From the Guidelines
Opioids indirectly stimulate the parasympathetic nervous system. When opioids bind to their receptors, particularly mu-opioid receptors, they not only produce analgesic effects but also trigger parasympathetic responses throughout the body. This parasympathetic stimulation leads to several characteristic side effects including miosis (pupillary constriction), bradycardia (decreased heart rate), respiratory depression, increased smooth muscle tone in the gastrointestinal tract (while decreasing motility), urinary retention, and bronchial constriction. The mechanism involves both central effects on brainstem nuclei that regulate parasympathetic outflow and peripheral effects at nerve terminals, as described in the study by 1.
This parasympathetic predominance explains why patients on opioid medications often experience constipation, urinary difficulties, and other autonomic effects. Understanding this physiologic impact is crucial for clinicians managing patients on opioid therapy, as these parasympathetic effects may require monitoring or intervention, particularly in patients with pre-existing autonomic disorders or those on medications with similar effects. The most recent study by 1 highlights the importance of considering the side effects of opioids, including their impact on the parasympathetic nervous system, when prescribing them for pain management.
Key points to consider include:
- Opioids stimulate the parasympathetic nervous system, leading to various side effects
- The mechanism involves central and peripheral effects on brainstem nuclei and nerve terminals
- Patients on opioid medications may experience constipation, urinary difficulties, and other autonomic effects
- Clinicians should monitor and intervene as necessary to manage these parasympathetic effects, especially in patients with pre-existing autonomic disorders or those on similar medications, as recommended by 1 and 1.
From the FDA Drug Label
Effects on the Endocrine System: Opioids inhibit the secretion of adrenocorticotropic hormone (ACTH), cortisol, and luteinizing hormone (LH) in humans [see Adverse Reactions (6)] . They also stimulate prolactin, growth hormone (GH) secretion, and pancreatic secretion of insulin and glucagon
- The endocrine system is the physiologic system that is indirectly stimulated by opioids.
- Opioids have indirect effects on the body that stimulate the endocrine system by influencing the secretion of various hormones, including prolactin, growth hormone, insulin, and glucagon 2
From the Research
Opioids' Indirect Effects on the Body
Opioids have indirect effects on the body that stimulate the following physiologic systems:
- The hypothalamic-pituitary-adrenal (HPA) axis, which is critical in regulating responses to physiological and psychological disturbances 3, 4, 5
- The sympathetic nervous system, which is involved in the body's "fight or flight" response 4
- The endocrine system, which regulates hormone secretion, including the release of adrenocorticotropin (ACTH), cortisol, and other hormones 3, 4, 6
- The autonomic nervous system, which controls involuntary functions such as heart rate, blood pressure, and digestion 4, 7
Key Findings
Some key findings related to opioids' indirect effects on the body include:
- Chronic opioid dependence may cause reduced function of the HPA axis, while opioid withdrawal may decrease the response of the pituitary to CRH and increase the adrenal response to ACTH 3
- Brain beta-endorphin and other opioids are involved in restraint stress-induced stimulation of the HPA axis, the sympathetic nervous system, and the adrenal medulla in rats 4
- Opioids have complex effects on the HPA axis, and they stimulate the sympathetic nervous system 4, 7
- The opioid system in humans plays a central role in pain control and is a key mediator of hedonic homeostasis, mood, and well-being 7