H.M.J. Anesthesia & I C Department
HERBAL MEDICINES AND ANESTHESIA
Individual Herbs Commonly Encountered
Although there are many different herbs used for
medicinal purposes, this discussion will be limited to several herbs that are
most often encountered and used by the general population (Table
1). Additional information can be found on the
Internet as well as in the Physician's Desk Reference for Herbal Medicine.5
Echinacea (Echinacea purpurea) - The "Purple Cone-flower" is native to North America. It was used by the Plains Indians for its medicinal properties and the Indians introduced it to European settlers. Currently, it is usually marketed alone or in combination with other herbs as a purported "immune booster", especially for the prevention or treatment of colds. In 1998, a double-blind, randomized study of 302 military volunteers given echinacea for prevention of upper respiratory infections (URI) speculated that there may be a 10-20% risk reduction for contracting an URI, even though a definitive prophylactic effect could not be demonstrated.6
The plant contains water-soluble polysaccharides that strongly affect the immune system. Effects include stimulating phagocytosis, increasing motility of leukocytes, and increasing the production of T lymphocytes and interferon.7 Similarly, animal studies show that components of echinacea increase the number of circulating white blood cells, enhance phagocytosis, stimulate cytokine production, and trigger the alternative complement pathway.8
Although echinacea is generally thought to be "safe", it does have the potential for side effects such as allergic reactions, especially in atopic patients, nausea and vomiting, and hepatotoxicity if used with other potentially hepatotoxic drugs.36 Other possible problems with echinacea include suppression of the immune system if used chronically.
Ephedra (ma huang) (Ephedra sinensis) - Native to central Asia, Ephedra has been used in traditional Chinese medicine for more than 5,000 years. It is used primarily as a remedy for bronchial asthma, but is also used to treat symptoms of cold and flu, including fever, chills, cough, wheezing, headache, and nasal congestion. The plant contains the alkaloids ephedrine and pseudoephedrine, which are central nervous system stimulants. They enhance the release of norepinephrine and stimulate both alpha and beta-adrenergic receptors. Desired effects induce bronchodilation, decreased bronchial edema, and vasoconstriction. Ephedra is also used as a stimulant and appetite suppressant. The weight loss mechanisms of action include an anorectic effect via adrenergic pathways in the hypothalamus and a thermogenic effect due to increased metabolic rate.
Side effects that may be associated with the use of Ephedra include insomnia, nervousness, irritability, dry mouth, headache, generalized weakness and dizziness. Hypertension, palpitations, tachycardia, stroke and seizures are all signs of severe cardiovascular instability that been reported following Ephedra use.
Feverfew (Tanacetum parthenium) - This daisy-like perennial commonly found in gardens and along roadsides is used for moderation and prevention of migraine headaches. It has been used since ancient times for its pain-relieving properties as well as an antipyretic. The first century Greek physician Dioscorides prescribed feverfew for "all hot inflammations."8 It has been used as a folk medicine for menstrual cramps since Greco-Roman times. In modern times, Canadian health officials recently approved encapsulated feverfew leaves as an over-the-counter medication for migraine prophylaxis. This indication was based on a double-blind, placebo controlled trial of 270 patients in which feverfew use was associated with a 70% reduction in migraine frequency and severity.9 Other studies did not show the same rate of migraine prevention, possibly because a different source of the herb was used. This discrepancy points out the difficulties in herbal studies, due to the variability of the contents and effects of different preparations of the same herb, as well as the inability to standardize the samples to identical ingredients. Laboratory evidence indicates that feverfew causes vasodilatation and reduces inflammation. Active ingredients inhibit phagocytosis, platelet aggregation, and secretion of inflammatory mediators such as arachidonic acid and serotonin.10 Feverfew is thought to down-regulate the cerebrovascular response to endogenous amines, consistent with its ability to prevent but not abort headaches. Side effects include up to a 15% incidence of users developing aphthous ulcers and/or gastrointestinal tract irritation. Rebound headaches may occur with the sudden discontinuation of the herb.
