Opioids: Names, potency, and mechanism of action

• Study notes on Opioids

Names of the Drugs & Mnemonics

• Common Opioids by potency/use mnemonic: "My Friend Has Some Craving But May Never Quit"
• The mnemonic represents: Morphine, Fentanyl, Hydromorphone, Sufentanil, Codeine, Buprenorphine, Methadone, Naloxone and Quit = withdrawal meds.

Mechanism of Action (Detailed)

• Primary Receptor Targets: Mu, Delta, and Kappa opioid receptors in the brain and spinal cord
• Mu-opioid receptors (μ) are the main site of analgesia, euphoria, respiratory depression, and dependence
  • Located in the periaqueductal gray (PAG), thalamus, brainstem, and spinal cord dorsal horn
• Delta (δ) receptors modulate analgesia and mood regulation
  • Found in the limbic system, cortex, and spinal cord
• Kappa (κ) receptors contribute to analgesia, dysphoria, and sedation
  • Located in the spinal cord and hypothalamus
• Brain Regions Affected: Periaqueductal gray (PAG): Pain modulation, Thalamus & somatosensory cortex: Pain perception, Ventral tegmental area (VTA): Reward pathway (dopamine release), Locus coeruleus: Arousal, stress (inhibition = sedation), Brainstem (medulla): Respiratory center
• Neurotransmitter Effects: Inhibit release of excitatory neurotransmitters (e.g., glutamate, substance P), Activate Gi protein-coupled receptors → inhibit adenylyl cyclase → ↓ cAMP, Open K⁺ channels (hyperpolarization) and close Ca²⁺ channels → ↓ neurotransmitter release

Indications

• Severe acute pain (e.g., post-surgical, trauma) – Morphine, Hydromorphone, Fentanyl
• Chronic cancer pain – Oxycodone, Methadone
• Breakthrough pain – Fentanyl patches or lozenges
• Moderate pain – Codeine, Tramadol
• Opioid Withdrawal Management:
  • Methadone: Full agonist, long half-life, prevents withdrawal symptoms
  • Buprenorphine: Partial agonist; less risk of overdose, ceiling effect
  • Naltrexone: Opioid antagonist; relapse prevention
  • Clonidine (off-label): For withdrawal symptoms (not an opioid)

Side Effects

• Common to All Opioids: Respiratory depression, Sedation, Nausea, vomiting, Constipation (very common), Miosis (pinpoint pupils), Euphoria → Addiction risk, Tolerance & dependence
• Severe/High-Risk Side Effects: Respiratory arrest (esp. fentanyl, high-dose morphine), Severe hypotension (IV use), Overdose → coma, death, Hyperalgesia (increased pain sensitivity with chronic use)
• Drugs with Most Harmful Side Effects:
  • Fentanyl: High potency = high overdose risk
  • Methadone: Risk of QT prolongation, respiratory depression
  • Heroin (illicit morphine derivative): High abuse/death rate
• Drugs with Least Harmful Side Effects:
  • Tramadol: Less respiratory depression, but seizure risk
  • Buprenorphine: Safer in overdose due to ceiling effect
  • Codeine: Mild, but not suitable in CYP2D6 ultrarapid metabolizers (↑ morphine conversion)

Contraindications

• Avoid or use cautiously in:
  • Respiratory disorders (COPD, sleep apnea)
  • Concurrent CNS depressant use (benzos, alcohol)
  • History of substance use disorder (unless used in MAT)
  • Head injury (↑ intracranial pressure)
  • Pregnancy (esp. early trimester or chronic use)