Advertisement

Clinical Reviews in Allergy & Immunology

, Volume 46, Issue 1, pp 54–64 | Cite as

The Effects of Opioids on the Lung

  • Joshua B. Radke
  • Kelly P. Owen
  • Mark E. Sutter
  • Jonathan B. Ford
  • Timothy E. Albertson
Article

Abstract

The term opioid refers to a broad class of medications that are used most frequently for their analgesic effects. Along with this effect, they also produce euphoria, and it is for this reason that they have been used illicitly, as well as medicinally, for thousands of years. While the most well-known complications of opioid use and misuse include respiratory and central nervous system depression, there are many other toxicities that have been associated with these drugs. Many complications can occur with multiple different opioids, such as non-cardiogenic pulmonary edema, while many of the complications are unique to the opioid used as well as the route of administration. This review focuses on the pulmonary complications associated with opioid use and abuse, but opioids can affect nearly every organ system. Their effects on the pulmonary system can be direct, such as causing granulomatous change, but they can also work indirectly. For example, opioids cause respiratory depression by decreasing sensitivity of peripheral chemoreceptors to carbon dioxide and decreasing activity in the central respiratory centers. Opioids have also been reported to affect the immune system, and place users at increased risk for many different infectious complications. Patients can have a wide array of signs and symptoms, sometimes making it difficult to recognize opioids as a cause for a patient’s clinical picture. Due to the sedative effects of opioids, patients are also often not able to provide a reliable history. Knowledge of the possible toxicities of opioids can help prepare a physician to recognize the many complications associated with opioid use.

