HERBAL SUPPLEMENT & MARIJUANA USE PRE- & POST-TRANSPLANT Mariesa Cote, PharmD Clinical Pharmacist – Solid Organ Transplant Massachusetts General Hospital October 4 th , 2018
STATEMENT OF DISCLOSURE I have no conflicts of interest
OBJECTIVES Identify the risks associated with herbal supplement use pre-transplant Identify major drug interactions with herbal supplements Explain the risks of marijuana use post-transplant
ALTERNATIVE MEDICINE Form of medical therapy used as a substitute for conventional medicine Naturopathic medicine Homeopathic medicine Chinese medicine Aromatherapy Massage therapy Use of a special diet or herbal remedy to cure or alleviate the symptoms of a condition Kaye, et al. Anesthesiology Clin Am. 2004
HISTORY OF HERBAL THERAPY Ancient middle-eastern civilizations used herbal therapy extensively Herbal gardens were created to grow medicinal plants for medical schools Early colonial days relied on herbal therapy to provide medical care in the home Herbal therapy re-emerged in the U.S. in the 1960s The Office of Alternative Medicines by the National Institutes of Health was established in 1992 Kaye, et al. Anesthesiology Clin Am. 2004
REGULATIONS Dietary Supplement Health and Education Act (DSHEA) of 1994 Defines dietary supplements as “a product to supplement the diet” Considered food, not drugs No requirements for safety & efficacy testing Food and Drug Administration (FDA) Included in the “supplement” category, not classified as a drug Manufacturers exempt from approval by FDA No protocol for standardization of these herbal supplements Lack of standard regulations and good manufacturing practice (GMP) leads to products available of variable quality and content Kaye, et al. Anesthesiology Clin Am. 2004 Gabardi S, et al. Clin J Am Soc Nephrol. 2007. Ang-Lee MK, et al. JAMA. 2001.
DIETARY SUPPLEMENTS Vitamins Minerals Herbs Amino Organ Enzymes acids tissues Metabolites Kaye, et al. Anesthesiology Clin Am. 2004
FORMULATIONS Extracts Concentrates Tablets Capsules Gelcaps Liquids Powders Oils Kaye, et al. Anesthesiology Clin Am. 2004
HERBAL THERAPY & DIETARY SUPPLEMENTS There are >20,000 nutraceuticals available in the United States Approximately 36% of the population use nutraceuticals in conjunction with prescription drugs Majority of patients report utilizing these products to “cure” chronic conditions Misconception that these products are “natural” so they must be safe Only 12% of supplement users seek care from a physician or licensed complementary and alternative medicine provider Kaye, et al. Anesthesiology Clin Am. 2004 Gabardi S, et al. Clin J Am Soc Nephrol. 2007.
HERBAL THERAPY & DIETARY SUPPLEMENTS 70% of patients failed to disclose their herbal supplement use Rationale: Thoughts that physicians are not knowledgeable about herbal supplements Patient’s fear admitting to providers their use of non-standard therapy Thoughts that herbal supplement use is unrelated to their medical care Herbal supplements not considered medications that require reporting Providers should seek out a history of herbal supplement use! Ang-Lee MK, et al. JAMA. 2001
TOP 10 BEST SELLING HERBAL PRODUCTS Cranberry Saw palmetto Soy Garlic Gingko Echinacea Milk Thistle Black cohosh St. John's Wort Ginseng https://www.takingcharge.csh.umn.edu/explore-healing-practices/botanical-medicine/10-top-best-selling-botanicals-what-they-do
PERI-OPERATIVE USE
SURGICAL CONCERNS Applicable to both organ donors and recipients Decreased platelet aggregation or inhibition of clotting Bleeding Central nervous system (CNS) depression Potentiation of anesthesia American Society of Anesthesiologists recommends that patients discontinue use of herbal supplements 2-3 weeks before surgery Kaye, et al. Anesthesiology Clin Am. 2004
