Gastroenterology: Pharmacology - Prokinetics

Question 1

Describe the effects of 5HT, motilin and dopamine as enteric nervous system neurotransmitters

Answer 1

1. 5HT:
   - Released from enterochromaffin cells
   - Act on 5HT-3 receptors of extrinsic afferents to cause nausea, vomiting, and abdominal pain
   - Act on 5HT-1P and 5HT-4 receptors of intrinsic primary afferent nerves (IPANs) to stimulate myenteric plexus interneurons important in controlling peristalsis
2. Motilin:
   - Stimulates excitatory neurons or muscle cells directly to increase peristalsis
3. Dopamine:
   - Inhibits oesophageal and gastric contraction

Question 2

Pharmacodynamics of bethanechol

Answer 2

Cholinomimetic agonist which stimulates M3 receptors on muscle cells and at myenteric plexus synapses to increase gastric motility

Question 3

Clinical uses of neostigmine in GI conditions

Answer 3

Used for treatment of pseudo-obstruction: 2mg IV results in evacuation of flatus and faeces

Question 4

Neostigmine drug class

Answer 4

Acetylcholinesterase inhibitor

Question 5

Metoclopramide drug class

Answer 5

D2-receptor antagonist

Question 6

Domperidone drug class

Answer 6

D2-receptor antagonist

Question 7

Pharmacodynamics of D2-receptor antagonists

Answer 7

Activation of D2-receptors in GIT causes inhibition of cholinergic smooth muscle stimulation: blockade of this effect is prokinetic
Blockade of D2-receptors in the chemoreceptor trigger zone of the medulla (area postrema) is antiemetic

Question 8

Three prokinetic effects of D2-receptor antagonists

Answer 8

1. Increased oesophageal peristalsis
2. Increased lower oesophageal sphincter pressure
3. Enhanced gastric emptying

NOTE: no effect on small intestine or colonic motility

Question 9

5 clinical uses of D2-receptor antagonists

Answer 9

1. GERD
2. Impaired gastric emptying
3. Non-ulcer dyspepsia
4. Antiemetic
5. Postpartum lactation stimulation

Question 10

Adverse effects of D2-receptor antagonists. Do these occur with both metoclopramide and domperidone?

Answer 10

1. Central: restlessness, drowsiness, insomnia, anxiety, agitation
2. EPSE (including tardive dyskinesia with long-term use of metoclopramide)
3. Hyperprolactinaemia

Both metoclopramide and domperidone can cause hyperprolactinaemia, other adverse effects are mainly seen with metoclopramide (as domperidone does not cross the BBB as readily)

Question 11

Mechanism of action of macrolides as prokinetics

Answer 11

Stimulate motilin receptors

Question 12

Clinical uses of macrolides in GI conditions

Answer 12

Erythromycin may be used in setting of gastroparesis or with acute UGIB to promote gastric emptying of blood prior to endoscopy