A Call for Cases of *Adverse Reactions to Chinese Medicines*
Yue Fengxian
Chinese medicine has no concept of adverse reactions to Chinese medicines; it borrows the term from Western pharmacology's adverse drug reaction.
Adverse drug reaction was originally a Western pharmacological term for the harm a Western drug does to the body — both foreseeable and unforeseeable harm. It includes side effects, toxic effects, allergic reactions, sequelae, etc., sometimes abbreviated toxic side effect. On the concept of adverse drug reaction, Chinese Drug Adverse Reaction Bulletin (issue 1, 2002), co-sponsored by China's ADR Monitoring Center and the SDA's Drug Evaluation Center, defines it as: "a harmful or unexpected response that occurs when a drug is used in its normal manner and dose for prevention, diagnosis, treatment, or regulation of physiological function. It does not include reactions caused by unintentional or intentional overdose, or by inappropriate use." Professor Sun Zhongshi of the SDA Drug Evaluation Center, in the Link section of Monitoring Adverse Reactions, Securing Safe Medication, writes: "Drug adverse reactions ... refers to harmful reactions, irrelevant to the intended purpose or unexpected, that occur with qualified drugs in normal manner and dose; does not include harmful reactions caused by drug-quality problems or inappropriate use." As stated, the inner content of the adverse-reaction concept is the WHO's definition. From this, confirming an adverse drug reaction can be summarized as three prerequisites and one related content. The three prerequisites: (1) qualified drug; (2) normal manner; (3) normal dose. The related content: irrelevant to the purpose of medication. If under these three prerequisites and the related content harm to the body appears, then this is an adverse drug reaction; otherwise it cannot be called an adverse drug reaction.
Since Chinese-medicine adverse reaction is a borrowing of the Western pharmacological term, in confirming a Chinese-medicine adverse reaction one should likewise satisfy the related conditions — the three prerequisites and the related content. From the angle of TCM, these should be understood as follows:
(1) Qualified drug. Drug here means preparation. Currently, for the vast majority of raw Chinese herbs the constituent makeup is not yet fully known, so qualified Chinese drug can only be defined and assured along these lines. First, the species of the raw herb must be correct. Second, the processing of raw herbs into yinpian (sliced medicinal pieces) — its technique and conditions — must be correct, i.e., yinpian prepared according to the standard of Chinese-medicine processing. Third, preparations made from yinpian must follow TCM's traditional requirements, i.e., meet the preparation requirements for pills, powders, pastes, dan, decoctions, and other dosage forms. Drugs meeting these three points, and not spoiled by improper storage, may be considered qualified Chinese drugs. Otherwise, they are not. Only adverse reactions arising from qualified Chinese drugs are properly called Chinese-medicine adverse reactions; from unqualified drugs, they cannot be so called.
(2) Normal manner. This includes route of administration, daily frequency, timing per dose, etc. — all must meet requirements. The most prominent content of normal manner is: use according to TCM theory. Only adverse reactions occurring under such normal use can be called Chinese-medicine adverse reactions. By present practice, sometimes so-called Chinese drugs are used by Western pharmacological theory — i.e., the Chinese drug is used as if a Western drug. Adverse reactions arising in such cases can be called only Western-drug adverse reactions, not Chinese-medicine adverse reactions. For example, huanglian and garlic. As Chinese drugs, huanglian is bitter-cold, garlic is pungent-hot. Modern science shows both have antibacterial action and can serve as anti-bacterial, anti-inflammatory Western drugs. Clinical reports show: applied to bacterial infection of replete-heat pattern, huanglian treats without adverse reaction; applied to deficient-cold patterns, though it inhibits bacteria, the patient gets abdominal distension and poor appetite — adverse reaction. Garlic applied to deficient-cold bacterial infection treats without adverse reaction; applied to replete-heat bacterial infection, though it inhibits bacteria, the patient gets upward-fire symptoms — mouth blisters, an adverse reaction. By TCM theory, huanglian fits replete-heat bacterial infection, garlic fits deficient-cold bacterial infection — this is normal use. Disregard this, and it is abnormal use; adverse reactions arising from abnormal use cannot be called Chinese-medicine adverse reactions. So the reactions of huanglian in deficient-cold patients or garlic in replete-heat patients should not be called Chinese-medicine adverse reactions of huanglian or garlic. If huanglian and garlic are taken merely as antibacterials of these two drugs, then for both replete-heat and deficient-cold patients use is normal — and adverse reactions thereby fall under Western-drug adverse reactions of huanglian or garlic.
