British journal of anaesthesia
-
Review
Simultaneous targeting of multiple opioid receptors: a strategy to improve side-effect profile.
Opioid receptors are currently classified as mu (mu: mOP), delta (delta: dOP), kappa (kappa: kOP) with a fourth related non-classical opioid receptor for nociceptin/orphainin FQ, NOP. Morphine is the current gold standard analgesic acting at MOP receptors but produces a range of variably troublesome side-effects, in particular tolerance. There is now good laboratory evidence to suggest that blocking DOP while activating MOP produces analgesia (or antinociception) without the development of tolerance. ⋯ For example linking the MOP agonist oxymorphone to the DOP antagonist naltrindole produces a MOP/DOP bivalent ligand that should produce analgesia with reduced tolerance. The type of response/selectivity produced depends on the pharmacophore combination (e.g. oxymorphone and naltrindole as above) and the space between them. Production and evaluation of bivalent ligands is an emerging field in drug design and for anaesthesia, analgesics that are designed not to be highly selective morphine-like (MOP) ligands represents a new avenue for the production of useful drugs for chronic (and in particular cancer) pain.
-
Immunotherapy in the critically ill is an appealing notion because of the apparent abnormal immune and inflammatory responses seen in so many patients. The administration of a medication that could alter immune responses and decrease mortality in patients with sepsis could represent a 'magic bullet'. ⋯ However, in some respects, research along these lines has been unsuccessful or disappointing at best. The current state of knowledge is summarized with particular reference to sepsis and the acute respiratory distress syndrome.
-
Despite major advances, emesis remains a major problem in the context of cancer chemotherapy and in the postoperative period. A better understanding of the relevant neurocircuitry, especially the central pattern generator responsible for emesis and the central role of substance P, led to the development of a new class of antiemetics: the neurokinin-1 (NK1) receptor antagonists. Aprepitant is the first NK1 receptor antagonist approved for use in postoperative nausea and vomiting, but several other compounds are currently being investigated for their potential as antiemetics in the postoperative and cancer chemotherapy settings.
-
Anaesthetists are confronted on a daily basis with patients with coronary artery disease, myocardial ischaemia, or both during the perioperative period. Therefore, prevention and ultimately adequate therapy of perioperative myocardial ischaemia and its consequences are the major challenges in current anaesthetic practice. This review will focus on the translation of the laboratory evidence of anaesthetic-induced cardioprotection into daily clinical practice.