Reducing the harm of opioid overdose with the safe use of naloxone: A pharmacologic review

Expert Opinion on Drug Safety

Volumn 14, Issue 7, 2015, Pages 1137-1146

  Kim, Hong K ^a   Nelson, Lewis S ^b  

^a UNIVERSITY OF MARYLAND SCHOOL OF MEDICINE   (United States)

^b BELLEVUE HOSPITAL CENTER   (United States)

Author keywords

Naloxone; Opioid intoxication reversal; Opioid toxicity

Indexed keywords

BUPRENORPHINE; FENTANYL; HYDROCODONE; HYDROMORPHONE; METHADONE; MORPHINE; NALOXONE; OPIATE; OPIATE ANTAGONIST; OXYCODONE; OXYMORPHONE; PETHIDINE; SUFENTANIL; TRAMADOL; NARCOTIC ANALGESIC AGENT; NARCOTIC ANTAGONIST;

ADVERSE DRUG REACTION; ARTICLE; DEPRESSION; DRUG ABUSE; DRUG BIOAVAILABILITY; DRUG DOSE TITRATION; DRUG INTOXICATION; DRUG METABOLISM; DRUG RECEPTOR BINDING; DRUG SAFETY; DRUG STRUCTURE; EPIDEMIC; HARM REDUCTION; HUMAN; LIPOPHILICITY; LOW DRUG DOSE; OPIATE OVERDOSE; PHARMACODYNAMICS; PUBLIC HEALTH; DRUG OVERDOSE; TREATMENT OUTCOME;

ANALGESICS, OPIOID; DRUG OVERDOSE; HUMANS; NALOXONE; NARCOTIC ANTAGONISTS; TREATMENT OUTCOME;

EID: 84931838999     PISSN: 14740338     EISSN: 1744764X     Source Type: Journal    
DOI: 10.1517/14740338.2015.1037274     Document Type: Article

References (109)

