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Copyright 2015 by Current Reviews®. Reproduction in whole or in part prohibited except by written permission. All rights reserved. Information has been obtained from sources believed to be reliable, but it’s accuracy and completeness, and that of the opinions based therein are not guaranteed. Printed in U.S.A. Current Reviews® is published biweekly by Current Reviews®, 1828 S.E. First Avenue, Ft. Lauderdale, FL 33316. POSTMASTER: Send address changes to Current Reviews®, 1828 S.E. First Avenue, Ft. Lauderdale, FL 33316 or email [email protected]. Perioperative Implications of Medications

Jeffrey B. Dobyns, DO Assistant Professor of Anesthesiology and Perioperative Medicine University of Alabama at Birmingham School of Medicine Birmingham, Alabama

LESSON OBJECTIVES 5. Compare and contrast the effect of herbal Upon completion of this lesson, the reader medications on commonly used pharma- should be able to: ceuticals. 1. Explain the role of the Food and Drug 6. Discuss the perioperative implications of Administration in the regulation of her- commonly used . bal medications. 7. Describe the anesthesia-specific impli- 2. Discuss the ASA recommendations for ctions of commonly used herbals. perioperative use of herbal medications. 8. Integrate herbal medications into medi- 3. Differentiate direct and indirect health cation reconciliation. effects associated with herbal remedies. 9. Identify common perioperative problems 4. List common reasons why patients are stemming from herbal medication use. reluctant to disclose herbal medication 10. Explain the importance of quality medi- use. cation reconciliation.

® Current Reviews for Nurse Anesthetists designates this lesson for 1 CE contact hour in clinical pharmacology/therapeutics.

Introduction ments in 2015, and if protein powders are included in the above calculations, the herbal and supplement have been used for medicinal purposes for market is as big as the entire organic food market. thousands of years, with reports dating back to 3000 Such widespread use of herbal medications presents BC in the Chinese work Shennong Bencao Jing by numerous perioperative risks for potential adverse Shennong. The isolation of from Papaver drug-herb interactions. somniferum (opium) in 1803 by the pharmacist Friedrich Wilhelm Adam Sertürmer marked the beginning of the extraction process of active ingre- Regulation of dients from plants for medicinal purposes. Since Herbal Medications then other substances have been isolated, such as digitalis from purple foxglove, quinine and quinidine Herbal medicines are regulated as food supple- from Cinchona, and atropine from belladonna. Some ments under the Health of these substances are still found in anesthesia drug and Education Act (DSHEA) of 1994. As such, trays and medicine cabinets today. there are no quality assurance requirements for The use of herbal medications and remedies is manufacturing and labeling. Claims on the labels becoming increasingly widespread, likely driven by about efficacy or use are loosely regulated by the the notion that natural substances have fewer side DSHEA, which only requires the following dis- effects than pharmaceuticals. Approximately 1 in 5 claimer on package labeling: "This (statement about US adults takes herbal supplements, but the actual use of the product) has not been evaluated by the number is probably higher. Americans will spend FDA. This product is not intended to diagnose, treat, approximately $21 billion on herbals and supple- cure, or prevent any disease."

Curr Rev Nurs Anesth 38(17):209-220, 2015 211 Under DSHEA, once the product is marketed the affected by growing conditions, altitude, storage, Food and Drug Administration (FDA) must prove the temperature, handling and preparation. There may substance is unsafe before it can be withdrawn from be up to a 10,000-fold difference in potency based the market. Due to resource limitations, the FDA upon changes in these factors. only spot tests 1% of the 65,000 dietary supplements During growth and fertilization, the herb may be on the market. Consequently, herbal products are exposed to pesticides or molds and fungi. Following readily available and widely promoted, often with cultivation and harvesting, the active component is unsubstantiated claims of benefit and seldom with extracted by chemical means such as distillation, any mention of potential harm. fractionation, or concentration, using extraction sol- vents such as , , aromatic hydro- ASA Recommendation carbons, or olive oil. The solvent is then extracted leaving an isolated oil or powder. Some volume of for Perioperative Use of final product is lost in the extraction process, and Herbal Medications that volume may be made up with other substances, referred to as “undeclared pharmaceuticals,” such as The American Society of Anesthesiologists mandrake () or snakeroot (reserpine) in (ASA) recommends the discontinuation of all some preparations. The isolated oil or pow- herbal medications and supplements at least der is then complexed with various gelatins, dex- two weeks in advance of scheduled surgery. trans or other polysaccharides to form soft geltabs or Realizing that this is not always feasible with urgent powdered tablets. and emergent surgical procedures, the ASA further recommends that anesthesia providers have know- ledge of herbal medications and their potential peri- There is essentially no regulatory over- operative interactions. sight of herbal medications.

