A 55-year-old woman is diagnosed with metastatic breast cancer. The patient is treated with an opioid analgesic for bone pain that is well controlled during the first week of therapy. The following week, the analgesic dose becomes ineffective and the patient reports nausea, itching, and constipation. She has become very weak and is unable to walk due to the pain. The opioid dose is increased. The patient is concerned about side effects with higher dosages, noting that her son has a history of opioid dependence, and "I watched him suffer a lot of bad reactions." The physician explains the concept of tolerance to opioids and that high doses are commonly required to control pain. Over the next few weeks, the patient would likely experience which of the following?
Opioid therapy is the first-line treatment for chronic cancer pain, with effective management commonly requiring higher doses over prolonged periods. An increase in dosage is often necessary to maintain adequate pain control following the development of tolerance to analgesic effects. Tolerance to most opioid side effects is also expected to occur. However, tolerance to constipation and miosis does not readily occur, and constipation is the most common and persistent opioid side effect.
Opioids stimulate mu receptors in the gastrointestinal tract, causing decreased secretions and gastric motility. Normal bowel function rarely resumes. Patients who require prolonged opioid therapy should receive a prophylactic bowel regimen (increased fluid intake, dietary fiber, and laxatives) to minimize constipation.
(Choice A) Opioids can produce significant euphoria, mood alterations, and rewarding pleasurable effects. The mechanism of euphoria and rewarding properties may involve dopaminergic pathways in the nucleus accumbens. Tolerance to euphoric effects develops rapidly, underlying the addictive potential of this medication class.
(Choice B) In most cases, opioid-induced pruritus is mild and tolerance develops.
(Choice C) Nausea with or without vomiting is a common side effect during initiation of opioid therapy, but tolerance develops within days and persistent nausea is uncommon. Opioids stimulate the chemoreceptor trigger zone, leading to emesis.
(Choice D) Respiratory depression is the most serious, yet rare, side effect of opioid therapy. Opioids depress respiration by reducing responsiveness of brainstem respiratory centers to increased levels of carbon dioxide. Patients who take opioids regularly are unlikely to develop respiratory depression as tolerance to this side effect develops rapidly.
(Choice E) Sedation typically occurs during initiation of therapy and usually disappears after several days. It is not unusual for patients to be drowsy and sleep more during the first days of therapy.
(Choice F) Opioids block urinary voiding reflexes and also increase sphincter tone and bladder volume. This results in an antidiuretic effect and urinary retention. Tolerance to these effects develops rapidly.
Educational objective:
Chronic opioid use leads to the development of tolerance to analgesic effects and most side effects, with the exception of constipation and miosis. To prevent bowel complications, it is recommended that patients be treated prophylactically with adequate fluid intake and daily laxatives.