B5.063 Prework 4: Constipation

Question 1

effect of opioids on GI mobility

Answer 1

-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

Question 2

signaling pathways affected by mu and delta opiod recepts

Answer 2

1. inhibit adenylate cyclase
2. activate K+ channels
3. inhibit Ca2+ channels

Question 3

effects of signaling pathway changes

Answer 3

suppress enteric neuron activity
-membrane hyperpolarization (K+)
-decreased neurotransmitter release (Ca2+)
-decreased cAMP and PKA activity (adenylate cyclase)
contribute to constipating activity

Question 4

macroscopic changes in GI motility with opioid use

Answer 4

slower gastric emptying
less frequent power propulsions
non propulsive motility of intestine
increased sphincter spasm/ increased anal tone…less urge to defecate

Question 5

intended consequences of opioids

Answer 5

cross BBB and induce analgesia

Question 6

delivery of naloxegol

Answer 6

peripheral restriction
doesn’t cross BBB
central mediated analgesia is maintained

Question 7

effect of naloxegol on enteric nervous system

Answer 7

displaces opioids from gut receptors and prevents dysmotility

Question 8

effect of naloxegol on intestinal secretions

Answer 8

antagonizes the decreased secretion of electrolytes and water into the lumen, resulting in a less dry and softer stool

Question 9

effect of naloxegol on anal sphincter

Answer 9

prevents dyscoordination
decreases resting tone
less straining and easier evacuation

Question 10

host factors contributing to IBS

Answer 10

altered GI motility
visceral hypersens
altered brain-gut interactions
increased intestinal permeability
gut mucosal immune activation

Question 11

luminal factors contributing to IBS

Answer 11

dysbiosis
neuroendocrine mediators
bile acids

Question 12

environmental factors contributing to IBS

Answer 12

psychosocial distress
food
meds
supplements
antibiotics
enteric infection

Question 13

treatment options for mild “gut” predominant IBS

Answer 13

antispasmodics
antidiarrheals
dietary modifications
fiber supplements
serotonin modulators

Question 14

treatment options for severe “brain” predominant IBS

Answer 14

antidepressants
psychotherapy, behavioral therapy, hypnotherapy
somatization-disorder management

Question 15

dietary manipulation in treatment of IBS-C

Answer 15

low FODMAP diet and low gluten maybe

may improve bloating and pain

Question 16

fiber supplements in IBS-C anf FC

Answer 16

not useful in IBS-C
mild to moderate benefit for stool consistency in FC
may worsen bloating in both

Question 17

probiotic in IBS-C

Answer 17

possible benefit, esp for bloating

Question 18

osmotic and stimulant laxative in IBS and FC

Answer 18

improves stool consistency and frequency in both

doesn’t help pain in IBS

Question 19

5-HT4 agonists in IBS and FC

Answer 19

tegaserod for pain, frequency, and bloating in IBS

prucalopride and velusetrag in FC

Question 20

prosecretory agents (lubiprostone, linaclotide) in IBS and FC

Answer 20

improves symptoms in both

Question 21

antispasmodics in IBS and FC

Answer 21

helps pain in IBS

makes FC worse

Question 22

antidepressants in IBS

Answer 22

decrease pain but doesn’t help bowel habits

Question 23

psych therapy in IBS

Answer 23

improvement of all symptoms