Perioperative Implications Anesthetic Implications It has been found that morbidity associated of Cytochrome P450 with may be more prevalent in the perioperative period because of an in- Cytochrome P450 (CYP450) is a host of creased physiological susceptibility to adverse found in the liver and small intestine that are effects and multiple drug use. The reluctance of responsible for the metabolism of drugs, endogenous patients to report herbal medication use to their substances such as steroids, herbal medications, and physicians further complicates the problem (Table 1). other toxins. Studies have found that well over 50% In one study, more than 70% of patients failed to of commonly administered medications, including disclose their use of herbal medications during rou- anesthetic medications, are metabolized by CYP450 tine perioperative assessment. or its associated isoforms. Many herbals have inducing or inhibiting effects on the various Direct Health Effects isoforms of CYP450. The implications of this are Direct health risks associated with herbal rem- significant, especially if the patient does not disclose edies include recognized pharmacological effects, the use of herbal medications, and may result in such as hypertension secondary to licorice or ephedra altered metabolism of anesthetic agents or other use, unexpected allergic and anaphylactic reactions, and the very real potential for untoward drug-herb interactions. Table 1 Reasons for Failure of Disclosure Indirect Health Effects The use of herbal medications may result in sub- Patients may be reluctant to disclose the optimal therapy with conventional medications by use of herbal medications for the reducing plasma levels, counteracting therapeutic following reasons: effects, or increasing toxicity. Conversely, conven- #A belief that because such products tional medications may increase the toxicity of are “natural,” therefore, they must the herbal medication. Patients may also decrease, be entirely safe delay or discontinue conventional medication therapy #Fear of how healthcare providers in favor of herbal medications, and may subsequently may respond to self-medication have a less favorable result. #Fear that their physician may have Some imported herbal medications may biases against the use of herbal contain toxic levels of heavy metals, such as medications mercury, lead, arsenic or other contaminants. #A belief that herbals are not Contaminants may be introduced during the growing considered a medication and fertilizing stage or during processing. Potency is

® 212 Current Reviews for Nurse Anesthetists Table 2 Anesthetic Medications Altered by Cytochrome P450 Induction or Inhibition

Cytochrome P450 Isoform 3A4 2D6 2C9 2C19 2E1 Fentanyl Codeine Losartan Sufentanil Morphine Hydromorphone Hydromorphone Beta-blockers Ketamine Rocuronium PPIs Vecuronium Celecoxib Neostigmine Methadone Ibuprofen Statins Antiarrhythmics Warfarin Apixiban Immunosuppressants Buprenorphine

crucial pharmaceuticals such as cardiac medications tions metabolized by CYP450. The use of echinacea or immunosuppressants (Table 2). for greater than 8 weeks has been associated with an increased risk of poor wound healing and opportu- Profiles of Commonly nistic infections, illustrating a short-term immuno- stimulatory effect with a long-term immunosup- Used Herbal Medications pressant effect. Chronic use of echinacea can result Many studies have been undertaken and are cur- in hepatic insufficiency, which can then enhance the rently in progress investigating the potential inter- hepatotoxic effects of drugs such as amiodarone and actions of herbal medications and anesthetic agents. . Consequently, many properties of herbal medications (Tables 3 and 4) have been documented which are of significance to the anesthetist in the perioperative Perioperative morbidity is higher when period. patients use herbal medications.

