Herb-Drug Interaction Introduction

• Herbal drugs are defined as any form of a plant or plant product that contains a single herb or combinations of herbs that are believed to have complementary effects.

• Although they are considered to be safe, because they are natural, they may have various adverse effects, and may interact with other herbal products or conventional drugs. These interactions are especially important for drugs with narrow therapeutic indices. • Because herbs are sold as food supplements, companies are not required to prove their efficacy. • Side effects or interactions are also not required to be determined or disclosed. • No government agency reviews these products for safety, dosage, or quality. • However, 2621 adverse events associated with dietary supplements, including 101 deaths, were reported to the FDA over a 5-year period. • Multiple ingredients are present in the same bottle. • Products are sometimes mislabeled or misidentified • Potency can vary depending on the climate and soil in which the herbs are grown. Drug-Herb Interactions

• Pharmacokinetic interactions : Having to do with absorption, distribution, and metabolism. • Pharmacodynamic interactions: Additive activity meaning that certain herbs increase the actions of certain medications. Pharmacokinetic Interactions: Absorption

• Some herbs have hydrocollated carbohydrate components such as gums and mucliage. • These are soluble in water but poorly absorbable. • Examples are psyllium, , flaxseed, and marshmallow. • Bind to other drugs, particularly when consumed in their whole or powdered forms. • Psyllium inhibits the absorption of lithium. • Rhubarb and can cause which reduces the actions of drugs that have a narrow therapeutic index (digoxin, warfarin) Pharmacokinetic Interactions: Distribution

• Meadowsweet and black willow contain pain reducing salicylates. • These may displace highly protein bound drugs such as warfarin and carbamezepine (Tegretol). • This increases the adverse effects of these drugs. • Do not take these products concurrently Pharmacokinetic Interactions: Metabolism

• When taken as an herb, licorice decreases the metabolism of corticosteroids. • This leads to adverse and toxic effects from the buildup of corticosteroids. • St. John’s wort increases the metabolism of drugs in the liver. Pharmacodynamic Interactions

• Additive activity • The hypnotic activity of benezodiazepines is increased by valerian. • Anticoagulant action of warfarin is enhanced by ginko • Used by elderly persons because of its ability to improve cognitive function in persons with Alzheimer’s and dementia. • Reports of bleeding associated with ginkgo use have been reported. Ginkgo

• Patients ranged from 33 to 78 years old • One person was taking no other drugs concurrently. • Others were taking aspirin, warfarin, acetaminophen, or an ergotamine-caffeine preparation concurrently. • Episodes were both minor and major • One death from cerebral hemorrhage. • Caution patients who are also taking Vitamin E, warfarin, aspirin, and low molecular weight heparin about the potential interactions with ginkgo. Flaxseed (Linum usitatissimum)

• Flax is one of the oldest cultivated plants in the world. • A bulk-producing, stool softening agent that lowers levels of , triglycerides, and low-density lipoproteins. • Binds to bile acids in the intestinal tract and interferes with the reabsorption of fats. • When soaked, flaxseeds can bind with other drugs, especially cardiac glycosides rendering them unabsorable. • Take flaxseed wither two hours before or two hours after taking other meds. • Concurrent use with and stool softeners should be avoided because of possible potentiation of the effect. Ginger (Zingiber officinale)

• Used and tested as an antinausea and antispasmodic agent with good results. • Potent inhibitor of thromboxane synthetase. • Prolongs bleeding times. • If taking warfarin or other drugs that affect platelet activity, avoid ginger in tablet form. Kava Kava (Piper methysticum)

• Relieves anxiety, nervousness, and tension. • Does not affect alertness. • Acts as a dopamine antagonist. • May increase tremor and decrease response to anti-Parkinsonian meds. • Potentiates alcohol • Potentiates tranquilizers • Potentiates antidepressants • Do not take any of these concurrently with Kava St. John’s Wort (Hypericum perforatum)

• One of the most popular herbs in the US for the treatment of depression. • Current research shows that it acts as a selective serotonin reuptake inhibitor (SSRI) • Because of this, concurrent use with SSRIs is prohibited. • Patients should wait 2 weeks after taking an SSRI before beginning St. John’s wort. Implications For Anesthesia and Moderate Sedation • Morbidity secondary to botanical product use may be more prevalent in the perioperative period because of multiple drug use and increased physiological susceptibility to adverse effects. • The problem is complicated by patients’ reluctance to report their use of herbal medicines or dietary supplements. • 70% of presurgical patients failed to disclose their use of such products during routine preoperative assessment. Reasons For Not Reporting Use of Herbal Medications 1. A belief that because such products are “natural,” they must be safe. 2. Fear of how healthcare providers would respond to self-medication. 3. Fear that their physician may be prejudiced against use of botanicals. Adverse Effects 1. Cardiac Instability 2. Electrolyte disturbances 3. Prolonged bleeding 4. Excessive sedation Ephedra Alkaloids

• Also known as ma-huang • Common ain many herbal and energy boosters • Often packaged in combination with guarana (caffeine) • Use has been linked to hypertension, palpitations, tachycardia, seizures, stroke, heart attack, and sudden death. • Ephedra has been identified as the herbal product with the greatest potential for harm in perioperative patients. Prolonged Bleeding

• Feverfew, Ginger, Gingko, Horse chestnut, Danshen, Garlic • Gingko has been linked to a spontaneous hyphema in a 70 year old man who took 40mg of Gingko extract twice a day along with 325 mg of Aspirin daily for one week. • Also bilateral subdural hematomas in a 33 year old woman who took 60 mg of Gingko twice a day for two years. Prolonged Bleeding

Certain herbs increase INR 1. Danshen 2. Dong quai (Used primarily in China but gaining popularity in the US) Certain herbs contain coumarin or coumarin derviatives 1. Angelica root 2. Anise 3. Licorice 4. Red clover 5. Rue Ruta graveolens ; promote the onset of menstruation and of uterine contractions Prolonged Bleeding

Antiplatelet activity 1. Tumeric (Curcuma longa) 2. Clove 3. Onion 4. Bromelain extract derived from the stems of pineapples 5. Willow bark 6. Meadowsweet