Figure 4.

Pharmacological principle of naloxegol under normal conditions (left column), during opioid treatment (middle) and opioid and naloxegol treatment (right).

Notes: First row: opioids in the systemic circulation cross the blood–brain barrier and induce analgesia. Peripheral restriction prevents naloxegol from crossing the blood–brain barrier, thus centrally mediated analgesia is maintained. Second row: opioids bind to enteric nervous system μ-opioid receptors and cause non-propulsive motility. Due to higher affinity, naloxegol displaces opioids from the receptors in the gut and thus prevents dysmotility. Third row: naloxegol antagonizes the decreased secretion of electrolytes and water to the intestinal lumen, which results in a less dry, softer stool. Fourth row: in the gastrointestinal sphincters (here illustrated by the anal sphincter), naloxegol (at least theoretically) prevents sphincter dyscoordination and increased resting tone, with a net result of less straining and easier evacuation.

Abbreviations: ENS, enteric nervous system; BBB, blood–brain barrier.