Echinacea purpurea Echinacea is considered a useful prophylactic Ephedra vulgaris and therapeutic agent in the treatment and preven- Ephedra was considered useful for promoting tion of viral, bacterial and fungal infections of the weight loss, increasing energy and for treating most upper respiratory tract. Echinacea is believed to respiratory tract infections. Its therapeutic actions improve the immune system through modulation of likely result from its active metabolites, such as cytokine signaling and stimulation of macrophages ephedrine, pseudoephedrine, methylephedrine and and natural killer cells. While the immunostim- norepinephrine. Prolonged use of ephedra pro- ulatory properties of echinacea have been studied, duces a catecholamine-depleted state, which very little information is available which addresses may result in marked hemodynamic instability the use of echinacea in patients taking immuno- during anesthesia, and tachyphylaxis to other suppressant medications, such as patients having sympathomimetic drugs. Side effects are predict- received organ transplants. Case reports describe able and include palpitations, hypertension, tachy- acute rejection of renal transplants with the cardia, hyperthermia, and seizures. Chronic use has initiation of echinacea. Therefore, the general been associated with cardiomyopathy, myocardial consensus is that echinacea should be avoided in infarction, stroke, fatal arrhythmias in the presence patients necessitating immunosuppression. of halothane, acute hepatitis, and psychosis. Con- The immunostimulatory effects of echinacea may current use with MAOI inhibitors may result in antagonize the immunosuppressive actions of cortico- severe hypertension, hyperthermia, or coma. steroids and cyclosporine. Echinacea can cause inhi- Over the course of two years, the FDA received bition of CYP450, and there are numerous reports of over 1000 reports of adverse effects related to adverse drug reactions from toxicity of other medica- ephedra with 155 deaths, including that of Baltimore

Curr Rev Nurs Anesth 38(17):209-220, 2015 213 Table 3 Systemic Effects of Selected Herbal Medications

Increase Herbal Increase Clotting Hepatic Immuno- Immuno- Induce Inhibit MAO Hypo- Hyper- Arrhyth- Seda- Medication Bleeding RIsk Toxicity stimulant suppressant CYP450 CYP450 Inhibit tension tension mia tion Echinacea % % % % % Ephedra % % % Garlic % % % % % % % % % % % % % % St. John’s % % % % % Wort Saw % % % Palmetto Ginseng % % % Valerian % % % % % % % Garcinia % % % % %

Orioles pitcher Steve Bechler. Subsequently, the Allium sativum (Garlic) FDA banned the use of ephedra as a weight loss Garlic is thought to have beneficial cardiovasc- supplement in 2004. After a series of legal and con- ular effects as well as beneficial effects in diabetes, gressional challenges, the FDA ban was upheld. This infection and some cancers. These actions are was the first such ban of an herbal supplement by believed to be due to the cysteine contained in garlic, the FDA. Ephedra has now become a drug of abuse, which decreases thromboxane formation and alters with street names of ‘Herbal Ecstasy’ and ‘Cloud 9,’ arachidonic acid metabolism. and remains easily obtainable from a multitude of Garlic inhibits platelet aggregation in a dose- websites. Entering ‘ephedra’ into a popular online dependent fashion, although this has not been dem- retail site yields 609 ephedra-containing products onstrated consistently in volunteers. It can poten- available for purchase. tiate the antiplatelet effects of aspirin and non-

Table 4 Herbal Medications Cited

Herbal Medicaton Common/Trade Name Echinacea Esberitox®®; Yummi-Bears ; Strepsil® Ephedra Ma Huang; MetaboLife®®; Yellow Fire ; Yellow Bullet® Garlic Kyolic®®; Aged Garlic ; Atharva® Ginkgo Maine Coast Herbals®®; Ginkgo Forte ; Curcumin Turmeric®®; Turmeric Extract ; Curcumin® Ginger Forever Active HA®®; Sunthi ; Ginger Root® St. John’s Wort Sari Kantaron®®; Hyperiforce ; Brain Boost® Saw Palmetto Prostasan®; Prostate SR®; MegaMen®®; Prostacin Ginseng QuattroG®®; Aksuvit ; Shen Ling® Valerian Luna®®; Quick Sleep Kava Anxietall®®; Securus ; Kava Kava® Garcinia Garcinia Cambogia Extreme®

Note: Many of these commercial preparations are combinations of herbal substances; many are marketed by their herbal name.

