Opioid Use Disorder

OUD Basics - The Poppy Problem

• Definition: A problematic pattern of opioid use leading to clinically significant impairment or distress (DSM-5). ICD-11: Opioid Dependence. Key features: craving, tolerance, withdrawal.
• Common Opioids:
  • Natural: Opium, Morphine, Codeine.
  • Semi-synthetic: Heroin (diacetylmorphine), Buprenorphine, Oxycodone.
  • Synthetic: Fentanyl, Methadone, Tramadol, Pethidine.
• Routes of Administration: Oral, intranasal (snorting), intravenous (IV), inhalation (smoking, e.g., "chasing the dragon").
• Indian Epidemiology (AIIMS, 2019): Approx. 2.8% of population (10-75 yrs) reported past-year opioid use; ~2.1% are users of concern. Heroin is the most common illicit opioid.

⭐ Heroin (diacetylmorphine) is rapidly hydrolyzed to 6-monoacetylmorphine (6-MAM) and then to morphine in the body, both of which are active. This contributes to its potent and rapid effects.

Brain Hijack - How Opioids Work

Opioids bind to μ, κ, δ receptors, primarily Gi-coupled.

• Receptor Functions:
  • μ (Mu): Euphoria, analgesia, respiratory depression, miosis, ↓GI motility. 📌 Key for analgesia & addiction.
  • κ (Kappa): Spinal analgesia, dysphoria, sedation, miosis.
  • δ (Delta): Analgesia, antidepressant/anxiolytic effects.
• Cellular Mechanism:
  • ↓Adenylyl cyclase → ↓cAMP.
  • Postsynaptic: ↑K+ efflux → hyperpolarization.
  • Presynaptic: ↓Ca2+ influx → ↓neurotransmitter release.
• Reward Pathway Activation:
  • VTA: μ-agonism inhibits GABAergic neurons.
  • → Disinhibition of VTA dopamine neurons.
  • → ↑Dopamine in Nucleus Accumbens (NAc) → euphoria & reinforcement.
• Neuroadaptation:
  • Tolerance: ↓Receptor response → ↓drug effect.
  • Dependence: Physiological adaptation; withdrawal on cessation.

⭐ The μ (mu) opioid receptor is primarily responsible for euphoria and respiratory depression.

Signs & Symptoms - Highs and Lows

Opioid Intoxication vs. Withdrawal

-   📌 Mnemonic: e.g., 'MY LEGS CRAMP' (Myalgia, Yawning, Lacrimation, Emesis, Gooseflesh, etc.)
-   COWS Scale (Severity): Mild **5-12**, Mod **13-24**, Mod Sev **25-36**, Sev **>36**.

• ⭐ > Piloerection ("gooseflesh") during opioid withdrawal is the origin of the term "cold turkey".

Flowchart: Opioid Withdrawal Timeline

Diagnostic Criteria (DSM-5/ICD-11)

• Problematic opioid use → impairment/distress. ≥2 criteria/12mo (e.g., tolerance, withdrawal, craving, loss of control).

Treatment Toolkit - Road to Recovery

• Pharmacological Management

  • Detoxification:

    • Clonidine, lofexidine for autonomic symptoms.
    • Gradual opioid agonist taper (e.g., methadone, buprenorphine).

  • Maintenance Therapy:

    Drug	MOA	Key Pro(s)	Key Con(s)	Critical Dosing/Timing
    Methadone	Full $\mu$-agonist	Effective, ↓craving	QTc risk, OD risk	Start 20-30mg, supervised
    Buprenorphine	Partial $\mu$-agonist; $\kappa$-antagonist	Ceiling effect (safer), ↓stigma, sublingual	Precipitated withdrawal	Start COWS ≥8-12; often +Naloxone
    Naltrexone	$\mu$-antagonist	Non-addictive, oral/IM	Needs full detox, hepatotoxicity	Opioid-free 7-10 days

• Non-Pharmacological Interventions: Key psychosocial interventions include:

  • Cognitive Behavioral Therapy (CBT)
  • Motivational Interviewing (MI)
  • Contingency Management (CM)
  • Support groups (e.g., Narcotics Anonymous - NA)

• Harm Reduction Strategies: Strategies to minimize negative consequences:

  • Needle and syringe programs (NSPs)
  • Distribution of naloxone kits for overdose reversal

⭐ Buprenorphine's ceiling effect on respiratory depression makes it safer in overdose than full agonists like methadone.

High‑Yield Points - ⚡ Biggest Takeaways

• Opioid intoxication triad: pinpoint pupils (miosis), respiratory depression, altered mental status/coma.
• Naloxone is the life-saving antidote for acute overdose, rapidly reversing respiratory depression.
• Opioid withdrawal: severe flu-like symptoms (lacrimation, rhinorrhea, mydriasis, piloerection, muscle aches); not typically life-threatening.
• Methadone (long-acting agonist) and buprenorphine (partial agonist) are crucial for Opioid Substitution Therapy (OST/MAT).
• Naltrexone (antagonist) aids relapse prevention in detoxified individuals.
• Clonidine alleviates autonomic hyperactivity during withdrawal.