Pharm for Motility Disorders Flashcards
What are two levels of nervous control of esophagus motility?
Mostly vagus control.
Enteric neurons relay signals to the smooth muscle.
Which part of the bowel is particularly sensitive to constipation / fecal incontinence after spinal cord trauma?
The rectum, as it has less intrinsic control.
Review: What is the gradient of neuron cell types in the esophagus like?
More cholinergic neurons proximal.
More non-cholinergic (most NO-ergic) neurons distal.
What are 2 ways to modify esophagus motility?
Reduce LESP.
Reduce vigor of lower esophageal contractions.
3 pathophysiological causes of achalasia?
Loss of inhibitory, NO-ergic neurons of the myenteric plexus.
Degeneration of dorsal vagal nerve/plexus.
Dorsal vagal nucleus lesion.
Treatments for achalasia?
Botox injections -> relaxation (don’t work well).
Heller myotomy - cut the LES.
What’s a pharmacological way to decrease the vigor of esophageal contractions?
5’-phosphodiesterase (5-PDE) inhibitors (eg. Viagra).
These cause smooth muscle relaxation.
If for some reason you ever do a vagotomy, what must you also do?
Pyloroplasty - cut open the pyloric sphincter so that stuff can get out of the stomach.
What are the cells that mainly drive gastric motility?
ICCs - interstitial cells of Cajal
What are the serotonin receptors on excitatory neurons in the gut? (name 2)
5-HT3
5-HT4
What are 5-HT receptors on inhibitory neurons in the gut? (name 3)
5-HT7
5-HT1D
5-HT1A
What cells in the gut secrete serotonin in response to mechanical pressure?
Enterochromaffin cells.
What’s the cell / signaling pathway from mechanical pressure in the gut to contraction?
Pressure -> ECs secrete 5-HT -> IPAN cells -> interneurons
Interneurons act on excitatory (Cholinergic) and inhibitory (NO-ergic) motor neurons.
Three ways to alter gastric motility?
Speed up gastric emptying.
Delay gastric emptying.
Improve fundic accomodation.
How does metroclopramide (Reglan) work? What does it do?
5-HT4 agonist.
Dopamine antagonist.
Improves gastric emptying and is an antiemetic.
2 classes of drugs that slow gastric emptying? (examples?)
Anticholinergics (Dicyclomine, Hyoscyamine) Somatostatin analogs (Octreotide) - inhibit 5-HT and motilin release.
What’s a drug that improves fundic and pyloric accomodation? What is it’s mechanism?
Buspirone - 5HT1A receptor agonist (which inhibits 5-HT release and increases NO release)
Does diarrhea necessarily mean increased motility and constipation decreased motility?
No… there can periodically be the opposite. But this concept isn’t actionable yet.
How do most common, over-the-counter laxatives work?
By drawing water into the bowel.
Except for “stimulant” laxatives, which irritate the bowel.
How does lubriprostone help constipation?
Activates Cl- channel for increased Cl- secretion into the lumen, which water follows. (it gives you Cholera. but not really)
How does tagaserod relieve constipation?
5-HT4 partial agonist.
Are tap water / soapy water enemas a good idea?
Nope.
Tap water -> “water intoxication” (hyponatremia?)
Soapy water -> colitis / necrosis.
Which antiemetic is a 5-HT3 antagonist?
ondansetron (Zofram)
How can you get the anti-emetic effects of marijuana without smoking it?
Dronabinol.
What receptor do pro-emetic sensors in the stomach use?
5-HT3
