Opioid Analgesics

Opioid Analgesics are powerful pain-relieving drugs that act on opioid receptors to reduce moderate to severe pain.

Definition of Opioid Analgesics:

• Opioid analgesics are drugs that relieve moderate to severe pain by binding to opioid receptors in the central and peripheral nervous system.
• They mimic the action of endogenous opioids like endorphins and enkephalins.

Opioid Receptors:

Receptor	Location	Effects
Mu (μ)	Brain, spinal cord	Analgesia, respiratory depression, euphoria, sedation, physical dependence
Kappa (κ)	Spinal cord, brain	Analgesia (spinal), dysphoria, sedation
Delta (δ)	Brain	Analgesia, mood modulation

Mechanism of Action:

• Opioids activate μ, κ, and δ receptors.
• This leads to:
  • Inhibition of adenylate cyclase
  • Decrease in cAMP
  • Opening of K⁺ channels (hyperpolarization)
  • Closing of Ca²⁺ channels (↓ neurotransmitter release)
• Net effect: Inhibition of pain signal transmission in spinal cord and brain.

Classification of Opioid Analgesics:

1. Natural Opioids (Opiates)

   • Derived from the opium poppy
   • Examples:
     • Morphine
     • Codeine

2. Semi-Synthetic Opioids

   • Chemically modified natural opioids
   • Examples:
     • Hydromorphone
     • Oxycodone
     • Oxymorphone
     • Heroin (diacetylmorphine) – not used medically in most countries

3. Synthetic Opioids

   • Fully synthetic compounds
   • Examples:
     • Fentanyl (very potent, rapid onset)
     • Methadone (used for pain and opioid dependence)
     • Meperidine (not preferred due to toxic metabolite – normeperidine)
     • Tramadol (weak μ-agonist + serotonin/norepinephrine reuptake inhibition)
     • Tapentadol (μ-agonist + norepinephrine reuptake inhibitor)

4. Endogenous Opioids

   • Naturally occurring in the body
   • Examples:
     • Endorphins
     • Enkephalins
     • Dynorphins

5. Mixed Agonist-Antagonists

   • Act as agonists at one type of receptor and antagonists at another
   • Examples:
     • Buprenorphine: Partial μ-agonist, κ-antagonist
     • Nalbuphine: κ-agonist, μ-antagonist
     • Pentazocine: κ-agonist, weak μ-antagonist

Pharmacological Effects:

1. Central Effects

   • Analgesia
   • Sedation
   • Euphoria (μ receptor)
   • Respiratory depression (dose-dependent, major cause of death in overdose)
   • Antitussive (cough suppression – especially codeine, dextromethorphan)
   • Miosis (pinpoint pupils)

2. Peripheral Effects

   • Constipation (decreased GI motility)
   • Biliary colic (spasm of sphincter of Oddi)
   • Urinary retention
   • Hypotension (due to histamine release – especially morphine)
   • Nausea/vomiting (via stimulation of chemoreceptor trigger zone)

Therapeutic Uses:

• Moderate to severe acute and chronic pain
• Anesthesia adjuncts (e.g., fentanyl)
• Cough suppression (e.g., codeine, dextromethorphan)
• Diarrhea (e.g., loperamide, diphenoxylate)
• Opioid dependence (e.g., methadone, buprenorphine)

Adverse Effects:

1. Central Nervous System:

   • Sedation, dizziness
   • Euphoria → dependence, tolerance
   • Respiratory depression (dose-limiting)
   • Miosis (pinpoint pupils)

2. Gastrointestinal:

   • Constipation (no tolerance develops)
   • Nausea, vomiting (via CTZ stimulation)

3. Cardiovascular:

   • Hypotension, bradycardia (with high doses)

4. Urinary:

   • Urinary retention

5. Skin:

   • Itching, urticaria (histamine release)

Tolerance and Dependence:

• Tolerance: Develops to analgesia, euphoria, sedation, respiratory depression
• No tolerance: To miosis and constipation
• Physical dependence: Withdrawal symptoms on abrupt cessation

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