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However, which signaling pathway produces the unwanted side effects (such as respiratory suppression and constipation) is currently controversial: one view is that it is caused by -arrestin signal transduction, and the other view suggests that the respiratory depression by opioids is caused due to G protein-gated inwardly rectifying potassium (GIRK) channel signaling

Persistent bleeding over multiple bowel movements, bleeding that increases in volume rather than resolving, or new-onset bleeding in patients aged 45 or older should trigger urgent medical assessment

doi: 10.7863/ultra.34.3.469