1. Okie S. A flood of opioids, a rising tide of deaths. N Engl J Med 2010;363:1981-5
2. Paulozzi LJ; Centers for Disease C, Prevention. Drug-induced deaths-United States, 2003-2007. MMWR Surveill Summ 2011;60(Suppl):60-1
3. Substance Abuse and Mental Health Services Administration. Office of Applied Studies. The DAWN Report: Trends in emergency department visits involving nonmedical use of narcotic pain relievers. Rockville, MD; June 18 2010. Available from: http://store. samhsa.gov/product/Trends-in-Emergency-Department-Visits-Involving-Nonmedical-Use-of-Narcotic-Pain-Relievers/DAWN10-0618 [Last accessed 14 June 2014]
4. Substance Abuse and Mental Health Services Administration. Results from the 2012 National Survey on Drug Use and Health: Summary of National Findings, NSDUH Series H-46, HHS Publication No. (SMA) 13-4795. Substance Abuse and Health Services Administration, Rockville, MD; 2013. Available from: http://www.samhsa.gov/data/NSDUH/2012 SummNatFindDetTables/NationalFindings/NSDUHresults2012. htm [Last accessed 14 June 2014]
5. Warner M, Chen LH, Makuc DM, et al. Drug poisoning deaths in the United States, 1980-2008. NCHS Data Brief. 2011;81:1-8
6. Kochanek KD, Xu J, Murphy SL, et al. Deaths: Preliminary data for 2009. Natl Vit Stat Rep 2011;59:51
7. Volkow ND, Frieden TR, Hyde PS, Cha SS. Medication-assisted therapies-tackling the opioid-overdose epidemic. N Engl J Med 2014;370:2063-6
8. Centers for Disease C, Prevention. Vital signs: Risk for overdose from methadone used for pain relief-United States, 1999-2010. MMWR. Morb Mortal Wkly Rep 2012;61:493-7
9. Foldes FF. The human pharmacology and clinical use of narcotic antagonists. Med Clin North Am 1964;48:421-43
10. Foldes FF, Duncalf D, Kuwabara S. The respiratory, circulatory, and narcotic antagonistic effects of nalorphine, levallorphan, and naloxone in anaesthetized subjects. Can Anaesth Soc J 1969;16:151-61.
11. Dahan A, Aarts L, Smith TW. Incidence, reversal, and prevention of opioidinduced respiratory depression. Anesthesiology 2010;112:226-38
12. Lewenstein MJ, Fishman J. Morphine derivative. US3254088; 1966. Available from: http://www. freepatentsonline.com/3254088.html [Last accessed 21 June 2014].
13. Martin WR. Naloxone. Ann Intern Med 1976;85:765-8
14. Foldes FF, Lunn JN, Moore J, Brown IM. N-Allylnoroxy-morphone: A new potent narcotic antagonist. Am J Med Sci 1963;245:23-30
15. Sgherza AL, Axen K, Fain R, et al. Effect of naloxone on perceived exertion and exercise capacity during maximal cycle ergometry. J Appl Physiol 2002;93:2023-8
16. Mannelli M, Maggi M, De Feo ML, et al. Effects of naloxone on catecholamine plasma levels in adult men. A dose-response study. Acta Endocrinol (Copenh) 1984;106:357-61
17. Jasinski DR, Martin WR, Haertzen CA. The human pharmacology and abuse potential of N-allylnoroxymorphone (naloxone). J Pharmacol Exp Ther 1967;157:420-6
18. Foldes FF, Schapira M, Torda TA, et al. Studies on the specificity of narcotic antagonists. Anesthesiology 1965;26:320-8
19. Berkowitz BA. The relationship of pharmacokinetics to pharmacological activity: Morphine, methadone and naloxone. Clin Pharmacokinet 1976;1(3):219-30
20. Dowling J, Isbister GK, Kirkpatrick CM, et al. Population pharmacokinetics of intravenous, intramuscular, and intranasal naloxone in human volunteers. Ther Drug Monit 2008;30:490-6
21. Middleton LS, Nuzzo PA, Lofwall MR, et al. The pharmacodynamic and pharmacokinetic profile of intranasal crushed buprenorphine and buprenorphine/naloxone tablets in opioid abusers. Addiction 2011;106:1460-73
22. Harris DS, Jones RT, Welm S, et al. Buprenorphine and naloxone coadministration in opiate-dependent patients stabilized on sublingual buprenorphine. Drug Alcohol Depend 2000;61:85-94
23. Weinberg DS, Inturrisi CE, Reidenberg B, et al. Sublingual absorption of selected opioid analgesics. Clin Pharmacol Ther 1988;44:335-42
24. Nelson LS, Howland MA. Opioid Antagonists. In: Hoffman RS, Howland MA, Lewin NA, et al. Goldfrank's Toxicologic Emergencies, 10th edition. McGraw-Hill; New York: 2015
25. Berkowitz BA, Ngai SH, Hempstead J, Spector S. Disposition of naloxone: Use of a new radioimmunoassay. J Pharmacol Exp Ther 1975;195:499-504
26. Kaufman JJ, Semo NM, Koski WS. Microelectrometric titration measurement of the pKa's and partition and drug distribution coefficients of narcotics and narcotic antagonists and their pH and temperature dependence. J Med Chem 1975;18:647-55
