orphine-like activity have been identified throughout the brain and spinal cord and are likely to play a role in the expression and perception of analgesic effects. In addition, opioid receptors have also been identified within the peripheral nervous system (PNS). The role that these receptors play in these drugs’ analgesic effects is unknown.
Effects on the Central Nervous System (CNS)
The principal therapeutic action of oxymorphone is analgesia. Oxymorphone causes respiratory depression, in part by a direct effect on the brainstem respiratory centers. The respiratory depression involves a reduction in the responsiveness of the brain stem respiratory centers to both increases in carbon dioxide tension and electrical stimulation. Oxymorphone depresses the cough reflex by direct effect on the cough center in the medulla.
Oxymorphone causes miosis, even in total darkness. Pinpoint pupils are a sign of opioid overdose but are not pathognomonic (e.g., pontine lesions of hemorrhagic or ischemic origin may produce similar findings). Marked mydriasis rather than miosis may be seen with hypoxia in overdose situations [see Overdosage (10)]. Other therapeutic effects of oxymorphone include anxiolysis, euphoria, and feeling of relaxation, drowsiness and changes in mood.
Effects on the Gastrointestinal Tract and on Other Smooth Muscle
Gastric, biliary and pancreatic secretions are decreased by oxymorphone. Oxymorphone causes a reduction in motility and is associated with an increase in tone in the antrum of the stomach and duodenum. Digestion of food in the small intestine is delayed and propulsive contractions are decreased. Propulsive peristaltic waves in the colon are decreased, while tone is increased to the point of spasm. The end result is constipation. Oxymorphone can cause a marked increase in biliary tract pressure as a result of spasm of the sphincter of Oddi, and transient elevations in serum amylase. Oxymorphone may also cause spasm of the sphincter of the urinary bladder.
Effects on the Cardiovascular System
Oxymorphone produces peripheral vasodilation which may result in orthostatic hypotension. Release of histamine can occur and may contribute to opioid-induced hypotension. Manifestations of histamine release may include orthostatic hypotension, pruritus, flushing, red eyes, and sweating.
Effects on the Endocrine System
Opioid agonists have been shown to have a variety of effects on the secretion of hormones. Opioids inhibit the secretion of ACTH, cortisol, and luteinizing hormone (LH) in humans. They also stimulate prolactin, growth hormone (GH) secretion, and pancreatic secretion of insulin and glucagon.
Effects on the Immune System
Opioids have been shown to have a variety of effects on components of the immune system in in vitro and animal models. The clinical significance of these findings is unknown.
12.2 Pharmacodynamics
Concentration-Efficacy Relationships
The minimum effective plasma concentration of oxymorphone for analgesia varies widely among patients, especially among patients who have been previously treated with agonist opioids. As a result, individually titrate patients to achieve a balance between therapeutic and adverse effects. The minimum effective analgesic concentration of oxymorphone for any individual patient may increase over time due to an increase in pain, progression of disease, development of a new pain syndr |
