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Aaronson/Spillane - opioid epidemic crisis
- 1. JOE SPILLANE PHARM.D.,DABAT PATRICKAARONSON PHARM.D., DABAT CLINICAL PHARMACIST - EMERGENCY MEDICINE UNIVERSITY OF FLORIDA HEALTH– JACKSONVILLE JOE.SPILLANE@JAX.UFL.EDU AARONSON@POISON.UFL.EDU The Opioid Epidemic: Intercity Perspective
- 2. Opioid Epidemic.. Objectives • Genesisof the Opioid Crisis • Prescription Drug Abuse Heroin • HeroinFentanyl & Fentanyl Analogs • Naloxone
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- 4. Early Opioid Research •Short duration – 4-8 weeks • Lower doses – Much lower than current dosing • Excluded at risk patients • Adverse effects?? NEJM 1980;302;123. Pain 1986;25:171-186.
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- 6. Opioid Prescribing • “Safeand Effective” • Little risk of opioid addiction • Problematic alternatives – Acetaminophen – NSAIDS • “Epidemic of untreated pain” • Pain as 5th vital sign J Med Tox 2012;8:393-99.
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- 9. “By 2010, enoughopioid pain relievers were sold to medicate every American adult with a typical dose of 5 mg of hydrocodone every 4 hrs for 1 month”
- 10. “ Did Iteach about pain management, specifically opioid therapy, in a way that reflects misinformation? Well against the standards of 2012, I guess I did” ---Russell Portenoy, MD
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- 12. Florida Drug DeathCauses Oxycodone vs Heroin 0 200 400 600 800 1000 1200 1400 1600 Oxycodone Heroin 1516 48 Florida Medical Examiners Report (2010 data)
- 13. Florida Drug DeathCauses Oxycodone vs Heroin 0 200 400 600 800 1000 1200 1400 Oxycodone Heroin 1247 57 Florida Medical Examiners Report (2011 data)
- 14. Florida Drug DeathCauses Oxycodone vs Heroin 0 100 200 300 400 500 600 700 800 Oxycodone Heroin 735 108 Florida Medical Examiners Report (2012 data)
- 15. Florida Drug DeathCauses Oxycodone vs Heroin 0 100 200 300 400 500 600 Oxycodone Heroin 534 193 Florida Medical Examiners Report (2013 data)
- 16. Florida Drug DeathCauses Oxycodone vs Heroin 370 380 390 400 410 420 430 440 450 460 470 Oxycodone Heroin 470 408 Florida Medical Examiners Report (2014 data)
- 17. Florida Drug DeathCauses Oxycodone vs Heroin 0 100 200 300 400 500 600 700 800 Oxycodone Heroin 565 733 Florida Medical Examiners Report (2015 data)
- 18. Florida Drug DeathCauses Oxycodone vs Heroin 0 100 200 300 400 500 600 700 800 900 1000 Oxycodone Heroin 723 952 Florida Medical Examiners Report (2016 data)
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- 21. Why Heroin? PillMill Closures, increased enforcement E-FORCSE New prescribing/dispensing requirements Abuse deterrent formulations Concern among prescribers-chilling effect? Alternative heroin sources Overwhelming demand for addiction treatment MMWR 2014;63(26):569-77.
- 22. www.theguardian.com “They tried tomake me to go to rehab, but I said no, no, no”
- 23. The Changed HeroinAbuser Heroin Abuser of the 60’s, 70’s, 80’s Young men Inner city Mixed races 1st opioid=heroin Heroin Abuser of the 2000’s Slightly older men & women Less urban more rural White 1st opioid=Rx drugs JAMA Psych 2014:71(7):821-826.
- 24. “If I havemoney to spend, I want to spend it on something I know is going to get me high. I and all my friends are middle class white kids (not even kids 25-41yrs old) and we’re not looked at as being addicts because everyone thinks heroin addicts are all homeless, shady looking, dirty junkies ” --- Recent heroin abuse initiate JAMA Psych 2014;71(7):821-826.
