RT Book, Section A1 Butterworth IV, John F. A1 Mackey, David C. A1 Wasnick, John D. SR Print(0) ID 1161426602 T1 Analgesic Agents T2 Morgan & Mikhail's Clinical Anesthesiology, 6e YR 2018 FD 2018 PB McGraw-Hill Education PP New York, NY SN 9781259834424 LK accessanesthesiology.mhmedical.com/content.aspx?aid=1161426602 RD 2024/10/08 AB KEY CONCEPTS The accumulation of morphine metabolites (morphine 3-glucuronide and morphine 6-glucuronide) in patients with kidney failure has been associated with narcosis and ventilatory depression. Rapid administration of larger doses of opioids (particularly fentanyl, sufentanil, remifentanil, and alfentanil) can induce chest wall rigidity severe enough to make ventilation with bag and mask nearly impossible. Prolonged dosing of opioids can produce “opioid-induced hyperalgesia,” in which patients become more sensitive to painful stimuli. Infusion of large doses of (in particular) remifentanil during general anesthesia can produce acute tolerance, in which much larger than usual doses of opioids are required for postoperative analgesia. The neuroendocrine stress response to surgery is measured in terms of the secretion of specific hormones, including catecholamines, antidiuretic hormone, and cortisol. Large doses of opioids inhibit the release of these hormones in response to surgery more completely than volatile anesthetics. Aspirin is unique in that it irreversibly inhibits COX-1 by acetylating a serine residue in the enzyme. The irreversible nature of its inhibition underlies the nearly 1-week persistence of its clinical effects (eg, inhibition of platelet aggregation to normal) after drug discontinuation.