Opioid Antagonist

OPIOID ANTAGONISTS

Drugs included:

• Naloxone, Naltrexone & Nalmefene:
  • Potent µ-receptor antagonist
  • Significant blocking action at κ and δ-receptors.
• Methylnaltrexone, Alvimopan & Naloxegol:
  • Peripheral opioid antagonists

Individual drugs:

• Naloxone:
  • Ineffective orally & given parenterally.
  • Very short acting drug.
• Nalmefene:
  • Given parenterally.
  • Longer half-life.
• Naltrexone:
  • Orally-effective.
  • Long-acting.

Actions of opioid antagonist:

• Mainly reverses opioid effects on i.v. administration.
• Precipitates withdrawal symptoms in opioid-dependent subjects.

Uses:

1. Naloxone:

• Drug of choice for acute opioid poisoning. Yet, dosage needs repeated administration.
• Neonatal resuscitation for reversing opioid effects (opioids used during labor).
• Should not be used, when mother (baby in utero) is dependent on opioid.
• Disadvantages: Precipitates withdrawal.

2. Naltrexone:

• As a maintenance drug for opioid poisoning.
• Used for preventing relapse, after opioid de-addition.
• Used to decrease craving in chronic alcoholics.

3. Combination drugs:

• Naltrexone + bupropion – Obesity treatment.

Effects of combination:

• On oral combination of naloxone + opioid:
  • Only opioid is absorbed, not naloxone. 
  • Hence, opioid produces its desired action.
• On i.v. route of addiction:
  • Both opioid & naloxone are absorbed. 
  • Naloxone stops euphoria.

4. Uses of peripheral opioid antagonist:

• Methylnaltrexone, Naloxegol & Alvimopan – Indicated for opioid-induced constipation.

NOTE ON OPIOID DE-ADDICTION:

• Chronic intake of opioids → Causes physical & psychological dependence.
• On sudden stoppage → Severe withdrawal symptoms.
• Aim: 
  • 1^st aim – Stop further drug usage → Followed by maintenance of de-addiction & prevent relapse.

1. For short duration/small doses of addiction:

• Sudden stoppage of drug therapy can be attempted.
• Mild withdrawal symptoms.
• Treatment:
  • β-blockers/clonidine/lofexidine.

• Sudden withdrawal of offending drug is dangerous.
• Cause severe withdrawal symptoms.
• Treatment:
  • Methadone maintenance.
  • Addictive drug replaced by equivalent dose of methadone.
  • Prevents withdrawal symptoms by opioid receptors stimulation, yet with much less addiction. 
  • Methadone dose gradually decreased & finally stopped.

3. For relapse prevention after de-addiction:

• Naltrexone – Mainly prevents euphoric action by blocking µ receptors.

4. On retaking opioid (after de-addiction):

• No euphoria.
• Person’s resolution to quit addiction strengthens.