Which opioid side effect does NOT develop tolerance?

• A. Constipation
• B. Nausea
• C. Sedation
• D. Euphoria

Answer: (A)

Tolerance to opioid side effects varies by system. With chronic use, people often build tolerance to central nervous system effects such as sedation, euphoria, and nausea—the body adjusts and these symptoms lessen over time. In contrast, constipation from opioids is typically not subject to meaningful tolerance. The constipation arises from mu-receptor activation in the GI tract, which slows intestinal motility and increases water absorption; this enteric effect tends to persist despite longer treatment or higher doses. So, among the options, constipation is the side effect that does not reliably develop tolerance. Clinically, this means ongoing bowel management is usually required.