Garlic (Allium sativum) - Garlic is one of the world's most-used herbs, both now and throughout history. Louis Pasteur first demonstrated its antiseptic activity. Its uses now include therapy for atherosclerosis, antibacterial, antiviral, antifungal, and even as an anticancer agent. The main purported active ingredient is allicin, which is thought to be effective in blood lipid reduction (mainly low-density lipoprotein). Allicin is also reported to decrease platelet aggregation and increase fibrinolytic activity, clotting time, and streptokinase-induced plasminogen activation. The activity of the herb is destroyed by heat and acid; thus, raw garlic cloves, or enteric-coated tablets need to be consumed to optimize its effects. Side effects include malodorous body odor, allergies to the enteric coating, contact irritation, heartburn, and flatulence. As with many herbal products, the quality of commercial preparations varies greatly, and many products contain far less of the active ingredient than is indicated on the label.
Ginger (Zingiber officinale) - Ginger has been a popular culinary and medicinal herb for thousands of years. The Chinese, as well as numerous other cultures and civilizations, have used it in ancient times as a digestive aid and antiemetic. References to it have been recorded in early Chinese and Sanskrit texts, and in ancient Greek, Roman, and Arabic medical literature. The ginger root contains oleoresin (composed of gingerols and shogaols), as well as non-pungent substances and volatile oils. The exact mechanism of antiemetic action is not known for certain, but several of the active components are known to antagonize serotonin type 3 receptors. Extracts of the root have also been shown to inhibit thromboxane synthetase and reduce thromboxane B2 formation and platelet prostaglandin endoperoxides.11
Although ginger is commonly used for nausea and vomiting, if taken in large quantities, it may cause heartburn or stomach distress. Tachycardia and hypertension are also side effects that may be associated with the use of ginger.
Ginkgo (Ginkgo biloba) - The ginkgo tree is the world's oldest living tree species. Its seeds and fruits have been used as medicine in China since 2800 B.C.E. It has become an increasingly popular herbal remedy for improvement of circulation, memory and mental function, as well as a possible treatment and prevention for Alzheimer's disease. A recent review showed positive results in treatment of Alzheimer's disease with ginkgo.12 Other reports have reported a slight decrease in the rate of decline in patients with mild to moderately severe dementia due to Alzheimer's disease.13 Extracts of the leaves are used as a dietary supplement. The extract contains three types of flavonol glycosides, which are believed to have antioxidant activity. Terpene lactones also found in the extract improve the circulation by a dilatory effect on the blood vessels. Hence the use of ginkgo to treat circulatory disorders such as varicosities, postthrombotic syndrome, chronic cerebral vascular insufficiency, tinnitus, vertigo, claudication, and Raynaud's disease. Both types of active constituents appear to inhibit platelet aggregation. Side effects may include headache, gastrointestinal disturbances, and allergic skin reactions. Increased bleeding may occur, especially in patients taking ginkgo along with other anticoagulants such as coumadin, heparin, aspirin, or even NSAID's. Other drug interactions may include hypertension when ginkgo is used along with thiazide diuretics.
Ginseng (Panax ginseng) Panax quinquefolius - American ginseng - endangered species, Eleutherococcus senticosus - Siberian ginseng - Not in the Panax (true ginseng) genus, but has similar chemical actions. However, several other products labeled as ginseng do not contain the active ingredients ginsenosides. Consumers should beware of anything labeled "American Red Ginseng", "wild American Ginseng," or "wild Red Desert Ginseng", as these herbs are not botanically, chemically, or pharmacologically related to the true ginseng root.