Keywords

Opioid Opiate Toxicity Pulmonary toxicity Intravenous drug abuse 

References

  1. 1.
    Lao PN (1997) The effects of opiates on the lung. Clin Rev Allergy Immunol 15:291–305PubMedCrossRefGoogle Scholar
  2. 2.
    Nelson L, Lewin N, Howland MA, Hoffman R, Flomenbaum N (2007) Opioids, in Goldfrank's toxicologic emergencies by Lewis Goldfrank, 9th edn. McGraw-Hill Medical Pub, New York, pp 483–499Google Scholar
  3. 3.
    Center for Behavioral Health Statistics and Quality (2010) Results from the 2010 national survey on drug use and health: summary of national findings. Results from the 2010 NSDUH: Summary of National Findings, SAMHSA, CBHSQGoogle Scholar
  4. 4.
    Manchikanti L, Helm S II, Fellows B et al (2012) Opioid epidemic in the United States. Pain Phys J 15:ES9–S38Google Scholar
  5. 5.
    Waldhoer M, Bartlett S, Whistler J (2004) Opioid receptors. Annu Rev Biochem 73:953–990PubMedCrossRefGoogle Scholar
  6. 6.
    Koob G (2004) Neurobiological mechanisms in the transition from drug use to drug dependence. Neurosci Biobehav Rev 27:739–749PubMedCrossRefGoogle Scholar
  7. 7.
    Selley DE, Cao CC, Sexton T, Schwegel JA, Martin TJ, Childers SR (2001) Mu opioid receptor-mediated G-protein activation by heroin metabolites: evidence for greater efficacy of 6-monoacetylmorphine compared with morphine. Biochem Pharmacol 62:447–455PubMedCrossRefGoogle Scholar
  8. 8.
    Bishay A, Amchentsev A, Saleh A, Patel N, Travis W, Raoof S (2008) A hitherto unreported pulmonary complication in an IV heroin user. Chest 133:549–551PubMedCrossRefGoogle Scholar
  9. 9.
    Dettmeyer RB, Verhoff MA, Brückel B, Walter D (2010) Widespread pulmonary granulomatosis following long time intravenous drug abuse—a case report. Forensic Sci Int 197:E27–30PubMedCrossRefGoogle Scholar
  10. 10.
    Arnett EN, William E, Battle RJV, Roberts WC (1976) Intravenous injection of talc-containing drugs intended for oral use: a cause of pulmonary granulomatosis and pulmonary hypertension. Am J Med 60:711–718PubMedCrossRefGoogle Scholar
  11. 11.
    Cohen J (2012) Miracle on 34th street: success with injectors. Science 337:178–180PubMedCrossRefGoogle Scholar
  12. 12.
    Orangio GR, Pitlick SD, Della Latta P et al (1984) Soft tissue infections in parenteral drug abusers. Ann Surg 199:97–100PubMedCrossRefGoogle Scholar
  13. 13.
    Murphy EL, DeVita D, Liu H et al (2001) Risk factors for skin and soft tissue abscesses among injection drug users: a case control study. Clin Infect Dis 33:35–40PubMedCrossRefGoogle Scholar
  14. 14.
    Grassin-Delyle S, Buenestado A, Naline E et al (2012) Intranasal drug delivery: an efficient and non-invasive route for systemic administration: focus on opioids. Pharmacol Ther 34:366–379CrossRefGoogle Scholar
  15. 15.
    Huang HC (2009) Transnasal butorphanol for pain relief after uvulopalatopharyngoplasty—a hospital-based, randomized study. Chang Gung Med J 32:390–399PubMedGoogle Scholar
  16. 16.
    Desjardins P (2000) Analgesic efficacy of intranasal butorphanol (Stadol NS) in the treatment of pain after dental impaction surgery. J Oral Maxillofac Surg 58:19–26PubMedCrossRefGoogle Scholar
  17. 17.
    Greene D (2005) Total necrosis of the intranasal structures and soft palate as a result of nasal inhalation of crushed OxyContin. Ear Nose Throat J 84(8):512–516PubMedGoogle Scholar
  18. 18.
    Lofwall MR, Moody DE, Fang WB, Nuzzo PA, Walsh SL (2012) Pharmacokinetics of intranasal crushed OxyContin and intravenous oxycodone in nondependent prescription opioid abusers. J Clin Pharmacol 52:600–606PubMedCrossRefGoogle Scholar
  19. 19.
    Kass-Hout T, Kass-Hout O, Darkhabani MZ, Mokin M, Mehta B, Radovic V (2011) “Chasing the dragon”—heroin-associated spongiform leukoencephalopathy. J Med Toxicol 7:240–242PubMedCentralPubMedCrossRefGoogle Scholar
  20. 20.
    Wolters E (1982) Leucoencephalopathy after inhaling "heroin" pyrolysate. Lancet 320:1233–1237CrossRefGoogle Scholar
  21. 21.
    Prowse SJ, Lima T, Irion KL, Burhan H, Hochhegger B, Marchiori E (2011) Valsalva manoeuvre effect on distribution of lung damage in heroin inhalation. Br J Radiol 84:E200–201PubMedCrossRefGoogle Scholar
  22. 22.
    Chapman E, Leipsic J, Satkunam N, Churg A (2012) Pulmonary alveolar proteinosis as a reaction to fentanyl patch smoke. Chest 141:1321–1323PubMedCrossRefGoogle Scholar
