Historical overview of (non-opioid) reversal agents of opioid-induced respiratory depression (OIRD): Lessons from the past and new developments
Abstract
The development of respiratory stimulants and opioid antagonists to
treat opioid induced respiratory depression remains one of the biggest challenges in
respiratory research. A variety of substances with stimulatory effects on respiration have
been shown to be of little use in clinical practice, either because of narrow margins of safety or due to serious side effects. With the introduction of naloxone a safe treatment for OIRD came within reach, although it reverses all opioid effects, thereby also affecting analgesia. This makes naloxone a very useful drug to treat life-threatening OIRD, but not efficacious for prevention of OIRD. Recent studies have shown that the development of ampakines and potassium-channel blockers such as GAL021 make prevention of OIRD without incidence of serious side effects possible. In the forthcoming years these respiratory stimulants might become a valuable addition to the anesthesiologists’ armamentarium. The development of respiratory stimulants and opioid antagonists to treat opioid induced respiratory depression remains one of the biggest challenges in respiratory research. A variety of substances with stimulatory effects on respiration have been shown to be of little use in clinical practice, either because of narrow margins of safety or due to serious side effects. With the introduction of naloxone a safe treatment for OIRD came within reach, although it reverses all opioid effects, thereby also affecting analgesia. This makes naloxone a very useful drug to treat life-threatening OIRD, but not efficacious for prevention of OIRD. Recent studies have shown that the development of ampakines and potassium-channel blockers such as GAL021 make prevention of OIRD without incidence of serious side effects possible. In the forthcoming years these respiratory stimulants might become a valuable addition to the anesthesiologists’ armamentarium.