Ginseng is one of the most popular and expensive herbs in the world. In ancient China it was considered to be a panacea, and the common name of ginseng ("man-root") stems from a belief that, because this root is humanoid in appearance, it can benefit all aspects of the human body. Its genus name of Panax means "cure-all". More than six million Americans use this root for medicinal purposes. Retail sales in 1998 were more than $95 million. Most of the uses of this root are as a tonic or adaptogen that enhances physical performance (including sexual), promotes vitality, and increases resistance to stress and aging. It has antioxidant properties as well as appears to have a modulating effect on the hypothalamic-pituitary-adrenal axis by inducing secretion of ACTH. Ginseng increases the life span of cells in culture and stimulates nerve growth factor. It has been shown to decrease platelet adhesiveness in animal models, and may have a variable effect on the International Normalized Ratio (INR) clotting time. Adverse reactions to ginseng are rare, but may include nervousness and excitation, diarrhea, skin eruptions, and hypoglycemia.14 Rare endocrinologic effects include mastalgia and post-menopausal bleeding. Ginseng can interact with antihypertensives, and Siberian ginseng has been shown to interfere with digoxin levels.15
Goldenseal (Hydrastis canadensis) - Goldenseal was used by the American Cherokee Indians who introduced it to the European settlers primarily as a topical antiseptic and systemically for curing infections. It has recently become popular again because of the widespread, but mistaken, belief that it can mask illicit drugs in urine toxicology screens. It is currently used as an antiseptic, and to treat digestive disorders (both diarrhea and constipation), fluid overload, acne, sore throat, and to ward off infections (especially when taken with echinacea and zinc). Its active substances are alkaloids (hydrastine, berberine, canadine, and berber-astine). One of its main bioactive components, berberine, is an effective antidiarrheal agent. One controlled study showed it to reduce stool volumes and duration of diarrhea in patients suffering from the effects of E. coli and V. cholera.16 Berberine is thought to act intraluminally and not systemically. It exerts antimicrobial activity against several species of bacteria, fungi, and protozoa. Additionally, it blocks adhesion of bacteria to epithelial cells, and protects intestinal cells from the effects of toxins. Berberine also stimulates uterine smooth muscle through an oxytocic effect and may induce abortions at high doses. Another active component, hydrastine, has been reported to lower blood pressure and stimulate peristalsis. It is also reported to be an antitussive (cough suppressant). Because goldenseal has several active ingredients, undesirable side effects may be present if it is taken in large doses. These side effects may include mucosal irritation, GI tract upset, uterine contractions, neonatal jaundice, hypertension, seizures, inotropic cardiac effects, and respiratory failure. Large doses may also oppose the anticoagulant effects of heparin and coumadin.17
Kava-kava (Piper methysticum) - This member of the pepper family has been described as a natural sedative or "an herbal alternative to Valium". It has become a popular anti-stress herb. In folklore it is known for its anti-convulsive and sedative effects. Kava has played an important role in many South Pacific societies. It is used in many of their most important rituals. Recently, a man from the island of Tonga was arrested in San Mateo, California, for driving while impaired after a six-hour kava ceremony at his church. He appeared to be "driving under the influence" and was weaving between lanes although he had not consumed any alcohol.18 Pyrones, the active agents in kava, seem to act as a muscle relaxant and produce sedation. Additional effects may include loss of coordination, sluggish motor reflexes, and, with heavy use, dilated pupils. Kavalactones (found in the root) have been shown to relieve anxiety and pain, as well as to relax muscles in laboratory animals. In humans, they have been shown to change brain activity (as measured by EEG) without producing sedation.19 Reported side effects include muscle spasms, and an increase in episodes and duration of impaired movements in a patient with Parkinson's disease.
St. John's Wort (Hypericum perforatum) - This yellow wildflower that grows wild throughout much of the world has been used for thousands of years for a variety of conditions. It is named for St. John the Baptist because it blooms around his feast day (June 24) and exudes a red color symbolic of his blood. It is used commonly as an antidepressant, but is being investigated for its anti-inflammatory, anti-infective, antiviral and antineoplastic effects. Several studies and meta-analyses have concluded that it is significantly more effective than placebo in treating mild to moderate depression.20 It is prescribed as an antidepressant by physicians in Germany up to four times more often than Prozac®(fluoxetine).8 The mechanism of St. John's wort's anti-depressant effects is only partially known. It was initially thought to be via an MAOI-like action. Some in vitro studies demonstrated MAO inhibition, but only at concentrations not found in vivo.21 The active ingredient is thought to be hypericin, which has a high affinity for gamma-aminobutyric acid (GABA). The stimulation of GABA receptors is known to have antidepressant effects. Other studies suggest that hypericin inhibits the re-uptake of serotonin and may possibly inhibit the reuptake of norepinephrine and dopamine as well. Altered receptor regulation is consistent with the several week lag between drug ingestion and clinical effects.
Photosensitivity is a side effect associated with St. John's wort, especially in fair-skinned individuals. It may exacerbate sunburn or sun sensitivity if used with other photosensitizing drugs. Other reported reactions include hypertension, headaches, nausea and vomiting, and stiff neck.
Saw Palmetto (Serenoa repens) - Extracts from the fruit of the saw palmetto have been used historically to treat urogenital problems. It is a first-line treatment in much of Europe to improve the signs and symptoms of benign prostatic hypertrophy.22 Saw palmetto extract works by inhibiting the 5a-reductase enzyme, which blocks the conversion of testosterone to dihydroxytestosterone, a major growth stimulator of the prostate gland. The extract also blocks the prostatic uptake of testosterone and dihydroxytestosterone without affecting serum testosterone levels. Saw palmetto has an anti-inflammatory effect that is thought to play a role in decreasing edema in the prostate.