27. Kim S, Wagner HN Jr, Villemagne VL, et al. Longer occupancy of opioid receptors by nalmefene compared to naloxone as measured in vivo by a dualdetector system. J Nucl Med 1997;38:1726-31
28. Melichar JK, Nutt DJ, Malizia AL. Naloxone displacement at opioid receptor sites measured in vivo in the human brain. Eur J Pharmacol 2003;459:217-19
29. Yassen A, Olofsen E, van Dorp E, et al. Mechanism-based pharmacokineticpharmacodynamic modelling of the reversal of buprenorphine-induced respiratory depression by naloxone : A study in healthy volunteers. Clin Pharmacokinet 2007;46(11):965-80
30. van Dorp E, Yassen A, Dahan A. Naloxone treatment in opioid addiction: The risks and benefits. Expert Opin Drug Saf 2007;6:125-32
31. Hospira, Inc. Package insert: Naloxone hydrochloride. Available from: http://www.hospira.com/Images/EN-1367-32-5515-1.pdf [Last accessed 1 May 2014]
32. Carroll FI, Lewin AH, Mascarella SW, et al. Designer drugs: a medicinal chemistry perspective. Ann N Y Acad Sci 2012;1248:18-38
33. Kane BE, Svensson B, Ferguson DM. Molecular recognition of opioid receptor ligands. AAPS J 2006;8:E126-37
34. Portoghese PS, Sultana M, Takemori AE. Design of peptidomimetic delta opioid receptor antagonists using the messageaddress concept. J Med Chem 1990;33:1714-20
35. Olofsen E, van Dorp E, Teppema L, et al. Naloxone reversal of morphineand morphine-6-glucuronide-induced respiratory depression in healthy volunteers: a mechanism-based pharmacokinetic-pharmacodynamic modeling study. Anesthesiology 2010;112:1417-27
36. Yassen A, Olofsen E, Romberg R, et al. Mechanism-based PK/PD modeling of the respiratory depressant effect of buprenorphine and fentanyl in healthy volunteers. Clin Pharmacol Ther 2007;81:50-8
37. Rosado J, Walsh SL, Bigelow GE, Strain EC. Sublingual buprenorphine/naloxone precipitated withdrawal in subjects maintained on 100mg of daily methadone. Drug Alcohol Depend 2007;90:261-9
38. Walsh SL, Eissenberg T. The clinical pharmacology of buprenorphine: extrapolating from the laboratory to the clinic. Drug Alcohol Depend 2003;70:S13-27
39. van Dorp E, Yassen A, Sarton E, et al. Naloxone reversal of buprenorphineinduced respiratory depression. Anesthesiology 2006;105:51-7
40. Sarton E, Teppema L, Dahan A. Naloxone reversal of opioid-induced respiratory depression with special emphasis on the partial agonist/antagonist buprenorphine. Adv Exp Med Biol 2008;605:486-91
41. Yassen A, Olofsen E, Dahan A, Danhof M. Pharmacokinetic-pharmacodynamic modeling of the antinociceptive effect of buprenorphine and fentanyl in rats: role of receptor equilibration kinetics. J Pharmacol Exp ther 2005;313:1136-49
42. van Dorp E, Sarton E, Romberg R, et al. Naloxone reversal of buprenorphineinduced respiratory depression. Anesthesiology 2006;105:51-7
43. Boas RA, Villiger JW. Clinical actions of fentanyl and buprenorphine. The significance of receptor binding. Br J Anaesth 1985;57:192-6
44. Volpe DA, McMahon Tobin GA, Mellon RD, et al. Uniform assessment and ranking of opioid mu receptor binding constants for selected opioid drugs. Regul Toxicol Pharmacol 2011;59:385-90
45. Maio RF, Gaukel B, Freeman B. Intralingual naloxone injection for narcotic-induced respiratory depression. Ann Emerg Med 1987;16:572-3
46. Tandberg D, Abercrombie D. Treatment of heroin overdose with endotracheal naloxone. Ann Emerg Med 1982;11:443-5
47. Mycyk MB, Szyszko AL, Aks SE. Nebulized naloxone gently and effectively reverses methadone intoxication. J Emerg Med 2003;24:185-7
48. Evans JM, Hogg MI, Lunn JN, Rosen M. Degree and duration of reversal by naloxone of effects of morphine in conscious subjects. BMJ 1974;2:589-91
49. Wanger K, Brough L, Macmillan I, et al. Intravenous vs subcutaneous naloxone for out-of-hospital management of presumed opioid overdose. Acad Emerg Med 1998;5:293-9
50. Ngai SH, Berkowitz BA, Yang JC, et al. Pharmacokinetics of naloxone in rats and in man: basis for its potency and short duration of action. Anesthesiology 1976;44:398-401
51. Moreland TA, Brice JE, Walker CH, Parija AC. Naloxone pharmacokinetics in the newborn. Br J Clin Pharmacol 1980;9:609-12
52. Kart T, Christrup LL, Rasmussen M. Recommended use of morphine in neonates, infants and children based on a literature review: Part 1-Pharmacokinetics. Paediatr Anaesth 1997;7:5-11
