Are Your Patients Taking Herbal Meds?
Alternative medicine has achieved widespread popularity in the United States in recent years. One survey of trends in alternative medicine use found that people in the U.S. visit alternative medicine practitioners more frequently than primary care physicians.1 Another recent survey of alternative medicine use in 3,106 pre-surgical patients found that 22 percent of patients were taking herbal remedies and 51 percent were taking vitamins.2 The greatest use of these therapies occurred among women between the ages of 40 and 60. The most common herbs used were echinacea, gingko biloba, St. John’s wort, garlic and ginseng.2 Through the wealth of information available on the Internet and via the media, consumers often choose to take herbs, vitamins and other supplements prior to consulting with their primary care provider. Since these products are marketed as “natural,” consumers are led to believe that dietary supplements are safe and free of side effects and/or potential complications. However, unlike prescription medications, dietary supplements and herbs are not regulated by the Food and Drug Administration (FDA). As a result, these products are not required to go through the FDA approval process or comply with quality assurance measures. Therefore, product consistency is often unreliable. For example, an analysis of ginseng products found that the amount of active ingredient varied 10-fold between brands, with some brands containing no active ingredient at all.3 Undocumented use of dietary supplements can cause a number of problems, especially in the perioperative period. Potential problems of herbs include toxicity due to overdose, contamination, quality control, physiological changes on bodily systems and adverse drug reactions.4 In addition, the use of herbs can potentially cause coagulation disorders, cardiovascular side effects, water and electrolyte disturbances, endocrine effects, hepatotoxicity and/or prolongation of the effects of anesthesia. Given these potential side effects, it is imperative to question patients specifically about herbs and supplements prior to performing any surgical procedure. To complicate the situation, rigorous studies have yet to be conducted on the effects and potential drug interactions of most of the herbs and dietary supplements used by patients today.4 Much of the information currently known about problems associated with herb and/or dietary supplement use comes from case reports. In such cases, dosages and other concomitant drug use are not often mentioned. The paucity of experimental data on the side effects and potential drug interactions of dietary supplements warrant caution whenever they are used in the perioperative period. As a result, the American Society of Anesthesiology recommends that physicians specifically ask about preoperative herb and supplement use, and that patients stop taking herbal preparations two weeks prior to any procedure.5 With this in mind, we will take a closer look at the potential physiologic effects and drug interactions of some of the most commonly used herbs and dietary supplements, specifically gingko biloba, garlic, St. John’s wort, ginseng and echinacea. A Closer Look At Gingko Biloba Gingko biloba is an extract from the leaves of the gingko tree, the world’s oldest living tree. It is recommended primarily for dementia and intermittent claudication, but is often used to treat depression, erectile dysfunction of vascular origin, macular degeneration and vertigo as well.6 Glycosides and terpene lactones are two active ingredients in gingko. The glycosides are responsible for the antioxidant activity of gingko as well as inhibition of platelet aggregation. The terpene lactones increase circulation to the brain and other parts of the body, and may exert a protective effect on nerve cells.6 The usual dose of gingko is 120 to 240 mg QD. Side effects include mild headache, stomach upset and prolonged bleeding time.6 In addition, some serious bleeding problems have occurred secondary to the use of gingko. One 61-year-old man taking 120 mg of gingko QD for six months developed prolonged bleeding with a subsequent subarachnoid hemorrhage.7 After the patient discontinued the gingko, his bleeding time returned to normal. A 72-year-old woman taking 150 mg of gingko QD for six months developed a left frontal subdural hematoma.8 In addition, a 70-year-old man taking 40 mg tablets of concentrated gingko developed spontaneous hyphema.9 Given the fact that gingko has been reported to increase bleeding time and has been associated with serious bleeding problems, caution is advised for patients taking gingko concurrently with any anticoagulant medications. In addition to its anticoagulant effects, gingko reportedly interacts with thiazide diuretics and trazadone (see the above chart “Common Herbs: A Guide To Possible Side Effects And Drug Interactions”). A patient taking a thiazide diuretic and gingko concurrently developed dangerously high blood pressure.10 In addition, an elderly woman taking gingko and trazadone spontaneously went into a coma.11 When it comes to assessing patients, who are taking gingko, for surgery, one should take appropriate precautions for any patients with a past history of bleeding problems, those taking anticoagulants or anyone taking trazadone or thiazide diuretics. If you are considering surgery for patients with a past history of bleeding problems or those taking anticoagulants, you should measure their bleeding time preoperatively as gingko affects platelet function rather than the clotting cascade. If any doubt exists, have the patient stop taking the gingko two weeks prior to the procedure and consult an anesthesiologist. What About The Potential Effects Of Garlic? Garlic reportedly inhibits platelet aggregation, increases fibrinolysis and exhibits antioxidant activity.6 As a result, garlic has been recommended for atherosclerosis, hypertension, hypercholesterolemia, intermittent claudication and decreasing the risk of colon cancer.6 The usual dose of garlic is one to two raw cloves QD or 600-900 mg QD of odor-controlled enteric-coated tablets. Side effects include heartburn, flatulence and increased bleeding time.6 Potential drug interactions include decreased absorption of the muscle relaxant chlorzoxazone and potentiation of anticoagulants.12 Several practitioners have noted an increase in prothrombin times and International Normalized Ratios (INRs) in patients on warfarin after they started taking garlic.13 Garlic was also reported as the cause of dysfunctional platelets in an 87-year-old man, who suffered a spontaneous spinal epidural hematoma.14 Furthermore, a randomized, placebo-controlled study of healthy men found that administration of aged garlic extract had an anti-platelet effect.15 When considering surgery for patients who take garlic, you should exercise caution with patients who have a past history of bleeding problems, those taking anticoagulants or anyone taking chlorzoxazone. Be sure to measure their bleeding time in addition to PT and PTT preoperatively. If you have any doubts, advise the patient to stop taking garlic two weeks prior to the procedure and consult an anesthesiologist. What You Should Know About St. John’s Wort St. John’s Wort, also known as Klamath weed, has been recommended primarily for depression, seasonal affective disorder and anxiety.6 Researchers have proposed that inhibition of serotonin, norephinephrine and dopamine reuptake may cause the antidepressant effects that one sees with the use of St. John’s Wort.6 The recommended dose of St. John’s Wort is 500 to 1,500 mg QD. Side effects include stomach upset, fatigue, itching, sleep disturbance, rash and increased susceptibility to sunlight.6 A woman taking 500 mg QD St. John’s Wort for four weeks reportedly developed neuropathy after going out in the sun.16 Also be aware that St. John’s Wort may trigger a manic episode and should therefore be avoided in bipolar or hypomanic patients.17 Reported drug interactions include decreased therapeutic efficacy of cyclosporine, digoxin, indinavir, theophylline, oral contraceptives and warfarin.6 Since St. John’s Wort inhibits monoamine oxidase (MAO) and the reuptake of serotonin and norepinephrine, it can potentially prolong the effects of anesthetics and/or cause cardiovascular side effects.4 In addition, St. John’s Wort has the potential to increase side effects of selective serotonin reuptake inhibitors (SSRIs), causing serotonin syndrome. As a result, caution is advised with foods containing tyramine and/or concomitant use of SSRIs or MAOIs.4 If any doubt exists when assessing these patients for surgery, you should advise the patient to cease taking St. John’s Wort two weeks prior to the procedure and consult an anesthesiologist. Why You Should Be Cautious When Treating Patients Who Take Ginseng Ginseng is an extract made from the root of the ginseng plant. American ginseng, Asian ginseng and Siberian ginseng are three common types of ginseng. This herb has been recommended for glucose control, epilepsy, erectile dysfunction, male infertility and increasing immune response and athletic performance.6 The recommended dose of ginseng is 1 to 4 grams QD for non-standardized extracts and 200 to 500 mg QD for standardized extracts. Side effects include insomnia, menstrual problems and an increased bleeding risk.6 In addition, patients taking the antidepressant phenelzine with ginseng have reportedly developed headache and tremor as well as manic episodes.18 In laboratory animals, ginseng has been found to decrease platelet adhesiveness and