7/10/2019 #FSHP2019 Disclosure #FSHP2019 I do not have (nor does any immediate family member have): Antidotes & Anecdotes: – a vested interest in or affiliation with any corporate organization offering financial support or grant monies Reversal Agents in Emergency Medicine for this continuing education activity – any affiliation with an organization whose philosophy Joe Spillane, Pharm.D.,DABAT could potentially bias my presentation Emergency Medicine Pharmacist/Clinical Toxicologist UF Health Jacksonville 12 #FSHP2019 #FSHP2019 Antidotes & Anecdotes: Antidotes & Anecdotes: Reversal Agents in Emergency Medicine Reversal Agents in Emergency Medicine Objectives Objectives At the completion of this presentation, the participant should be able to… At the completion of this presentation, the participant should be able to… 1. State the relative importance of antidotes in the management of overdose patient. 34 #FSHP2019 #FSHP2019 Antidotes & Anecdotes: Antidotes & Anecdotes: Reversal Agents in Emergency Medicine Reversal Agents in Emergency Medicine Objectives Objectives At the completion of this presentation, the participant should be able to… At the completion of this presentation, the participant should be able to… 1. State the relative importance of antidotes in the management of overdose patient. 1. State the relative importance of antidotes in the management of overdose patient. 2. Recall which antidotes are used for which toxic situations. 2. Recall which antidotes are used for which toxic situations. 3. Explain the indications, dosing/administration, and potential problems with naloxone, flumazenil, physostigmine, and bleeding reversal agents. 56 1 7/10/2019 #FSHP2019 #FSHP2019 Naloxone (Narcan) • Indications: • Altered mental status/coma-->unknown cause • Opioid or clonidine overdose , propoxyphene, FENTANYL & ANALOGS http://fortune.com/2018/06/05/naloxone-recall-pfizer-hospira/ 78 #FSHP2019 #FSHP2019 Naloxone (Narcan) Naloxone (Narcan) • Indications: • Indications: • Altered mental status/coma-->unknown cause • Altered mental status/coma-->unknown cause • Opioid or clonidine overdose • Opioid or clonidine overdose • Dose: • Dose: • Adults: 0.1-10mg IV repeat PRN • Adults: 0.1-10mg IV repeat PRN • Children: 0.1mg/kg 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 MMWR 2012;61(6):101-5 Addict Sci Clin Pract 2017;12(4):DOI 10.1186/s13722-016-0068-3 910 #FSHP2019 #FSHP2019 B Med J 2013;346:f174 doi:10.1136/bmj.f174 http://intranasal.net/OpiateOverdose/ Statnews.com J Subst Abuse Treatment 2013;44:241-7 11 12 2 7/10/2019 #FSHP2019 #FSHP2019 www.jems.com J Emer Med 2003;24(3):185-187. Am J Emer Med 2013;31:585-588. addictionandrecoverynews.wordpress.com 13 14 Opioid Overdose #FSHP2019 Opioid Overdose #FSHP2019 “Classic Triad” “Classic Triad” . CNS/Respiratory Depression . CNS/Respiratory Depression . Hypotension 15 16 Opioid Overdose #FSHP2019 Opioid Overdose #FSHP2019 “Classic Triad” Clinical Manifestations . Vital Signs: . CNS/Respiratory Depression . Hypotension . Miosis New Eng J Med 2012;367:146-155. 17 18 3 7/10/2019 Opioid Overdose #FSHP2019 Opioid Overdose #FSHP2019 Clinical Manifestations Clinical Manifestations . Vital Signs: . Vital Signs: . Decreased pulse, BP, respirations . Decreased pulse, BP, respirations . Neuro: 19 20 Opioid Overdose #FSHP2019 Opioid Overdose #FSHP2019 Clinical Manifestations Clinical Manifestations . Vital Signs . Vital Signs . Decreased pulse, BP, respirations . Decreased pulse, BP, respirations . Neuro: . Neuro: . Sedation, convulsions . Sedation, convulsions . Pulmonary: 21 22 Opioid Overdose #FSHP2019 Opioid Overdose #FSHP2019 Clinical Manifestations Clinical Manifestations . Vital Signs . Vital Signs . Decreased pulse, BP, respirations . Decreased pulse, BP, respirations . Neuro: . Neuro: . Sedation, convulsions . Sedation, convulsions . Pulmonary: . Pulmonary: . Respiratory depression apnea, bronchospasm, pulmonary edema . Respiratory depression apnea, bronchospasm, pulmonary edema . GI/GU: 23 24 4 7/10/2019 Opioid Overdose #FSHP2019 #FSHP2019 Clinical Manifestations Opioid Overdose . Vital Signs . Decreased pulse, BP, respirations • Treatment • Symptomatic/supportive care . Neuro: • AIRWAY!!!! . Sedation, convulsions • Hypotension • Neurotoxicity (convulsions) . Pulmonary: . Respiratory depression apnea, bronchospasm, pulmonary edema • Cardiotoxicity • Naloxone . GI/GU: . Decreased GI motility, nausea & vomiting, urinary retention New Eng J Med 2012;367:146-155. 