53. Foldes FF, Davidson GM, Duncalf D, et al. The respiratory, circulatory, and analgesic effects of naloxone-narcotic mixtures in anaesthetized subjects. Can Anaesth Soc J 1965;12:608-21
54. Sadove MS, Balagot RC, Hatano S, Jobgen EA. Study of a narcotic antagonist-N-allyl-noroxymorphone. JAMA 1963;183:666-8
55. Boyer EW. Management of opioid analgesic overdose. N Engl J Med 2012;367:146-55
56. Anderson JA. Reversal agents in sedation and anesthesia: a review. Anesth Prog 1988;35(2):43-7
57. Longnecker DE. Anesthesiology. 2nd edition. McGraw-Hill Professional; New York: 2012
58. Tintinalli JE, Stapczynski JS. Tintinalli's emergency medicine: a comprehensive study guide. 7th edition. McGraw-Hill; New York: 2011
59. Longo DL. Harrison's principles of internal medicine. 18th edition. McGraw-Hill; New York: 2012
60. Stone CK, Humphries RL. Current diagnosis & treatment emergency medicine. 6th edition. McGraw-Hill; New York: 2008
61. Rosen P, Marx JA. Rosen's emergency medicine : concepts and clinical practice. 8th edition. Elsevier/Saunders; Philadelphia, PA: 2013
62. Connors NC, Nelson LS. Wide variation in naloxone dosing recommendations for acute opioid toxicity. J Med Tox 2014;10:76-7
63. Atchabahian A, Cupta R. The anesthesia guide. 1 edition. McGraw-Hill Medical; New York: 2013
64. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN guidelines): Adult Cancer Pain. 2014. Available from: http://www.nccn. org/professionals/physician-gls/pdf/pain. pdf [Last accessed 19 July 2014]
65. Hoffman RS, Goldfrank LR. The poisoned patient with altered consciousness. Controversies in the use of a 'coma cocktail'. JAMA 1995;274:562-9
66. Kim HK, Nelson LS. Effectiveness of low dose naloxone to reverse respiratory depression in opioid intoxication. Platform presentation at the North American Congress of Clinical Toxicology; Las Vegas, NV 2007
67. Mills CA, Flacke JW, Flacke WE, et al. Narcotic reversal in hypercapnic dogs: comparison of naloxone and nalbuphine. Can J Anaesth 1990;37:238-44
68. Mills CA, Flacke JW, Miller JD, et al. Cardiovascular effects of fentanyl reversal by naloxone at varying arterial carbon dioxide tensions in dogs. Anesth Analg 1988;67:730-6
69. Lewis JM, Klein-Schwartz W, Benson BE, et al. Continuous naloxone infusion in pediatric narcotic overdose. Am J Dis Child 1984;138:944-6
70. Bradberry JC, Raebel MA. Continuous infusion of naloxone in the treatment of narcotic overdose. Drug Intell Clin Pharm 1981;15:945-50
71. Coyne PJ, Hansen LA, Laird J, et al. Massive hydromorphone dose delivered subcutaneously instead of intrathecally: guidelines for prevention and management of opioid, local anesthetic, and clonidine overdose. J Pain Symptom Manage 2004;28:273-6
72. Gourlay GK, Coulthard K. The role of naloxone infusions in the treatment of overdoses of long half-life narcotic agonists: application to nor-methadone. Br J Clin Pharmacol 1983;15:269-71
73. Chamberlain JM, Klein BL. A comprehensive review of naloxone for the emergency physician. Am J Emerg Med 1994;12:650-60
74. Goldfrank L, Weisman RS, Errick JK, Lo MW. A dosing nomogram for continuous infusion intravenous naloxone. Ann Emerg Med 1986;15:566-70.
75. Full prescribing information-Evzio. Available from: http://evzio.com/pdfs/Evzio PI.PDF [Last accessed 18 November 2014]
76. Yassen A, Kan J, Olofsen E, et al. Mechanism-based pharmacokineticpharmacodynamic modeling of the respiratory-depressant effect of buprenorphine and fentanyl in rats. J Pharmacol Exp Ther 2006;319:682-92
77. Christoph T, Kogel B, Schiene K, et al. Broad analgesic profile of buprenorphine in rodent models of acute and chronic pain. Eur J Pharmacol 2005;507(1-3):87-98
78. Dum JE, Herz A. In vivo receptor binding of the opiate partial agonist, buprenorphine, correlated with its agonistic and antagonistic actions. Br J Pharmacol 1981;74(3):627-33
79. Estilo AE, Cottrell JE. Naloxone, hypertension, and ruptured cerebral aneurysm. Anesthesiology 1981;54:352
80. Johnson C, Mayer P, Grosz D. Pulmonary edema following naloxone administration in a healthy orthopedic patient. J Clin Anesth 1995;7:356-7
81. Nath SS, Tripathi M, Pandey C, Rao B. Naloxone-induced pulmonary edema: a potential cause of postoperative morbidity in laparoscopic donor nephrectomy. Indian J Med Sci 2009;63:72-5
