Mais la polymyxine n'est pas du tout absorbée dans le sang du système gastro-intestinal et n'a d'effet que dans l'intestin et est utile pour le traitement des infections intestinales azithromycine prix Internet en y faisant des achats permettant d’économiser jusqu'à soixante-dix pour cent, tout en étant sûr de la qualité des produits pharmaceutiques.
Review of adverse events related to chinese medicines
Review of Adverse Events Related to Chinese Medicines
in Hong Kong, July 2004 - June 2005
Dr Anna Wong1
Dr Constance Chan2
Investigation on Chinese medicine-related adverse events is important for monitoring
the safety of Chinese medicines. At present, the Department of Health (DH) receives
reports of adverse events suspected to be related to the use of Chinese medicines
through various channels. Upon receipt of the report, a multidisciplinary team of the
DH will start investigation. The team comprises public health physicians, Chinese
medicine practitioners (CMPs), Chinese medicine experts and pharmacists. Assistance
will be sought from the Government Laboratory to perform analytic tests on the
Chinese medicines involved. The information so gathered would guide the
formulation and implementation of public health measures to ensure their safe use.
In September 2004, an article reviewing the adverse events reported in the period
between January 2000 and June 2004 was published in the Public Health and
Epidemiology Bulletin.1 This paper is a review of cases reported to the DH from July
All suspected Chinese medicine-related adverse events reported to the DH from July
2004 to June 2005 were studied. Relevant data on patients' demographics, Chinese
medicines incriminated, causes and outcome of the adverse events were analyzed.
A total of 80 suspected cases was reported to the DH. After investigation, 39 cases
were found to be unlikely due to use of Chinese medicines either because there were
other diagnoses made for patients' presentations or the relationship with use of
Chinese medicine could not be established. Another four cases were regarded as
inconclusive due to insufficient information. For the remaining 37 cases, 38 patients
were involved, of whom 15 were male and 23 were female. The patients' age ranged
from nine days to 83 years, with a median age of 50.5 years. Public hospitals were the
major source of reporting (28 cases). Other sources included other public agencies,
private doctors, the media and the public. Among these 38 patients, 26 patients
required hospitalization, of whom six patients were admitted to intensive care unit and
In terms of the type of involved medicines, 21 cases were found related to Chinese
herbal medicines, 15 cases were related to proprietary Chinese medicines (pCm) and
one case involved both. Chinese herbal medicines usually refer to the dried form of
the herbal medicines. Those commonly used in Hong Kong are listed in Schedule 1
and Schedule 2 of the Chinese Medicine Ordinance (Chapter 549). For pCm, they
refer to proprietary products composed solely of Chinese herbal medicines or any
materials of herbal, animal or mineral origin customarily used by the Chinese as
active ingredients, that are formulated in a finished dose form.
In 17 cases, the patients took Chinese medicines without prior consultation with
CMPs while another 19 cases consumed Chinese medicines that were prescribed by
CMPs. For one case, it was unsure whether the patient got his medicines from the
Majority (30 cases, 81%) used Chinese medicines for treatment of a variety of
conditions ranging from minor ailments to acute or longstanding diseases while five
of them used Chinese medicines for weight reduction and two for general health
Although the majority (28 cases, 76%) bought the Chinese medicines in Hong Kong,
a significant portion (eight cases, 22%) purchased the medicines outside, mainly in
Mainland China. In one case, the source of Chinese medicines could not be
ascertained as the patient refused to disclose further information.
The most frequently incriminated Chinese medicines were aconitine-containing (eight
cases) which involved either processed Radix Aconiti (製川烏), processed Radix
Aconiti Kusnezoffii (製草烏) and/or processed Radix Aconiti Lateralis (製附子).
This was followed by aristolochic acid-containing herbs (four cases) which involved
Radix Aristolochiae Fangchi (廣防己) and Herba Aristolochiae Mollissimae (尋骨風).
Table 1 summarizes the Chinese medicines incriminated, the toxic components of the
medicines and the causes for the adverse events.
