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.
Regardless of how expertly surgical and anesthetic procedures are performed, appropriate use of analgesic drugs such as local anesthetics, opioids, ketamine, gabapentinoids, acetaminophen, and cyclooxygenase (COX) inhibitors can make the difference between a satisfied and an unsatisfied postoperative patient. Moreover, studies have shown that outcomes can be improved when analgesia is provided in a “multimodal” format (typically minimizing opioid use) as one part of a well-organized plan for enhanced recovery after surgery (ERAS; see Chapter 48).
Opioids bind to specific receptors located throughout the central nervous system and other tissues. Four major opioid receptor types have been identified (Table 10–1): mu (μ, with subtypes μ1 and μ2), kappa (κ), delta (δ), and sigma (σ). All opioid receptors couple to G proteins; binding of an agonist to an opioid receptor causes membrane hyperpolarization. Acute opioid effects are mediated by inhibition of adenylyl cyclase (reductions in intracellular cyclic adenosine monophosphate concentrations) and activation of phospholipase C. Opioids inhibit voltage-gated calcium channels and activate inwardly rectifying potassium channels. Opioid effects vary based on the duration of exposure, and opioid tolerance leads to changes in opioid responses.
TABLE 10–1Classification of opioid receptors.1 ||Download (.pdf) TABLE 10–1 Classification of opioid receptors.1
|Receptor ||Clinical Effect ||Agonists |
|μ || |
Supraspinal analgesia (μ1)
Respiratory depression (μ2)
|κ || |
|δ || |
|σ || |