- 25. Florida Drug DeathCauses Oxycodone vs Heroin 0 100 200 300 400 500 600 700 800 900 1000 Oxycodone Heroin 723 952 Florida Medical Examiners Report (2016 data)
- 26. statnews.com/2016/09/29/fentanyl-heroin-photo-fatal-doses/ dea.gov/divisions/hq/2016/hq092216_attach.pdf Trending in theEmergency Department: Fentanyl Analogs
- 28. Emerging Threat Report:DEA Drug Seizures Mid-year 2017 546 • Fentanyl Analogs • Furanylfentanyl (137) 477 • Synthetic Cannabinoids • FUB-AMB (260) 121 • Cathinones • N-Ethylpentylone (61) Emerging Threat Report Mid-Year 2107
- 29. Year Deaths Rank 2013185 10/10 2014 397 7/10 2015 705 5/10 2016 1390 2/10 Comparison of Drug Caused Deaths 2013 – 2016
- 30. Fentanyl Deaths Duval County #1 Fentanyl Analog Deaths Duval County #5
- 31. Poison Center /Emergency Department Data • Lag time between experimentation and academic outlet • Poison center data less useful (disguised substances, familiar toxidrome) • Nonfatal fentanyl cases attributed to heroin • ELISA reports Fentanyl unless GC/MS was utilized to detect analogs Clinical Toxicology 2016;54(10): 924-1109 Clinical Toxicology 2015;53(10): 962-1146 Clinical Toxicology 2014;52(14): 1032-1283 Annals of Emergency Medicine 2014;64(6):637-639 MMWR Morb Mortal Wkly Rep. 2013;62:703-704 Year Cases Deaths National 2015 1402 47 2014 1418 5 2013 1486 12 Year Cases Florida 2017 69 2016 83 2015 83
- 32. Fentanyl Crisis: Trajectories •Early recreational use of drugs • Intergenerational use of opioids • Opioid prescriptions for pain management • Drug Trafficker profitability • Less to smuggle • Pills for broader access National Drug Early Warning System: New Hampshire Hotspot study September 2017
- 33. Enormous Profit Potential •Fentanyl Powder (1,000 g) = $2,000.00 • ~ 1 mg fentanyl/pill = 1 million pills • $10-20/pill = $10-20 million dollars DEA-DCT-DIB-021-16 July 2016 dea.gov/divisions/hq/2016/hq092216_attach.pdf
- 34. Fentanyl Analogs: GlobalSupply DEA-DCT-DIB-021-16 July 2016
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- 37. 4-anilino-N-phenethylpiperidine (4-ANPP) Psychiatry 2017110(8):1-14 swgdrug.org/Monographs/4ANPP.pdf
- 38. Carfentanyl 1974 10,000 x 4-chloroisobutyryl* 4-fluoroisobutryryl 4-fluorobutyryl 4-methoxybutyryl butyryl 7x Cyclopentyl* α-methyl 1978 50x 3-methyl 1978,1988 7,000 x Ocfentanil* 1990 Acryloyl 100x Acetyl 80 x Tetrahydrofuranyl* Furanyl Designer Fentanyl Analogs 2012 2015 2016 * Analog not scheduled
- 39. Occurrence of FentanylAnalogs in Florida: 2016
- 40. Carfentanil • Veterinary Usefor large animals • Special DEA license for procurement • 10,000 x morphine, 4,000 x heroin, 100 x fentanyl • 2002 hostage crisis in Moscow: 120 deaths • 42 y/o splashed 1.5 mg in mouth • Symptoms in 2 min • Naltrexone 100 mg IV = 200 mg of Naloxone Am J Emerg Med (2010) 28(4):530–2 zoopharm. net/products.php. Accessed Seot 28, 2017 Ann Emerg Med 2003;41(5):700-5
- 41. Carfentanil • 10/6/17 23y/o M had 55 grams in home • Sarasota County • 10 mg could kill 500 people • 1 g could kill 50,000 people • 55 g could kill 2.7 million people heraldtribune.com/news/20171006/sarasota-man-gets-12-years-for-selling-Carfentanil heraldtribune.com/news/20170511/sarasota-men-accused-of-selling-carfentanil-10000-times-stronger-than-morphine Int J Addict. 1969;4:1–24