Side effects from saw palmetto are rare, but may include gastrointestinal tract upset, headache, and possible interactions with other hormonal therapies.
Valerian (Valeriana officinalis) - Valerian has been used since the ninth century, A.D. as a calming and sleep-promoting agent. It acts as a sedative, antispasmodic, and diuretic, and is used today to treat a myriad of disorders including nervousness, anxiety, restlessness, headache, hysteria, tension, headaches, fever, digestive problems, urinary tract disorders, insomnia, depression, sleep disorders, pre-menstrual syndrome (PMS), hyperactivity and hypochondria. Called the "Valium of the nineteenth century", valerian is recognized world-wide for its relaxing effect on the body. German health officials have approved it for use as a mild sedative and sleep aid, based on several European clinical trials that demonstrate these effects. The major constituents of the volatile oil found in the valerian root include bornyl acetate, valerenic acid, and other sesquiterpenes. Some of these have been shown to have a direct action on the amygdaloid body of the brain. Valerenic acid has been shown to inhibit enzyme-induced breakdown of GABA in the brain, resulting in sedation.23 Recent studies have shown that the aqueous extract of the roots not only has effects on GABA(A) receptors, but can also interact at other presynaptic components of GABAergic neurons.24
Valerian has a synergistic effect with alcohol, which may exaggerate the side effects of each. A small percentage of consumers have experienced paradoxical stimulation, consisting of restlessness and palpitations.25
There is known variation between labeled and actual content of pharmacologically active components in many different herbal products. Several consumer reports have shown vast brand-to-brand variation. Variation in potency among different brands, as well as batches within a brand, is most likely related to natural variation in crop conditions and yield. The uncertainty as to how many species were used and how the herbs were gathered, which plant parts were used, and how they were prepared also lead to the unpredictability of the final product's active ingredient(s). Herbal preparations that contain different plant subspecies, allergens, pollen, molds, or other contaminants may have different pharmacological properties or strengths. In addition, there are some herbs that are edible when immature, but may be actually poisonous at maturity. Because of the lack of regulation in the gathering and manufacturing of herbal products, many manufacturing companies may not employ rigid quality control standards and do not evaluate their products for purity and quality.
Plant Misidentification or Adulteration
Many different types of contaminants such as heavy metals, e.g., lead, arsenic, and mercury, as well as pesticides, microbes, or microbial toxins have been found in various herbal preparations. Certain Chinese herbs have been found to contain as many as 41 different types of drug adulterants in up 32% of pills.26 Indian traditional medicines sometimes contain bhasmas (metal oxides intended for internal use), which are intentionally included in some products. In a report of a 5-year study assessing the toxicological problems associated with the use of traditional and herbal remedies in the United Kingdom, 12 cases of poisoning by lead, arsenic, and mercury were identified.27 Acute aconitine poisoning has been reported in the Chinese literature and is a known entity to practicing herbalists, although "Western" trained physicians may be less aware of the possibility.28 Aconitine, the poisonous alkaloid in the plant acotine, is cardiotoxic and can induce life-threatening arrhythmias.
Herb-drug interactions are an important consideration, especially regarding pharmaceutical products with narrow therapeutic indices. Several medicinal herbs and pharmaceutical drugs are therapeutic at one dose but toxic at another. Interactions between the herbs and the drugs may increase or decrease the pharmacological or toxicological effects of either component. Synergistic therapeutic effects may complicate the dosing of long-term medications. Because herbs are frequently marketed as multi-herb products, the potential of drug and herb interactions are exponentially increased in these products.
Several commonly used herbs have the potential for causing troublesome reactions in patients, especially those undergoing surgical procedures (Table 2). Patients may manifest certain signs and symptoms intraoperatively due to "unknown" causes unless it is realized that the patient is taking herbs.
Increased Bleeding Potential
Special care should be taken in patients who are using several of the popular herbal products currently available. Many of them, including feverfew, garlic, ginkgo, ginger, and ginseng may alter platelet function, and increase bleeding potential, especially in patients receiving concomitant anticoagulant or antithrombotic therapy. Modes of action of the platelet dysfunction include inhibition of platelet aggregation, decreased platelet adhesiveness, and inhibition of platelet activating factor. Patients taking coumadin, heparin, aspirin, or nonsteroidal anti-inflammatory drugs should be specifically educated as to possible side effects of increased bleeding.
