prn8099 - Number 31, February 2001

PRN assigned to coordinate research for Tobacco control in South East Asia

Two aspects of tobacco control were discussed -- economics of tobacco and research and surveillance requirement for tobacco control in Southeast Asia.

PRN with its mission to promote health through the rigorous dissemination of ill effects on smoking has been designated as the country coordinator for research and surveillance in tobacco control. The consensus was agreed upon by a core group meeting of 16 representatives from Thailand, Cambodia, Vietnam and the USA. PRN participated in the meeting held from 14-16^th January 2001 at Bangkok Thailand.

This responsibility was assigned by the Alliance of Southeast Asian Tobacco Control Advocates to which the Centre is affiliated with. Two aspects of tobacco control were discussed during the meeting i.e economics of tobacco in Southeast Asia and research and surveillance requirement for tobacco control in the region.

As a background to the network, the Southeast Asian Tobacco Control Alliance was initiated as a supportive base for government and non-government tobacco control workers in the region. By subscribing to the network, members' organizations would foster and support the development of regional tobacco control movements and act as a regional leader on issues which affect all countries in the Alliance.

Key components of the alliance are to promote a regional clearing house in the region, capacity building which include skill workshops and annual SEA conference for sharing of tobacco control activities, conducting research for policy advocacy through the commissioning of joint research and collective advocacy under the Framework Convention for Tobacco Control.

The key research areas identified from the Bangkok meeting are:

• estimating the price and income elasticity of cigarette and other tobacco product demand

• estimating the impact of  tobacco control policies, tobacco control advertising and promotion and socioeconomic/demographic factors on the demand for tobacco products

• examining issues related to the globalization of the tobacco industry on the region, including the impact of liberization of trade in tobacco and tobacco products on tobacco use and tobacco growing and manufacturing

• examining the macroeconomic implications of tobacco growing and manufacturing and of tobacco control efforts which include looking at the impact of higher tobacco taxes on employment in tobacco farming, tobacco product manufacturing and estimating the impact of higher tobacco taxes

• estimating the gross and net health care costs associated with tobacco use as well as estimating other social costs resulting from tobacco use

• examining the impact of tobacco use on household expenditures

• examining the issue related to smuggling including estimating the share of current tobacco product consumption originating from illegal market

• examining key morbidity and mortality indicators

• conducting tobacco industry surveillance and the impact of tobacco marketing to key populations such as school children, health professionals, girls, teachers and politician

As an outcome of the workshop, PRN will be conducting a follow-up workshop in Penang this coming July with the objectives of training further tobacco control activists from the alliance on the following aspects:

• Access/use tobacco control evidence

• Evaluate national surveillance data

• Develop a study protocol

• Implement the industry surveillance protocol

• Communicate study findings to policy makers/media/public. 

Poison in the Bathroom

Detergent 

PRN CONSULT

Review on

Adverse effects of Herbs and Modern Drug-Herbal Interactions

Introduction

Herbal medicines refer to the use of whole plant remedies for the promotion of healing and maintenance of health. It is said that it originated in Egypt dating back to 1550 BC although it is known that man has started to use plants for food since the beginning of time. Although herbs have been used since time in memorial, many of their pharmacologic effects remain poorly understood. Out of the estimated 800,000 plant species on Earth (von Reis, 1997), about a quarter of the plants have been categorized and only small percent of these plants have been examined for pharmacologic efficacy while the rest remains largely unexplored. Hence, there remains a large void of information on world plants that are largely untested and therefore remain obscure for practical use. The search continues for more medications to help treat the many diseases which still plaque society.

An herb is defined as a plant or plant part used for its aromatic, savory, medicinal or cosmetic properties. In practice, generally the whole plant or plant parts are used singly or in combination with more than one plant for the purpose of treatment. However, in the current development of herbal industry, one could observe the evolution of newer herbal products in the market containing extract of isolated chemicals or single plants mimicking the modern pharmaceutical drugs dosage forms. This has drawn some disagreement among traditional herbal practitioners who support the use of the whole plant or plant parts arguing that there is synergism or antagonism among the many constituents and the pharmacological activity depending on their combined effects.

