Toxicology and Clinical Pharmacology of Herbal Products pdf

Karch, MD, SERIES EDITOR TOXICOLOGY AND CLINICAL PHARMACOLOGY OF HERBAL PRODUCTS, edited by Melanie Johns Cupp, 2000 CRIMINAL POISONING: INVESTIGATIONAL GUIDE FOR LAW ENFORCEMENT, TOXICO

Toxicology and Clinical Pharmacology of Herbal Products

Forensic Science and Medicine Steven B Karch, MD, SERIES EDITOR

TOXICOLOGY AND CLINICAL PHARMACOLOGY OF HERBAL PRODUCTS,

edited by Melanie Johns Cupp, 2000

CRIMINAL POISONING: INVESTIGATIONAL GUIDE FOR LAW ENFORCEMENT,

TOXICOLOGISTS, FORENSIC SCIENTISTS, AND ATTORNEYS,

by John H Trestrail, III, 2000

A PHYSICIAN'S GUIDE TO CLINICAL FORENSIC MEDICINE,

edited by Margaret M Stark, 2000

Toxicology and Clinical Pharmacology of Herbal Products

Edited by Melanie Johns Cupp, PHARMD, BCPS West Virginia University Morgantown, WV

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of the information published and to describe generally accepted practices The contributors herein have carefully checked to ensure that the drug selections and dosages set forth in this text are accurate and in accord with the standards accepted at the time of publication Notwithstanding, as new research,

changes in government regulations, and knowledge from clinical experience relating to drug therapy and drug reactions constantly occurs, the reader is advised to check the product information provided by the manufacturer of each drug for any change in dosages or for additional warnings and

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Toxicology and clinical pharmacology of herbal products / edited by Melanie Johns Cupp

p ; cm.—(Forensic science and medicine)

Includes bibliographical references and index

ISBN 0-89603-791-6 (alk paper)

1 Herbs—Toxicology 2 Materia medica, Vegetable—Toxicology I Title:Herbal products II Cupp, Melanie Johns III Series

[DNLM: 1 Herbs adverse effects 2 Plants, Medicinal adverse effects 3

Pharmacology QV 767 T755 2000]

RA 1250 T68 2000

615.9'52—dc21

99-046505

Heroin and cocaine may not be the only drugs to come from plants, but a practicing physician or

toxicologist might be forgiven for thinking so In 1998, 1264 papers were published about cocaine and only 17 about kava kava, an abused herb that is not without toxic side effects Unfortunately, the

majority of the papers about kava kava were published in journals not found in ordinary hospital

libraries In recognition of this fact, and of the obvious need for a reliable reference work on herbal

toxicology, The Toxicology and Clinical Pharmacology of Herbal Products was an early addition to our new series in Forensic Science and Medicine It is very badly needed.

The reason that herbalists and physicians use different terminology, and the reason that most herbal medicine books are of little use to the physician confronted with a desperately ill patient, is that

herbalists and traditional physicians think about diseases (and the medicines used to treat them)

differently Of course many of the drugs first used in modern medicine are extracted from plants But herbalists use whole plants and traditional physicians use purified ingredients derived from plants Traditional physicians and scientists generally believe that, if a plant has any medicinal value at all, it is because it con-

tains one "active" ingredient that must be isolated and purified Herbalist believe results are better when the whole herb is used, because different components of the plant act synergistically

There are risks and benefits to both approaches If an "active" ingredient is isolated, then it can be given

in a more concentrated form This means that the effects, both therapeutic and toxic, will be

exaggerated On the other hand, if the whole plant (or leaves, or roots, depending on the plant) is used, the concentration of the active ingredient may or may not be sufficient to produce the desired

therapeutic result, but the chances for toxicity are decreased The low concentration of active

ingredients may explain why, given the enormous numbers of people taking herbal products, relatively few toxic reactions have been reported Coca leaf is a good example Indians who chew the leaves never achieve blood cocaine concentrations high enough to produce serious toxicity But the results of recent studies suggest that coca leaf chewers do absorb other ingredients from the leaves that prevent high-altitude sickness

