GI Pharmacology — Erythromycin & Emptying

Physiology of Gastric Emptying

Gastric emptying

• Fluids have half-time of 30mins in stomach
• Solids have half-time of 2 hours in stomach

Gastric receipt of food bolus:

1. Peristaltic wave moves down the oesophagus, propelling food bolus
   • Controlled by mesenteric plexus with input from vagus nerve
2. Upon swallowing, the lower oesophageal sphincter and stomach relax until the oesophageal peristaltic wave has passed
3. Following food bolus passage, the LOS tone increases to prevent reflux
4. Food bolus reaching the stomach causes a vagal-mediated relaxation of the stomach, to accommodate gastric distension and food storage

Gastric mixing and emptying:

1. Spontaneous mixing waves move down the stomach every 15-20 seconds
   • Stronger waves propel gastric contents towards the pylorus (pyloric pump)
2. High pyloric sphincter tone
   • Allows through well-mixed liquid chyme
   • Restricting gastric emptying of solids, causing mixing (retropulsion)

Control

Gastric emptying is controlled by the balance between stimulatory gastric factors and inhibitory duodenal factors

Factors promoting gastric emptying:

1. Increased stomach wall stretch
   • Stimulates pyloric pump
   • Reduces pyloric tone
2. Parasympathetic vagal stimulation
   • Stimulates pyloric pump
3. Gastrin
   • Stimulates pyloric pump
   • From G cells in antrum
     • In response to presence of protein (esp. meat) in stomach
4. Motilin
   • Stimulates pyloric pump
     • During fasting
5. From M cells in duodenum (external antigen stimulus)
6. Carbohydrate: rapid emptying

Factors inhibiting gastric emptying:

1. Nervous reflexes via enteric nervous system, local sympathetic trunk, and the vagal nerve to the brainstem
   • in response to local conditions in the duodenum: Distension, Irritation, Acidity of chyme, Hyper- or hypo- tonicity of chyme, Breakdown products, Especially AA and FA
   • Inhibit pyloric pump
   • Increase pyloric sphincter tone
2. Hormones (inhibit pyloric pump)
   • Cholecystokinin (CCK)
     • From I cells of duodenum
     • In response to presence of fat and proteins
   • Secretin
     • From S cells of duodenum
     • In response to presence of acids
   • Gastric inhibitory peptide (GIP)
     • From K cells of duodenum
     • In response to presence of fats, proteins and carbohydrate
3. Other Factors :
   • Sympathetic stimulus:
     • Decreases contractility and reduces gastric emptying
   • Dopamine:
     • Decreases intragastric pressure and lower oesophageal sphincter tone
     • reduces gastric emptying

Alternate: This section can also be approached as:

• Local factors
  • Gastric Factors: pump, Stomach wall distension, Amino acid
  • Duodenal Factors: Type of food, stretch of wall, irritation, hyperosmolaroty, acidity, amino acid and FA content
• Neural factors
  • Symptathetic
  • Parasympathetic
• Hormonal factors
  • Dopamine
  • Gastrin
  • Motilin
  • Secretin
  • CCK
  • Somatostatin
  • GIP

Mooney / Sakurai / JC 2019

Erythromycin

• Action:
  • Agonist at motilin receptors on GI muscle
  • Enchances motilin release from M cells in duodenum
• Promotes onset, frequency and duration of migrating motor complex
• Increases lower oesophageal tone
• May eliminate normal gut flora

Answer by JC, Mooney, Sakurai