Critical Care Nurse. 2002;22: 22-32
Copyright © 2002 by the American Association of Critical-Care Nurses.
Cover Article
CE
Herbal Remedies: Drug-Herb Interactions
Merrily A. Kuhn, RN, PhD
Merrily A. Kuhn is president of Educational Services in Hamburg, NY, and is an associate professor at Daemen College in Amherst, NY.
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This article has been designated for CE credit. A closed-book, multiple-choice examination follows this article, which tests your knowledge of the following objectives:
- Identify issues related to standardization and quality control for herbal preparations
- Describe the pharmacokinetic interactions of herbs on drugs
- Discuss potential interactions of selected popular herbs and drug therapies
Herbs have been used for medicinal purposes since the beginning of recorded time. Although most people in the United States believe that herbs are harmless plants, about one third of our drugs (including digitalis, morphine, atropine, and several chemotherapeutic agents) were developed from plants. So, indeed, herbs can be potent products. Herbs can affect body functions; therefore, when herbs are taken concurrently with drugs, interactions are possible.
Botanical medications have increased in popularity. In the United States, botanical products are now a $1.5 billion per year industry. It is estimated that 60% to 70% of the American population is taking botanical products, but less than one third of these persons inform their medical practitioners of such use.1
Today, our understanding of the interactions between drugs and herbs and between drugs and food is still in its infancy. Much research is still required in herbal therapy to examine individual plant constituents and to determine how plants interact with drugs and food. Some researchers2 suggest that drug-herb interactions occur less often than predicted. If an interaction between an herb and a drug does occur, conventional drugs are usually the culprits because they are more pharmacologically active.2,3 In this review article, I discuss several popular herbs and provide a comprehensive table that summarizes drug-herb interactions (see Table
).
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STANDARDIZATION AND QUALITY CONTROL
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Because herbs are sold as food supplements, companies are not required to prove the efficacy of the herbs or determine the side effects or interactions of these products. Often, multiple ingredients are present in the same bottle, and products are sometimes mislabeled, misidentified, and adulterated. Currently, 30 herb companies have begun to share information on research, quality control, and processing; changes may therefore occur in the future. The potency of herbs can also vary depending on the climate and soil conditions where they were grown. When a drug is prescribed, the dosage and quality of the product is more or less assured; such is not the case with herbs. Even with these drawbacks, herbs are an effective form of therapy.
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DRUG INTERACTIONS
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The first book on drug interactions was published in 1974. Since then, hundreds of texts have been compiled and written on this topic. A drug interaction is defined as any modification caused by another exogenous chemical (drug, herb, or food) in the diagnostic, therapeutic, or other action of a drug in or on the body. The possibilities of drug interaction are endless, because more than 30000 over-the-counter products; more than 1000 unique chemical substances from which prescription drugs are produced; and hundreds of herbs, vitamins, and minerals are available. The risk for drug interactions increases with the number of products consumed: for 2 products, the risk is 6%; for 5 products, 50%; and for 8 or more products, 100%.22 The mechanisms for drug interaction can be divided into several general categories: pharmacokinetics (absorption, distribution, metabolism, and excretion of a drug) and pharmacodynamic interactions (the combined pharmacological effects of a drug).
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DRUG-HERB INTERACTIONS
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The mechanism of action of many herbs has not been determined. Therefore, the exact mechanisms of drug-herb interaction are also unknown. To date, several pharmacokinetic drug-herb interactions (absorption, distribution, metabolism), and several additive pharmacodynamic interactions have been identified.
Pharmacokinetic Interactions
Absorption.
Herbs that have hydrocolloidal carbohydrate components such as gums and mucilage are soluble in water but poorly absorbable; examples include psyllium, rhubarb, flax-seed, marshmallow, and aloe. These compounds are apt to bind to other drugs, particularly when consumed in their whole or powdered forms. For example, psyllium (an herb high in mucilage) inhibits the absorption of lithium. Rhubarb and aloe can cause diarrhea, which reduces the action of drugs that have a narrow therapeutic index (eg, digoxin, warfarin).3 In order to prevent an herb from binding with drugs, the drug should be taken 1 hour before or 2 hours after these herbal products.23
Distribution.
Herbs such as meadowsweet and black willow, which contain pain-reducing salicylates, may displace highly protein-bound drugs such as warfarin and carbamazepine (Tegretol),2,3 thus increasing the adverse effects of the drugs. These products should not be taken concurrently.