- 42. Fentanyl Analogs: Pharmacokinetics DrugOnset Duration Morphine IV 1 min 2 - 4 h Heroin IV 5 min 4 - 5 h Fentanyl IV 1 min 30 - 60 min Fentanyl IN 7 min 1 - 2 h Acetylfentanyl oral 1 - 10min 1 - 2 h Acryloylfentanyl IN 1 - 5 min 10 - 30 min Butyrylfentanyl oral 15 - 30 min 3 - 4 h 4-fluorobutyrylfentanyl IN 1 min 30 - 60 min Furanylfentanyl oral 1 - 10 min 1 - 3 h U-47700 oral 15 min 1 - 2 h Naloxone IV 2 min 45 – 90 min dea.gov/druginfo/fentanyl-faq.shtml Frontiers in Psychiatry 2017;8:article110 Ann Emerg Med 1983;12:438-45 Sublimaze (fentanyl citrate injection) package insert 2016
- 43. Treatment: Naloxone dosing J.Med Tox 2016;12:276-281 Ann Emerg Med 1983;12(7):438-445 Am J Dis Child 1980;134(2)156-158. Anesth Analg 1973;52(3):447-453 9/25 20 mg10 mg1 mg0.1 mg
- 44. Fentanyl Analogs: Treatment •1st responders: dermal absorption unlikely • Carfentanil: nitrile gloves, N95 respirator • 20% ED physicians feel prepared • Respiratory support • Naloxone: “Mega doses” (up to 10 – 20 mg)? • Repeat every 20 min, consider Drip • Supportive care for acute withdrawal Clin Tox 2017 Sept ahead of print West J Emerg Med. 2013;14:467-470 J. Med Tox 2016;12:276-281
- 45. Naloxone (Narcan) • Indications: –Altered mental status/coma-->unknown cause – Opioid or clonidine overdose • Dose: – Adults: 0.1-10mgs IV repeat PRN – Children: 0.1mg/kg IV repeat PRN • Cautions/Warnings: – short duration, arousal complications, w/d – larger doses with methadone , propoxyphene, FENTANYL & ANALOGS
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- 49. Opioid Overdose “Classic Triad” CNS/Respiratory Depression Hypotension Miosis NEJM 2012;367:146-155.
- 50. Opioid Overdose Clinical Manifestations Vital Signs decreased pulse, BP, respirations Neuro: sedation, convulsions Pulmonary: respiratory depression apnea, bronchospasm, pulmonary edema GI/GU: Decr GI motility, n&v, urinary retention
- 51. Opioid Overdose • Treatment –symptomatic/supportive care – AIRWAY!!!! – hypotension – neurotoxicity (convulsions) – cardiotoxicity – naloxone
- 52. Opioid Overdose • Treatment –symptomatic/supportivecare –AIRWAY!!!! – hypotension – neurotoxicity (convulsions) – cardiotoxicity – naloxone
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- 54. Naloxone at Home •Advocated by the AMA & APHA • Over 25,000 opioid reversals • Lazarus Project – decr OD death rate from 46.629/100,000 • Operation Opioid Safe—Ft Bragg MMWR 2012;61(6):101-05. Pain Med 2011;12:s77-s85. MMWR 2015;64(23):631-5.
- 55. Problems w/Take HomeNaloxone • Research methodology issues – no randomization – high attrition – reporting bias • EMS is accessed less often – symptomatic/supportive care/AIRWAY – EMS called 62% w/out naloxone, 23% w/naloxone BMC Pub Hlth 2014;14:297-308. BMJ 2013;346:f174. J Comm Hlth 2013;38:133-41 J Urb Hlth 2003;80(2):291-301.
- 56. Problems w/ TakeHome Naloxone • Delays in calling EMS – “wait and see” – delays in definitive treatment – mixed overdoses – slower routes of administration • Attempts to titrate response – difficult to accomplish – additional delays Pain Med 2016;17:85-98. Ther Drug Monit 2008;30:490-6. BMJ 2017356:j760. J Addict Med 2014;8(3):153-63.
- 57. Problems w/Take HomeNaloxone • Redosing of opioids to self-treat withdrawal – longer acting opioids and resedation – worsens initial overdose • Fentanyl and Fentanyl Analogs – adequate dosing/routes of administration? • Increased opioid use – Dealers selling naloxone – “Narcan Parties” Am J Emer Med 2013:31:585-88. Harm Reduct J 2006;3(19):1-7.
- 58. Opioid Epidemic.. Summary • Genesisof the Opioid Crisis – Well meaning efforts + questionable research= unintended consequences • Prescription Drug Abuse Heroin • HeroinFentanyl • FentanylElefentanyls • Opioid overdose and Naloxone – Well meaning efforts->?