CPS: Gut Motility and AntiNausea

Question 1

Rome criteria for IBS

Answer 1

recurrent abdominal pain at least 1 day/week in the last 3 months, plus 2 of either 1. onset associated with a change in stool frequency, 2. onset associated with a change in stool form 3. related to defecation. Has to be here for at least 3 months with symptom onset at least 6 months before diagnosis.

Question 2

vagal nerves transmit ____ to brain, whereas intestinal pain is transmitted via ___ nerves

Answer 2

vagal nerves transmit VISCERAL SIGNS to brain, whereas intestinal pain is transmitted via SPINAL nerves

Question 3

M cells vs dendritic cells

Answer 3

M cells are found in peyers patches of gut and are involved in sampling antigens in the lumen. based onthe antigen, the peyer patch B and T cells can then synthesize iGAs to neutralize the antigen and prevent bacteria colonization

dendritic cells are also antigen samplers, but they are located in random areas and are more involved with tolerance. they can also move around via the lymph and make their ways to the nodes where they can activate more plasma and T cells.

Question 4

function of intraepithelial lymphocytes

Answer 4

found on the intestinal epithelium cells and have cytotoxic function where they can secete cytokines.

Question 5

nonpharmacolic therapy for IBS

Answer 5

fiber, and low FODMAPS

plus CBT to control stress which exacerbates symptoms

Question 6

how is peristalsis movement mediated

Answer 6

5HT released by enterochromaffin cells stimulate enteric nervous system which secretes acetyl choline onto motor neurons

Question 7

gastroparesis and waht can this cause

Answer 7

impaired gastric emptying. Can alsolead to dumping sydrome– gastric emptying is impaired in such a way that it emptys suddenly– sudden nutrient release into small intestine. this nutrien load can cause massive release of vasoactive hormones (5hT).

Can also cause bezoar.

Question 8

ileus

Answer 8

lack of movement somewhere in the intestines that leads to a build up and potential blockage of food material.

Question 9

colonic motility disoders (caused by drugs, surgery, hypothyroidim, smooth muscle diseases etc) can cause megacolon, constipation, pain, and bloating. What is the clinical classification of megacolon?

Answer 9

1. congenital (hirschsprung dz- lack of peristalsis)
2. acquired (constipation)
   - idiopathic
   - secondary (nerve, muscle, metabolic, inflammation due to UC or mechanical aspects cause colonic motility dysfunction which lead to megacolon)

Question 10

treatment for functional constipation IBS-C

Answer 10

1. eliminate medications that can cause or worsen constipation
2. treat constipation (fiber and water), osmotic laxatives, stimulant laxatives, pro-secretory agents, pro-motility agents.

Question 11

what is an osmotic laxative

Answer 11

• laxative is not absorbed in small bowel
• causes net water and electrolyte secretion to reduce stool viscosity.
• can cause diarrhea

examples include lactulose and PEG

Question 12

what is a stimulant laxative

Answer 12

• stimulates motility, prostaglandin release, increae water and electrolyte secretion

Use sparingly and for short term only - dependence
Ø Diphenylmethane derivatives (bisacodyl, sodium
picosulfate) Ø Anthraquinone derivatives (cascara, aloe, senna

Question 13

mechanism for chloride secretagogues

Answer 13

drug binds to GC receptor and stimulates production of cGMP. cGMP reduces pain firing and increases Cl- efflux into lumen. Na+ follows Cl-, and water follows Na, causing more water in stool and alleving constipation.

Question 14

promotility agents

Answer 14

§ 5-HT4 receptors are abundant in the gut and important
in mediating effects of serotonin in GIT
—5-HT4 agonists stimulate ACh release from myenteric neurons,
stimulating GI peristalsis and secretion

Question 15

classifications of diarrhea symptomatic therapies

Answer 15

-bile acid sequestraqnts (cholestyramine): Bile acids effect on the colon:
• Induce cyclic AMP-mediated H2O secretion
• Increase mucosal permeability
• Alter motilit

• mu receptor agonists: Decrease ACh release and stimulate NO release
  § Decrease peristalsis, fluid and electrolyte secretion

Question 16

drug that helps both pain and motility and secretion (IBD-C)

Answer 16

§ 5HT3 antagonists [number needed to treat = 7]
§ Receptors on sensory neurons: decrease pain, motility and secretion
—Alosetron; women only
§ Effective at relieving pain and decreasing stool frequency;
§ Restricted – ischemic colitis [0.95/1000 patient years or ~1:800]
§ Severe constipation [0.36/1000 patient years] —Ramosetron [2.5 mcg po daily]; men and women
§ Constipation and hard stools; no reports of ischemic colitis
§ Efficacious in both men and women

Question 17

Question 18

In general, whether it be IBS-D or IBS-M or IBS-C, all involve pain and bloating. what are some treatments to alleviate pain?

Answer 18

§ Antispasmodics
—Anti-cholinergic (Dicyclomine), anti-muscarinic agents (Hyoscyamine),
direct smooth muscle (pinaverium) relaxants —Short term relief
§ LOW quality of evidence

§ Peppermint oil
—Smooth muscle relaxant
—Global improvement of IBS Sx and abdominal pain (NNT = 4)
—Reflux is the most common side effect

Question 19

For IBS-C, you should first try a chloride secretagogue (linaclotide), then what?

Answer 19

SSRI

helps to increase motility and visceral pain.

Question 20

Using SSRI vs TCA in IBS

Answer 20

SSRI for constipation cause it increases 5HT concentrations and increases motility/peristaltic motion

TCA for IBS-D or M because it decreaes motility and has anti-cholinergic effects.

Both help with pain.

Question 21

signs of gastroparesis

Answer 21

Delayed gastric emptying § Symptoms:
§ Early satiety § Post-prandial fullness § Nausea /vomiting § Bloating § Upper abdominal pain

Question 22

Functional Dyspepsia

Answer 22

basically indigestion for more than 3 months.

§ One or more of:
Bothersome postprandial fullness
Bothersome early satiation
Bothersome epigastric pain
Bothersome epigastric burning
AND
No evidence of structural disease that is likely to explain the symptoms

usually due to H Pylori, PUD/GERD, IBS-D (treat with TCA), or psychiatric.

Question 23

2 anti-nausea medications

Answer 23

1. antihistamines
2. ondansetron

Question 24

prokinetics

Answer 24

good to improve gastric contraction (probably for diarrhea and gastroparesis)

• metoclopramide
• Domperidone (less CNS side effects)

both are D2Ras, can cause QT prolongation

• erythromycins. Motilin agonist. helpful for gastroparesis and functional dyspepsia.