  23. 23.
    Mrvos R, Feuchter A, Katz K, Duback-Morris L, Brooks D, Krenzeolak E (2012) Whole fentanyl patch ingestion: a multi-center case series. J Emerg Med 42:549–552PubMedCrossRefGoogle Scholar
  24. 24.
    Barrueto F Jr, Howland MA, Hoffman RS, Nelson LS (2004) The fentanyl tea bag. Vet Hum Toxicol 46:30–31PubMedGoogle Scholar
  25. 25.
    Janssen Pharmaceutical Inc. (2012) Duragesic: fentanyl transdermal system. WebGoogle Scholar
  26. 26.
    Carson HJ, Knight LD, Dudley MH, Garg U (2010) A fatality involving an unusual route of fentanyl delivery: chewing and aspirating the transdermal patch. Legal Med 12:157–159PubMedCrossRefGoogle Scholar
  27. 27.
    Miller DR, Harden JL, Currie GP (2006) A case of self-inflicted bilateral pneumothorax. Resuscitation 71:122–123PubMedCrossRefGoogle Scholar
  28. 28.
    Corzo JE, Lozano De Leon F, Gomez-Mateos J, Lopez-Cortes L, Vazquez R, Garcia-Bragado F (1992) Pneumothorax secondary to septic pulmonary emboli in tricuspid endocarditis. Thorax 47:1080–1081PubMedCrossRefGoogle Scholar
  29. 29.
    Torre M (1998) Spontaneous pneumothorax in cocaine sniffers. Am J Emerg Med 16:546–549PubMedCrossRefGoogle Scholar
  30. 30.
    Seaman ME (1990) Barotrauma related to inhalational drug abuse. J Emerg Med 8:141–149PubMedCrossRefGoogle Scholar
  31. 31.
    Alexander D, Alexander K, Valentino J (2012) Intranasal hydrocodone-acetaminophen abuse induced necrosis of the nasal cavity and pharynx. Laryngoscope 122:2378–2381PubMedCentralPubMedCrossRefGoogle Scholar
  32. 32.
    Yewell J, Haydon R, Archer S, Manaligod JM (2002) Complications of intranasal prescription narcotic abuse. Ann Otol Rhinol Laryngol 111:174–177PubMedGoogle Scholar
  33. 33.
    Hillstrom RP, Cohn AM, McCarroll KA (1990) Vocal cord paralysis resulting from neck injections in the intravenous drug use population. Laryngoscope 100:503–506PubMedCrossRefGoogle Scholar
  34. 34.
    White JM, Irvine RJ (1999) Mechanisms of fatal opioid overdose. Addiction 94:961–972PubMedCrossRefGoogle Scholar
  35. 35.
    Yeadon M, Kitchen I (1989) Opioids and respiration. Prog Neurobiol 33:1–16PubMedCrossRefGoogle Scholar
  36. 36.
    Santiago TV, Edelman NH (1985) Opioids and breathing. J Appl Physiol 59:1675–1685PubMedGoogle Scholar
  37. 37.
    Jungquist C, Flannery M, Perlis ML, Grace JT (2012) Relationship of chronic pain and opioid use with respiratory disturbance during sleep. Pain Manag Nurs 13:70–79PubMedCrossRefGoogle Scholar
  38. 38.
    Glick C, Evans OB, Parks BR (1996) Muscle rigidity due to fentanyl infusion in the pediatric patient. South Med J 89:1119–1120PubMedCrossRefGoogle Scholar
  39. 39.
    Streisand JB, Bailey PL, LeMaire L et al (1993) Fentanyl-induced rigidity and unconsciousness in human volunteers incidence, duration, and plasma concentrations. Anesthesiology 78:629–634PubMedCrossRefGoogle Scholar
  40. 40.
    Viscomi C (1997) Opioid-induced rigidity after intravenous fentanyl. Obstet Gynecol 89:822–824PubMedCrossRefGoogle Scholar
  41. 41.
    Van Der Lee R, Ceelie I, De Wildt SN (2009) Morphine-induced muscle rigidity in a term neonate. Ann Pharmacother 43:1724–1726PubMedCrossRefGoogle Scholar
  42. 42.
    Goldstein D, Karpel J, Appel D, Williams M (1986) Bullous pulmonary damage in users of intravenous drugs. Chest 89:266–269PubMedCrossRefGoogle Scholar
  43. 43.
    Da Costa JL, Tock EPC, Boey HK (1971) Lung disease with chronic obstruction in opium smokers in Singapore: clinical, electrocardiographic, radiological, functional, and pathological features. Thorax 26:555–571PubMedCrossRefGoogle Scholar
  44. 44.
    Buster MCA, Van Den Brink W, Van Brussel GHA, Van Ree JM (2011) Influence of treatment with inhalable heroin on pulmonary function. Eur Addict Res 17:136–138PubMedCrossRefGoogle Scholar
  45. 45.
    Buster MCA, Rook L, Van Brussel GHA, Van Ree J, Van Den Brink W (2002) Chasing the dragon, related to the impaired lung function among heroin users. Drug Alcohol Depend 68:221–228PubMedCrossRefGoogle Scholar
  46. 46.
    Mell HK, Sztajnkrycer MD (2006) Clinical images in medical toxicology: heroin overdose with non-cardiogenic pulmonary edema. Clin Toxicol 44:399CrossRefGoogle Scholar
  47. 47.
