Opioid Analgesics: Morphine, Oxycodone, and Fentanyl

Morphine

• Use: Moderate to severe pain management
• Pharmacodynamics: Agonist at mu-opioid receptors, altering pain perception and response in the central nervous system
• Pharmacokinetics: Metabolized in the liver to active and inactive metabolites; excreted renally; half-life ~2-4 hours
• Details: Risk of respiratory depression; adjust dose for renal impairment to prevent metabolite accumulation

Oxycodone

• Use: Moderate to severe pain relief
• Pharmacodynamics: Mu-opioid receptor agonist; inhibits ascending pain pathways
• Pharmacokinetics: Absorbed in GI tract, metabolized in the liver (CYP3A4 and CYP2D6), excreted in urine; half-life ~3-6 hours
• Details: Available in immediate and extended-release forms; monitor for misuse and respiratory depression

Fentanyl

• Use: Severe pain management, often in surgical or cancer settings
• Pharmacodynamics: Potent mu-opioid receptor agonist; rapid onset and short duration of action
• Pharmacokinetics: Highly lipophilic; metabolized in the liver (CYP3A4); excreted in urine; half-life 2-4 hours (IV)
• Details: Not for opioid-naïve patients; available in transdermal, buccal, and IV forms

Methadone

• Use: Chronic pain and opioid dependence treatment
• Pharmacodynamics: Mu-opioid receptor agonist with NMDA receptor antagonist properties; reduces pain and opioid cravings
• Pharmacokinetics: Long half-life (15-60 hours); metabolized in the liver; excreted in urine and bile
• Details: Prolongs QT interval; careful monitoring needed to avoid overdose

Hydrocodone

• Use: Moderate to severe pain relief
• Pharmacodynamics: Mu-opioid receptor agonist; inhibits ascending pain pathways
• Pharmacokinetics: Metabolized in the liver (CYP2D6) to hydromorphone; half-life ~4 hours
• Details: Often combined with acetaminophen; monitor for hepatotoxicity

Naloxone (Narcan®)

• Use: Reversal of opioid overdose
• Pharmacodynamics: Opioid receptor antagonist; displaces opioids from receptors, reversing respiratory depression
• Pharmacokinetics: Onset varies by route (IV fastest); duration 20-90 minutes
• Details: May precipitate withdrawal in opioid-dependent individuals; multiple doses may be needed for long-acting opioids

Buprenorphine

• Use: Opioid dependence treatment and chronic pain management
• Pharmacodynamics: Partial mu-opioid receptor agonist and kappa-opioid receptor antagonist; offers pain relief with a ceiling effect on respiratory depression
• Pharmacokinetics: Metabolized in the liver (CYP3A4); excreted in bile and urine; half-life ~24-42 hours
• Details: Often combined with naloxone to deter misuse

Ketamine

• Use: Anesthetic and adjunct for pain management
• Pharmacodynamics: NMDA receptor antagonist; reduces central sensitization to pain
• Pharmacokinetics: Rapid onset (IV); metabolized in the liver; excreted in urine; half-life ~2.5 hours
• Details: Can cause dissociative effects and hallucinations; used in low doses for pain, higher doses for anesthesia

Diazepam (Valium®)

• Use: Anxiety, muscle spasms, and seizures
• Pharmacodynamics: Benzodiazepine enhancing GABA-A receptor activity; produces sedation and muscle relaxation
• Pharmacokinetics: Long half-life (20-50 hours); metabolized in the liver; excreted in urine
• Details: Risk of dependence and sedation; use cautiously with opioids

Clonazepam (Klonopin®)

• Use: Seizure disorders and panic disorders
• Pharmacodynamics: Enhances GABA-A receptor activity; provides anxiolytic and anticonvulsant effects
• Pharmacokinetics: Metabolized in the liver (CYP3A4); half-life ~20-40 hours
• Details: Monitor for sedation and dependence

This lesson covers the key aspects of opioid analgesics, focusing on morphine, oxycodone, and fentanyl. It details their uses in pain management, pharmacodynamics as mu-opioid receptor agonists, and pharmacokinetics including metabolism and elimination. Special considerations include respiratory depression risk and adjustments for renal impairment.