1/23/2019 Pharmacy Technician Learning Objectives • Review the history, mechanism of action, off‐label uses, and common Kratom: An side effects of kratom • Distinguish between state and federal laws for kratom and why this is Herbal relevant to patient’s use Supplement of • Identify possible treatments for kratom overdose Atomic Concern? Taylor Conklin, PharmD PGY1 Pharmacy Resident Northwestern Memorial Hospital January 22, 2019 Advisor: Robert Pecho, PharmD Clinical Pharmacist PGY1 Pharmacy Practice Coordinator Northwestern Memorial Hospital Disclosures Background on Taylor Conklin and Robert Pecho do not have any conflicts of interest to disclose regarding the subject matter Kratom Pharmacist Learning Objectives Kratom in the Media • Review the history, pharmacology, off‐label indications, and side effect profile of kratom • Distinguish current federal and state legislation regarding kratom and question how it relates to current use • Discuss historical strategies for management of kratom intoxication and outline plans to treat patients https://www.youtube.com/watch?v=P9SIjuHaiXA Image from Joe Rogan Experience (Podcast) http://podcasts.joerogan.net/. Accessed December 23, 2018. Mark Hay. “Inside Kratom, the Gas Station Drug That Could End the Opioid Crisis. https://www.vice.com/en_us/article/gyd587/kratom-opioid-crisis. Accessed December 23, 2018. Joe Rogan Podcast https://www.youtube.com/watch?v=P9SIjuHaiXA. Accessed December 23, 2018. 1 1/23/2019 Patient Case #1 Growth to Western Civilization Sally Sassafras PubMed - Articles on Kratom 50 • EMS responds to a call of an unresponsive woman on the boardwalk 45 of Navy Pier. 40 − Down ~15 minutes • She does not respond to sternal rubs and has minimal respiratory 35 drive 30 25 • A bystander hands you a brownish‐green powder from a baggie 20 15 • What are your next steps? 10 5 0 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010 2009 2008 2007 2006 2005 2004 2003 2002 2001 2000 1999 1998 1997 1996 1995 1994 1991 1989 1988 1987 1983 1978 1976 1975 1974 1973 1972 1971 1970 1969 1968 1967 1966 1965 1964 1963 1953 1950 J Am Osteopath Assoc. 2012 Dec;112(12):792-9. Patient Case #2 Exposures Reported to Poison Centers P.B. Morbidity and Mortality Weekly Report, U.S. 2010‐2015 • CC: “I wanna stay clean. You ‘gon help me Mr. Pharmacist?” 24.5% Minor • HPI: 18‐year old homeless male presents to ED with complaints of • Minimal signs or symptoms, resolved rapidly withdrawal symptoms − Subjective: Irritability, agitation, anxiety 41.7% Moderate − Objective: Sweating, diarrhea • Non-life threatening, but requiring treatment • Past Medical History: heroin use disorder (Jan 2016‐Jan 2018) 7.4% Major • Medications: • Life-threatening signs of symptoms, residual − Tylenol 500 mg PO q4‐6h prn disability − Kratom 2 grams PO TID Drug Detection 26.2% • Urine toxicology screening Unknown Cannabis Negative • No effects were reported Cocaine Negative Opioids Negative Benzodiazepines Negative Anwar M, Law R, Schier J. Notes from the Field. Kratom (Mitragyna speciosa) Exposures Reported to Poison Centers — United States, 2010–2015. MMWR Morb Mortal Wkly Rep 2016;65:748–749. DOI: http://dx.doi.org/10.15585/mmwr.mm6529a4 Kratom 2017 Human Exposures to Drugs of Abuse Mitragyna speciosa American Association of Poison Centers’ National Poison Data System (NPDS) Background Drug of Abuse Increase Exposures Increase 95% CI (%/year) (last 52 weeks) (Exposures/year) • Tree native to Southeast Asia • Rubiaceae family Synthetic Opioids 242% 25 1.17 [0.509, 1.82]* • Street names: “Biak‐biak,” Use in Southeast Asia “Ketum” “Kahuam” “Ithang” • Enhance mood and well‐being Kratom 63.3% 529 6.44 [2.91, 9.98]* “Thom” • Increase work efficiency and Heroin 20.9% 4186 16.8 [4.05, 29.57]* Consumption tolerate heat • Heroin addiction • Ingestion of raw leaves Methamphetamines 13.1% 3766 9.49 [-12.6, 31.5] • Crushed leaves − Smoked Cocaine 0.817% 1371 0.215 [-5.60, 6.03] − Brewed with tea − Powder for capsules Image courtesy of USADA. https://www.usada.org/substance‐profile‐kratom/. Accessed December 23, 2018. Raffa RB (ed) Kratom and other mitragynines: the chemistry and pharmacology of opioids from a non-opium source. 2017 Annual Report of the American Association of Poison Control Centers’ National Poison Data CRC Press, Boca Raton, FL, pp 309–320 System (NPDS): 35th Annual Report https://doi.org/10.1080/15563650.2018.1533727 2 1/23/2019 NPDS 10‐year Trends of Drugs of Abuse Pharmacology Heroin, Methamphetamines, Cocaine Kratom • Kratom leaves contain over 25 alkaloids − Mitragynine (66%) − 7‐OH mitragynine (2%) − Speciociliatine (7%) − Paynantheine (9%) − Speciogynine (1%) • Mitragynine − Structurally similar to yohimbine Biomed Res Int. 2015; 2015: 968786. 2017 Annual Report of the American Association of Poison Control Centers’ National Poison Data System (NPDS): 35th Annual Report https://doi.org/10.1080/15563650.2018.1533727 Int J Legal Med. 2016 Jan;130(1):127-38. doi: 10.1007/s00414-015-1279-y. Epub 2015 Oct 28. Accessed December 23, 2018 NPDS 10‐year Pharmacology of Kratom Compounds Trends: Drugs of Abuse Alkaloids Mechanism of Action Kratom Mitragynine Activity on μ, δ, and κ receptor Stimulates postsynaptic α2-adrenergic receptors 5-HT2A receptor antagonist 7-OH Mitragynine 13- and 46-fold higher potency than morphine and mitragynine, respectively Speciociliatine ACh receptor antagonist 2017 Demographic Profile of Single Substance Exposure Paynantheine Inhibits muscarinic receptors on ileal smooth muscle No. Case No. of Treated in Outcome Mentions Single Age < 20 Health Care Exposure Facility None Minor Moderate Major Death Speciogynine Inhibits muscarinic receptors on ileal smooth muscle 372 240 210 196 18 63 89 20 1 2017 Annual Report of the American Association of Poison Control Centers’ National Poison Data System (NPDS): 35th Annual Report https://doi.org/10.1080/15563650.2018.1533727 J Am Osteopath Assoc. 2012 Dec;112(12):792-9. Accessed December 23, 2018. Illinois Poison Center Brainstorming Cases Managed What drugs or drug classes does kratom resemble? 20 18 16 14 12 10 8 6 4 2 0 2014 2015 2016 2017 2018 Email from Carol DesLauriers, PharmD, DABAT. Illinois Poison Center. Illinois Health and Hospital Association. December 27, 2018 Image courtesy of Gfycat. https://gfycat.com/slightbackdugong. Accessed December 23, 2018. 