Pathophysiology and management of opioid-induced constipation: a narrative review

Background: Treatment of chronic pain is among the primary tasks of palliative care. Among the most commonly prescribed analgesics are opioid agents. Opioids, in addition to being highly effective in controlling severe pain, have a high risk of adverse effects (AEs). The most common gastrointestinal AE is opioid-induced constipation (OIC). Methods: A search through online databases was conducted including Google Scholar and PubMed and key information on the pathophysiology, epidemiology, diagnosis and current therapeutic options for OIC has been collected. Results: The pathophysiology of OIC is primarily related to the direct action of opioids on opioid receptors located in the wall of gastrointestinal tract. This leads to deregulation of the mechanisms responsible for the motor and secretory functions of the gastrointestinal tract. That results in impaired digestion and delayed intestinal transit, leading to the development of constipation. Opioid-induced constipation leads to a significant reduction in patients' quality of life, an increase in the cost of treatment and can lead to serious complications such as gastrointestinal perforation. Patients receiving palliative care due to their multiple burdens require a holistic diagnostic approach and thorough differential diagnosis of OIC. Among therapeutic approaches, we distinguish between non-specific methods related to lifestyle changes and laxatives, and cause-directed pharmacological methods related to the use of peripherally acting opioid receptor antagonists (PAMORA). The most commonly used PAMORA for the treatment of OIC include naloxegol, methylnaltrexone and naldemedine. Numerous clinical studies demonstrate the efficacy and high safety profile of PAMORA in the treatment of OIC. Conclusions: Proper diagnosis of OIC among patients taking opioid drugs allows for the implementation of effective therapeutic measures. Appropriate treatment reduces the risk of OIC-related complications and leads to an increase in patients' quality of life.Treatment of chronic pain is among the primary tasks of palliative care. Among the most commonly prescribed analgesics are opioid agents. Opioids, in addition to being highly effective in controlling severe pain, have a high risk of adverse effects (AEs). The most common gastrointestinal AE is opioid-induced constipation (OIC). In our work, we have collected key information on the pathophysiology, epidemiology, diagnosis and current therapeutic options for OIC. The pathophysiology of OIC is primarily related to the direct action of opioids on opioid receptors located directly in the wall of gastrointestinal tract. This leads to deregulation of the mechanisms responsible for the motor and secretory functions of the gastrointestinal tract. That results in impaired digestion and delayed intestinal transit, leading to the development of constipation. OIC leads to a significant reduction in patients' quality of life, an increase in the cost of treatment and can lead to serious complications such as gastrointestinal perforation. Patients receiving palliative care due to their multiple burdens require a holistic diagnostic approach and thorough differential diagnosis of OIC. Among therapeutic approaches, we distinguish between non-specific methods related to lifestyle changes and laxatives, and cause-directed pharmacological methods related to the use of peripherally acting opioid receptor antagonists (PAMORAs). The most commonly used PAMORAs for the treatment of OIC include naloxegol, methylnaltrexone and naldemedine. Numerous clinical studies demonstrate the efficacy and high safety profile of PAMORAs in the treatment of OIC