Two further distinctions under normal manner: First, many new Chinese drugs of recent years describe function in TCM terms. Their correct use requires consideration of both function and indication together — especially indication, which must accord with the TCM function for use to be normal. To ignore the TCM function and use by Western indications alone is abnormal use. If a Chinese drug has function pungent-cool surface-release, heat-clearing toxin-resolving, with indications including bacterial- and viral-infectious diseases (gastroenteritis, pneumonia, tonsillitis, mumps), then to ignore the function and use only by indication is in fact Western-drug normal use, not Chinese-drug normal use; adverse reactions arising are Western-drug adverse reactions, not Chinese-medicine adverse reactions. Objectively speaking, bacterial-infection patients may be replete-heat or deficient-cold; one drug cannot fit two patterns. Disregarding the TCM function content is plainly not Chinese-drug normal use; adverse reactions arising are not Chinese-medicine adverse reactions. Second, new Western drugs derived from Chinese herbs — berberine, ephedrine — are placed in the Western section of the pharmacopoeia; in themselves they have no Chinese-medicine properties and are used only by Western pharmacological theory. Adverse reactions in use can be called only Western-drug adverse reactions, not Chinese-medicine adverse reactions.
(3) Normal dose. By current regulation, dose must be within pharmacopoeial range to be normal; otherwise abnormal. Adverse reactions from abnormal dose plainly cannot be called Chinese-medicine adverse reactions. As for the related content — irrelevant to the purpose of medication — that is to say, temporary discomfort to the body bound up with the purpose of medication cannot be casually called a Chinese-medicine adverse reaction.
In recent years, articles reporting Chinese-medicine adverse reactions have grown markedly. Especially in discussion pieces, the seriousness of Chinese-medicine adverse reactions is loudly proclaimed and the strengthening of Chinese-medicine toxicology research urged. The view is offered that the rise in serious Chinese-medicine adverse reactions reflects a deeper understanding of Chinese-medicine toxicity. The cumulative impression is: that the Chinese-medicine adverse-reaction problem has reached a degree affecting the use of Chinese medicines, and that the past judgment of low toxicity was merely uninformed. Setting aside the different concepts of Chinese and Western pharmacology on drug toxicity, let us first look at the facts. I have surveyed the past ten years of Chinese and Western pharmaceutical journals for review, discussion, and case-report articles on Chinese-medicine adverse reactions. The survey may not be complete, but on what I have seen — comparing with the adverse-reaction concept — it is extremely rare to see reports truly belonging to Chinese-medicine adverse reactions, especially case reports. The reasons typically cited for the supposed rise in adverse reactions are: wrong species, lack of proper processing, overdose, failure to use by TCM theory, witch-doctor medication, blind faith in folk and secret formulas, Western drug used as Chinese drug, mixed use of Chinese and Western drugs. Plainly, all these are within the prerequisites to be excluded in confirming an adverse drug reaction. Examples, in line with the three prerequisites:
First, some used shanglu (pokeweed) as tu renshen and gave it as a tonic — poisoning. The doctor's prescription was cheqianzi (plantain seed); the pharmacy gave maqianzi (nux vomica) — poisoning. These are unqualified-drug cases.
Second, an old woman with rheumatic arm pain heard raw caowu (raw aconite kun) could treat it. She bought 200 g and decocted it herself — fatal. Abnormal dose.
Third, a young couple about to enter the bridal chamber heard ginseng was a tonic, bought tens of grams and decocted it before the wedding night. Result: excess excitation, clouded spirit, deranged speech — only the hospital ward could receive them. This is abnormal use. TCM does view renshen as a tonic, but its prominent function is supplementing qi; for the qi-deficient it supplements, for non-deficient young people use is plainly abnormal. The harm of using renshen without TCM theory has long been recognized — called renshen abuse syndrome.
As for some articles calling the harms of witch-doctor use of Chinese drugs Chinese-medicine adverse reactions — this is in fact exonerating the witch doctor and shifting the blame to Chinese medicine. Harm from pianfang (folk one-off formulas) — pianfang are formulas outside TCM theory, using Chinese herbs as folk plant remedies rather than as TCM drugs. To call this Chinese-medicine adverse reactions is to confound the concept of Chinese drug and negate TCM. To put berberine and ephedrine adverse reactions into the Chinese-medicine adverse reactions category is plain disregard of fact, since these are clearly Western drugs in the pharmacopoeia. The kidney damage from Longdan Xiegan Wan, in the past several years loudly discussed and widely cited as a prominent example, has not yet had a case report of Longdan Xiegan Wan used according to TCM theory and causing kidney damage — only reports of harm from use in some Western hospitals. Longdan Xiegan Wan as a drug can be Chinese or Western: if used without TCM theory, by Western pharmacological theory, the harm is Western-drug Longdan Xiegan Wan adverse reaction, not Chinese-medicine Longdan Xiegan Wan adverse reaction.
In sum, on my survey of the literature, it is genuinely hard to find true Chinese-medicine adverse-reaction cases. Hence this article, titled A Call for Cases of "Chinese-Medicine Adverse Reactions," in hope of seeing true cases and so raising the level of understanding.
Originally in Bulletin of the China Academy of Chinese Medical Sciences, third edition.
Note: the author formerly served as Director and Researcher of the Chinese-Medicine Theory Research Office, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences.