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Some Supplement and Drug Interactions Anticoagulant/Antiplatelet Drugs: Licorice May Potentiate Activity and Lead to Complications of Bleeding

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Some Supplement and Drug Interactions Anticoagulant/Antiplatelet Drugs: Licorice May Potentiate Activity and Lead to Complications of Bleeding inhibitors like Prilosec, used to enhance antibiotic absorption and macrolide antibiotics, azithromycin (Zithromax), clarithromycin cellular penetration, decrease formation of stomach acid, permitting (Biaxin) and telithromycin (Ketek) and antifungals like fluconazole overgrowth of bacteria and/or yeast in the stomach and upper (Diflucan), ketoconazole (Nizoral) and itraconazole (Sporanox) are gastrointestinal tract. This is also true for other agents that lower inhibitors of specific CYP enzymes, which can increase the blood stomach acid, such as Zantac and Pepcid. Microbial overgrowth level of drugs. Prilosec is also a CYP inhibitor. may be associated with gastrointestinal symptoms like diarrhea and bloating3 and may cause malabsorption of nutrients. Prolonged use Some interactions demonstrated in clinical studies cannot be of stomach acid lowering agents has been associated with decreased anticipated from laboratory experiments. The herb Echinacea, used absorption of vitamin B12, zinc, and carotene, and may create a need for immune stimulation, has different effects on CYP enzymes in for supplementation4. different parts of the body, so it may increase or decrease the levels of a co-administered drug, depending upon the extent to which it Drugs, supplements and food may affect drug metabolism. The is metabolized by CYP. Unexpected results also occur with milk cytochrome P450 (CYP) system is extensively involved in drug thistle, an herb used to support liver function that contains a metabolism and may be strongly inhibited or stimulated by drugs, group of bioflavonoids called silymarin. Although silymarin may foods or dietary supplements. CYP enzymes are most active in the inhibit liver CYP (which should increase drug levels), concomitant liver, intestines, lungs and kidneys. Humans have over 20 different administration of milk thistle significantly decreased the blood levels CYP enzymes, all of which use oxygen to change the structure and of metronidazole (a drug used to treat the cyst form of Borrelia).5 function of the drugs they metabolize. CYP oxidation of drugs This interaction could not have been predicted from knowledge of may produce metabolites that are less active or more active than the herb’s effects on drug-metabolizing enzymes. Moreover, vitamin the parent compound. The exact effect of inhibiting or stimulating C (500 mg/day) and vitamin E (400 units/day) decreased the any CYP enzyme will therefore depend upon the specific clinical effectiveness of metronidazole in treating H. pylori infection of the circumstances and cannot necessarily be predicted from experiments stomach.6 The mechanism of this interaction is unknown but suggests done in a test tube. that antioxidants should not be used with metronidazole therapy. Inhibition of intestinal CYP by grapefruit juice or other natural substances can increase absorption of drugs that are broken down by CYP, raising their concentration in blood. St. John’s wort is one of the few products that stimulate intestinal CYP. Taking St. John’s wort can decrease the plasma concentration of those same drugs and underlies many of the adverse drug interactions (particularly blood thinners and birth control drugs) reported for this herb. Rifampin (an antibiotic sometimes used to treat Bartonella) and artemisin (a derivative of the herb Artemisia annua, a natural anti- malarial herb that may be used in the treatment of Babesiosis) may also stimulate some CYP enzymes, which decrease the blood levels of some drugs. If given long term, some physicians suggest three weeks on and one week off , so that the CYP enzymes are not over stimulated, leading to decreased blood levels of the drug. In contrast, Some Supplement and Drug Interactions Anticoagulant/Antiplatelet Drugs: Licorice may potentiate activity and lead to complications of bleeding. Licorice MAO-inhibitors (MAO-I): Licorice may potentiate activity of MAO-I. Cytochrome P450: Preliminary evidence indicates that ginkgo can affect the cytochrome enzymes 1A2, 2D6, and Gingko 3A4, however controversial data exists regarding whether it induces or inhibits the individual enzymes. Anticoagulant / Antiplatelets: Reishi may increase the risk of bleeding. Reishi Antihypertensives: Reishi may further lower blood pressure. Oral contraceptives: May decrease effectiveness by lowering levels to sub-therapeutic. St. John’s Anti-coagulants: May lower the effectiveness by increasing metabolism. Wort There are no data on grapefruit seed extract, although some physicians believe that it interferes with antibiotics. Grapefruit We do know that it takes lots of grapefruit juice to produce clinically significant drug interaction effects (a quart Seed Extract of double strength juice a day is used in many studies). The active ingredient is probably a substance called bergamotin, but we don’t know if that is in the seed extract. Fall 2008 41.
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