® 214 Current Reviews for Nurse Anesthetists steroidal anti-inflammatory drugs (NSAIDs), as well as warfarin and heparin, resulting an in increased Table 6 risk of intraoperative and postoperative bleeding. Common Uses of Ginger This effect may be irreversible. Garlic at normal dietary doses of 4.2 grams or less, or about 2 cloves, #Prophylaxis of PONV did not adversely affect platelet function. #Nausea and vomiting due to An animal study also reported a depressant seasickness # effect on cardiac chronotropy and ionotropy, thus Nausea and vomiting due to suggesting a $-adrenergic antagonist action modu- chemotherapy #Hyperemesis gravidarum lated by garlic. Garlic is rich in iodine content and #Motion sickness inhibits uptake of iodine by the thyroid. While data #Sore throat suggest no effect on therapeutic levels of levothy- #Respiratory congestion roxine, garlic may otherwise have complex inter- #Hypoglycemia actions on thyroid function. #Vertigo Garlic has complex interactions with CYP450, causing inhibition of some isoforms while inducing others. This activity on CYP450 is dependent on the specific constituents of the garlic formulation being used. been documented, including subdural hematoma, vitreous hemorrhage, subarachnoid bleeding, and hematoma formation following plastic surgery. Patients may be reluctant to disclose Therefore, concomitant use of gingko biloba with herbal use. aspirin, NSAIDs, warfarin and heparin is not recom- mended due to the increased potential for bleeding in Ginkgo biloba these patients. While ginkgo biloba has been used medicinally Other constituents of ginkgo inhibit the binding for 1000 years, recently ginkgo leaf extract has been of platelet-activating factor (PAF) to its membrane utilized for a number of vascular conditions, and its . Inhibition of PAF leads to bronchodilation antioxidant properties are thought to be neuro- and decreased airway hyperactivity. PAF inhibition protective by improving cerebral metabolism. Con- may also improve cardiac contractility and coronary sequently, it is frequently used for the treatment of blood flow. memory loss, dementia, and macular degeneration. Ginkgo inhibits CYP450 and prolongs the effect Ginkgo may increase cholinergic transmission in the of medications metabolized by this pathway. In brain via inhibition of acetylcholinesterase, which addition, it has been recommended that ginkgo could impact Alzheimer’s disease therapies. Some should be avoided in patients taking tricyclic anti- ginkgo extracts serve as free-radical scavengers that depressant agents because it might potentiate the may serve to mitigate some of the neurologic dam- seizure threshold-lowering action of these drugs. age of Alzheimer’s disease. The vascular effects of ginkgo are thought to be due to vasodilation secon- Curcumin longa (Turmeric) dary to stimulation of the endothelium-derived Turmeric has been used since ancient times as relaxing factor and prostacyclin release. both a food spice and medicinal agent. Curcumin, Ginkgo also decreases serum fibrinogen levels the yellow coloring principle in turmeric, is poly- and extracts inhibit platelet aggregation. While phenolic and the major active constituent. Curcumin ginkgo did not demonstrate significant effects on possesses potent antioxidant and anti-inflammatory laboratory tests of platelet aggregation, PT, or PTT, effects as well as thrombolytic and anticarcinogenic numerous case reports of increased bleeding have properties. Studies in mice demonstrated a neuroprotective effect following cerebral ischemia. Additional studies Table 5 noted that chronic dietary curcumin use lowered Medication Effects Prolonged by Turmeric amyloid-$ protein deposition, a finding that may have favorable implications in Alzheimer’s disease. The following medications may have According to the National Institutes of Health, prolonged duration of action with turmeric acts as a free radical scavenger and is also the use of Turmeric: a potent inhibitor of CYP450 and can decrease the #Fentanyl metabolism of many drugs used in the perioperative #Midazolam period (Table 5). Interference with antacid medi- #Lidocaine cations is a possible side effect of turmeric, and may # channel blockers result in increased stomach acid if taken with ant- #Warfarin acid drugs such as H-2 blockers or PPIs. Curcumin #Theophylline also has described immunosuppressant activity as an mTOR (mechanistic target of rapamycin) inhibitor.