Herbalists also believe that combining herbs improves efficacy and reduces adverse effects When compounded by knowledgeable practitioners, some of the remedies do make sense The combination of Devil's claw, white willow, and tumeric, all agents with antiinflammatory effects, is rational, and quite probably effective But combining St John's Wort, which contains a selective serotonin reuptake

inhibitor, with Ephedra, which causes increased catecholamine release, is both dangerous and ill

advised

Whether a particular combination of herbs produces good or bad results depends on who is doing the compounding Under current US laws, anyone is free to market any combination of ingredients, no matter how misguided the underlying science Herbalists are not the only ones who combine agents So

do patients And they often forget to tell their physicians about it Occassionally, this leads to dire

results Terpenoids contained in Gingko biloba interact with platelet-activating factor Fatal brain

hemorrhages have occurred in anticoagulated patients who self-medicated with gingko Traditional physicians generally avoid drugs in combination, because combinations often turn out to be

counterproductive or, as in the case of gingko, outright dangerous For example, tetracycline and

penicillin would never be given at the same time, because the former slows bacterial growth, while the later exerts its bactericidal effects only in growing bacteria

Even without isolating the active principle, some herbal products are very toxic Comfrey may be an effective treatment for bruises and sprains, but it also contains pyrrazolidine alkaloids which can cause severe liver damage The alkaloid content is higher in comfrey's roots than in its leaves and higher

accessible to practicing physicians and laboratory scientists, not to mention consumers who would be well advised to read about any remedy, whether it is prescribed by their physician or their herbalist The

28 subsections of this book deal with the herbs that are most often encountered Hundreds of other herbs exist, but reliable information about them is difficult to acquire As more is learned, it will be incorporated into future editions

STEVEN B KARCH, MDBERKELEY, CA

PREFACE

Sales of herbal products have increased dramatically over the past five years Unfortunately, the

knowledge base devoted to the adverse effects of these products has not grown in proportion to their increased usage Data of questionable accuracy, often designed to sell products rather than to provide objective information, can be found in the print and electronic media, most notably on the Internet Even in medical journals, misleading information about the beneficial and adverse effects of herbs can

be found

Toxicology and Clinical Pharmacology of Herbal Products is designed to provide medical examiners,

toxicologists, and health care providers with an objective review of the available information on the pharmacology and toxicology of commonly used herbs Clinical and pathological findings from case reports of herbal adverse effects are described in detail Sections on the relevant pharmacokinetics, chemical analysis, and analysis of biofluids are unique to this volume, and will be of use to pathologists and forensic scientists, as well as to clinicians Animal, human, and in vitro data are presented on the known pharmacologic and toxicologic effects of each herb, arranged by organ, organ system, or

therapeutic/toxicologic effect A good deal of pharmacology and therapeutics information is included in this section, not only because toxicology is an extension of pharmacology, but also to make the book useful for a wide variety of applications by professionals with various interests Adverse effects noted

in clinical trials are noted in this section as well At the end of the book, a summary table lists herbal toxicities by affected organ, provides a list of herbs involved in drug interactions, and indicates the type

of data supporting the reported toxicities

Each herbal monograph begins with a discussion of the herb's uses, products, and the dosage forms available This information, in conjuction with color photographs1 of some of the most popular

products, can be of assistance in those situations where the identity of an herbal product is in question

A chapter on the legal aspects of herbal products provides an overview of the regulation of herbal products in the US and abroad In addition, each herbal monograph reviews the herb's status

internationally, including approved uses

The incidence of adverse effects associated with the use of herbal products is unknown, and may be underreported Without a foundation of knowledge upon which to inquire whether an herbal product might be the cause of a given finding, further exploration of the possibility of an herb-induced toxicity might not be undertaken Even if an herbal product is suspected of causing an adverse outcome, without information about similar cases, toxicological analysis of biofluids, or the pharmacologic or toxicologic

effects of the herb, further investigation might prove difficult or impossible Toxicology and Clinical

Pharmacology of Herbal Products is designed to provide the necessary knowledge base upon which

such investigations may efficaciously proceed

MELANIE JOHNS CUPP

1 I want to acknowledge Mark Branciaroli of Elkins, WV for producing the photographs of the herbal products.

Legal/Regulatory Aspects of Herbal Products

Melanie Johns Cupp

Chapter 1: Legal/Regulatory Aspects of Herbal Products 3

Case Reports of Toxicity Due to Commercially Available Products

Forouzandeh Mahdavi and Melanie Johns Cupp

John T Schwarz and Melanie Johns Cupp

Melanie Johns Cupp

Amy Meadows and Melanie Johns Cupp

Regulatory Status

Angela Morgan and Melanie Johns Cupp

Angela J Lawson and Melanie Johns Cupp

Michael Newton and Melanie Johns Cupp

Amy Renner and Melanie Johns Cupp

Rayna De Rosa and Melanie Johns Cupp

Melissa Dawn Bostic and Melanie Johns Cupp

SUMMARY OF TOXICITIES AND DRUG INTERACTIONS

Chapter 1: Summary of Toxicities and Drug Interactions 301

CONTRIBUTORS

JAMES ALLMAN • West Virginia University School of Pharmacy, Morgantown, WV

JENNIFER ANNON • West Virginia University School of Pharmacy, Morgantown, WV

MELISSA DAWN BOSTIC • West Virginia University School of Pharmacy, Morgantown, WV

