Dopamine Receptor Antagonists

Question 1

Characteristics of Dopamine Antagonists and Serotonin Agonists

Answer 1

Dopamine Antagonists: inhibitory effects on motility
- decreased esophageal and gastric contractions
*increase esophageal peristaltic amplitude
*Increase lower esophageal sphincter pressure
*Enhance gastric emptying

Serotonin Agonists
- Produced by EC cell
- Triggers the peristaltic reflex

Question 2

Metoclopramide

Answer 2

Type: D2 Antagonist

MOA: Effects are confined to the upper digestive tract
- simulates contractions
- increases LES tone
Use: Gastroparesis, Prevention of vomiting
(chemotherapy), GERD
AES:
- CNS
* Restlessness, drowsiness, insomnia, anxiety and
agitation (10-20%)
* Extrapyramidal effects (dystonia, akathisia,
parkinsonianfeatures) (acutely in patients given
high doses)
* Severe (long-term use): Tardive dyskinesia
- increase Prolactin/ hormonals
* Galactorrhea/Menstrual disorders
* Gynecomastia/ Impotence

Question 3

Cisapride

Answer 3

Type: Serotonin Receptor Agonists

MOA: Stimulate 5-HT4 receptors

Use: Gastroparesis, GERD

PK: Hepatic (CYP3A4) metabolism

AES: FATAL CARDIAC ARRHYTMIAS, TDP

***No longer generally available/ restricted access

DDIs: Agents that interfere with Cyp3A4 metabolism

Question 4

Erythromycin

Answer 4

Type: Motilides

MOA: Mimick the effects of motilin –> increases contraction of upper GIT

Use: Diabetic Gastroparesis

AES: Tolerance, Antibiotic effect