Curr Rev Nurs Anesth 38(17):209-220, 2015 215 Zingiber officinale (Ginger) Table 8 Ginger is commonly used by patients preoper- Proposed Mechanisms atively for the prevention of nausea. Other common of Actions of Ginseng uses are listed in Table 6. A study comparing the effects of ginger versus found that #Augmentation of adrenal there were statistically significant lower incidences steroidogenesis of nausea in the group that received ginger. #Increased IgG and IgM production Ginger has been found to cause hyperglycemia. #Increased interferon production It has also been found to be a potent inhibitor of #Enhancement of cell-mediated thromboxane synthetase and can prolong bleeding immunity time. Study reports indicated that some ginger #Enhancement of natural killer cell compounds and derivatives are more potent activity antiplatelet agents than aspirin. Large quan- tities of ginger may also cause cardiac arrhythmias, central nervous system depression, and potentiation of the effect of calcium channel blockers. France has banned the use of St. John’s Wort Herbal preparations may contain toxic products based on a report issued by the French chemicals. Health Product Safety Agency warning of significant interactions between St. John’s Wort and conven- tional medications. Several other countries, includ- Hypericum perforatum (St. John’s Wort) ing Japan, the United Kingdom, and Canada, now St. John’s Wort is most commonly used for include drug-herb interaction warnings on St. John’s depression and related conditions such as anxiety, Wort products. tiredness, loss of appetite and . Its postu- lated mechanism of action is that it exerts its effects by inhibiting , norepinephrine, (-amino- Many herbal medications adversely effect butyrate (GABA), and reuptake by neur- platelet aggregation. ons. Additionally, irreversible monoamine oxidase (MAO) inhibition activity has been noted in vitro. St. John's Wort also induces the CYP450, which Serenoa repens (Saw Palmetto) may lower the blood levels of other drugs that are Saw palmetto is widely used to treat benign metabolized by this system, including anesthetic prostatic hyperplasia. The principal active ingredi- agents, , and analgesics. The most affected ents are sterols and free fatty acids. The mecha- appears to be CYP450-3A4. Several cases nism of action is unclear, and many have been pro- posed (Table 7). Saw palmetto has been associated of cardiac and renal transplant rejection have with excessive intraoperative bleeding attributed been reported in patients whose previously primarily to inhibition of cyclooxygenase and platelet stable level of cyclosporine was lowered after dysfunction. initiation of St. John's Wort. Although no detailed studies have been done Concomitant use of St. John’s Wort is not rec- with regard to the anesthetic interactions, caution ommended with monoamine oxidase inhibitors, beta- should be used if the patient is using benzodiaz- sympathomimetic amines, or selective serotonin re- epines because saw palmetto can alter the pharma- uptake inhibitors. One case report describes delayed cokinetics of these medications. Saw palmetto does emergence with St. John’s Wort when taken peri- not appear to influence CYP450, so its effect on ben- operatively. zodiazepines is by another mechanism.

Table 7 Panax ginseng (Ginseng) Proposed Mechanisms Ginseng is an expensive herb with purported of Action of Saw Palmetto benefits such as immunomodulation, hypoglycemia and antioxidant, mood enhancement and aphrodisiac #Inhibition of estrogen receptors effects. Its pharmacologic profile is incompletely #Prevention of conversion of understood because of the heterogeneous and some- to times opposing effects of its constituents. Proposed #Blocking of prolactin receptor signal mechanisms of action are numerous (Table 8). The transduction hypoglycemic effect is likely mediated via panaxans #Interference with fibroblast and ginsenosides. proliferation Ginseng should be avoided in patients on anti- #Induction of apoptosis coagulant medications such as warfarin, heparin, #Alpha-1 receptor antagonism NSAIDs, and aspirin, as ginsenosides inhibit platelet #Anti-inflammatory effects aggregation in vitro and result in prolongation of PT and PTT. The platelet inhibitory effect is likely

