B5.063 Prework 4: Constipation Flashcards
effect of opioids on GI mobility
-bind enteric neurons of the myenteric plexus
-inhibits ACh release on excitatory motor neuron (inhibits muscarinic neurotransmission)
-activation of inhibitory neurons to reduce NO synthesis and VIP release
all of this contributes to reduced intestinal motility
signaling pathways affected by mu and delta opiod recepts
- inhibit adenylate cyclase
- activate K+ channels
- inhibit Ca2+ channels
effects of signaling pathway changes
suppress enteric neuron activity
-membrane hyperpolarization (K+)
-decreased neurotransmitter release (Ca2+)
-decreased cAMP and PKA activity (adenylate cyclase)
contribute to constipating activity
macroscopic changes in GI motility with opioid use
slower gastric emptying
less frequent power propulsions
non propulsive motility of intestine
increased sphincter spasm/ increased anal tone…less urge to defecate
intended consequences of opioids
cross BBB and induce analgesia
delivery of naloxegol
peripheral restriction
doesn’t cross BBB
central mediated analgesia is maintained
effect of naloxegol on enteric nervous system
displaces opioids from gut receptors and prevents dysmotility
effect of naloxegol on intestinal secretions
antagonizes the decreased secretion of electrolytes and water into the lumen, resulting in a less dry and softer stool
effect of naloxegol on anal sphincter
prevents dyscoordination
decreases resting tone
less straining and easier evacuation
host factors contributing to IBS
altered GI motility visceral hypersens altered brain-gut interactions increased intestinal permeability gut mucosal immune activation
luminal factors contributing to IBS
dysbiosis
neuroendocrine mediators
bile acids
environmental factors contributing to IBS
psychosocial distress food meds supplements antibiotics enteric infection
treatment options for mild “gut” predominant IBS
antispasmodics antidiarrheals dietary modifications fiber supplements serotonin modulators
treatment options for severe “brain” predominant IBS
antidepressants
psychotherapy, behavioral therapy, hypnotherapy
somatization-disorder management
dietary manipulation in treatment of IBS-C
low FODMAP diet and low gluten maybe
may improve bloating and pain