    Sterrett C (2003) Patterns of presentation in heroin overdose resulting in pulmonary edema. Am J Emerg Med 21:32–34PubMedCrossRefGoogle Scholar
  48. 48.
    Horng HC, Ho MT, Huang CH, Yeh CC, Cherng CH (2010) Negative pressure pulmonary edema following naloxone administration in a patient with fentanyl-induced respiratory depression. Acta Anaesthesiol Taiwan 48:155–157PubMedCrossRefGoogle Scholar
  49. 49.
    Hamilton RJ, Olmedo RE, Shah S et al (2002) Complications of ultrarapid opioid detoxification with subcutaneous naltrexone pellets. Acad Emerg Med 9:63–68PubMedCrossRefGoogle Scholar
  50. 50.
    Kienbaum P, Thurauf N, Michel MC, Scherbaum N, Gastpar M, Peters J (1998) Profound increase in epinephrine concentration in plasma and cardiovascular stimulation after mu-opioid receptor blockade in opioid-addicted patients during barbiturate-induced anesthesia for acute detoxification. Anesthesiology 88:1154–1161PubMedCrossRefGoogle Scholar
  51. 51.
    Frand U, Shim C, Williams H (1972) Heroin-induced pulmonary edema: sequential studies of pulmonary function. Ann Intern Med 77:29–35PubMedCrossRefGoogle Scholar
  52. 52.
    Sporer KA (2001) Heroin-related noncardiogenic pulmonary edema: a case series. Chest 120:1628–1632PubMedCrossRefGoogle Scholar
  53. 53.
    Porter R, O'Reilly H (2011) Pulmonary hemorrhage. Pediatr Emerg Care 27:742–744PubMedCrossRefGoogle Scholar
  54. 54.
    Griffith C, Raval J, Nichols L (2012) Intravascular talcosis due to intravenous drug use is an underrecognized cause of pulmonary hypertension. Pulmonary Medicine (in press)Google Scholar
  55. 55.
    Kringsholm B, Christoffersen P (1987) The nature and the occurrence of birefringent material in different organs in fatal drug addiction. Forensic Sci Int 34:53–62PubMedCrossRefGoogle Scholar
  56. 56.
    Marchiori E, Lourenço S, Gasparetto TD, Zanetti G, Mano CM, Nobre LF (2010) Pulmonary talcosis: imaging findings. Lung 188:165–171PubMedCrossRefGoogle Scholar
  57. 57.
    Davis LL (1983) Pulmonary "mainline" granulomatosis: talcosis secondary to intravenous heroin abuse with characteristic X-ray findings of asbestosis. J Natl Med Assoc 75:1225–1228PubMedGoogle Scholar
  58. 58.
    Randall D, Degenhardt L, Vajdic CM et al (2011) Increasing cancer mortality among opioid-dependent persons in Australia: a new public health challenge for a disadvantaged population. Aust N Z J Public Health 35:220–225PubMedCrossRefGoogle Scholar
  59. 59.
    Gach K, Wyrębska A, Fichna J, Janecka A (2011) The role of morphine in regulation of cancer cell growth. Naunyn-Schmiedeberg's Arch Pharmacol 384:221–230CrossRefGoogle Scholar
  60. 60.
    Zagon I (2003) Opioids and the apoptotic pathway in human cancer cells. Neuropeptides 37:79–88PubMedCrossRefGoogle Scholar
  61. 61.
    Oliver R (1986) Bronchospasm and heroin inhalation. Lancet 327:915CrossRefGoogle Scholar
  62. 62.
    Cygan J (2000) Inhaled heroin-induced status asthmaticus: five cases and a review of the literature. Chest 117:272–275PubMedCrossRefGoogle Scholar
  63. 63.
    Withington DE, Patrick JA, Reynolds F (1993) Histamine release by morphine and diamorphine in man. Anaesthesia 48:26–29PubMedCrossRefGoogle Scholar
  64. 64.
    Tsapas A, Paletas K, Vlachaki E, Bekiari E, Spanos C, Economidis D (2008) Eosinophilic pneumonia associated with heroin inhalation: a case report. Wien Klin Wochenschr 120:178–180PubMedCrossRefGoogle Scholar
  65. 65.
    Banerjee A, Strazza M, Wigdahl B, Pirrone V, Meucci O, Nonnemacher MR (2011) Role of mu-opioids as cofactors in human immunodeficiency virus type 1 disease progression and neuropathogenesis. J Neurovirol 17:291–302PubMedCentralPubMedCrossRefGoogle Scholar
  66. 66.
    Nath A (1999) Pathobiology of human immunodeficiency virus dementia. Semin Neurol 19:113–127PubMedCrossRefGoogle Scholar
  67. 67.
    Hauser K, Fitting S, Denver S, Podhaizer E, Knapp P (2012) Opiate drug use and the pathophysiology of NeuroAIDS. Curr HIV Res 10:435–452PubMedCentralPubMedCrossRefGoogle Scholar
  68. 68.
    Wang J, Barke RA, Charboneau R, Roy S (2005) Morphine impairs host innate immune response and increases susceptibility to Streptococcus pneumoniae lung infection. J Immunol 174:426–434PubMedGoogle Scholar
  69. 69.