Herbal usage

There is little doubt that the use of herbal medicines is growing. Worldwide, the usage increases at rate of 10-20% annually (Philipson, 1995). Alternative medicine therapies have become increasingly popular, and it has been estimated that one third of all Americans use herbal products (Johnstone, 1997). In 1997, herbal medicine sales in the United States reached an estimated total of about US $3.24 billion (~RM12.3 billion) while in the same year, Malaysian spend about RM2.0 billion. With approximately 22 million and 273 million population respectively, we Malaysian, spend on average, about RM91.00 per person per year on herbals in comparison to about RM45.00 per person per year in the United States. This speaks for itself the volume and potential of herbal market in our country. In 1999, more than eight thousand herbal products have been registered with the Ministry of Health. Despite the paucity of knowledge of pharmacologic efficacies of herbals, sales of tested, partially tested and untested preparations either manufactured locally or imported into Malaysia are on the rise. Of primary concern is the quality and reliability of the products available in the marketplace today. The status of our herbal products are probably at the same stage as their US counterparts - safety and efficacy prior to marketing are not guaranteed and no outside monitoring of the identity or potency of the herbals is produced or required. This is in sharp contrast to the strict requirements and stipulations for each pharmaceutical products that need to be adhered prior registration.

The safety of herbal medicine is of particular importance because the majority of these products is self-prescribed and is used to treat minor and often chronic condition. However, most patients consuming herbal preparation are not and should be, aware of the potential adverse effects these preparations may produce. Despite widespread use of herbal therapies, scientific data about their safety and efficacy are lacking in most cases.

Why do people resort to herbals?

It has been estimated that 80% of the world population use some form of herbal medicine. For certain fraction of the population, herbal use is intrinsically part of the culture and believes and is use daily or from time to time to maintain health or to treat certain ailments. Basically, herbal use could be classified into four groups:

1. those who solely use herbals for therapeutic purposes while dismissing the efficacy of modern drugs. This group is fast disappearing as the world becomes more develop and modern society becomes more pervasive.
2. those who use more herbals than conventional modern drugs for therapeutic purposes.  In some cases, patients who leave mainstream medicine do so only after realizing the letter has nothing more to offer to treat their health problems e.g for treating chronic conditions with which western medicine has little success.
3. those who use more modern drugs than herbals for therapeutic purposes. This group, most probably, constitutes the majority of the Malaysian population.
4. those who use modern drugs and do not believe in the efficacy of herbals. Unfortunately, this group of people do not know the evolution of modern drugs and the role of herbal/plants in modern drug development.

Second reason for the increase use of herbals is the relatively cheaper cost of herbal product and hence is affordable to the lower income group bracket. Generally, this is particularly true a few years ago. Nowadays, it is not surprising to find some herbal products in the local market which are expensive; in fact, more expensive than the cost of conventional modern drugs and yet are still in demand. Also, the easy availability of herbals make them more accessible in comparison to conventional medicines where one has to visit a doctor to get prescription for their medications. The explosion of information with the advent of internet certainly has some effect on the increase trend of self-medication.

The third reason is the general public impression of herbals being natural and anything which is natural is safe and less harmful. There is also this notion that herbal products do not contain chemicals. The connotation of chemicals, only found in synthetic modern drugs and not in herbal products, has always been linked to toxicity, more adverse effects and hence more harmful. These misinformation and superstitions are being propagate by irresponsible, uneducated and unscrupulous salesperson at the 'pasar malam' and bazaars and unfortunately has been broadcasted in privately sponsored radio programmes.

Adverse effects of herbals

It is undeniable that plants has an important role in the development of modern drugs. More than 60-70% of modern drugs in the world market are directly of indirectly derived from plant or plant products. Herbal compounds have a definite place in medical practice and in the last few years, a lot of research has come out about interesting and beneficial chemicals in herbs. However, there is nothing about herbs that automatically makes them non-toxic just because they are natural. Medicinal herbs contain powerful, pharmacologically active compounds. While some herbs in common use appear to be fairly safe, all drugs, herbal or otherwise, should be use with caution.