Potentiation of Anesthetic Agents
Several herbal products act on the central nervous system and may potentiate the effects of anesthetic agents. Valerian, kava-kava, and St. John's wort may potentiate barbiturates and benzodiazepines and may cause a prolongation of anesthetic effects.
Induction of the Cytochrome P450 System - Decreased Drug Bioavailability
Extracts of St. John's wort contain naphtodiantrons, which induce the CY P3A isoenzyme of the cytochrome P450 complex. Additionally, the extract may induce intestinal P-glycoprotein drug transporter, which may further contribute to a decreased oral bioavailability of many drugs. Decreased plasma levels of drugs metabolized through the P450 system may adversely affect patients. Examples of drugs that may be affected include those used to treat heart disease (digoxin, diltiazem, nifedipine, digitoxin, and beta adrenergic blockers), depression (imipramine, amoxapine, and amitriptyline), seizures (carbamazepine, phenytoin, and phenobarbital), certain cancers (cyclophosphamide, tamoxifen, taxol, and etoposide) or to prevent transplant rejection (cyclosporine, rapamycin, or tacrolimus) or pregnancy prevention (ethinyl estradiol).29 Specific examples include the decreased bioavailability of digoxin by 25-30% after a 14-day administration of St. John's wort. Cases of decreased cyclosporine bioavailability have been reported in cardiac transplant patients taking St. John's wort, resulting in cellular transplant rejection.30 Similarly, plasma concentration of indinavir (a protease inhibitor used to treat HIV), decreased by more than 50% in patients taking St. John's wort.31 A Food and Drug Administration public health advisory was issued (February 10, 2000) to warn health care professionals about the dangers associated with decreased drug bioavailability associated with the concomitant administration of St. John's wort.
Ephedra has been implicated
in causing strokes, angina, arrhythmias, headaches, memory loss, panic attacks,
and death. Because of a number of reports of adverse events associated with the
ingestion of Ephedra, the Food and Drug Administration recently proposed limits
on dosage and duration of use,32 as well as
requested an independent review of those reports of adverse events related to
the use of Ephedra alkaloids to estimate the level of risk in using these herbal
products. That article by Haller and Benowitz, which appeared in The New England
Journal of Medicine in December of 2000, concluded that there might be a health
risk to some people with the use of Ephedra.33
The authors reviewed 140 reports of adverse events related to the use of dietary
supplements containing Ephedra alkaloids that were submitted to the FDA between
June 1, 1997 and March 31, 1999. They concluded that 31% of events were either
definitely or probably related to Ephedra use, and 31% were possibly related.33
Of those adverse events reported, almost half involved cardiovascular symptoms
and 18% involved the central nervous system. Hypertension was the single most
frequent adverse effect, followed by palpitation, tachycardia, stroke and
seizures. Ten events resulted in death and 13 events produced permanent
Earlier in 2000, in the published minutes from the Public Meeting on the Safety of Dietary Supplements Containing Ephedrine Alkaloids, American Herbal Products Association (AHPA) President, Michael McGuffin, summarized an Ephedra Survey undertaken by AHPA in early 2000. Their survey queried 42 manufactures and/or marketers whose products had been listed in the FDA's initial Adverse Event Report on June 4, 1997. Fourteen companies (33%) responded, and the survey's conclusions were based on those responses. In summary, the AHPA Ephedra Survey estimated total sales of products containing ephedrine alkaloids to have been greater than 3 billion servings in 1999. They found that almost all of the ephedrine products marketed by the Survey's respondents were in full conformity with the industry established standards. Finally, the Survey recorded that consumers of these products reported very few serious adverse events. AHPA's conclusions from the compiled data were that "supplement products containing ephedrine alkaloids are safe when responsibly manufactured, labeled and marketed and responsibly used by consumers."
