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Heroin

; ; ; .

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Last Update: April 19, 2021.

Continuing Education Activity

Heroin, also known as diacetylmorphine, is derived from the opium poppy plant. Professionals initially touted morphine as a substitute with less misuse potential. Heroin currently has no FDA-approved indications for use. Heroin is a Schedule I drug under the Controlled Substances Act of 1970, with no approved medical use in the United States. Though people in other countries use heroin, in the United States, it has no recognized therapeutic role in managing opioid use disorder. This activity outlines the indications, mechanism of action, pharmacodynamics, significant adverse effects, and toxicity of heroin and increases the knowledge of practitioners regarding how to approach this substance should they encounter patients who use it in their practice.

Objectives:

  • Explain the mechanism of action of heroin.
  • Identify the original indications of heroin before it was made illegal in the USA.
  • Review the adverse effects and toxicity of heroin.
  • Outline interprofessional team strategies for improving care coordination and communication to advance improved outcomes when encountering a patient with heroin use disorder, and how to work collaboratively to guide them to a positive outcome.
Earn continuing education credits (CME/CE) on this topic.

Indications

Heroin, also known as diacetylmorphine, is derived from the opium poppy plant.[1] Bayer Pharmaceuticals developed the diacetylmorphine molecule in 1898 as an antitussive.[1]  Professionals initially touted morphine as a substitute with less addiction potential. Heroin currently has no FDA-approved indications for use. Heroin is a Schedule I drug under the Controlled Substances Act of 1970, with no approved medical use in the United States.[2] The United Kingdom allows the use of heroin, known under the generic name of diamorphine, for diverse analgesic indications such as postoperative pain, chronic pain, palliative care, and even post-cesarean section.[3]

Heroin's chief place in American healthcare remains problematic. As an illicit opioid, people have misused heroin for decades.[4] In the 21st century, the use of heroin has caused a surge in both dependence and overdose deaths.[5] Though people in other countries use heroin, in the United States, it has no recognized therapeutic role in managing opioid addiction. 

Mechanism of Action

Heroin is synthetically derived from the morphine alkaloid in opium and is approximately twice as potent as morphine. Heroin acts agonistically on central nervous system (CNS) opioid receptors mu, kappa, and delta.[1] Mu receptor effects account for both the analgesic effects (Mu1) and the respiratory depression and euphoria (Mu2).[6] Activation of Mu2 receptors also causes miosis, reduced gastrointestinal (GI) motility, and physiologic dependence. Kappa receptor activation causes some degree of analgesia as well.[6] Delta receptors are more involved in spinal analgesia phenomena.

Heroin metabolizes in the CNS to monoacetylmorphine, which is a more potent mu-receptor agonist than morphine.[6] Peripheral tissues metabolize heroin to 6-monoacetylmorphine and then morphine.[1] Many state toxicology labs use the 6-monoacetylmorphine to determine which overdose deaths were due to heroin.

When taken orally, heroin undergoes first-pass metabolism to morphine via deacetylation. Therefore, unlike intravenous administration, oral ingestion does not cause a rapid onset of effects and is less desirable to users. 6-monoacetylmorphine and morphine activate opioid receptors.[7]

Administration

As mentioned above, practitioners in the United States do not administer heroin in any sanctioned healthcare setting. Illicitly, people misuse heroin via subcutaneous, intranasal, intramuscular, intravenous methods. Heroin is highly lipophilic and, therefore, rapidly crosses the blood-brain barrier.[1] All routes of administration lead to the rapid absorption of heroin. Peak serum levels in each of these routes are as follows: five to ten minutes subcutaneously, three to five minutes intranasally and intramuscularly, and less than one minute intravenously.[8]

Once absorbed into the serum, heroin reaches the brain in 15 to 20 seconds. While less than 5% of intravenous morphine reaches the brain, 68% of intravenous heroin makes contact with receptors in the brain. This rapid effect gives the user a rush that typically leads to continued use with hopes of achieving that same first experience of euphoria.[9]

Adverse Effects

The intended effects of heroin misuse are those classically associated with any opioid effects. These are analgesia, euphoria, and often alleviation of opioid withdrawal symptoms. All other effects of heroin could be considered adverse. Respiratory depression is likely the most concerning adverse effect, leading to death in an increasing number of misusers. The extreme physiologic dependence also represents a major concern in those who misuse heroin.

