Motility Drugs

Question 1

What common chronic disease is associated with gastroparesis?

Answer 1

DM due to peripheral neuropathy

Question 2

What two opioid receptors are targeted in diarrhea Tx? Common drug?

Answer 2

• Mu - inhibit contractility of SI
• Delta - inhibit secretion
• Loperamide OTC (minimal CNS activitiy - effluxed from CNS)

Question 3

General MOA of constipation?

Answer 3

• increased bulk/water stim mechanoreceptors = peristalsis

- diminish segmental contractions (favors propulsive)

Question 4

Laxative vs. cathartics?

Answer 4

• Laxative = 1-3 days

- Cathartics = overnight, 6-8 hours

Question 5

Major contraindication to laxative use?

Answer 5

rule out OBSTRUCTION!

Question 6

Consequences of bacterial fermentation of soluble fibers?

Answer 6

• short chain FA’s are produced = promotes peristalsis, increases bulk

Question 7

What is Metamucil?

Answer 7

Psyllium (soluble fiber) - laxative

Question 8

What is Miralax? General MOA?

Answer 8

Polyethylene glycol (PEG) = OSMOTIC

Question 9

How does lactulose work as a laxative?

Answer 9

• disaccharide = OSMOTIC

- hepatic encephalopathy = converts ammonia to ammonium by decreasing pH of feces (traps ammonium)

Question 10

What does mineral oil do? Concern with ingested low viscosity HC?

Answer 10

• low viscosity hydrocarbon = mixing softens stool
• inhibits absorption of fat soluble vitamins
• aspiration = lipid pneumonitis (low viscosity) (don’t induce vomiting)

Question 11

How long should laxatives commonly be used?

Answer 11

< 2 weeks w/out doctor supervision (OTC)

Question 12

What are cathartics generally?

Answer 12

Stimulants - inhibit mixing, increase peristalsis (and stool water) by creating low-grade inflammation (activates NT’s in ENS)

Question 13

What is Dulcolax?

Answer 13

cathartic = Bisacodyl (stimulant)

Question 14

Plant product cathartic?

Answer 14

Senna, aloe = stimulants (no FDA approval - Dietary Supplement Act)

Question 15

MOA of saline laxatives?

Answer 15

• cathartic
• osmotic - Mg or Na salts
• no longer OTC = renal, cardiac concerns

Question 16

Function of purgatives?

Answer 16

water bowel evacuation in 1-3 hours

Question 17

Purgative before colonoscopy?

Answer 17

PEG with electrolytes to create MASSIVE osmotic gradient (4 L total - 2 at night and 2 before procedure)

Question 18

What oil is use as a purgative?

Answer 18

Castor oil

Question 19

Prokinetic used for gastroparesis and as an anti-emetic?

Answer 19

Metoclopramide

Question 20

MOA of metaclopramide?

Answer 20

• agonist of 5HT4 in ENS - sensitizes/stimulates ACh release

- antagonist of D2 and 5HT3 (prevents ACh release) receptors

Question 21

Tx effects of metaclopramide?

Answer 21

• receptor effect combo = coordinated and enhanced transit
• inc LES tone, antral and and SI peristalsis
• MINIMAL effects on COLON

Question 22

Problem with metaclopramide?

Answer 22

extra-pyramidal symptoms (children, YA’s) due to D2 antagonism = motor dysfunction (dystonia, tardive dyskinesia, galactorrhea - blocks prolactin, feeling of doom)

Question 23

How long should metaclopramide be used?

Answer 23

< 12 weeks

Question 24

Macrolide antibiotic pro-kinetic?

Answer 24

• Erythromycin
• inhibit protein synthesis in bacteria
• stimulates motilin receptors

Question 25

Pro-kinetic that inhibits CYP3A4?

Answer 25

erythromycin (azithromycin does not)

Question 26

How does lubiprostone work?

Answer 26

• NOT a pro-kinetic
• PGE analog that acts on EP4 receptors to increase Cl- secretion into lumen (misoprostol inhibits EP3 receptor on parietal cells)

Question 27

What is lubiprostone used to Tx?

Answer 27

constipation-predominant IBS

Question 28

Antidepressant role in IBS Tx?

Answer 28

increases serotonin in gut; Tx anxiety symptoms associated with disease

Question 29

Where is the chemoreceptor trigger zone found?

Answer 29

• area postrema
• outside BBB so tests systemic blood
• receptors: 5HT3, D2, M1, CB1

Question 30

Where does area postrema project?

Answer 30

• emetic center in medulla

- solitary tract nucleus

Question 31

Receptors blocked by general purpose anti-emetics?

Answer 31

• scopolamine (M)
• diphenhydramine (benadryl), promethazine (phenergan) = H1
• all have some cross-selectivity toward M, H1, and D2 receptor blocking effects = “dirty drugs”

Question 32

MOA of ondansetron?

Answer 32

5HT3 antagonist

Question 33

Aprepitant MOA?

Answer 33

NK1 antagonist (blocks neurokinin receptor for substance P) - newer and expensive

Question 34

Two functions of metaclopramide?

Answer 34

anti-emetic and pro-kinetic (remember dopamine ant extra-pyramidal Sx)