Gastroprokinetic agents

Gastroprokinetic agents are medications that promote the movement of food, liquids, and drugs through the digestive system. They enhance the frequency and strength of gastric and intestinal muscle contractions.

Indications for Use

  • Useful in treating various digestive disorders:

    • Gastroparesis: Condition marked by slow food movement in the stomach. Example: Diabetic gastroparesis

    • Gastroesophageal Reflux Disease (GERD): Condition caused by acid reflux.

    • Irritable Bowel Syndrome (IBS): Affects the bowel leading to symptoms like cramps and bloating.

    • Functional Dyspepsia: A chronic upper digestive disorder without an identifiable cause.

    • Multiple Sclerosis: Affects the central nervous system and may lead to digestive issues.

Mechanisms of Action

Metoclopramide

  • Dopamine D2 Receptor Antagonism: Blocks dopamine D2 receptors in the gastrointestinal tract. dopamine normally inhibits gastric motility by reducing release of acetylcholine. blocking dopamine enhances acetylcholine release

  • Serotonin 5-HT4 Receptor Agonism: Enhances activity at serotonin receptors which promotes acetylcholine release further enhancing gastric motility

  • Anti-emetic Properties: Antagonist action at dopamine D2 receptors in the chemoreceptor trigger zone (CTZ) of the brain.

Side Effects of Metoclopramide

  • Menstrual Irregularities: Changes in menstrual cycle.

  • Anxiety: Increased feelings of worry or nervousness.

  • Dystonic Reactions: Involuntary muscle contractions.

  • Tardive Dyskinesia: Movements that are uncontrollable and often irreversible.

  • Oculogyric Crisis: Involuntary eye movement where the eyes move upward.

Prucalopride

Selective 5-HT4 Agonist Increases acetylcholine release, contracting colon muscles to facilitate digestion. Indicated for Chronic Idiopathic Constipation (CIC) in adults when other treatments fail.

side effects: decreased appetite, increased urinary frequency

Linaclotide

Guanylate Cyclase-C (GC-C) Activation: Stimulates GC-C on intestinal surfaces; converts GTP to cGMP. cGMP participates in fluid secretion and muscle contraction. It also stimulates intestinal wall muscle contraction, facilitating quicker food and waste movement.

Side Effects of Linaclotide: Decreased appetite, increased urinary frequency.

  • Indicated for:

    • Chronic Idiopathic Constipation (CIC)

    • Irritable Bowel Syndrome with Constipation (IBS-C)

    • Opioid-Induced Constipation (OIC)

Side Effects of Linaclotide

  • Diarrhea: Increased frequency of bowel movements.

  • Abdominal Pain: Discomfort in the abdomen.

  • Nausea: Feeling of sickness with an urge to vomit.