Table 1 Summary of Adverse Events Related to Chinese Medicines
Reported to the DH, July 2004 - June 2005
Toxic or Potent
Chinese Herbal Medicines
Kusnezoffii (製草烏) and/or Processed Radix Aconiti Lateralis (製附子) Radix Aristolochiae Fangchi
(廣防己) Herba Aristolochiae Mollissimae
including gold and bird's nest prepared into a paste
Rheumatic Capsules (特效李三連蛇骨風濕丸)
Wilfordii Capsule (雷公籐多甙膠囊)
Note: * Number of cases (number of patients)
The same case involved both Chinese herbal medicines and proprietary Chinese medicines.
Major Causes of Adverse Events
Quality defect was one of the main causes of adverse events for this series. Among
these, adulteration of pCm products with western medicines accounted for most of the
cases (ten cases). Western medicines were added to the products illegally to enhance
the apparent efficacy of the products. These were mainly steroid and slimming agents.
All patients presented with the adverse effects that are known side effects of the
Three patients developed Cushingoid features after consuming Chinese medicines that
contained steroid for a long time. They took the Chinese medicines for treating
eczema, shortness of breath and joint pain respectively.
Another three patients who took Chinese medicines for slimming purpose developed
known problems of the adulterated western medicines. The medicines involved were
N-nitrosofenfluramine, sibutramine and fenfluramine which led to acute liver failure
requiring liver transplantation, convulsion and valvular heart disease respectively.
The other ingredients adulterated in four cases were sulfamethazine,
tetrahydropalmatine, diclofenac, chlorpromazine, and rosiglitazone. Sulfamethazine
caused methaemo-globinaemia; rosiglitazone caused oedema and the others led to
Another major cause for the adverse events in this series was misuse of the Chinese
medicines. There were three main problems, namely, overdose, excessive long
duration of use and inappropriate decoction. Among the 12 cases due to misuse, one
third involved self-prescription without proper consultation with health care
professionals. The rest were due to inappropriate formulation or improper decoction.
More than half of these cases (seven cases) involved aconitine-containing herbs and
the main reason was overdose. One of the patients required admission to intensive
care unit. All the patients recovered. Aconitine-containing herbs should be decocted
for one to two hours before boiling with other herbs.6,7 This is an important step to
reduce its toxicity.2,7 Those self-prescribed were not aware of this crucial step.
Chinese Medicines Containing Strychnine and Brucine
Two patients suffered from toxic effects of Semen Strychni (馬錢子) overdose. The
herb could cause adverse effects which include headache, dizziness, irritability,
muscle spasm, mental confusion, tachypnoea, dilated pupils, arrhythmia and
circulatory failure.7 One of them learnt from a Chinese medicine book that Semen
Strychni (馬錢子) was good for his trigger finger. As a result, he self-prescribed
Semen Strychni (馬錢子) for three doses with each dose one to four grams, which
exceeded the recommended dosage of 0.3-0.6 gram.8 Another patient was a CMP who
mistook a self-made pill containing Semen Strychni (馬錢子) for another self-made
one. Both pills were only prepared for his own consumption. These two patients
In one case, a five-year-old boy suffered from adverse effects after consumption of
Fructus Xanthii (蒼耳子). He later recovered. When used for children, the dosage of
Fructus Xanthii should be adjusted accordingly. In this case, the dosage used was
relatively high for a child which was believed to be the reason for the toxic effects.
Moreover, during investigation, it was also found that the herb in the market was not
properly fried and the spikes which contain higher concentration of the toxins had not
Rhizoma Dioscoreae Bulbiferae (黃藥子)
In one case, a patient developed liver derangement after prescribed with 70 doses of
Rhizoma Dioscoreae Bulbiferae (黃藥子). All the 70 doses exceeded the
recommended dosage. Rhizoma Dioscoreae Bulbiferae (黃藥子) is known to be
hepatotoxic. The patient gradually recovered.
