treated with LGT experienced sig. improvement • One study found that LGT have a powerful suppressive effect on human immune responses for tx of RA • mech : inhibition of PG E2 secretion from monocytes & inhibited IL1, IL6 , IL8 & TNF) • Another RCT showed that use of LGT for 20 wks showed therapeutic benefit in patient with RA refractory to standard western drug tx

  14. Overdosage • Entire tripterygium plant is toxic • Toxicity : root & bark > other parts • fresh form > dried • Daily dose – between 5-12 gms • MAX dose 15 gms

  15. Overdosage • Toxic sign : local irritation of the GIT , damage to CNS , internal bleeding and necrosis of organs • In severe cases, gross overdose may cause bleeding in the stomach, intestine, liver and lungs • Other symptoms – dizziness , dry mouth, palpitation, necrosis of mucous membranes and irregular menses

  16. Overdosage • Any adverse reaction – generally occur within 2-3 hrs after ingestion • Headache, dizziness, palpitation, fatigue, severe vomiting, chills , fever, abd pain, diarrhea, generalized aches and pain, tachycardia, irregular heart rhythms, urinary frequency & urgency

  17. Overdosage • Delayed symptoms- 2-3 days • LBP, hair loss ,facial edema, ↑or ↓u/o, ↓BP, ↓temp, altered consciousness, convulsions, difficult respiration • One case report – after ingesting the herbs, the patient developed hypovolemic shock and cardiac damage, and died three days later..

  18. Side effects • Common SE 45% • Skin rashes , skin pigmentation, stomatitis and softening of finger nails • Female –reduction of menses (1mth), amenorrhea (3-6mths) • Male – sperm count & motility was reduced & the sperm disappeared completely (1 mth)

  19. Side effects • Decrease total blood cell counts • Mutation type of illness • Using Lei Gong Teng tincture for external use can cause mutation type of illness • Long term • Significant decrease bone mineral density in female SLE • Hair loss & malfct of immune system • Larger doses &/or long term usage can be toxic to Kidney

  20. Antidotes for Toxicity • Emetic method and gastric lavage if early • In early stage, use adrenocorticol hormone • Dexamethasone 5-10mg with added 40 ml D50 IVI followed with dexa of 1.5 mg tds for 2-3 wks • Use dextran 40 500 ml IVI, when toxic has been absorbed but no symptom of toxication. Mannitol / Furosemide can be used. • Attention to balance of electrolyte and correct acidosis

  21. Antidotes for Toxicity • Skin allergy • Antihistamine OR traditional Chinese herbs for dispersing heat and neutralizing toxin • Chinese herbs Treatmnet • Feng wei cao • San qi

  22. Prevention • For external use – use ointment & avoid tincture • Pay attention to the dosage according to body constitution of individual patient • Daily dose – between 5-12 gms , MAX 15gms • Pay attention to the use of the drug • Need to peel & discard the root bark of this herb before decocting • Should be cooked for at lease 60 mins before the addition of other herbs, then cooked for another 15 min • Prolonged decoction (1-2 hrs) is recommended to decrease its toxicity

  23. Prevention • Avoid using in patient with liver problem • Contraindicated in pregnancy • Caution in geriatric & pediatric patient • Caution in patient with heart, stomach & spleen disorders • Should not use in patient with compromised hepatic function

  24. Discussion • 雷公滕片 vs 雷公滕 herb ? • Formulation in Chinese herbs • Raw herb • Capsule / pill • Powder • Water decoction • Alcohol extract • Etc…. • Different formulation – different efficacy? Different toxicity?

  25. Thank You

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