II. Epidemiology

  1. Incidence Opioid misuse in U.S.: 11.5 Million (in 2016)
  2. Incidence of those meeting diagnostic criteria for Opioid Use Disorder in U.S.: 2.1 Million (in 2016, age >12 years)
  3. Substance Use Disorder involving prescription Pain Medications in U.S.: 1.8 Million (in 2016)
  4. Fatal Opioid Overdoses in U.S.: >500,000 for the 15 years between 2000 to 2015
    1. Opioid Overdose killed 47,000 in U.S. in 2017 and 56,000 in 2019
    2. Opioid Overdose killed 75,000 in U.S. in the first year of Covid epidemic (starting April 2020)
    3. Opioid Overdose is the number one cause of death in U.S. for age <50 years old
    4. Opioid Use Disorder confers a 10 fold higher risk of death over the general population
    5. One year mortality after non-fatal Overdose 5.5%, with 20% of deaths in the first month
  5. Associated comorbid conditions
    1. HIV Infection
    2. Hepatitis B Infection
    3. Hepatitis C Infection
    4. Tuberculosis

III. Pathophysiology

  1. Opioids activate Mu Opioid receptors in the Midbrain and forebrain's reward center (mesolimbic)
    1. Mediated by Dopamine release with secondary euphoria and pain relief
    2. Normal behaviors stimulate emotion, motivation and pleasure
  2. Opioids, esp. in higher doses, over-stimulate the region and reinforce drug use
    1. Tolerance develops with longer standing use
      1. Increasing doses are needed over time to release the same Dopamine
    2. Withdrawal symptoms are mediated by altered Norepinephrine regulation
  3. Opioid Addiction alters neurologic pathways in the longterm
    1. Abstinence fails as a treatment strategy with or without counseling

IV. Risk Factors

  1. Family History of Substance Abuse (strong risk factor)
  2. Mental illness
  3. Childhood adverse events
  4. Trauma History

V. Preparations

  1. Direct Opium Derivatives
    1. Morphine (Morphine Sulphate, "White Stuff", "M")
    2. Codeine (methyl-Morphine, "School boy")
  2. Morphine Derivative
    1. Dilaudid (Hydromorphone)
    2. Heroin (Diacetyl-Morphine)
      1. Street Names: H, Horse, Junk, Smack, Scag, Stuff
      2. Administered: IV, "snorted" or smoked
      3. Injectable Heroin is typically prepared from "Black Tar" or "China White"
        1. Heroin is heated in a cooker (e.g. spoon with lighter underneath) often with water
        2. Cotton swab is placed in cooker as filter
        3. Solution is drawn up into syringe through filter
        4. Arm is prepped, Tourniquet applied and injected
  3. Semi-Synthetics and Synthetics
    1. Methadone (Dolophine amidone, "Dolly")
    2. LAAM
    3. Propoxyphene
    4. Meperidine
    5. Fentanyl
      1. Has been reconstituted into tablets appearing similar to Oxycodone and Hydrocodone
      2. High potency and risk of lethal Overdose
  4. Other abused Opioids
    1. See Krokodil
    2. Loperamide (Imodium, "Poor-man's Methadone")
      1. Users take more than 64 mg (4 fold higher than the total daily dose) to get high
      2. Misuse increasing in 2016 and associated with Arrhythmia and Cardiac Arrest deaths
      3. (2016) Presc Lett 23(7): 37-8
    3. Dextromethorphan
      1. See Dextromethorphan Abuse
    4. Kratom
      1. Herbal stimulant at low dose and with Opioid effects at higher dose
      2. Derived from tropical tree (within coffee family)
      3. Currently legal in U.S. to purchase (as of 2016)
      4. Kratom withdrawal is similar to Opioid Withdrawal
      5. (2016) Presc Lett 23(11)
    5. Pink (U-47700)
      1. Pink crystals or powder (may also be clear to yellow)
      2. Mu receptor Agonist (Opioid)
      3. Not identified on routine toxicology screen
      4. Has been found mixed with other street drugs
      5. May be potent and is linked to U.S. Overdose deaths

VI. Pharmacokinetics

  1. Methadone (35-180 mg): 18-24 hour duration
  2. Heroin (2-8 mg): 4-6 hour duration
    1. Rapidly metabolized to Morphine

VII. History

  1. See Substance Abuse Evaluation
  2. Single Screening Question: "In the last week, have you struggled with painkillers or used Heroin or Fentanyl?"

