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Weeks 4-8 often bring the first subtle improvements

Their activation results in opioid-induced adverse gastrointestinal effects: increased sphincter tone, reduced secretions and increased water absorption, reduced gastric emptying, and reduced propulsion of chime through the intestine (34)

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The cGMP also activates PKGI isoforms resulting in the phosphorylation and activation of myosin light chain phosphatase resulting in phosphate removal from myosin light chains contributing to vasodilation