L22- GIT Drugs I (prokinetic agents)

Question 1

list the molecular targets of GI peristalsis

Answer 1

(myenteric plexus)

• motilin –> motlin R
• ACh –> M1
• serotonin –> 5-HT4R

Question 2

describe the goal (target) of prokinetic agents

Answer 2

• enhance COORDINATED GI motility

- ideally act upstream from ACh –> at receptor sites on enteric neuron or higher

Question 3

discuss the use of ACh and its analogs as prokinetic agents

Answer 3

• produces little or no net propulsive activity
• uncoordinated contractions

-M1 receptor enhances contractions, but uncoordinated

Question 4

(1) is an antibiotic used as a prokinetic agent, as it activates (2). (3) is its indication, (4) is its limitation.

Answer 4

1- erythromycin
2- motilin R
3- diabetic gastroparesis
4- short courses (rapid downstream regulation of motilin R –> easy tolerance of drug)

Question 5

Cisapride:

• (1) MOA
• (2) indications
• (3) AEs

Answer 5

1- 5-HT4 agonist, 5-HT3 antagonist => smooth muscle stimulant

2- GERD, gastroparesis

3- fatal cardiac ventricular arrhythmias (no longer used in USA)

Question 6

describe the MOA of Metoclopramide

Answer 6

• 5-HT4 agonist
• vagal / central 5-HT3 antagonist
• D2 antagonist

Effects confined to upper GI:

• inc LES tone
• stimulates antral / SI contractions

Question 7

list the indications for metoclopramide

Answer 7

• gastroparesis
• anti-emetic

-previous GERD but acid suppression is more efficacious

Question 8

metoclopramide adverse effects

Answer 8

• extrapyramidal effects via D2 antagonism (young adults and children at high doses)
• galactorrhea –> D2 anatagonism –> inc PRL release (rarely seen clinically)