Heroin reliably causes decreased GI motility, which commonly leads to constipation.[10] This decreased motility can be problematic enough for users that they may require medical attention to relieve constipation. Miosis represents a minimal concern to healthcare providers or those abusing the drug, though this effect can have diagnostic value.

Some practitioners have described severe, life-threatening pulmonary edema in patients who misuse or overdose on heroin.[11] This edema is noncardiogenic and likely relates to increased pulmonary vascular permeability.

Practitioners have also attributed cases of compartment syndrome to heroin use.[12]

Contraindications

Because the FDA recognizes no medical use for heroin, it has not specified any contraindications. In countries where people use the drug for medicinal purposes, hypersensitivity, and potential for misuse or dependence could be perceived contraindications.

Canada lists heroin as a Schedule I drug in the Controlled Drugs and Substances Act.[13] Various countries have enforced different levels of criminal regulation related to heroin. 

Monitoring

Again, with no approved use for heroin, no therapeutic index exists. However, pharmacodynamically, heroin could be considered to have a very narrow therapeutic window. Due to variations in potency and concentration, users are not aware of the actual amount of the active drug in any given sample[14]. Therefore the same apparent dose that causes euphoria one day could very well lead to an overdose the next.

Drug levels are not typically useful, though toxicology assessments post-mortem may quantify several metabolites.[7] 

Toxicity

Professionals thoroughly describe heroin toxicity in the literature and popular media. With the high rate of prescription opioid addiction (see opioid use disorder), and the lower cost of heroin, many individuals have developed heroin dependence.[15] As discussed above, heroin (especially if administered intravenously) is very likely to cause an overdose and death due to respiratory depression. From 2002 through 2013, heroin overdoses went from 0.7 deaths per 100,000 to 2.7.[16] In 2013, roughly 517,000 people reported heroin use in the past year, 1.5 times the amount in 2007.[17] State and federal legislation are implementing diverse methods to curb this epidemic of heroin overdose deaths. The many infectious and economic effects of heroin dependence add to the risk of death.

The antidote for heroin overdose or poisoning is naloxone. Naloxone binds with high affinity to the Mu receptors in the CNS[18]. Administration of naloxone is an inverse agonist and, if given in high enough dose, will induce withdrawal in an opioid-dependent patient.[18] Naloxone is also believed to block the binding of endogenous opioids. Practitioners can administer naloxone intravenously, intramuscularly, and increasingly intranasally. Many first responders now carry intranasal naloxone kits to reverse heroin or opioid overdose in field settings. 

Naltrexone, a long-acting opioid antagonist, is available both orally and as a long-acting intramuscular injection. The risk of precipitating a prolonged withdrawal syndrome, however, prohibits the use as an antidote for initial reversal.[19] Clinicians are using these long-acting opioid antagonists in medication-assisted treatment for patients with opioid use disorder. 

Enhancing Healthcare Team Outcomes

Medication-assisted treatment represents an effective option for the treatment of heroin dependence and opioid use disorder in general. Buprenorphine and methadone are the chief agents used, with buprenorphine being more safe and effective. Buprenorphine also has a higher affinity for the mu-opioid receptors than does heroin.[20]

