- Naloxone, Naltrexone & Nalmefene:
- Potent µ-receptor antagonist
- Significant blocking action at κ and δ-receptors.
- Methylnaltrexone, Alvimopan & Naloxegol:
- Peripheral opioid antagonists
- Ineffective orally & given parenterally.
- Very short acting drug.
- Given parenterally.
- Longer half-life.
Actions of opioid antagonist:
- Mainly reverses opioid effects on i.v. administration.
- Precipitates withdrawal symptoms in opioid-dependent subjects.
- 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.
- 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.
C/I peripheral opioid antagonist:
- Biliary colic –
- Due to increased intrabiliary pressure.
- Asthmatics –
- Due to bronchoconstriction aggravate in by releasing histamine (C/I in asthmatics).
- Spinal or epidural opioid administration –
- Results in intense pruritus over lips & torso.
- Due to histamine release.
NOTE ON OPIOID DE-ADDICTION:
- Chronic intake of opioids → Causes physical & psychological dependence.
- On sudden stoppage → Severe withdrawal symptoms.
- 1st 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.
- Sudden withdrawal of offending drug is dangerous.
- Cause severe withdrawal symptoms.
- 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.
- Naloxone, Naltrexone & Nalmefene are potent µ-receptor antagonist
- Methylnaltrexone, Alvimopan & Naloxegol are peripheral opioid antagonists
- Naloxone is ineffective orally & given parenterally.
- Nalmefene is given parenterally.
- Naltrexone is orally-effective.
- Opioid antagonist mainly reverses opioid effects on i.v. administration.
- Main uses of naloxone are drug of choice for acute opioid poisoning & neonatal resuscitation for reversing opioid effects.
- Naloxone precipitates withdrawal symptoms.
- Naltrexone used as for maintenance drug for opioid poisoning, for preventing relapse, after opioid de-addition & decreases craving in chronic alcoholics.
- Naltrexone along with bupropion for obesity treatment.
- Peripheral opioid antagonist indicated for opioid-induced constipation.
- For short duration/small doses of opioid addiction – Stoppage of drug attempted & treated with β-blockers/clonidine/lofexidine.
- For long duration/large dosage addiction – Sudden withdrawal is dangerous & treated with Methadone maintenance.
- For relapse prevention after de-addiction, Naltrexone is used.
- Naltrexone mainly prevents euphoric action by blocking µ receptors.