Countermeasures of opioid-induced respiratory depression

Abstract

The red line through my thesis is therefore our ability or inability to reverse opioid-induced respiratory depression with such countermeasures. I discuss the opioid-receptor antagonist naloxone, among other respiratory stimulants, (Chapter 1), the partial opioid-receptor agonist buprenorphine

(Chapter 6), and two agnostic respiratory stimulants (tianeptine, Chapter 5, and thyrotropin releasing hormone, TRH, Chapters 3 and 4) that do not interact with the endogenous opioid system and consequently leave the opioid effect on the brainstem respiratory network intact but stimulate breathing through specific stimulatory neuronal pathways. Apart from the respiratory stimulants that I discuss here, various respiratory stimulants and other countermeasures are being developed and/or studied. These include (See Table 1 for efficacy and limitations):2 nonopioid scheduled substances such as cannabinoid type 2 receptors and ketamine, hormones such as oxytocin, nicotinic acetylcholine receptor

agonists, ampakines, serotonin receptor agonists (note that some 5HT agonists produce respiratory

depression)3, antioxidants, drugs that mimic hypoxia at the carotid bodies, sequestration or scrubber techniques including container molecules and vaccination against opioids, and finally opioids with high receptor affinity but minimal respiratory action such as nalbuphine and butorphanol, next to buprenorphine.