Ginseng has been implicated in causing tachycardia and/or hypertension, especially when used concomitantly with other stimulants (such as caffeine). The Ginseng Abuse Syndrome has been described as occurring in people who took relatively large doses of the root (more than 3 gms/day). Symptoms included diarrhea, skin eruption, nervousness, sleeplessness and hypertension.34
Hepatotoxicity is a
potentially fatal side effect of certain herbal medications. Although the
causality is difficult to prove, risks of toxicity are associated with the use
of certain herbal products.35
The use of echinacea can potentially cause hepatotoxicity with chronic use and therefore should not be used with other known hepatotoxic drugs, such as anabolic steroids, amiodarone, methotrexate, and ketoconazole. However, echinacea lacks the 1,2 saturated necrine ring associated with hepatotoxicity of pyrrolizidine alkaloids.36 Several cases of acute hepatitis have been reported in patients taking herbal preparations containing valerian for stress,37 but no experimental data have been forthcoming to support the toxicity. A prospective study from Sweden showed that liver enzyme abnormalities were more frequent in patients who took herbal preparations, and that those abnormalities disappeared in patients who discontinued taking the herbs.38 Patients with known liver dysfunction or receiving known hepatotoxic drugs should be specifically warned about the use of herbals
Goldenseal root functions as an aquaretic, not a diuretic. Diuretics enhance the excretion of both sodium and water, while aquaretics only cause water excretion. Because it can cause excretion of free water, but not sodium, goldenseal may actually worsen edema and/or hypertension in patients taking this herb.
With the rapidly increasing usage of herbal products,
it is essential that the medical community recognize the fact that many patients
are taking potent "medicines" that were not prescribed by a physician, and that
these "medicines" may have serious consequences and side effects. Many questions
may be raised concerning the clinical implications of treating patients who are
taking various herbal remedies. The use of regional anesthetics, the appropriate
dose of heparin in patients undergoing cardiothoracic surgery, and the
adjustment of Dilantin doses are but a few of the questions that come to mind.
Until research has been done to address these and similar issues, there are no
specific guidelines to follow. To date, there is a paucity of anesthesia
literature addressing the use of herbs. An article in Anesthesiology appeared
recently describing which herbs were most commonly used and the patient profile
of those most likely to use herbal medications,39 but little else can be found
in "our" scientific literature. Both the American Society of Anesthesiologists
(ASA) and the New York State Society of Anesthesiologists (NYSSA) have addressed
some of the general problems associated with herbal medicines and anesthesia.
This information can be found on their web sites.40,41
ourselves (as well as our patients) about these alternative forms of treatment, and to realize the implications that these herbal remedies may have on our medical care of the patients. Extra care should be taken to obtain a complete "herbal history" when seeing the patient preoperatively (Table 3). Patients should be taught the need to discuss herbal usage with their health care providers, as well as the importance of discontinuing those herbs prior to a surgical procedure (Table 4). Encouragement of open communication and greater knowledge of alternative medical therapies by healthcare providers may help to prevent adverse reactions or complications in today's surgical patients
Eisenberg DM, Davis RB, Ettner SL, et al: Trends in alternative medicine use in the United States, 1990-1997: results of a follow-up national survey. JAMA 1998; 280:1569-75
Bauer B: Herbal therapy: what a clinician needs to know to counsel patients effectively. Mayo Clin Proc 2000; 75:835-41
Hobbs C: An Outline of the History of Herbalism: An overview and literature Resource List, Health World Online. http://healthy.net/asp/templates/article.asp?PageType= Article&ID=901
Ko RJ: Adulterants in Asian patent medicines. N Engl J Med 1998; 339:847
Physicians Desk Reference for Herbal Medicine. Montvale, NJ: Medical Economics Co. Inc., 2nd Edition, 2000.