Erroneous substitution of Chinese herbal medicines with a more toxic herb is not
uncommon. This is partly because the naming of Chinese medicines is sometimes
confusing. The same Chinese medicine may have several names while one name may
mean totally different herbs. Another reason is that the appearance of some Chinese
In this series, the substitution cases were mainly the mixing up of Radix Aristolochiae
Fangchi (廣防己) and Radix Stephaniae Tetrandrae (防己) (three cases). Both herbs
have similar names, appearance and indications.9 Actually, they are from different
families of plants. The former is of Family Aristolochiaceae (馬兜玲科) and the latter
is of Family Menispermaceae (防己科). Radix Aristolochiae Fangchi (廣防己)
contains aristolochic acid while Radix Stephaniae Tetrandrae (防己) does not.
Aristolochic acid (AA)-containing herbs were banned for import and sale in Hong
Kong on 1 June 2004 due to its renal toxicity and carcinogenic effects 10-12. One of the
patients recovered after treatment. The other two patients had other underlying renal
diseases and their renal function remained abnormal. The AA-containing herb was
thought to aggravate their renal problems.
Adverse events could also be a result of other causes like allergic reaction, intrinsic
toxicity of the Chinese medicines or drug interaction.
Two cases were related to the use of Ganoderma Lucidum spores (靈芝孢子). One
patient developed tongue swelling after taking the product which was thought to be
due to allergic reaction. Another patient developed diarrhoea and vomiting after
One patient took an AA-containing herb Herba Aristolochiae Mollissimae (尋骨風)
prescribed by a CMP in Mainland China where its use is not banned. He developed
Another patient presented with mucositis, facial pigmentation and telangiectasia
which are known side effects of the herb Radix Tripterygii Wilfordii (雷公籐) that the
One patient had renal toxicity after taking a slimming agent containing anthraquinone
for five weeks followed by a non-steroidal anti-inflammatory drug (NSAID),
diclofenac for two days for pain relief. Literature review showed a case report by
Queen Mary Hospital and Princess Margaret Hospital published in 2004, revealing
that renal toxicity of NSAID may be aggravated by anthraquinone.14
Adulteration of western medicines accounted for a large proportion of the cases. In
the reporting year, there were ten such cases. At present, there is a routine
surveillance system to screen for western medicines in pCm. Every pCm product
imported to Hong Kong for the first time will be screened and products on sale in the
market will be sampled for testing for adulteration. Those containing western
medicine ingredients are regarded as unregistered pharmaceutical products under the
Pharmacy and Poisons Ordinance and will be recalled.
Measures have been taken to deal with the quality problems of herbs. In view of the
importance of proper use and processing of the herb Fructus Xanthii (蒼耳子), a
guideline was drawn up by the DH in January 2005 in consultation with the Chinese
Medicines Board and the Chinese Medicine Practitioners Board of the Chinese
Medicine Council of Hong Kong, and was issued to all CMPs and traders in January
2005 so as to promote the safe use and handling of the herb.15
In this series, four cases were due to erroneous substitution. At present, a licensing
system is in place for those traders who are involved in the manufacture, wholesale
and retail of Chinese medicines. Chinese medicine traders have to comply with the
requirements including proper storage, labelling and standard naming of herbs. Herb
dispensing has to be conducted or supervised by qualified persons. These measures
help reducing the problem of erroneous substitution. The Chinese medicine traders
associations are also concerned about this long-standing problem. They took the
initiative to conduct researches and published a book “Hong Kong Commonly
Confused Chinese Medicines” in 2005 which illustrates the differences of Chinese
medicines commonly confused in Hong Kong. The book can be downloaded from the
They have also collaborated with the DH to
organize publicity programmes to heighten the awareness of the professions and trade,
Misuse of medicines remained a major problem. One third of the misuse cases
involved self prescription. There are possibly some misconceptions among the public.
Firstly, it is a common belief that Chinese medicines are derived from natural source
and the effects and side-effects of Chinese medicines are usually slower and milder.
Secondly, some may think that since Chinese medicines have been used for a long
time, they are very safe and should be free from any unknown adverse effects. These
misconceptions may lead to a less prudent use by the public. In fact, Chinese
medicines can be harmful and even fatal if inappropriately used. More public
education on safe use of Chinese medicines is needed.
