OPIOID ANTAGONIST

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.