3 1/23/2019 Pharmacokinetics Kratom Withdrawal Symptoms Singh et al. Parameters Mean ± SD Tmax (h) 0.83 ± 0.35 Category Symptoms Terminal T1/2 (h) 23.24 ± 16.07 Physical Lethargy, irritability, frequent yawning, runny nose, muscular pain, cramps, Vd/F (L/kg) 38.04 ± 24.32 joint pain, diarrhea, sweating CL/F (L/hr kg) 98.1 ± 51.34 Restlessness, anxiety, depression, aggression, sadness, nervousness, • Large volume of distribution Psychological delusions, hallucinations, intense craving − Mainly distributed out of circulation • Linear (first order) pharmacokinetics • Metabolism: − Likely hepatic − Strong CYP2D6 inhibitor − Urine excretion: 0.14%, unchanged drug Drug Alcohol Depend. 2014 Jun 1;139:132-7. doi: 10.1016/j.drugalcdep.2014.03.017. Epub Pharmacognosy Res. 2013 Oct;5(4):241-6. doi: 10.4103/0974-8490.118806. 2014 Mar 22. Drug Des Devel Ther. 2015 Apr 29;9:2421-9. doi: 10.2147/DDDT.S79658. eCollection 2015. Off‐Label* Indications and Side Effects Strains* Indications Dose Side Effects -Stimulant 1-5 grams Mild stimulant effect Increased alertness and physical energy Pleasant euphoria Loss of muscle coordination Anxiety and internal agitation Red Vein White Vein Green Vein -Chronic pain management 5-15 grams Analgesia Pontianak Red Horn, Red Thai, Pontianak White Horn, White Vein Malaysian Green and Pontianak -Acute opioid withdrawal Constipation Borneo Red, Red Vein Sumatra Sumatra, Borneo White Green Horn -”Legal high” Euphoria Best selling Known as stimulant and Mild energy booster Sedation positive mood enhancer Pleasant and calming effects More subtle effects on pain Acute or chronic toxic > 15 grams Seizures Coffee-mimetic ingestion Psychosis Prevent withdrawal symptoms Relieves social fears Intrahepatic cholestasis of opioids Commonly mixed with red Thyroid dysfunction strains *Quality randomized controlled trials do not exist to describe these subjective effects *Quality randomized controlled trials do not exist to describe these subjective effects Brain Res Bull. 2016 Sep;126(Pt 1):41-46. doi: 10.1016/j.brainresbull.2016.05.004. Epub 2016 May 10. https://www.kratomgardens.com/en/kratom-strains. Accessed December 23, 2018. Addictive Nature Drug Screening and Analysis Vicknasingam et al. Concomitant Drug Use and Short-term user Chronic-user • Undetectable on standard toxicology screening Reason for Using Kratom Ever used heroin 55.6% 34.4% • Methods of detection (urine and blood) Induces euphoria 5.6% 12.5% − High‐performance liquid chromatography Helps decrease addiction to other 95.8% 82.8% − Linear ion trap mass spectrometry drugs Reduces withdrawal symptoms 87.5% 79.7% Perceived Benefit Short-term user Chronic-user Helps me work harder 87.5% 76.6% Makes me more active 86.1% 76.6% Increases sex desire 84.7% 73.4% Increases appetite 77.8% 57.8% Reduces heroin withdrawal 62.5% 46.9% symptoms J Anal Toxicol. 2012 Nov-Dec;36(9):616-25. doi: 10.1093/jat/bks073. Epub 2012 Sep 28. Int J Drug Policy. 2010 Jul;21(4):283-8. doi: 10.1016/j.drugpo.2009.12.003. Epub 2010 Jan 25. 4 1/23/2019 Accessibility and Cost Technician Assessment For what off‐label indication is P.B. using kratom? • Locations: Chicago, St. Louis, Dallas, Los Angeles A. Social anxiety B. High blood pressure C. Heroin addiction • Cost D. Seizures − 10 grams: $9.95 − 10 capsules: $7.95 Photos taken by Taylor Conklin January 7, 2019. http://cbdkratomshops.com/about/. Accessed December 23, 2018. CBD/Kratom Supply Technician Assessment You are working as a pharmacy technician at CVS. A patient approaches the counter asking for an over‐the‐counter urine drug test kit. Which of the following drugs is NOT detectable? A. Cannabis B. Cocaine C.