® 216 Current Reviews for Nurse Anesthetists Kava may also act through inhibition of sodium and Table 9 calcium channels to cause direct decreases in Potential Perioperative systemic vascular resistance and blood pressure. Complications with Kava Kava inhibits cyclooxygenase and thromboxane synthetase, both of which reduce platelet aggregation #Prolonged sedation (Table 9). #Perioperative hypotension #Myocardial depression Garcinia cambogia #Delayed emergence Garcinia cambogia is a tropical fruit, the rind of # which is used as a popular weight-loss supplement, #Platelet dysfunction and as an adjunct for the treatment of diabetes and hyperlipidemia. It is thought to inhibit fat pro- duction by blocking the enzyme citrate lyase, and to irreversible, so ginseng should be discontinued at suppress the appetite by increasing levels of sero- least 1 week in advance of surgery. tonin in the brain to decrease feelings of hunger. Additionally, it lowers blood glucose levels and has (Valerian) been found to improve levels by lowering Valerian is used as a and . It triglycerides and LDL cholesterol while increasing produces dose-dependent sedation and hypnosis by HDL cholesterol. Garcinia is reported to be an modulation of GABA receptors, as demonstrated in immunostimulant, but this has not been verified in animal studies. Abrupt discontinuation may the scientific literature. precipitate a -like withdrawal The FDA issued a warning to discontinue the use syndrome, so tapering may be the more pru- of garcinia in 2009 due to reports of hepatotoxicity. dent strategy ahead of scheduled surgery. There are multiple potential drug interactions of Based upon laboratory studies demonstrating a garcinia perioperatively (Table 10). Adverse reac- GABA-inhibitory effect, it would be expected that tions have also been described with garcinia and valerian would potentiate the effects of anesthetic asthma and allergy medications. Based on a case agents. This has indeed been demonstrated in mice report of normalization of INR after a patient began and animals anesthetized with isoflurane and a taking garcinia, it is likely that it induces CYP450 combination of midazolam and valerian. Mice so activity. anesthetized took considerably longer to emerge from anesthesia than isoflurane plus either drug alone. Delayed emergence from anesthesia is Piper methysticum (Kava) possible with several herbal medications. Traditionally, kava was used to prepare a ceremonial drink in the South Pacific Islands. Its present day uses include the treatment of anxiety, Summary and Conclusion stress, and insomnia. The active ingredients (kava- (Tables 11, 12 and 13) pyrones) have central muscle–relaxing properties The American College of Medical Quality and The and activity. Joint Commission state that accurate medication Kava can potentiate the effect of barbiturates reconciliation can be very influential in reducing and and cause excessive sedation. adverse drug events and is therefore an integral component of patient safety. Accurate medication reconciliation should include not only pre- Table 10 scription medications, but nonprescription Medication Interactions with Garcinia medications, herbals and supplements. With #Interference with antiarrhythmics the enormous upsurge in the number of patients #Interference with nitrates #Interference with calcium channel blockers Table 11 #Potentiation of cardiac glycosides Herbals with Known Perioperative Risk #Increased risk of hypokalemia # #Potentiation of oral hypoglycemic Echinacea # medications Ephedra # #Potentiation of insulin effect Garlic # #Rhabdomyolysis with statins Gingko # #Increased metabolism of warfarin Ginseng # #Risk of arrhythmia with Kava # succinylcholine St. John’s Wort #Valerian

Curr Rev Nurs Anesth 38(17):209-220, 2015 217 using herbal medications over the last 30 years and Table 13 the lack of regulatory standards, patients may be Herbals Associated with unaware of the potential for drug-herb interactions. Transplant Rejection A detailed medication history that asks specifically about the use of herbal medications should be ob- #Turmeric tained at the perioperative anesthesia assessment. #Echinacea Failure to recognize the use of herbal medications #Garlic can have dangerous adverse results. #Ginkgo #Ginseng Medication reconciliation should include #Kava # herbal medications. St. John’s Wort