The number of reports of adverse effects of herbal medicine is now increasing due to increase use and also probably due to increase awareness among the consumers and clinical practitioners with regards to herbal adverse effects. In Malaysia, adverse effects of herbal (traditional) medicine are reported to the Malaysian Adverse Drug Reaction Advisory Committee (MADRAC), National Pharmaceutical Control Bureau, Ministry of Health, Malaysia. The number of reports of adverse reactions attributable to traditional medicine has increased from 11 in 1997 to 23 in 1999. The most common adverse effects reported are hepatic and renal problems. However, it is difficult to identify the causative agent associated with the adverse reactions encountered because traditional herbal preparations often contain multiple ingredients. The above number of reported cases most probably do not reflect the actual frequency of adverse reactions caused by traditional herbal preparations. Adverse effect or poisoning pertaining to herbals reported to the Pusat Racun Negara from 1995 to June 2000 are as follows: 8 cases (1995), 3 cases (1996), 5 cases (1997), 11 cases (1998), 7 cases (1999) and 9 cases (until June 2000). The list of herbals involved include Datura fastuosa, Datura metel, Datura stramonium, camphor, minyak serai, margosa oil, nutmeg oil, yohimbine, Air Abu Kansui, stephamine tablets, Pithecallobium jiringa (jering), eucalyptus oil, Minyak Rohini, Slimming gel, cassava (ubi kayu), ganoderam mycelium, fat burner, Yu Yee oil, 'Pil kuda'. minyak angin, plant seed, mushroom, unknowns (including traditional medicine products, tonic, chinese medicines, chinese oil) - (Pusat Racun Negara - personal communication). 

What are the modes of herbal toxicities?

Patients consuming herbal preparations should be aware that herbs could cause a variety of toxic reactions. Certain groups of the population should heed extra caution as they are more susceptible to herbal adverse reactions or toxicities. They include pregnant and nursing women; some compounds in herbs can cross the placenta and are clearly linked to birth defects or other problems in newborns. Children and infants are much more sensitive than adults to the effects of all medicines including herbs. Elderly with heart related problems, diabetes and other chronic disease may show exaggerated toxic/adverse reactions to herbs. Herbs can be hazardous in many ways. The modes of herbal toxicities can be divided as follows: 

1. Some herbals may contain toxic ingredients

Some herbs are found to contain intrinsically toxic constituents with various potential adverse effects. Pennyroyal oil contained a potent abortifacient compound and has also been reported to cause both liver and kidney damage and death (Center for Disease Control, 1978). Dobb and Edis (1984) reported neuropathy and coma in a patient who has taken a herbal laxative to control weight. The herbal laxative was found to contain podophyllin which is known to cause severe neurological symptoms. Noni juice (equivalent of our local Mengkudu) has been reported to contain high potassium and should be used with special caution in kidney patients because high levels of potassium in the latter may cause arrthymia and even heart attacks. The consumption of various herbs has been shown to be associated with hepatoxicity and in many cases the toxic compound has been shown to consist of pyrrolizidine alkaloids (MacGregor et al, 1989).

2. Unintentional substitutes of the herbal with a toxic species

The grim reminder of 105 severe kidney damaged patients in Belgium after taking Chinese herbal preparations for slimming treatment has caused everyone to be cautious when using herbals. The herbal treatment also caused 18 cases of cancer. Investigations have discovered that one of the ingredient of the weight reducing pills, Stephania tetrandra was replaced by Aristolochia fangchi, an herb related to herbs variously called birthwort, snakeroot and Dutchman's pipe. In animal studies, Aristolochia fangchi has caused kidney damage and cancer.

3. Intentional addition of active drugs (modern)

The addition of active modern drugs was purposely done to produce the therapeutic effects of potentiate the effects of the herbals. Toxic effects of Chinese herbal preparations adulterated with modern drugs have been reported (Anonymous, 1975) and analysis of these products were found to contain the following compounds: steroids, pain killer, skeletal muscle relaxant, minor tranquilizer and glyburide (oral antidiabetic agent). Recent report by the Minister of Health, Malaysia indicated that about 37% of 5000 kidney cases in Malaysia may be attributed to the chronic use of traditional herbal preparations. Many of the locally available herbal preparations have been found to be adulterated with steroids, modern, drugs, poisons and high levels of heavy metals (Ahsan, 2000). Subsequent report by the Ministry of Health stated that almost 95% of unregistered traditional herbal preparations in the local market are found to contain steroids (Shakri, 2000).

4. Environmental contamination of the herbs

Because herbal preparations are usually not evaluated for purity and consistency of active components, they often contain accidental contaminants. Chan et al (1997) reported a case of arsenic poisoning due to contamination of yellow root herbal tea in the southern U.S. The poisoning was probably due to soil and stream contamination in the plant's natural habitat.