DAVID BURCH • West Virginia University School of Pharmacy, Morgantown, WV

MELANIE JOHNS CUPP • WV Drug Information Center, Robert C Byrd Health Sciences, West Virginia University School of Pharmacy, Morgantown, WV

AMANDA DAILEY • West Virginia University School of Pharmacy, Morgantown, WV

TARA DALTON • West Virginia University School of Pharmacy, Morgantown, WV

JULIE DAVIS • Beckley Appalachian Regional Hospital, Beckley, WV

RAYNA DE ROSA • West Virginia University School of Pharmacy, Morgantown, WV

MARLEA GIVENS • West Virginia University School of Pharmacy, Morgantown, WV

DAVID HUTSON • West Virginia University School of Pharmacy, Morgantown, WV

STEVEN B KARCH • Assistant Medical Examiner, City and County of San Francisco, CA

A HEATHER KNIGHT-TRENT • West Virginia University School of Pharmacy, Morgantown, WV

ANGELA J LAWSON • West Virginia University School of Pharmacy, Morgantown, WV

FOROUZANDEH MAHDAVI • West Virginia University School of Pharmacy, Morgantown, WV

AMY MEADOWS • West Virginia University School of Pharmacy, Morgantown, WV

KIM MELGAREJO • West Virginia University School of Pharmacy, Morgantown, WV

CHARITY METZ • West Virginia University School of Pharmacy, Morgantown, WV

ANGELA MORGAN • West Virginia University School of Pharmacy, Morgantown, WV

MICHAEL NEWTON • Department of Pharmaceutical Services, West Virginia University Hospital,

Morgantown, WV

SHAWN REEDER • West Virginia University School of Pharmacy, Morgantown, WV

AMY RENNER • Mylan Pharmaceuticals, Morgantown, WV

BRIAN SCHULLER•West Virginia University School of Pharmacy,

Morgantown, WV

JENNIFER SCHUMACHER • West Virginia University School of Pharmacy, Morgantown, WV

JOHN T SCHWARZ • West Virginia University School of Pharmacy, Morgantown, WV

PART I—

LEGAL/REGULATORY ASPECTS OF HERBAL PRODUCTS

Chapter 1—

Legal/Regulatory Aspects of Herbal Products

Melanie Johns Cupp

The US Food, Drug, and Cosmetic Act mandates that drugs be proven safe and effective for their labeled use before marketing This requirement does not apply to herbs, because herbal products do not fall under the definition of a drug as long as they are not marketed for the prevention, diagnosis, cure, treatment, or mitigation of a disease Thus, herbal products do not have to be proven safe or effective before marketing (Kurtzweil, 1999)

Herbal products are classified as 'dietary supplements' and are marketed pursuant to the Dietary

Supplement Health and Education Act of 1994 (DSHEA) The passage of this act was a response to the Food and Drug Administration's (FDA's) intent to remove some herbal products from the market in the early 1990s Congress reportedly received more mail in 1993 protesting the FDA's restriction of

supplement availability than relating to any other issue since the Vietnam war Obviously, the American public is very interested in self-medication using herbal products (Vance, 1997)

The DSHEA can be regarded as a compromise between patient autonomy and paternalistic oversight by the FDA Because the cost of drug development may be more than $200 million per drug and usually takes longer than 10 yr, pharmaceutical manufacturers are unlikely to make the financial commitment necessary to amass safety and efficacy data for an herb that cannot be patented (Vance, 1997) Thus, the DSHEA allows consumers access to herbal products, but without the consumer protection provided by the FDA drug approval process It has been suggested that the dollar value provided by the

pharmaceutical manufacturers regarding the expense of developing a

From Forensic Science: Toxicology and Clinical Pharmacology of Herbal Products Edited by: M J Cupp ©

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