Melchart D, Walther E, Linde K, Brandmaier R, Lersch C: Echinacea root extracts for the prevention of upper respiratory tract infections: A double-blind, placebo-controlled randomized trial. Arch Fam Med 1998; 17:541-5
Muller J, Clauson K: Pharmaceutical considerations of common herbal medicine. Am J Man Care 1997; 3:1753-70
O'Hara M, Keifer D, Farrell K, Kemper K: A review of 12 commonly used medicinal herbs. Arch Fam Med 1998; 17:523-36
Murphy J, Heptinstall S, Mitchell JR: Randomized double-blind, placebo-controlled trial of feverfew in migraine prevention. Lancet 1988; 2:189-92
Heptinstall S, White A, Williamson L, Mitchell JR: Extracts of feverfew inhibit granule secretion in blood platelets and polymorphonuclear leukocytes. Lancet 1985; 11:1071-4
Murphy M: Nutraceuticals: effect of alternative medicine on the perioperative patient. Lecture in Aspen Anesthesia, 2001, Snowmass, CO. February 2001
Oken B, Storzbach DM, Kaye JA: The efficacy of Ginkgo biloba on cognitive function in Alzheimer disease. Arch Neurol 1998; 55:1409-15
Le Bars PL, Katz MM, Berman N, Itil TM, Freedman AM, Schatzberg AF: A placebo-controlled, double-blind, randomized trial of an extract of Ginkgo biloba for dementia. North American EGb Study Group. JAMA 1997; 278:1327-32
Brumley C: Herbs and the perioperative patient. AORN J 2000;72:785-94
McRae S: Elevated serum digoxin levels in a patient taking digoxin and Siberian ginseng. Can Med Assoc J 1996; 155:293-5
Rabbani G, Butler T, Knight J, Sanyal SC, Alam K: Randomized controlled trial of berberine sulfate therapy for diarrhea due to enterotoxigenic Escherichia coli and Vibrio cholerae. J Infect Dis 1987; 155:979-84
Newall C., Anderson L, Phillipson JD: Herbal Medicines: A Guide for Healthcare Professionals. London, England, Pharmaceutical Press; 1996
Wilson M: Driver busted for Kava tea. San Francisco Chronicle. Saturday, April 29, 2000
Herbs for Health staff, Kava-Kava: A calming herb from the South Pacific, Health World Online http://www.healthy.net/asp/templates/article.asp?PageType=Article&ID=305
Linde K, Ramirez G, Mulrow CD, Pauls A, Weidenhammer W, Melchart D: St. John's wort for depression: an overview and meta-analysis of randomized clinical trials. BMJ 1996; 313:253-8
Suzuki O, Katsumata Y, Oya M, Bladt S, Wagner H: Inhibition of monoamine oxidase by hypericin. Planta Med 1984; 50:272-4
Buck AC: Phytotherapy for the prostate. Br J Urol 1996; 78:325-36
Houghton PJ: The scientific basis for the reputed activity of Valerian. J Pharm Pharmacol 1999; 51:505-12
Ortiz JG, Nieves-Natal J, Chavez P: Effects of Valeriana officinalis extracts on [3H]flunitrazepam binding, synaptosomal [3H]GABA uptake, and hippocampal [3H]GABA release. Neurochem Res 1999; 24:1373-8
Hobbs C: Valerian: a literature review. Herbal-Gram 1989; 21:19-34
Chen YF, Chern HM, Chou MH: Identification of the adulteration in Chinese herbal preparations with chemical drugs and their toxicities. Ann Emerg Med 1995; 26:717
Shaw D, Leon C, Kolev S, Murray V: Traditional remedies and food supplements: a 5-year toxicological study (1991-1995). Drug Safety 1997; 17:342-56
Chan TYK: Monitoring the safety of herbal medicines. Drug Safety 1997; 17:209-15
Henney J: Risk of drug interactions with St John's wort. JAMA 2001; 283:1679
Ruschitzka F, Meier PJ, Turina M, Luscher TF, Noll G: Acute heart transplant rejection due to Saint John's wort. Lancet 2000; 355:548-9
Piscitelli SC, Burstein AH, Chaitt D, Alfaro RM, Falloon J: Indinavir concentrations and St John's wort. Lancet 2000; 355:547-8
"Ephedrine Alkaloids Proposal": Federal Register (62 FR 30678); June 4, 1997
Haller CA, Benowitz NL: Adverse cardiovascular and central nervous system events associated with dietary supplements containing ephedra alkaloids. N Engl J Med 2000; 343:1833-8
Siegel RK: Ginseng abuse syndrome. Problems with the panacea. JAMA 1979; 241:1614-5
Larrey D: Hepatotoxicity of herbal remedies. J Hepatol 1997; 26(suppl 1):47-51
Miller LG: Herbal medicinals: selected clinical considerations focusing on known or potential drug-herb interactions. Arch Intern Med 1998; 158:2200-11
MacGregor FB, Abernethy VE, Dahabra S, Cobden I, Hayes PC: Hepatotoxicity of herbal remedies. BMJ 1989; 299:1156-7
Carlsson C: Herbs and hepatitis. Lancet 1990; 336:1068
Tsen LC, Segal S, Pothier M, Bader A: Alternative medicine use in presurgical patients. Anesthesiology 2000; 93:148-51
Summary of Herbs and Their Potential Problems