Articles: opioid.
-
Prevention and control of postoperative pain are essential. Inadequate treatment of postoperative pain continues to be a major problem after many surgeries and leads to worse outcomes, including chronic postsurgical pain. Optimal management of postoperative pain requires an understanding of the pathophysiology of pain, methods available to reduce pain, invasiveness of the procedure, and patient factors associated with increased pain, such as anxiety, depression, catastrophizing, and neuroticism. Use of a procedure-specific, multimodal perioperative pain management provides a rational basis for enhanced postoperative pain control, optimization of analgesia, decrease in adverse effects, and improved patient satisfaction.
-
Opioid tolerance is a limiting factor in chronic pain. Delta opioid peptide (DOP)(δ) receptor antagonism has been shown to reduce tolerance. Here, the common clinical mu opioid peptide (MOP)(µ) receptor agonist fentanyl has been linked to the DOP antagonist Dmt-Tic (2',6'-dimethyl-L-tyrosyl-1,2,3,4-tetrahydrisoquinoline-3-carboxylic acid) to create new bivalent compounds. ⋯ The addition of a linker between fentanyl and Dmt-Tic did not alter the ability to bind to MOP and DOP, however a substantial loss in MOP functional activity was apparent. This highlights the difficulty in multifunctional opioid development.
-
Responses to pharmacotherapy for acute and chronic pain are highly variable, and efficacy is often compromised by some form of toxicity. To increase our understanding of complexities of pharmacotherapy, the authors discuss an approach to identify analgesic responder subgroups and predictors of response. Additionally, analgesic efficacy and toxicity were combined in a single risk-benefit index (utility function) to quantify the probability of side effects in high- vs low-analgesic responders. ⋯ An important observation was that, irrespective of dose, low-analgesic responders to fentanyl had a greater probability of respiratory depression than analgesia while the reverse was true for high-analgesic responders. These data show dissociation between 2 μ-opioid end-points and explain the danger of treating poor analgesic responders with increasingly higher opioid doses. Apart from being valuable in drug development programs, the outlined approach can be used to determine the choice of drug and dose in the treatment of pain in patients with potent and toxic analgesics.