82. Partridge BL, Ward CF. Pulmonary edema following low-dose naloxone administration. Anesthesiology 1986;65:709-10
83. Manfredi PL, Ribeiro S, Chandler SW, Payne R. Inappropriate use of naloxone in cancer patients with pain. J Pain Symptom Manage 1996;11:131-4
84. Flacke JW, Flacke WE, Williams GD. Acute pulmonary edema following naloxone reversal of high-dose morphine anesthesia. Anesthesiology 1977;47:376-8
85. Prough DS, Roy R, Bumgarner J, Shannon G. Acute pulmonary edema in healthy teenagers following conservative doses of intravenous naloxone. Anesthesiology 1984;60:485-6
86. Taff RH. Pulmonary edema following naloxone administration in a patient without heart disease. Anesthesiology 1983;59:576-7
87. Schwartz JA, Koenigsberg MD. Naloxone-induced pulmonary edema. Ann Emerg Med 1987;16(11):1294-6
88. Tanaka GY. Letter: Hypertensive reaction to naloxone. JAMA 1974;228:25-6
89. Azar I, Turndorf H. Severe hypertension and multiple atrial premature contractions following naloxone administration. Anesth Analg 1979;58:524-5
90. Michaelis LL, Hickey PR, Clark TA, Dixon WM. Ventricular irritability associated with the use of naloxone hydrochloride. Two case reports and laboratory assessment of the effect of the drug on cardiac excitability. Ann Thorac Surg 1974;18:608-14
91. Cuss FM, Colaco CB, Baron JH. Cardiac arrest after reversal of effects of opiates with naloxone. BMJ 1984;288:363-4
92. Andree RA. Sudden death following naloxone administration. Anesth Analg 1980;59:782-4
93. Kienbaum P, Thurauf N, Michel MC, et al. Profound increase in epinephrine concentration in plasma and cardiovascular stimulation after muopioid receptor blockade in opioidaddicted patients during barbiturateinduced anesthesia for acute detoxification. Anesthesiology 1998;88:1154-61.
94. Doyon S, Aks SE, Schaeffer S. Expanding access to naloxone in the United States. J Med Toxicol 2014;10:431-4
95. Davis CS, Ruiz S, Glynn P, et al. Expanded access to naloxone among firefighters, police officers, and emergency medical technicians in Massachusetts. Am J Public Health 2014;104:e7-9
96. Davis CS, Southwell JK, Niehaus VR, et al. Emergency medical services naloxone access: a national systematic legal review. Acad Emerg Med 2014;21:1173-7
97. Kim D, Irwin KS, Khoshnood K. Expanded access to naloxone: options for critical response to the epidemic of opioid overdose mortality. Am J Public Health 2009;99:402-7
98. Boyd JJ, Kuisma MJ, Alaspaa AO, et al. Recurrent opioid toxicity after pre-hospital care of presumed heroin overdose patients. Acta Anaesthesiol Scand 2006;50:1266-70
99. Vilke GM, Sloane C, Smith AM, Chan TC. Assessment for deaths in out-of-hospital heroin overdose patients treated with naloxone who refuse transport. Acad Emerg Med 2003;10:893-6
100. Wampler DA, Molina DK, McManus J, et al. No deaths associated with patient refusal of transport after naloxonereversed opioid overdose. Prehosp Emerg Care 2011;15:320-4
101. Eggertson L. Take-home naloxone kits preventing overdose deaths. CMAJ 2014;186:17
102. Enteen L, Bauer J, McLean R, et al. Overdose prevention and naloxone prescription for opioid users in San Francisco. J Urban Health 2010;87(6):931-41
103. Straus MM, Ghitza UE, Tai B. Preventing deaths from rising opioid overdose in the US- The promise of naloxone antidote in community-based naloxone take-home programs. Subst Abuse Rehabil 2013;2013
104. The Network for Public Health Law. Legal intervention to reduce overdose mortality: Naloxone access and overdose Good Samaritan laws. 2014. Available from: https://www. networkforphl.org/-asset/qz5pvn/network-naloxone.pdf [Last accessed 25 June 2014].
105. Centers for Disease Control and Prevention. Community-based opioid overdose prevention programs providing naloxone-United States, 2010. MMWR Morb Mortal Wkly Rep 2012;61:101-5
106. Baca CT, Grant KJ. Take-home naloxone to reduce heroin death. Addiction 2005;100:1823-31
107. Bazazi AR, Zaller ND, Fu JJ, Rich JD. Preventing opiate overdose deaths: examining objections to take-home naloxone. J Health Care Poor Underserved 2010;21:1108-13
108. Cassel JA, Daubert JD, DeHaven RN. [(3)H]Alvimopan binding to the micro opioid receptor: comparative binding kinetics of opioid antagonists. Eur J Pharmacol 2005;520:29-36
109. Apaydin S, Oktem HA. Effect of arachidonic acid on specific binding of [3H]naloxone to opioid receptors. Acta Neurobiol Exp(Wars) 2000;60:361-3