Pharmacologic Treatment of Motility

Question 1

Cardinal sign of achalasia

Answer 1

birds beak (+/- sigmoid esophagus)

Question 2

2 approaches to treating esophageal motility disorders

Answer 2

1. lower LES pressure, 2. reduce vigor of distal contractions

Question 3

Tx for achalasia

Answer 3

1. botulinum –> inhibits ACh release

2. heller myotomy, POEM

Question 4

Tx for esophageal hypercontractile state

Answer 4

PDE5I –> block no degradaition, prolong smooth muscle relaxation, reduce contractile amplitude and propagation velocity

Question 5

Tx of gastroparesis

Answer 5

pyloroplasty

Question 6

Which cells in the stomach create their own electrical activity?

Answer 6

interstitial cells of cajal –> slow wave activity –> modulated by vagus and enteric nerves

Question 7

2 important receptors in excitatory enteric cholinergic motor neurons

Answer 7

5HT3 and 5HT4

Question 8

3 important receptors in inhibitory enteric nitrergic motor neurons

Answer 8

5HT7, 5HT1A, 5HT1D

Question 9

Where is the majority of serotonin in body?

Answer 9

gut (95%)

Question 10

MOA Metoclopramide

Answer 10

serotonin 5HT4 agonist (promotes muscle conraction), D2 antagonist (dopamine inhibits muscle contraction) –> diabetic gastroparesis, antiemetic

Question 11

3 ways to delay gastric emptying

Answer 11

anticholinergic: dicylomine, hyoscyamine

somatostatin analog: octreotide (inhibit serotonin and motilin)

Question 12

Tx of poor accomodation

Answer 12

busiprone: 5HT1A receptor agonist–> increase NO release, inhibits ACh release –> tx of functional dyspepsia, improves accomodation

Question 13

Tx of constipation

Answer 13

water, fiber (only for mild/moderate), laxatives

1. mg, sulfate, phosphate hyperosmolar intraluminal envronment
2. PEG: isoosmotic, binds water molecules
3. Anthraquinone/diphenylmethanes: afferent nerve fiber irritants
4. lubiprostone
5. tegaserod

Question 14

Lubiprostone MOA

Answer 14

increase intestinal fluid secretion by activating CFTR

Question 15

Tegaserod MOA

Answer 15

5HT4 partial agonist –> improves constiption

Question 16

Dangers of tap water and soap suds enemas for constipation.

Answer 16

water: intoxication
soap: colitis/necrosis

Question 17

How do blood borne and local emetics cause emesis?

Answer 17

5HT3 release in stomach/small intestine –> vagus nerve afferent –> chemoreceptor trigger zone –> emetic center in medulla

Question 18

Types of anti-emetics

Answer 18

5HT3 antagonists (ondansetron), central dopamine antagonists, H1 antagonists, muscarinic antagonists, neurokinin antagonists, cannabinoid AGonists