Inappropriate formulation by CMPs was another cause leading to misuse. Besides
taking public health actions to protect the public from further occurrence, the DH
would disseminate information to CMPs and doctors through publication of review
articles. In addition, guidelines and briefing sessions would be arranged for CMPs and
Chinese medicine traders on how the Chinese medicines should be handled and used
Up till now, there is still limited information on the interaction between Chinese and
western medicines. We need to accumulate more knowledge of this kind in order to
pave way for the collaboration of the two disciplines, which is one of the initiatives of
the Government. For the case involving possible interaction between anthraquinone in
Chinese medicines and NSAID, all doctors in Hong Kong have been encouraged
through the Public Health and Epidemiology Bulletin issued in September 2004 to
report cases of renal failure suspected to be related to the interaction between NSAID
Chinese medicines, as part of our culture, serve us for thousands of year. The reported
adverse events should not eclipse the importance of Chinese medicines. Systematic
collection, investigation and analysis of adverse events are important for monitoring
the safe use of Chinese medicines. A reporting system for Chinese medicine-related
adverse events has been put in place and an Adverse Drug Reaction
(ADR)*. Reporting Arrangement has been further enhanced by the DH in January
2005 to receive reporting from both Chinese and western medicine practitioners. The
support of doctors and CMPs in reporting of cases to the DH is pledged as the
investigation results will be translated to effective measures and strategies to
*The World Health Organization defines Adverse Drug Reaction (ADR) as “a reaction to drug which is
noxious and unintended, and which occurs at doses normally used in man for the prophylaxis,
diagnosis, or therapy of disease, or for the modification of physiological function.”
1. Sin J, Chan C. Review of adverse events related to Chinese medicines in Hong Kong, January
2000-June 2004. Public Health and Epidemiology Bulletin. 2004;13(4):60-6.
2. 有毒中藥現代研究與合理應用.人民衛生出版社.杜貴友,方文賢主編 (2003 年第 1 版)
3. Martindale. A complete drug reference. 33rd edition.
4. British National Formulary (March 2004).
5. Graham M. Woolf et al. Acute Hepatitis Associated with the Chinese Herbal Product Jin Bu Huan.
Annals of Internal Medicine 1994;121:729-35.
6.毒性/烈性中藥應用常識.中醫藥發展籌傋委員會及香港衞生署出版 (1997 年 3 月)
7. 中華本草 (上海科學技術出版社) 1999 年版
8. Pharmacopoeia of the People's Republic of China (2005 edition).
9. 香港容易混淆中藥. 香港浸會大學中醫藥學院編著; 香港中藥聯商會督印 (2005)
10. Chen W, Chen Y. Li A. The clinical and pathological manifestations of aristolochic acid
nephropathy – the report of 58 cases. Zhonghua Yi Xue Za Zhi 2001;25:1101-5.
11. Nortier JL, Martinez M-C, Schmeiser HH, et al. Urothelial Carcinoma Associated with the Use of a
Chinese Herb (Aristolochia fangchi). NEJM 2000;342:1686-92.
12. Working Party on Herbal Medicinal Products. Position Paper on the Risks Associated with the Use
of Herbal Products containing Aristolochia Species. The European Agency of the Evaluation of
Medicinal Products. Evaluation of Medicines for Human Use. 31 October 2000.
13. Zhongyao Jiqi Zhiji Buliang Fanying Dadian (中藥及其製劑不良反應大典). Liaoning Science
and Technology Publishing House. First edition (May 2002).
14. Li FK, Lai CK et al. Aggravation of non-steroidal anti-inflammatory drug-induced hepatitis and
acute renal failure by slimming drug containing anthraquinones. Nephrology Dialysis Transplantation
15. Guideline on Proper Use of Fructus Xanthii. Department of Health of HKSAR (January 2005)
Reporting of Chinese medicine-related adverse events and ADR could be done with
forms which could be downloaded from the following websites respectively:
Medical and Health Officer 2
Assistant Director of Health
This chapter discusses a forward chaining rule based system and its expert system applications. It shows how the forward chaining system works, how to use it, and how to implement it quickly and easily using Prolog. A large number of expert systems require the use of forward chaining, or data driven inference. The most famous of these is Digital Equipment Corporation's XCON system. It configures
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