Metabolism
Licorice (as an herb, not a sweetener) decreases the metabolism of corticosteroids, leading to adverse and toxic effects from the buildup of corticosteroids. Recently, researchers2,3 discovered that St John’s wort can induce hepatic microsomal enzymes in the cytochrome P-450 system; thus, it increases the metabolism of drugs metabolized in this system, such as digoxin and theophylline, protease inhibitors, and cyclosporine. The drugs are thus rendered less effective, so concurrent use of licorice with these drugs is not recommended.
Pharmacodynamic Interactions
An example of a pharmacodynamic interaction is additive activity. For example, the hypnotic activity of benzodiazepines is increased by valerian, and the anticoagulant action of warfarin is enhanced by ginkgo and possibly by many other herbs (see Table
).3 It is best not to take these products concurrently.
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SELECTED POPULAR HERBS
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Ginkgo (Ginkgo biloba)
Ginkgo is often used by elderly persons because of its ability to improve cognitive function in persons with Alzheimer’s disease and dementia24,25 and to improve blood flow in persons with peripheral vascular disease, tinnitus, or memory impairment.26 To date, several reports of bleeding associated with use of ginkgo have been published.7,27–31 Patients who experienced bleeding were from 33 to 78 years old; one person was taking no other drugs concurrently, whereas several other patients were taking aspirin, warfarin, acetaminophen, or an ergotamine-caffeine preparation concurrently. Patients had both minor and major episodes of bleeding, and one person died of a massive cerebral hemorrhage.28
Patients taking other products known to affect platelet activity, such as vitamin E (>1200 IU), excessive garlic (the equivalent of 15 to 20 cloves/day), warfarin, aspirin, and low molecular weight heparins, should be cautioned about the potential interaction of those products with ginkgo. Patients taking ginkgo should be counseled to inform their health-care providers of unusual bleeding and bruising or a new onset of dizziness, headache, or blurred vision.
Flaxseed (Linum usitatissimum)
Flax is one of the oldest cultivated plants in the world. Flax is grown for its fiber (linen), seed oil (linseed oil), and seeds (flaxseed). Flax is a bulk-producing, stool-softening agent that lowers levels of cholesterol (9%), triglycerides, and low-density lipoproteins (18%).32 By binding to bile acids in the intestinal tract, flax interferes with the reabsorption of fats.33–36 When soaked, flaxseeds have mucilaginous properties and can bind with drugs, especially cardiac glycosides, rendering them unabsorbable. Therefore, flaxseed should be taken either 2 hours after or 2 hours before the consumption of other products (drugs, vitamins, and minerals). In addition, concurrent use of flaxseed with laxatives and stool softeners should be avoided because of the possible potentiation of the laxative effect.37
Feverfew (Tanacetum parthenium)
Feverfew is most commonly used to reduce the number and the severity of migraine headaches2,38 and has anti-inflammatory activity. Feverfew suppresses prosta-glandin production but does not inhibit cyclooxygenase.39 Feverfew inhibits platelet activity, so it should not be taken concurrently with warfarin or other drugs that affect clotting.40 Feverfew is also a member of the daisy family, and is therefore contraindicated in persons with allergy to ragweed.4
Ginger (Zingiber officinale)
Ginger has been used and tested as an antinauseant and antispasmodic agent with very good results.41–43 Ginger is a potent inhibitor of thromboxane synthetase and thus prolongs bleeding time.44 Therefore, persons taking warfarin or other drugs that affect platelet activity should refrain from taking ginger in tablet form.2,4,44 Using ginger as a spice is not a problem.
