The effect of opioids on gastrointestinal function in the ICU

Gastrointestinal (GI) dysfunction is common in the critical care setting and is highly associated with clinical outcomes. Opioids increase the risk for GI dysfunction and are frequently prescribed to reduce pain in critically ill patients. However, the role of opioids in GI function remains uncertain in the ICU. This review aims to describe the effect of opioids on GI motility, their potential risk of increasing infection and the treatment of GI dysmotility with opioid antagonists in the ICU setting.

The Birth of Naloxone: An Intellectual History of an Ambivalent Opioid

Naloxone, which reverses the effects of opioids, was synthesized in 1960, though the hunt for opioid antagonists began a half-century earlier. The history of this quest reveals how cultural and medical attitudes toward opioids have been marked by a polarization of discourse that belies a keen ambivalence. From 1915 to 1960, researchers were stymied in seeking a “pure” antidote to opioids, discovering instead numerous opioid molecules of mixed or paradoxical properties. At the same time, the quest for a dominant explanatory and therapeutic model for addiction was likewise unsettled. After naloxone’s discovery, new dichotomizing language arose in the “War on Drugs,” in increasingly divergent views between addiction medicine and palliative care, and in public debates about layperson naloxone access. Naloxone, one of the emblematic drugs of our time, highlights the ambivalence latent in public and biomedical discussions of opioids as agents of risk and relief.

Constipation and diarrhoea

Constipation is a common problem for palliative care patients, notably due to opioid-based pain management which physiologically impacts gut motility. Idiopathic diarrhoea is far less common in palliative care patients given opioid management. If present, it should be investigated, although it is often related to suboptimal constipation treatment. The management and treatment of both symptoms is largely a balance between pharmacological and non-pharmacological interventions. New treatments for the management of constipation using peripherally acting mu-opioid antagonists (PAMORAs) offer effective solutions as part of a range of clinical interventions to prevent and manage the problem successfully. A clear descriptive history is essential for optimal treatment of both constipation and diarrhoea.

ACE2 receptor, TRL-4 and SARS CoV-2: Do long acting opioids and opioid antagonists have potential for therapy?

Despite the advent of a vaccine, broadening the arsenal of drugs effective in the treatment and prevention of COVID-19 disease remains critical in the global effort to control the SARSCoV2 pandemic. Opioids and opioid antagonists may have a role in treating and in the prevention of this disease based on a number of observations: an unexpectedly low incidence of COVID-19 has been observed in patients treated for opioid dependency with long acting opioid drugs such as methadone; opioids bind to the ACE2 transmembrane protein, a molecule that is widely considered to be main host cell receptor for SARS CoV2 cell entry; opioids have systemic immunomodulatory effects which may influence the response to the virus; studies aimed at repurposing drugs for treatment of COVID-19 have identified that opioids have therapeutic potential and finally there are ongoing trials of some of these drugs. The interaction of long acting opioids or opioid antagonists with the ACE2 receptor and the possible effects on TLR4 function in SARS CoV2 infection should be given serious consideration when developing effective therapies. Note an updated version of this preprint is under review with the British Journal of Anaesthesia

ACE2 receptor, TRL-4 and SARS CoV-2: Do long acting opioids and opioid antagonists have potential for therapy?

Despite the advent of a vaccine, broadening the arsenal of drugs effective in the treatment and prevention of COVID-19 disease remains critical in the global effort to control the SARSCoV2 pandemic. Opioids and opioid antagonists may have a role in treating and in the prevention of this disease based on a number of observations: an unexpectedly low incidence of COVID-19 has been observed in patients treated for opioid dependency with long acting opioid drugs such as methadone; opioids bind to the ACE2 transmembrane protein, a molecule that is widely considered to be main host cell receptor for SARS CoV2 cell entry; opioids have systemic immunomodulatory effects which may influence the response to the virus; studies aimed at repurposing drugs for treatment of COVID-19 have identified that opioids have therapeutic potential and finally there are ongoing trials of some of these drugs. The interaction of long acting opioids or opioid antagonists with the ACE2 receptor and the possible effects on TLR4 function in SARS CoV2 infection should be given serious consideration when developing effective therapies.