antagonize platelet-activating factor, but no cases of adverse bleeding with ginseng have been documented at this time.4,19,20 On the contrary, ginseng decreased the INR of a 47-year-old man with a prosthetic heart valve who was taking warfarin.21 After two weeks of ginseng therapy, the patient’s INR decreased from 3.1 to 1.5. After he discontinued the herb, his INR returned to 3.3. Until further data are collected about the effect of ginseng on platelet function and the clotting cascade, patients should not take ginseng concurrently with any anticoagulants. When considering surgery for patients who are taking ginseng, one must exercise caution with those who have a past history of bleeding problems or those who are taking anticoagulants. One should check the given patient’s bleeding time in addition to PT and PTT as ginseng potentially affects platelet function as well as the clotting cascade. Also be cautious when patients are taking ginseng concurrently with phenelzine. If any doubt exists, you should encourage the patient to stop taking ginseng two weeks prior to the procedure and consult an anesthesiologist. Insights On Echinacea Echinacea is an extract from the purple coneflower. It purportedly activates white blood cells and increases the production of interferon. As a result, researchers have recommended it primarily for treating symptoms of the common cold/sore throat but it has also been used to increase immune function and treat gingivitis.6 The recommended dose of echinacea is 3 to 4 mL or 300 mg every two hours at the onset of flu symptoms and then TID for seven to 10 days.6 Echinacea should be avoided by patients with autoimmune conditions such as lupus, MS or HIV. One should also exercise caution in regard to echinacea for those who allergic to flowers in the daisy family or inulin (an ingredient in echinacea). In addition, long-term use (greater than eight weeks) of echinacea has been associated with hepatotoxicity.6 As such, concomitant use of echinacea and other hepatotoxic drugs (ketoconazole, methotrexate, amiodarone, anabolic steroids) should be avoided.13 No precautions for echinacea exist in regard to bleeding problems and/or prolonged anesthesia. Herbs And Supplements: Potential Anticoagulant Effects Potential prothrombopenic components Baikal skullcap root, sweet clover, tonka bean seeds, Woodruff plant Platelet aggregation inhibitors Bilberry, black currant seed oil, borage seed oil, bromelian, cayenne fruit, clove oil, Dan Shen, devil’s claw, evening primrose seed oil, feverfew, garlic, ginger, gingko, ginseng, horse chestnut seed extract, kava kava, papain, turmeric root, vitamin E Fibrin formation inhibitors Bladderwrack, bromelian, cayenne fruit, garlic, ginseng (Adapted from Norred and Brinker, 2001) Final Thoughts Numerous herbs and supplements have the potential to affect coagulation parameters (see “Herbs And Supplements: Potential Anticoagulant Effects” above). The mechanisms by which these supplements affect coagulation include coumadin-like activity, the inhibition of platelet aggregation and/or the inhibition of fibrin formation.22 Over 1,300 plants contain coumarin, the precursor to dicoumarol, the active ingredient in coumadin. In fact, coumadin was first discovered when a herd of livestock eating moldy sweet clover died from spontaneous hemorrhage. Upon investigation, it was discovered that the mold converted the coumarin in the sweet clover to dicoumarol, which, in turn, precipitated spontaneous bleeding in the animals.22 Although a large number of herbs contain coumarin, very few of these herbs are converted into derivatives with anticoagulant properties when they are ingested by humans.22 Most of the anticoagulant effects caused by herbs are from inhibition of platelet aggregation via altered prostaglandin production or decreased production of platelet-activating factors.22 As we mentioned previously, since many of these herbs affect platelet function rather than the clotting cascade, one should pursue preoperative coagulation panels including bleeding time as well as PT, PTT and INR. There is no question that herb and supplement use is on the rise, often with patients self-prescribing. Given the numerous side effects and potential drug interactions, it is important to ask patients specifically about herb and supplement use, and to assess any potential complications prior to performing any surgical procedure. Dr. Green is the Director of Podiatric Surgical Residency at the Scripps Mercy Medical Center in San Diego. He is a Fellow of the American College of Foot and Ankle Surgeons and has a private practice in San Diego. Dr. Halat is a first-year resident within the San Francisco Bay Area Foot And Ankle Residency Program of Kaiser Permanente in Oakland, Calif.
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