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How pethidine produces respiratory depression in neonates

by egpat        Posted on 01-10-2017


Pethidine,also called as meperidine, is a synthetic opioid that can be used in mild to severe pain.

One of the uses of pethidine is to control pain in pregnant woman during child birth. It is given in the early phases of labor to decrease the pain sensation.


How it works?

It acts as agonist on μ receptors of opioids and increases the opening of potassium channels leading to hyperpolarisation and neuronal inhibition. This reduces the pain transmission producing central analgesia. It can also act on kappa receptors producing analgesia at spinal level.

mechanism of action of pethidine

What are the side effects?

As it acts on μ receptors it can show all the side effects that were observed with morphine.



Few of the important side effects include

  • Constipation
  • Sedation
  • Nausea
  • Vomiting
  • Dizziness
  • Shortness of breath
  • Dry mouth

Dry mouth is due to its antimuscarinic action.

Side effects of pethidine and norpethidine

 It can also show few of other side effects on long term use due to accumulation of norpethidine.

  • Anxiety
  • Hypotension
  • Convulsions

What happens in neonates?

It is very important that pethidine should not be given few hours before the delivery as it continuously passes into the fetus and may produce few complications in the neonate.

Pethidine can be eliminated by metabolism mainly with cytochrome P450 system. One of the metabolic pathways converts it into norpethidine by demethylation. Similarly pethidine can also be metabolized by oxidation. All these metabolites are then conjugated and excreted.

But newborns have less developed excretory system with less conjugation and elimination.  This results in accumulation of pethidine and its metabolites in neonate.

Effect of pethidine in neonates

If the pethidine levels are reached at significant levels in the neonate they may cause respiratory depression in the new born.

Another metabolite, norpethidine is a potent convulsant and can induce life threatening convulsions in the neonate.



The respiratory depression can be reversed by naloxone injection which acts as opioid antagonist and inhibits pethidine induced respiratory depression.

Naloxone reverse pethide effects but not of norpethidine

At the same time, the convulsions induced by norpethidine are not reversed by this naloxone as the former is not an opioid but is a convulsant.

Conclusion

So use of pethidine in the delivery of pregnant woman is associated with risk of respiratory depression and convulsions. The risk can be minimized by avoiding the introduction of pethidine at late phase of pregnancy. Nowadays, pethidine is replaced by other drugs like fentanyl which is short acting.

Again due to accumulation of norpethidine, today pethidine is not used for long term and only used for acute pain conditions.





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