Pharm for Motility Disorders

Question 0

What are two levels of nervous control of esophagus motility?

Answer 0

Mostly vagus control.

Enteric neurons relay signals to the smooth muscle.

Question 1

Which part of the bowel is particularly sensitive to constipation / fecal incontinence after spinal cord trauma?

Answer 1

The rectum, as it has less intrinsic control.

Question 2

Review: What is the gradient of neuron cell types in the esophagus like?

Answer 2

More cholinergic neurons proximal.

More non-cholinergic (most NO-ergic) neurons distal.

Question 3

What are 2 ways to modify esophagus motility?

Answer 3

Reduce LESP.

Reduce vigor of lower esophageal contractions.

Question 4

3 pathophysiological causes of achalasia?

Answer 4

Loss of inhibitory, NO-ergic neurons of the myenteric plexus.
Degeneration of dorsal vagal nerve/plexus.
Dorsal vagal nucleus lesion.

Question 5

Treatments for achalasia?

Answer 5

Botox injections -> relaxation (don’t work well).

Heller myotomy - cut the LES.

Question 6

What’s a pharmacological way to decrease the vigor of esophageal contractions?

Answer 6

5’-phosphodiesterase (5-PDE) inhibitors (eg. Viagra).

These cause smooth muscle relaxation.

Question 7

If for some reason you ever do a vagotomy, what must you also do?

Answer 7

Pyloroplasty - cut open the pyloric sphincter so that stuff can get out of the stomach.

Question 8

What are the cells that mainly drive gastric motility?

Answer 8

ICCs - interstitial cells of Cajal

Question 9

What are the serotonin receptors on excitatory neurons in the gut? (name 2)

Answer 9

5-HT3

5-HT4

Question 10

What are 5-HT receptors on inhibitory neurons in the gut? (name 3)

Answer 10

5-HT7
5-HT1D
5-HT1A

Question 11

What cells in the gut secrete serotonin in response to mechanical pressure?

Answer 11

Enterochromaffin cells.

Question 12

What’s the cell / signaling pathway from mechanical pressure in the gut to contraction?

Answer 12

Pressure -> ECs secrete 5-HT -> IPAN cells -> interneurons

Interneurons act on excitatory (Cholinergic) and inhibitory (NO-ergic) motor neurons.

Question 13

Three ways to alter gastric motility?

Answer 13

Speed up gastric emptying.
Delay gastric emptying.
Improve fundic accomodation.

Question 14

How does metroclopramide (Reglan) work? What does it do?

Answer 14

5-HT4 agonist.
Dopamine antagonist.
Improves gastric emptying and is an antiemetic.

Question 15

2 classes of drugs that slow gastric emptying? (examples?)

Answer 15

Anticholinergics (Dicyclomine, Hyoscyamine)
Somatostatin analogs (Octreotide) - inhibit 5-HT and motilin release.

Question 16

What’s a drug that improves fundic and pyloric accomodation? What is it’s mechanism?

Answer 16

Buspirone - 5HT1A receptor agonist (which inhibits 5-HT release and increases NO release)

Question 17

Does diarrhea necessarily mean increased motility and constipation decreased motility?

Answer 17

No… there can periodically be the opposite. But this concept isn’t actionable yet.

Question 18

How do most common, over-the-counter laxatives work?

Answer 18

By drawing water into the bowel.

Except for “stimulant” laxatives, which irritate the bowel.

Question 19

How does lubriprostone help constipation?

Answer 19

Activates Cl- channel for increased Cl- secretion into the lumen, which water follows. (it gives you Cholera. but not really)

Question 20

How does tagaserod relieve constipation?

Answer 20

5-HT4 partial agonist.

Question 21

Are tap water / soapy water enemas a good idea?

Answer 21

Nope.
Tap water -> “water intoxication” (hyponatremia?)
Soapy water -> colitis / necrosis.

Question 22

Which antiemetic is a 5-HT3 antagonist?

Answer 22

ondansetron (Zofram)

Question 23

How can you get the anti-emetic effects of marijuana without smoking it?

Answer 23

Dronabinol.

Question 24

What receptor do pro-emetic sensors in the stomach use?

Answer 24

5-HT3