BLEEDING RISK Herbal Indication Perioperative Recommendation considerations ↑ bleeding risk through Garlic (Allium Vasodilatory effect D/C 7 days prior to surgery ↓cholesterol platelet dysfunction & ↑ sativum) fibrinolytic activity Ginger N/V, motion Potent inhibitor of D/C 14 days prior to surgery thromboxane; ↑ (Zingiber sickness, vertigo offcinale) bleeding risk Avoid w/ use of antiplatelets, anticoagulants & NSAIDs Gingko biloba Antioxidant, Inhibits platelet D/C 2 days prior to surgery activating factor; ↑ circulatory stimulant, dementia bleeding risk; gingko Avoid w/ use of antiplatelets, toxin anticoagulants & NSAIDs Avoid with anticonvulsants Kaye, et al. Anesthesiology Clin Am. 2004 Wong A, et al. Continuing Education in Anaesthesia, Critical Care & Pain. 2011
BLEEDING RISK Herbal Indication Perioperative Recommendation considerations Ginseng Mood enhancer, Irreversible platelet D/C 7 days prior to surgery inhibition Immunomodulation, ↑bleeding Hypoglycemic activity Avoid w/ use of antiplatelets, anticoagulants & NSAIDs ↓blood glucose ↑blood pressure Turmeric Anti-infective, Antiplatelet effects D/C 14 days prior to surgery analgesic, anti- inflammatory and anti- oxidant effects Kaye, et al. Anesthesiology Clin Am. 2004 Wong A, et al. Continuing Education in Anaesthesia, Critical Care & Pain. 2011 Natural Medicines Database
DRUG-DRUG INTERACTIONS Herbal Indication Perioperative Recommendation considerations St. John’s Antidepressant Inducer of CYP3A4 & D/C 5 days prior to surgery Wort 2C9 (Hypericum Drug interactions! perforatum) Sedative effects Echinacea Immunostimulatory Potential for D/C 14 days prior to properties anaphylaxis surgery Inhibits CYP3A4 Drug interactions! Kaye, et al. Anesthesiology Clin Am. 2004 Wong A, et al. Continuing Education in Anaesthesia, Critical Care & Pain. 2011
SEDATIVE EFFECTS Herbal Indication Perioperative Recommendation Complications Kava kava Anxiolytic/sedative Potentiation of the D/C 24 hours prior to (Piper effects of surgery methysticum) anesthesia/sedatives Valerian Anxiolytic/sedative Potentiation of the D/C 2 weeks prior to effects of surgery anesthesia/sedatives Melatonin Sedative Potentiation of the No general consensus effects of for when to D/C - anesthesia/sedatives recommend D/C 7-14 days prior to surgery Kaye, et al. Anesthesiology Clin Am. 2004 Wong A, et al. Continuing Education in Anaesthesia, Critical Care & Pain. 2011 Natural Medicines Database
RECOMMENDATION Providers should seek out a history of herbal supplement use Patients utilizing herbal supplements can be referred to pharmacy for consult All herbal supplements should be held at least 2 weeks prior to surgery
POST-TRANSPLANT USE
POST-TRANSPLANT CONSIDERATIONS Modulation of the immune system through “boosting” of the immune system Drug-drug interactions through alterations in cytochrome P450 metabolism and P-glycoprotein (P-gp) transporter function Direct toxic effects on the transplanted organ
IMMUNOMODULATION Herbal Indication Post-Transplant Concerns Recommendation Ginseng Mood enhancer, Stimulates the immune function by AVOID Immunomodulation, increasing T cell proliferation that may Hypoglycemic activity interfere with immunosuppressive therapy. Echinacea Immunostimulatory Stimulates immune function through AVOID properties activation of complement pathway increasing activity of T cells potentially interfering immunosuppressive therapy Melatonin Sedative Stimulates immune function through AVOID secretion of cytokines potentially interfering immunosuppressive therapy Case reports of autoimmune hepatitis Kaye, et al. Anesthesiology Clin Am. 2004 Wong A, et al. Continuing Education in Anaesthesia, Critical Care & Pain. 2011 Natural Medicines Database Kang S, et al. J Ginseng Res. 2012. Carrillo-Vico A, et alInternational Journal of Molecular Sciences. 2013.
DRUG-DRUG INTERACTIONS Herbal Indication Post-Transplant Recommendation Concerns St. John’s Wort Antidepressant Inducer of CYP3A4 & AVOID (Hypericum 2C9 Drug interactions! perforatum) ↓immunosuppression levels Sedative effects rejection Echinacea Immunostimulatory Inhibits CYP3A4 AVOID properties Drug interactions! ↑immunosuppression levels toxicity Turmeric Anti-infective, analgesic, Inhibits CYP3A4 AVOID anti-inflammatory and ↑immunosuppression levels toxicity anti-oxidant effects Kaye, et al. Anesthesiology Clin Am. 2004 Wong A, et al. Continuing Education in Anaesthesia, Critical Care & Pain. 2011 Natural Medicines Database
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