Clonidine and Narcan

[18G]

Until today I never realized that Narcan can be used to reverse the effects of clonidine toxicity. I finished the PEPP class today and it was mentioned.

Any thoughts or anyone have any experience with giving Narcan to a clonidine toxicity patient?

Note: I haven't had time to research much about this so any info on mechanism of action, site binding, etc. is appreciated.

 

[jjesusfreak01]

Note: I haven't had time to research much about this so any info on mechanism of action, site binding, etc. is appreciated.

From a quick look around the internets, it does not appear that this effect has anything to do with opiate binding sites.

Short Version:

Clonidine causes CNS depression, respiratory depression

Naloxone competitively inhibits opiate receptors (lowering effects of natural opiates) leading to a secondary compensation mechanism kicking in to reverse some effects

 

[fast65]

With a quick search I haven't been able to find an answer to why Narcan works, however, it appears this is a controversial treatment. I've found a few sources that say Narcan can cause either a hypotensive reaction, or severe hypertension. What they classify as severe hypertension, I do not know, but I would expect some hypertension to result as your removing the effects of a medication that's used to control it.

 

[systemet]

I took a (very) quick look, and found a toxicology text (Cassarett and Doull's Toxicology: The basic science of poisons (2007) ISBN: 9780071470513). They mention that although clonidine is typically thought of as an alpha-2 agonist, it also acts in the CNS to cause beta-endorphin (an endogenous opiate) to be released. So toxicity can produce some symptoms resembling opiate overdose, e.g. respiratory depression, pinpoint pupils.

These are reversible by narcan. But it's not an action of clonidine at opiate receptors, it's a consequence of clonidine-triggered beta-endorphin release. So narcan will only treat those symptoms resulting from the endorphins.