Kava Kava (Piper methysticum)
Kava kava is cultivated throughout the South Pacific and has been used for hundreds of years as a ceremonial drink. Kava kava relieves anxiety, nervousness, and tension without affecting alertness.2,33 Kava acts as a dopamine antagonist and therefore may increase tremor and make medications less effective in persons with Parkinson disease.2,45 Kava also potentiates alcohol, tranquilizers, and antidepressants, which should therefore not be taken concurrently with kava.2,45,46
St John’s Wort (Hypericum perforatum)
St John’s wort is one of the most popular herbs in the United States for the management of depression.2,4 For many years, St John’s wort was thought to act as a monoamine oxidase inhibitor, but this hypothesis has never been confirmed. Current research suggests that St John’s wort acts as a selective serotonin reuptake inhibitor (SSRI).47,48 Therefore, concurrent use of SSRIs with St John’s wort is contraindicated.15,49 Patients should wait at least 2 weeks after taking an SSRI before starting to take St John’s wort, or between stopping taking St John’s wort and starting to take an SSRI.33 The newest research suggests that St John’s wort may act in the cytochrome P-450 system of the liver. Concentrations of indinavir, a protease inhibitor used to treat infection with human immunodeficiency virus, were reduced, possibly leading to drug resistance and treatment failure.15,19,47 Markowitz et al14 studied the action of St John’s wort on the cytochrome P-450 system in the liver, and their results indicated that St John’s wort was unlikely to inhibit the CYP2D or CYP3A4 liver enzyme systems. More research is needed.
Other researchers15,20 today are suggesting that St John’s wort may have an effect like that of grapefruit juice on the metabolism of many drugs. In another study,16 2 transplant recipients who were taking cyclosporine (definitely metabolized in the liver) experienced transplant rejection.18,47 Much more research is needed to determine the effect of St John’s wort on the metabolism of other drugs.
St John’s wort also is associated with photosensitivity, so other photosensitizing herbs (eg, dong quai) or photosensitizing drugs (eg, tetracyclines and chemotherapeutic drugs) should not be taken concurrently.2,4 Persons taking St John’s wort should be careful about their exposure to sun.
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REPORTING INTERACTIONS
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In May 1998, the Food and Drug Administration (FDA) announced the development of a searchable database containing reports of adverse events associated with the use of special nutritional products (eg, dietary supplements, infant formulas, and medical foods). Reports are received from health professionals or patients and consumers via the FDA’s Med Watch program,50 FDA field offices, and other federal and local public health agencies or via correspondence received by the FDA. This system allows both reporting of adverse events and searching of events currently in the database. Access may be obtained via the Internet at http://vm.cfsan.fda.gov/~dms/aems.html or by telephoning (800) FDA–1088.
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IMPLICATIONS FOR NURSING
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Nurses should become educated about the herbal products that patients are consuming. Objective information about herbal products can be obtained in publications such as Alternative Medicine Alert [(800) 688–2421], Review of Natural Products [(314) 216–2100], Herbal Therapy and Supplements, A Scientific and Traditional Approach [(800) 724–9866], and Complementary Therapies for Health Care Providers [(800) 724–9866].
A comprehensive assessment requires the nurse to identify prescribed medications, over-the-counter medications, dietary supplements, and complementary therapies used by patients.4 Often, patients neglect to report use of herbal substances because they underestimate the significance of these substances in relation to the whole clinical picture. Some patients may be reluctant to divulge information about use of "unorthodox" therapies to persons seen as "conventional" healthcare providers.
Preoperative assessment of use of herbal products is important. Use of all herbal products should be discontinued 5 to 7 days before surgery. Because pharmacokinetic information on most herbs is not available, how long it takes for most herbal products to be cleared from the body is not known. If a patient is having an emergency procedure, nurses should specifically ask about herbs that affect clotting, including bromelain, cayenne pepper, chamomile, cinchona bark, dong quai, fenugreek, feverfew, garlic, ginger, ginkgo, ginseng, guggul, horse chestnut, vitamin E (>1200 IU), and willow bark (see Table). This information should be discussed with the medical staff.
Determining the use of herbal substances is an important aspect of patients’ assessment and may influence nursing interventions. Patients may also seek advice from nurses about the use of herbal substances and about the efficacy and safety of those herbal products.
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SUMMARY
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Controlled clinical studies are needed to clarify and determine the clinical importance of drug-herb interactions. However, it is unlikely that this information will be forthcoming except as anecdotal reports. Patients taking drugs with a narrow therapeutic index (cyclosporine, digoxin, hypoglycemic agents, lithium, phenytoin, procainamide, theophylline, tricyclic antidepressants, and warfarin) should be discouraged from using herbal products.2,51 All drugs with a narrow therapeutic index may either have increased adverse effects or be less effective when used in conjunction with herbal products. More research is required to define the interactions. When adverse reactions are experienced with drug therapy, patients must always be queried as to their intake of herbal products: what they are taking in pills and tincture form, what they are drinking as teas, and what they are eating from their garden.3,51
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Top
STANDARDIZATION AND QUALITY...
DRUG INTERACTIONS
