Chinese Medicine Toxicology

Dr. ML Tse

SMO AED

UCH

Many unknowns

• Reports not in major journal

• Unawareness: patient and Dr.

• Formula difficult to read

• Polypharmacy / substitution / contamination / adulteration

• Difficulty confirmatory test

• Faked TCM products

Recognition

• Adverse Drug ReactionTypes

A: dose related

B: idiosyncratic / immunological

C: cumulative effect

D: appear sometime after exposure

E: withdrawal

Recognition

Vigilance

Commonest Toxic syndromes

Call

26351111 HKPIC

Aconiti Root Toxidrome

• cured main root• Monkshood, helmet flower

• 12 men, 5 women total 17

• All ICU care, 5 Hospital, 1989—1991

• Largest series in Western Literature

• 12 men, 5 women total 17

• All ICU care, 5 Hospital, 1989—1991

• Inclusion based on history: “ingested a decoction…cured rootstocks of Aconitum carmichaeli, A kusnezoffii, and/or A brachypodium”

• Largest series in Western Literature

Aconiti Root Toxidrome

• Hx: herb for musculoskeletal pain• Rapid onset ½ to 4 hr • GI upset + neurological + CVS

– Vomit, diarrhoea, abd pain– Numbness, weakness– Hypotension, bradycardia (tachycardia), ventricular arrh

ythmias

• Formula: 川烏 , 草烏 , 附子• Overdose: iatrogenic, curing mistake, inadequate bo

iling, wine preparation, double dosing.

Multifocal VEB & short run VT

Management

– DC cardioversion and lignocaine seems in-effective

– Median of 2 antiarrhythmics used– Amiodarone, flecanide seems better 1st line dru

g choice– Magnesium?– Charcoal haemoperfusion

AnticholinergicToxidrome

洋金花

Anticholinergic Poisoning

• Hx: herb for resp symptoms

• Confused

• Red + Dry+ Blind + Mad + Full

• Formula: 凌霄花• Substition / contamination

Flos campsitisLing-hsiao-hua

• Flos Datura American campsitis

Mini-epidemic in 2004

• F/ 47, M /52 presented in 4 hours

• Anticholinergic toxidrome

• Direct questioning : herb intake ~4 hr before,

• formula and residual collected

Progress

• Health department informed ASAP

• MO came to see patient and sample collection

• Repeated Pyridostigmine for the 2nd patient

• D/C after 24 hr observation

• 3rd case came 3 days later

• Samples of Canzhu (Atractylodes Lancea)

+ve for anticholinergic compounds

Recall of all Can-zhu in HK

Only from single importer

Contamination ? Possible litigation

Kwai-Kuo Toxidrome

Gwai Kuo 鬼臼 / Bajiaolian 八角蓮

• Dysosoma pleianthum• Podophyllum emodi

• Mayapple family,

• Podophyllotoxin• Inhibit cell division

• Rx for genital wart

• Precursor of etopoxide

Cases1. 68/F, vomit, diarrhoea, numbness, after drinking h

erbal decoction, unarousable next day. BP 69/47 sinus rhythm.

Fung 1996HKJEM

2.Two neighbours drank herbal wine, dizzy & Vomit in ½ hour, numbness, progressive weakness, truncal ataxia over 5 days

3. Confused, visual hallucination, febrile, WCC , CSF protein, herbal soup ingestion 24 hour ago

information fromTWPCC

Clematis root 威 靈仙 Gentiana root 龍膽草

Dysosoma rhizome 鬼臼　　

Case 3

• 5 y.o. Herbal Rx for URTI

• Unconsicous + limb twitching + faecal incontinence 15 min after herb intake

• Improved spontaneously over 30 min.

• Formula looks benign?

• Consult HA TRL as moderate severity

Formula

• 蒼耳子 Chinese Cocklebur

• Atractyloside +ve

• Famous toxin in South Afica

• High Mortality and morbidity

• CNS hypoglycaemia

• Liver and renal toxicity

Aristolochic Acid Nephropathy(Chinese Herbal Nephropathy)

• Dialysis centre in Brussel, Belgium early 1992

• 2 women 42, 46 y.o. rapidly progressive renal failure Bx: extensive interstitial fibrosis, both Rx in Sliming Clinic X

• Epidemiological survey of 7 nephrology centres• 9 patients identified, 6 on dialysis

Sliming Regime

– Capsule B (New Formulation since May1990)• Carsara powder• Acetazolamide• Belladonna extract• Stephania tetradra powder 100—200mg• Magnolia offcinalis powder 100—200mg

Analysis on CapsulesMicroscopy:

calcium oxalate crystals in the “stephania” powders ??TLC Tetrandrine –ve

AA-veOchratoxinA –ve

Conclusion:

Unknown substituted herb induced nephropathy

Lancet; Mar 6, 1993

粉防己S tetradra

廣防己A fanji

2 women

9 women in the study June 92

48 women Feb 93

DNA-AA adduct measurement By Schmeiser et alCancer Research 1996

Other case seriesUrothelial Ca

The Story

105 patients 2000

12 Dialysis 31 Transplant 62 CRF

8 surgery 31 surgery

2 cases Uro Ca

Results:

39 patients

77 kidneys 78 ureters

Histology

18 urothelial Ca, mostly in pelvis & upper ureter

19 mild to moderate dysplasia

2 normal

• Structure of AA

DNA-AA adducts

7-(deoxyadenosine-N6-yl)-aristolactam I

7-(DA-N6-yl)-AAII

7-(DG-N6-yl)-AAI

Conclusions

• Confirmed the cause of CHN is exposure to Aristolochic acid containing plant: A. fangchi in this series

• High risk for Urothelial Ca

Patent Chinese Medicine

• 30% contamination / adulteration

• Heavy metals: lead

• Western pharmaceuticals

Thank You