IX. Diagnosis: Opioid Use Disorder DSM 5 Criteria

  1. Criteria: Two or more of the following 11 criteria in the last year
    1. Loss of control (2 criteria)
      1. Opioids are taken in larger amounts or for a longer period than intended
      2. Persistent desire or unsuccessful attempts to cut-down or control Opioid use
    2. Compulsivity (2 criteria)
      1. Considerable time spent in trying to obtain, use or recover from Opioids
      2. Craving or strong desire to use Opioids
    3. Continued use despite consequences (5 criteria)
      1. Recurrent Opioid use interferes with obligations at work, home or school
      2. Use continues despite social or interpersonal problems
      3. Important activities (social, occupational, recreational) are reduced or eliminated due to Opioid use
      4. Opioid use in physically hazardous situations
      5. Persistent or recurrent, related physical or psychological problem does not dissuade continued use
    4. Tolerance and Dependence (2 criteria)
      1. Tolerance (e.g. markedly increased amounts to achieve desired effect)
      2. Withdrawal syndrome from Opioids (or related agent used to prevent withdrawal symptoms)
  2. Qualifiers: Remission
    1. Early Remission (no Opioid use criteria met for at least 3 months)
    2. Sustained Remission (no Opioid use criteria met for at least 12 months)
  3. Qualifers: Management
    1. On maintenance therapy (e.g. Methadone, Buprenorphine)
    2. In controlled environment (Opioid access restricted)
  4. Qualifiers: Severity
    1. Mild
      1. Symptom Criteria: 2-3
    2. Moderate
      1. Symptom Criteria: 4-5
    3. Severe
      1. Symptom Criteria: 6 or more
  5. References
    1. (2013) DSM5, APA, p. 541-2

X. Management: Toxicity or Overdose

XI. Management: Treatment Options

  1. See Opioid Withdrawal
  2. Precautions
    1. Treat Opioid Addiction as a chronic disease
    2. Relapse is common, but roughly 35% of patients do not relapse in 1 year on medical therapy (e.g. Buprenorphine)
    3. Avoid stigmatizing patients for their Opioid use
    4. Employ an open door policy for patients to return for Chemical Dependency treatment when they are ready
    5. With continued Opioid use, help patients practice harm reduction (see below)
  3. Overall Recommended approach
    1. Prescribe intranasal Naloxone for home
    2. Initiate Opioid Agonist Therapy (OAT)
      1. Buprenorphine or Buprenorphine/Naloxone Initiation
    3. Refer to Outpatient-Based Opioid Treatment (OBOT)
    4. Social support or peer recovery coaches
  4. Counseling
    1. Chemical Dependency Rehabilitation
    2. Narcotics Anonymous
    3. Outpatient-Based Opioid Treatment (OBOT)
      1. Place referral at time of evaluation, initiation of medication management
  5. Medical Management: Single Agent Agonists (require special X-DEA Number to prescribe)
    1. Buprenorphine (Buprenex)
      1. See Buprenorphine for initiation protocols
      2. Highly effective in withdrawal and craving relief
      3. Approved for use in age 16 and older, and considered safe in pregnancy
      4. Partial opioid Agonist with effect ceiling and blocks other Opioids (e.g. Heroin)
      5. However, may be abused if crushed and injected
      6. Available as sublingual (Subutex), implants (Probuphine) and long-acting intramuscular (Sublocade)
    2. Buprenorphine/Naloxone (Suboxone, Zubsolv SL)
      1. Naloxone is inactive unless injected, hence countering Buprenorphine injection misuse
      2. Has been misused by snorting
      3. Buprenorphine/Naloxone may be referred to as dual therapy (in contrast to monotherapy with Buprenorphine alone)
    3. Methadone
      1. High risk for Opioid Overdose (typically administered by Methadone clinic)
      2. Approved for use in age 18 and older, and considered safe in pregnancy
    4. Levomethadyl (Orlaam)
      1. Methadone-like agent
  6. Medical Management: Single Agent Antagonists
    1. Naltrexone (Trexan, Vivitrol)
  7. Treatment strategy
    1. Used as long-term therapy for uncontrolled, refractory Opioid Abuse as a chronic illness
      1. Correct the misconception that patients are trading one addiction for another
      2. Reframe these agents for addiction, as similar to Insulin in Diabetes Mellitus
    2. Abstinence alone, even after CD treatment, is not typically effective
      1. Relapse rates after treatment approach 90% within one month
      2. Addiction medications (e.g. Buprenorphine, Methadone) are intended for longterm use to prevent relapse
    3. Goal is prevention of continued uncontrolled Opioid Abuse (e.g. Heroin Overdose)
      1. Mortality from uncontrolled Opioid Addiction is very high