    Rittner HL, Roewer N, Brack A (2010) The clinical (ir)relevance of opioid-induced immune suppression. Curr Opin Anaesthesiol 23:588–592PubMedCrossRefGoogle Scholar
  70. 70.
    Kaushik KS, Kapila K, Praharaj AK (2011) Shooting up: the interface of microbial infections and drug abuse. J Med Microbiol 60:4084–22CrossRefGoogle Scholar
  71. 71.
    Dublin S, Walker RL, Jackson ML et al (2011) Use of opioids or benzodiazepines and risk of pneumonia in older adults: a population-based case–control study. J Am Geriatr Soc 59:1899–1907PubMedCentralPubMedCrossRefGoogle Scholar
  72. 72.
    Jain V, Yang M, Kovacicovalezcano G, Juhle L, Bolger A, Winston L (2008) Infective endocarditis in an urban medical center: association of individual drugs with valvular involvement. J Infect 57:132–138PubMedCrossRefGoogle Scholar
  73. 73.
    Dettmeyer R, Friedrich K, Schmidt P, Madea B (2009) Heroin-associated Myocardial damages—conventional and immunohistochemical investigations. Forensic Sci Int 187:42–46PubMedCrossRefGoogle Scholar
  74. 74.
    Fowler VG, Miro JM, Hoen B et al (2005) Staphylococcus aureus endocarditis: a consequence of medical progress. JAMA 293:3012–3021PubMedCrossRefGoogle Scholar
  75. 75.
    Moreillon P, Que YA (2004) Infective endocarditis. Lancet 363:139–149PubMedCrossRefGoogle Scholar
  76. 76.
    Tan LKK, Powrie DJ, Rowland R, Cropley I, Lipman M (2007) Fever and haemoptysis in an injecting drug user. Eur Respir J 29:1061–1063PubMedCrossRefGoogle Scholar
  77. 77.
    O'Donnell A, Pappas L (1988) Pulmonary complications of intravenous drug abuse. Experience at an inner-city hospital. Chest 94:251–253PubMedCrossRefGoogle Scholar
  78. 78.
    O'Donnell AE, Selig J, Aravamuthan M, Richardson MS (1995) Pulmonary complications associated with illicit drug use: an update. Chest 108:460–463PubMedCrossRefGoogle Scholar
  79. 79.
    Grenfell P, Leite RB, Garfein R, Lussigny S, Platt L, Rhodes T (2013) Tuberculosis, injecting drug use and integrated HIV-TB care: a review of the literature. Drug Alcohol Depend 129:180–209PubMedCrossRefGoogle Scholar
  80. 80.
    Palmateer NE, Hope VD, Roy K et al (2013) Infections with spore-forming bacteria in persons who inject drugs, 2000–2009. Emerg Infect Dis 19:29–34PubMedCrossRefGoogle Scholar
  81. 81.
    Yuan J, Inami G, Mohle-Boetani J, Vugia DJ (2011) Recurrent wound botulism among injection drug users in California. Clin Infect Dis 52:862–866PubMedCrossRefGoogle Scholar
  82. 82.
    Kimura A, Higa J, Levin R, Simpson G, Vargas Y, Vugia D (2004) Outbreak of Necrotizing fasciitis due to Clostridium sordellii among black-tar heroin users. Clin Infect Dis 38:E87–91PubMedCrossRefGoogle Scholar
  83. 83.
    Passaro D, Werner B, McGee J, MacKenzie W, Vugia D (1998) Wound botulism associated with black tar heroin among injecting drug users. JAMA 279:859–863PubMedCrossRefGoogle Scholar
  84. 84.
    Shuster S (2011) The curse of the crocodile: Russia's deadly designer drug. Time. WebGoogle Scholar
  85. 85.
    Gahr M, Freudenmann RW, Heimke C, Gunst IM, Connemann BJ, Schonfeldt-Lecuona C (2012) Desomorphine goes "crocodile.". J Addict Dis 31:407–412PubMedCrossRefGoogle Scholar
  86. 86.
    Hassan Z, Muzaimi M, Navaratnam V et al (2013) From kratom to mitragynine and its derivatives: physiological and behavioral effects related to use, abuse, and addiction. Neurosci Biobehav Rev 37:138–151PubMedCrossRefGoogle Scholar
  87. 87.
    Kronstrand R, Roman M, Thelander G, Eriksson A (2011) Unintentional fatal intoxications with mitragynine and O-desmethyltramadol from the herbal blend krypton. J Anal Toxicol 35:242–247PubMedCrossRefGoogle Scholar
  88. 88.
    Siavash M, Janghorbani M, Gheshlaghi F et al (2009) A case series of abuse of a new opioid combination, norjizak. J Addict Dis 28:180–185PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Joshua B. Radke
    • 1
    • 2
  • Kelly P. Owen
    • 1
  • Mark E. Sutter
    • 1
  • Jonathan B. Ford
    • 1
    • 2
  • Timothy E. Albertson
    • 2
    • 3
  1. 1.Department of Emergency MedicineUniversity of California Davis Medical CenterSacramentoUSA
  2. 2.Department of MedicineVeterans Administration Northern California Health Care SystemMatherUSA
  3. 3.Department of Internal MedicineUniversity of California Davis Medical CenterSacramentoUSA

Personalised recommendations