What substances increase or decrease the tone of the lower esophageal sphincter (LES)?

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Lower Esophageal Sphincter Tone Modulation

Gastrin increases lower esophageal sphincter (LES) tone, while metoclopramide increases LES tone, nicotine decreases LES tone, and chocolate decreases LES tone. Therefore, the correct answer is (a).

Effects of Various Substances on LES Tone

Substances that Increase LES Tone:

  • Gastrin: Stimulates the cardiac sphincter to increase tone and augment resistance to reflux 1. Although there are some conflicting studies, with one showing a potential decrease in LES pressure during continuous gastrin infusion 2, the predominant evidence supports gastrin's role in increasing LES tone.
  • Metoclopramide: Increases the resting tone of the lower esophageal sphincter as stated in the FDA drug label 3. In patients with gastroesophageal reflux and low LES pressure, single oral doses of metoclopramide produce dose-related increases in LES pressure, with effects beginning at about 5 mg and increasing through 20 mg.

Substances that Decrease LES Tone:

  • Nicotine: Decreases LES tone, which can exacerbate gastroesophageal reflux disease (GERD) symptoms.
  • Chocolate: Decreases LES tone, making it a common trigger food for GERD symptoms.

Mechanism of Action

Gastrin

  • Gastrin appears to have a direct effect on the cardiac sphincter, increasing its tone independent of its acid secretory stimulus 1.
  • While some studies suggest variability in this effect 4, the predominant clinical understanding is that gastrin increases LES pressure.

Metoclopramide

  • Metoclopramide increases LES pressure through its prokinetic effects 3.
  • The American Gastroenterological Association notes that prokinetic agents like metoclopramide are not recommended as monotherapy for GERD due to limited efficacy and significant side effects 5.
  • In patients with gastroesophageal reflux and low LES pressure, metoclopramide produces dose-related increases in LES pressure that last between 45 minutes (5 mg dose) and 2-3 hours (20 mg dose) 3.

Clinical Implications

  • For GERD Management: Understanding LES tone modulators is crucial for managing GERD symptoms.
  • Medication Selection: Baclofen is recommended as first-line pharmacologic therapy for regurgitation or belch-predominant GERD symptoms as it inhibits transient lower esophageal sphincter relaxations 5.
  • Dietary Considerations: Avoidance of foods that decrease LES tone (like chocolate) may be beneficial in patients with GERD symptoms 6.

Important Caveats

  • The relationship between serum gastrin concentration and LES pressure is complex, with some studies showing variability in response 4.
  • While metoclopramide increases LES tone, its use is limited by significant adverse effects including drowsiness, restlessness, and extrapyramidal reactions 6.
  • The FDA has issued a black box warning regarding metoclopramide's adverse effects 6.
  • Dietary modifications should be tailored to individual triggers, as the data regarding avoidance of presumably refluxogenic foods in extraesophageal reflux are limited 6.

Understanding the effects of various substances on LES tone is essential for managing GERD and related conditions, with gastrin and metoclopramide increasing tone, while nicotine and chocolate decrease it.

References

5
Guideline

Gastroesophageal Reflux Disease (GERD) Management

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

6
Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

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This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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