25 26 #FSHP2019 #FSHP2019 Opioid Overdose Treatment of Poisonings • Treatment All Poisonings •Symptomatic/supportive care •AIRWAY!!!! • Hypotension • Neurotoxicity (convulsions) • Cardiotoxicity • Naloxone Symptomatic/Supportive Care Goldfranks Toxicologic Emergencies 10e Eds. Robert Hoffman 2015. 27 28 #FSHP2019 #FSHP2019 Treatment of Poisonings All Poisonings No Antidote Antidote Clin Tox 2018;Dec 21:1-203. Southernliving.com 29 30 5 7/10/2019 #FSHP2019 #FSHP2019 Walgreens.com 31 32 #FSHP2019 #FSHP2019 33 34 #FSHP2019 #FSHP2019 35 36 6 7/10/2019 #FSHP2019 #FSHP2019 Slideplayer.com Anticholinergic Drugs 37 38 #FSHP2019 #FSHP2019 39 40 #FSHP2019 #FSHP2019 41 42 7 7/10/2019 #FSHP2019 #FSHP2019 Slideplayer.com Anticholinergic Drugs 43 44 #FSHP2019 #FSHP2019 Litfl.com Mdedge.com 45 46 #FSHP2019 #FSHP2019 Physostigmine(Antilirium) • Indications: • Anticholinergic toxicity (no TCA overdose) , propoxyphene, FENTANYL & ANALOGS http://www.thepoisonreview.com/2015/02/18/do-medical-toxicologists-use-physostigmine-to-treat-anticholinergic-toxidrome/ 47 48 8 7/10/2019 #FSHP2019 #FSHP2019 Physostigmine (Antilirium) Physostigmine (Antilirium) • Indications: • Indications: • Anticholinergic toxicity-no wide QRS • Anticholinergic toxicity-no wide QRS • Dose: • Dose: • Adults: 0.5-2 mg IV slowly (5mins), repeat if necessary • Adults: 0.5-2 mgs IV slowly (5mins), repeat if necessary • Children: 0.02mg/kg max 0.05mg/kg IV slowly • Children: 0.02mg/kg max 0.05mg/kg IV slowly • Cautions/Warnings: • Cholinergic toxicity • Convulsions • AV blockade, asystole Howland M. Antidotes in Depth. In: Goldfranks Toxicologic Emergencies, 10e, Eds Robert S Hoffman 2015. 49 50 #FSHP2019 #FSHP2019 Medicalnews.com Drugline.com 51 52 #FSHP2019 #FSHP2019 Flumazenil(Romazicon) Flumazenil (Romazicon) • Indications: • Indications: • Benzodiazepine overdose , propoxyphene, FENTANYL & • Benzodiazepine overdose ANALOGS • Dose: • Adults: 0.2 mg IV, then 0.3mg IV, then 0.5mg IV • Children: 5-20mcg/kg IV max dose as in adults 53 54 9 7/10/2019 #FSHP2019 #FSHP2019 Flumazenil (Romazicon) • Indications: • Benzodiazepine overdose • Dose: • Adults: 0.2 mg IV, then 0.3mg IV, then 0.5mg IV • Children: 5-20mcg/kg IV max dose as in adults • Cautions/Warnings: • Tricyclic antidepressant overdose, benzodiazepine tolerance • Patients w/ seizure disorder Mobilizerescue.com Howland M. Antidotes in Depth. In: Goldfranks Toxicologic Emergencies, 10e, Eds Robert S Hoffman 2015. 55 56 #FSHP2019 #FSHP2019 N Eng J Med. 2017; 377(5):431-441. Justin Morgenstern, "Idarucizumab: Plenty of optimism, not enough science", First10EM blog, January 15, 2018. Drugs.healthgrades.com Available at: https://first10em.com/idarucizumab Empr.com 57 58 #FSHP2019 #FSHP2019 N Eng J Med. 2019;380:1326-35. Justin Morgenstern, "Andexanet Alfa: More garbage science in the New England Journal of Medicine", First10EM blog, February 11, 2019. Available at: https://first10em.com/andexanet-alfa/. Kcentra.com Emcrit.com 59 60 10 7/10/2019 #FSHP2019 #FSHP2019 Antidotes & Anecdotes: Reversal Agents in Emergency Medicine Objectives revisited… 1. State the relative importance of antidotes in the management of overdose patient. 2. Recall which antidotes are used for which toxic situations. 3. Explain the indications, dosing/administration, and potential problems with naloxone, flumazenil, physostigmine, and bleeding reversal agents Imgur.com 61 62 11.