Continuing Education / Review Questions

References

1.
Sneader W. The discovery of heroin. Lancet. 1998 Nov 21;352(9141):1697-9. [PubMed: 9853457]
2.
Rosen D, Hunsaker A, Albert SM, Cornelius JR, Reynolds CF. Characteristics and consequences of heroin use among older adults in the United States: a review of the literature, treatment implications, and recommendations for further research. Addict Behav. 2011 Apr;36(4):279-85. [PMC free article: PMC3127414] [PubMed: 21237575]
3.
Metrebian N, Mott J, Carnwath Z, Carnwath T, Stimson GV, Sell L. Pathways into receiving a prescription for diamorphine (heroin) for the treatment of opiate dependence in the United kingdom. Eur Addict Res. 2007;13(3):144-7. [PubMed: 17570910]
4.
Cicero TJ, Ellis MS, Surratt HL, Kurtz SP. The changing face of heroin use in the United States: a retrospective analysis of the past 50 years. JAMA Psychiatry. 2014 Jul 01;71(7):821-6. [PubMed: 24871348]
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Jiang R, Lee I, Lee TA, Pickard AS. The societal cost of heroin use disorder in the United States. PLoS One. 2017;12(5):e0177323. [PMC free article: PMC5448739] [PubMed: 28557994]
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Goldstein A. Heroin addiction: neurobiology, pharmacology, and policy. J Psychoactive Drugs. 1991 Apr-Jun;23(2):123-33. [PubMed: 1662715]
7.
Maas A, Madea B, Hess C. Confirmation of recent heroin abuse: Accepting the challenge. Drug Test Anal. 2018 Jan;10(1):54-71. [PubMed: 28681463]
8.
Dinis-Oliveira RJ. Metabolism and metabolomics of opiates: A long way of forensic implications to unravel. J Forensic Leg Med. 2019 Feb;61:128-140. [PubMed: 30621882]
9.
Gottås A, Arnestad M, Halvorsen PS, Bachs LC, Høiseth G. Pharmacokinetics of heroin and its metabolites in vitreous humor and blood in a living pig model. Forensic Toxicol. 2016;34(2):277-285. [PMC free article: PMC5018035] [PubMed: 27660664]
10.
Pasternak GW. Mu Opioid Pharmacology: 40 Years to the Promised Land. Adv Pharmacol. 2018;82:261-291. [PubMed: 29413524]
11.
Raja AS, Miller ES, Flores EJ, Wakeman SE, Eng G. Case 37-2017. A 36-Year-Old Man with Unintentional Opioid Overdose. N Engl J Med. 2017 Nov 30;377(22):2181-2188. [PubMed: 29171813]
12.
Benns M, Miller K, Harbrecht B, Bozeman M, Nash N. Heroin-Related Compartment Syndrome: An Increasing Problem for Acute Care Surgeons. Am Surg. 2017 Sep 01;83(9):962-965. [PubMed: 28958275]
13.
Prangnell A, Fairgrieve C, Nosova E, DeBeck K, Milloy MJ, Hayashi K. High Prevalence of Self-Reported Exposure to Adulterated Drugs Among People Who Experienced an Opioid Overdose in Canada: A Cohort Study. Subst Use Misuse. 2019;54(6):980-985. [PMC free article: PMC6476645] [PubMed: 30663484]
14.
Arens A, Olives T, Laes J, Cole J. It's not just heroin anymore. Clin Toxicol (Phila). 2017 Jul;55(6):608. [PubMed: 28440696]
15.
Faryar KA, Freeman CL, Persaud AK, Furmanek SP, Guinn BE, Mattingly WA, Wiemken TL, Buckner KA, Huecker MR. The Effects of Kentucky's Comprehensive Opioid Legislation on Patients Presenting with Prescription Opioid or Heroin Abuse to One Urban Emergency Department. J Emerg Med. 2017 Dec;53(6):805-814. [PubMed: 29102093]
16.
Hedegaard H, Chen LH, Warner M. Drug-poisoning deaths involving heroin: United States, 2000-2013. NCHS Data Brief. 2015 Mar;(190):1-8. [PubMed: 25932890]
17.
Jones CM, Logan J, Gladden RM, Bohm MK. Vital Signs: Demographic and Substance Use Trends Among Heroin Users - United States, 2002-2013. MMWR Morb Mortal Wkly Rep. 2015 Jul 10;64(26):719-25. [PMC free article: PMC4584844] [PubMed: 26158353]
18.
Skolnick P. On the front lines of the opioid epidemic: Rescue by naloxone. Eur J Pharmacol. 2018 Sep 15;835:147-153. [PubMed: 30092179]
19.
Bradley ES, Liss D, Carreiro SP, Brush DE, Babu K. Potential uses of naltrexone in emergency department patients with opioid use disorder. Clin Toxicol (Phila). 2019 Sep;57(9):753-759. [PMC free article: PMC6908461] [PubMed: 30831039]
20.
D'Onofrio G, Chawarski MC, O'Connor PG, Pantalon MV, Busch SH, Owens PH, Hawk K, Bernstein SL, Fiellin DA. Emergency Department-Initiated Buprenorphine for Opioid Dependence with Continuation in Primary Care: Outcomes During and After Intervention. J Gen Intern Med. 2017 Jun;32(6):660-666. [PMC free article: PMC5442013] [PubMed: 28194688]
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Bookshelf ID: NBK441876PMID: 28722906

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