The vast majority of herbal medications have or enhance biological activity, and they must be con- chem_background/exsumpdf/garciniac ambogiaext_ sidered active drugs. Accordingly, they should be 508.pdf. regulated as such. Until such time as they are, it is incumbent upon the anesthetist to maintain a Herbal and Dietary Supplement Use and Anesthesia American Society of Anesthesiologists [cited 2015 May working familiarity with herbal substances and their 11, 2015]. Available from: http://www.asahq.org/lifeline/ myriad of potential perioperative adverse interac- anesthesia topics/herbal supplements and anesthesia. tions. Heyneman CA. Preoperative considerations: which References herbal products should be discontinued before surgery? Crit Care Nurs 2003; 23(2):116-24. Ang-Lee MK, Moss J, Yuan CS. Herbal medicines and perioperative care. JAMA 2001; 286(2):208-16. Kaye AD, Clarke RC, Sabar R, et al. Herbal medicines: current trends in anesthesiology practice—a hospital Bone ME, Wilkingosn DJ, Young JR, et al. Ginder survey. J Clin Anesth 2000; 12(6):468-71. Root—A new Antiemetic. The effect of ginger root on postoperative nausea and vomiting after major Oshima Y, Konno C, Hikino H. Isolation and hypo- gynaecological surgery. Anaesthesia 1990; 45(8):669-71. glycemic activity of panaxans I, J, K, and L, glycans Borrelli F, Izzo AA. Herb-drug interactions with St. of panax ginseng roots. J Ethnopharmacol 1985; 14(2- John’s Wort (Hypericum perforatum): An update on 3):255-9. clinical observations. AAPS J 2009 Dec; 11(4):710-27. Pradhan SL, Pradha PA. Ayurvedic medicine and Chaplin RL, Jedynak J, Johnson D, et al. The effects of anaesthesia. Ind J Anaesth 2011; 55(4):334-39. valerian on the time course of emergence from general Raduege KM, Kleshinski JF, Ryckman JV, et al. anesthesia in Sprague-Dawley rats. J AANA 2007; Anesthetic considerations of the herbal kava. J Clin 75(6):431-35. Anesth 2004; 16(4):305-11. Fontanarosa PB, Rennie D, DeAngelis CD. The need Rudra A, Chatterjee S, Sengupta S, Kumar P, Das T, for regulation of dietary supplements: lessons from ephedra. JAMA 2003; 289:1568-70. Wankhede R, et al. Herbal medications and their anaesthetic implications. Internet Journal of Anesthes- Garcinia cambogia Extract: National Toxicology Pro- iology 2008; 19(1). gram National Cancer Institute; 2004 [May 20, 2015]. Available from: http://ntp.niehs.nih.gov/ntp/htdocs/ Scharbert G, Kalb ML, Duris M, Marschalek C, Kozek- Langenecker SA. Garlic at dietary doses does not impair platelet function. Anesth Analg 2007; 105(5): 1214-8. Table 12 Delayed Emergence Silva JOC, Costa RMR, Teixeira FM, et al. Processing and Herbal Medications and Quality Control of Herbal Drugs and Their Derivatives, Quality Control of Herbal Medicines and Delayed emergence from anesthesia is Related Areas, Prof. Yukihiro Shoyama (Ed.), 2011. possible with these herbal medications: ISBN: 978-953-307-682-9, InTech, Available from: #Valerian http://www.intechopen.com/books/quality-control-of- #Kava herbal-medicines-and-related-areas/processing-and- #Ginger quality-control-of-herbal-drugs-and-their-derivatives. #St. John’s Wort Wong A, Townley SA. Herbal medicines and anes- #Saw Palmetto thesia. Continuing Education in Anaesthesia, Critical Care & Pain 2011; 11(1):14-17.

® 218 Current Reviews for Nurse Anesthetists

Jeffrey B. Dobyns, DO

Dr. Dobyns is an Assistant Professor of Anesthesiology and Perioperative Medicine at the University of Alabama at Birmingham School ofMedicine and is certified in Medical Quality by the American College of Medical Quality. He is a graduate of Bowling Green State University with a Bachelor of Science in Biology, with a specialization in cellular and molecular biology. He graduated from the Ohio University College of Osteopathic Medicine and completed residency in Anesthesiology at the University of Toledo MedicalCenter in Toledo, Ohio, and the University of Colorado Health Sciences Center in Denver, Colorado.

Dr. Dobyns worked as a private practice anesthesiologist prior to joining the Department of Anesthesiology and Perioperative Medicine at the University of Alabama at Birmingham in 2012. His clinical interests include Vascular and Neurosurgical Anesthesia, Perioperative Medicine, and medical education. Both residents and medical students have consistently named him one of the Top 10 Teachers of the Year.

He lives with his wife and three sons in Hoover, Alabama.

Tips for your Clinical Practice: Key Points

#A marketed herbal supplement can only be withdrawn if the FDA can prove it is injurious. Only 1% of these products are spot tested. Many of these supplements increase or decrease the activity of CYP450. #Herbal medications can result in reduced efficacy of other medications by reducing their plasma levels or increasing their toxicity. #While useful in treatment and prevention of infections of the upper respiratory tract, echinacea, should be avoided in immunosuppressed patients. #Ephedra is used to promote weight loss, but it has many deleterious side effects including palpitations, hypertension, myocardial infarction hyperthermia and seizures. #Garlic has beneficial cardiovascular effects but, by inhibiting platelet aggregation, can potentiate the antiplatelet effects of aspirin and NSAIDs. #Patients with neurologic problems can derive benefit from ginkgo biloba, but this herb also decreases fibrinogen and inhibits platelet aggregation. Like garlic, it should not be used with aspirin and NSAIDs. #Tumeric increases bleeding time. It may increase cardiac arrhythmias, and produce CNS depression. #Concomitant use of St. John’s Wort with MOAIs, beta-adrenergic drugs, or selective serotonin reuptake inhibitors is discouraged.