XII. Prevention: Harm Reduction

  1. See Intravenous Drug Abuse
  2. See Opioid Use Disorder in Pregnancy
  3. Primary Prevention
    1. Best preventive strategy is to keep Opioid naive patients naive (avoid prescribing Opioids when possible)
    2. See Emergency Department Pain Management
  4. Secondary Prevention
    1. See Chemical Dependency treatment and maintenance therapy above
  5. Tertiary Prevention
    1. Harm reduction for patients unwilling to pursue treatment, ambivalent about their chemical abuse
    2. Continue to offer Chemical Dependency treatment and maintenance therapy
  6. Prescription Naloxone
    1. Available as a home intranasal or intramuscular prescription for emergency delivery in case of Overdose
    2. Naloxone may also be delivered intranasally with an adapter
    3. Some regions have built take-home kits with informational materials for use
  7. Needle exchange program
    1. Lowers risk of infection transmission (HIV Infection, Hepatitic C infection)
    2. Does not promote IV Drug Abuse
  8. Infectious disease screening
    1. HIV Infection
    2. Hepatitis C Infection
    3. Syphilis
    4. Tuberculosis
    5. Cervical Dysplasia
  9. Immunizations
    1. Hepatitis A Vaccine
    2. Hepatitis B Vaccine
  10. Contraception in women of child bearing age
    1. See Opioid Use Disorder in Pregnancy
    2. Reduce Unintended Pregnancy rates (very high rates among patient's with Substance Abuse)
    3. Long Acting Contraception is recommended (e.g. Intrauterine Device, Contraceptive Implant)
  11. Other measures (Heroin users)
    1. Wash hands before preparing Heroin
    2. Use a clean cooker (e.g. spoon), clean water, new cotton filter
    3. Use new sterile needles, syringe for each injection (do not share needles)
    4. Do not spit on or lick the needle or injection site before injection
    5. Alcohol swab the injection site before needle insertion

XIII. Resources

  1. SAM-HSA Help Line
    1. https://www.samhsa.gov/find-help/national-helpline
    2. Phone: 1800-662-HELP
  2. Narcotics Anonymous (NA)
    1. http://www.na.org
    2. Phone: 818-773-9999
  3. Nar-Anon Family Group Headquarters
    1. http://www.onlinerecovery.org/co/nfg
  4. Narcotic Treatment Programs Directory
    1. http://www.fda.gov/cder/compliance/ntpdir.pdf
  5. National Harm Reduction Coalition
    1. https://harmreduction.org/

XIV. References

  1. Long, katona, Kolb and dos Santos (2022) Crit Dec Emerg Med 36(9): 4-11
  2. Mason and Papp in Herbert (2015) EM:Rap 15(3): 13
  3. Orman and Stader in Herbert (2017) EM:Rap 17(12):12-3
  4. Strayer in Herbert (2020) EM:Rap 20(6):10-2
  5. Coffa (2019) Am Fam Physician 100(7):416-25 [PubMed]
  6. Krambeer (2001) Am Fam Physician 63(12):2404-10 [PubMed]
  7. Zoorob (2018) Am Fam Physician 97(5): 313-20 [PubMed]

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