title: Opiate antagonists in shock and trauma.
abstract: Circulatory shock and pain were associated as frequent consequences of surgery and trauma prior to the development of anesthetics. The recent discovery of the endogenous opioid systems affords the opportunity to link the occurrence of pain and circulatory shock at a functional level. The involvement of opioid systems in endogenously and exogenously induced analgesia is well established. In this review, evidence is presented indicating that endogenously activated opioid systems contribute to the pathophysiology of circulatory shock following such diverse causes as endotoxemia, hemorrhage, and spinal cord trauma. The opiate antagonist naloxone (Narcan), acting to oppose endogenous opiates, rapidly reverses the hemodynamic, metabolic, and biochemical sequelae of shock in experimental animal models. Additionally, naloxone has been shown to prevent paralysis following acute cervical spinal cord injury. As with all drugs, several physiologic and pathophysiologic circumstances limit the usefulness of naloxone in reversing shock and improving tissue perfusion. They include acidosis, hypothermia, interactions with administered steroids, and the potential for antagonizing opioid-induced analgesia, which may exacerbate pain in the traumatized patient. Two approaches have yielded potential ways to circumvent these limitations: first, the development of specific opioid-receptor antagonists, which reverse shock without affecting opioid analgesia, and second, the pharmacologic use of thyrotropin releasing hormone (TRH), which acts through its own effector system, independent of endogenous opioid receptors, to produce autonomic effects that reverse shock in experimental animals without affecting analgesia.
mesh_terms: D000818:Animals; D006801:Humans; D009270:Naloxone / Q000627:therapeutic use*; D009292:Narcotic Antagonists; D012377:Rodentia; D012769:Shock / Q000188:drug therapy* / Q000503:physiopathology; D012771:Shock, Hemorrhagic / Q000188:drug therapy / Q000503:physiopathology; D012772:Shock, Septic / Q000188:drug therapy / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000188:drug therapy / Q000503:physiopathology; D013973:Thyrotropin-Releasing Hormone / Q000627:therapeutic use; D014947:Wounds and Injuries / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D009292:Narcotic Antagonists; D009270:Naloxone; D013973:Thyrotropin-Releasing Hormone