Robert R. Kirby, M.D. Professor Emeritus of Anesthesiology University of Florida, College of Medicine

FRANK MOYA CONTINUING EDUCATION PROGRAMS, INC. & FACULTY DISCLOSURE

THIS AUTHOR’S AND FMCEP’S SPECIFIC DISCLOSURES: CThe author / faculty has indicated that there is no relevant financial interest or relationship with any commercial interest. CThe author / faculty has indicated that, as appropriate, he/she has disclosed that a product is not labeled for the use under discussion, or is still under investigation. CAs a matter of policy, FMCEP does not have any relevant financial interest or relationship with any commercial interest. In addition, all members of the staff, Governing Board, Editorial Board and CME Committee who may have a role in planning this activity have indicated that there is no relevant financial interest or relationship with any commercial interest. CCurrent Reviews is intended to provide its subscribers with information that is relevant to anesthesia providers. However, the information published herein reflects the opinions of its authors. Anesthesia practitioners must utilize their knowledge, training and experience in their clinical practice of anesthesiology. No single publication should be relied upon as the proper way to care for patients.

DESIGNATON OF SPECIFIC CONTENT AREAS: Current Reviews for Nurse Anesthetists (CRNA) is designed to meet the standards and criteria of the American Association of Nurse Anesthetists (AANA) for the prior-approved continuing medical education activity, Provider-Directed Independent Study, also known as home study. CRNA is an approved program provider. CRNA has designated the lessons which meet specific content areas such as pharmacology, HIV/AIDS, etc. However, only the Board of Nursing of an individual State is the final authority in the determination of whether or not these lessons meet the State’s licensure requirements.

Curr Rev Nurs Anesth 38(17):209-220, 2015 219 17 MARK ONLY THE ONE BEST ANSWER PER QUESTION ON YOUR ANSWER CARD. MARK THIS PAGE AND KEEP FOR YOUR RECORDS.

In accordance with AANA directives, you must get 80% of the answers correct to receive one credit for each lesson, and “if there is a failure, there is no retaking”.

POST-STUDY QUESTIONS

1. Concerning the regulation of herbal medications: 5. An herbal medication with MAO inhibitor effects is: G A. The FDA is responsible for assuring the quality G A. St. John’s Wort. and uniform potency of all herbal medications. G B. Saw Palmetto. G B. Herbal manufacturers must meet strict quality G C. Echinacea. assurance requirements. G D. Ginseng. G C. Approximately 1% of the herbal medications on the market are subject to spot testing. 6. Delayed emergence from general anesthesia may be G D. Herbal medications are regulated as Schedule seen with: IV controlled substances by the DEA. G A. Valerian. G B. Ginseng. C. Ginkgo. 2. ASA recommendations for the perioperative use of G G D. Ephedra. herbal medications state that: G A. Herbal medications can be continued on the day 7. Platelet aggregation is inhibited by: of surgery. G A. St. John’s Wort. G B. Herbal medications should be discontinued at G B. Ephedra. least two weeks prior to scheduled surgery. G C. Garcinia. G C. Herbal medications pose no perioperative risk. G D. Garlic. G D. Herbal medications are not in widespread use. 8. A perioperative complication associated with Kava 3. Patients may be reluctant to disclose their use of is: herbal medications due to: G A. Bleeding. G A. A belief that because herbal products are natural G B. Hypertension. they probably are not entirely safe. G C. Seizures. G B. Fear of how healthcare providers may respond G D. Bronchospasm. to self-medication. G C. The strict federal regulation of herbals as medi- 9. Hypoglycemia may be seen with: cations. G A. Ginseng. G D. Concerns that healthcare providers would rec- G B. Ginger. ommend expensive herbs. G C. Saw Palmetto. G D. Echinacea.

4. An INDIRECT health risk associated with the use of 10. Greater than 50% of commonly administered medi- herbal medications is: cations are metabolized by: G A. Recognized pharmacologic effects. G A. Pseudocholinesterase. G B. Toxicity due to contaminants. G B. Monoamine oxidase. G C. Anaphylaxis. G C. Cytochrome P450. G D. Drug-herb interactions. G D. HMG-CoA reductase.

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