5. Toxic when taken in combination with other combination with other compound e.g. modern drugs

When herbs with some potential for toxicity are mixed with modern drugs, there may be previously unknown consequences, as a result of the potentiation of the toxicity of the herb by the metabolic and physiological effects of the drugs. In some cases, herbal use may be contraindicated with certain disease states. Interaction of herbals with modern drugs may also bring about changes in the pharmacokinetic and pharmacodynamic of the latter. For example, herbal-modern drug interaction may cause decrease or increase in the absorption, distribution, metabolism and excretion of the modern drug. The interaction may also increase/decrease the desired pharmacological effects of the modern drugs.

Interactions between blood thinning herbs and prescription medications with the same action (e.g. warfarin, aspirin, heparin and coumarin) present perhaps the greatest risk of herb-drug interactions in modern practice. Herbal products that may potentially increase the risk of bleeding or potentiate the effects of the above named prescription medications include feverfew, garlic, ginger, ginkgo, licorice root, parsley, tumeric, ginseng and ephedra. These herbal product have the potential to cause unexpected bleeding in surgical patients. A case report showed that Ginkgo biloba extract caused spontaneous bleeding into the eye form the iris within a week of onset of daily Ginkgo biloba extract supplementation in a patient who had been taking aspirin to prevent a heart attack (Kleijnen and Knipschild, 1992). Another example, St. John's Wort, valerian and kava-kava may prolong the effects of some anesthetics and impair awakening from anaesthesia. A study by the National Institutes of Health found the popular herbal products can decrease the effectiveness of a variety of prescription medications used to teat HIV and AIDS, some cancers, heart disease and organ-transplant patients. They are also able to decrease the effectiveness of birth control pills by as much as fifty per cent. Studies conducted by the author have indicated various Malay, Indian, Chinese, Western herbal product and homeopathic preparations are able to influence the metabolism of a modern drug in-vitro. Parkia speciosa, locally known as petai, has been found to significantly affect liver drug metabolism invitro (Hussin et al, 1999) and in-vivo. Studies on Pithecal-lobium jiringa (jering) and Pithecallobium microcarpus (kerdas) also shoed similar significant increase in liver drug metabolism (Hussin et al, 2000).

Conclusion

When used wisely, herbal medicines have a place in treating certain ailments and diseases. From the above discussion, findings by many researches have reinforce the idea that the use of natural herbal medicines may not be without risk. In the U.S., nearly 70% of patients who use herbal medicines do not inform their health care providers about their use of herbal therapies (Eisenberg et al, 1993) and the frequency in Malaysia is not known. More research on adverse reactions on locally available herbal preparations should be encouraged and more public education on the good and bad effects of herbals need to be emphasized. Health care professionals should remain vigilant for potential interactions between herbals and prescription medications, especially medications with a narrow therapeutic index.

Clinical Updates

Family Poisoned By Mercury Vapour Inhalation

Author(s): Micheal T. Solis et.al

Source: Am J Emerg Med, 18, Pg 599-602, Yr 2000

Abstract: A case series is presented of a family who became exposed to mercury vapour. Three of  the eight victims were on mechanical ventilation, out of which two died due to irreversible pulmonary toxicity. The remaining survivors developed varying degrees of mercury toxicity.

Coma Mimicking Brain Death Following Baclofen Overdose

Author(s): M.E. Ostermann et.al

Source: Intensive Care Med, 26, Pg 1144-1146, Yr 2000

Abstract: Baclofen toxicity can cause a clinical picture of near brain death. The prognosis is good even in severe cases, provided it is recognized early enough, and appropriate supportive measures are instituted.

Current Management of Ethylene Glycol Poisoning

Author(s): Brent J.

Source: Drugs, Vol 61, Issue 7. Pg 979-988, Yr 2001

Abstract: Treatment of ethylene glycol poisoning consists of emergent stabilisation, correction of metabolic acidosis, inhibition of further metabolism and enhancing elimination of both unmetabolised parent compound and its metabolites. Historically, the prevention of ethylene glycol metabolism is with intoxicating doses of ethanol. A recent alternative to ethanol therapy is fomepizole which does not produce serious adverse effects and is metabolised in a predictable manner, allowing for the use of a standard, validated administration regimen.