FOR REVIEW - Role of Proton Pump Inhibitors (PPIs) in Gastroesophageal Reflux Disease (GERD) Management and PPIs Misuse

nazek hashem
Jan 30
3 min read

Updated: Feb 4

PPIs are drugs that bind to an enzyme, which is also a pump (H+/K+-ATPase) found in the stomach and prevent it from secreting gastric acid. While gastric acid has an important role in physiology, such as aiding in normal flora balance, food digestion, and preventing infections, its overproduction can lead to discomfort and long-term consequences.

One of the most common reasons people take PPIs is GERD. GERD is a common disorder with 20% prevalence in the USA. It is characterized by the regurgitation of gastric contents into the esophagus. Many people self-medicate with PPIs in ways that are not optimal.

What Are PPIs and How Do They Work?

PPIs bind to the enzyme responsible for the last step of acid secretion in the stomach: H+/K+-ATPase.
They only act on active pumps, meaning they block a portion of pumps initially. Over five days, blocked pumps reach a steady state, reducing gastric acid secretion by 60%.

Differences Between PPIs

All PPIs are equally effective. Clinical data does not suggest that one is better than another.
Dexlansoprazole is unique in that it can be taken with food and still be effective, while others must be taken on an empty stomach 30 minutes before food to avoid reducing their effectiveness.
Some PPIs require a prescription, while others are available over the counter. This difference depends on their dosage and intended use.

Role of PPIs in Treating GERD

For mild to moderate symptoms (less than two episodes per week), alternative medications such as H2 blockers (famotidine, cimetidine, or nizatidine) or antacids are preferred.
For severe symptoms (two or more episodes per week or symptoms affecting daily life), PPIs are the preferred choice. The selection of a PPI typically depends on cost, personal preference, or past experience.

Guidelines for Proper PPI Use

Complete the full course of therapy:
- PPIs have cumulative effects. Studies show that daily intake for the full recommended duration improves symptom control and quality of life.
- For GERD, an 8-week course is standard. After this, symptoms should be reassessed, and many patients can discontinue the medication. Prolonged therapy may indicate the need to investigate other underlying conditions.
Combine with lifestyle modifications:
- PPIs are most effective when paired with:
  - Avoiding trigger foods and drinks (e.g., fried foods, excessive alcohol, carbonated beverages).
  - Adjusting eating habits (e.g., avoiding large portions and late-night meals).
  - Making lifestyle changes if needed (e.g., losing excessive weight, avoiding tight clothing, and quitting tobacco use).
Do not stop PPIs abruptly:
- For those on long-term therapy (over six months), tapering is necessary to avoid rebound acid hypersecretion. This rebound can mimic disease recurrence but requires a different approach.
Limit long-term use:
- Avoid using PPIs longer than necessary to reduce risks of potential long-term side effects, including:
  - Drug interactions (e.g., with levothyroxine).
  - Increased risk of Clostridium difficile infection.
  - Chronic inflammation of the stomach lining (chronic atrophic gastritis).
  - Hypomagnesemia and B12 malabsorption.
  - Kidney disease.

New Developments in GERD Treatment

In July 2024, a new class of medication was approved for GERD treatment. However, since it has not been compared to PPIs in this context and is more expensive, PPIs remain the preferred choice.

Conclusion

PPIs are effective for GERD management when used correctly. Completing the recommended duration, combining treatment with lifestyle modifications, and avoiding prolonged unnecessary use are key to maximizing benefits and minimizing risks. For severe symptoms, PPIs continue to be a cornerstone of treatment, despite emerging alternatives.

References

Begg, M., Tarhuni, M., Fotso, M. N., Gonzalez, N. A., Sanivarapu, R. R., Osman, U., Kumar, A. L., Sadagopan, A., Mahmoud, A., & Khan, S. (2023). Comparing the safety and efficacy of proton pump inhibitors and histamine-2 receptor antagonists in the management of patients with peptic ulcer Disease: a Systematic review. Cureus. https://doi.org/10.7759/cureus.44341

Professional, C. C. M. (2024, December 19). Proton pump inhibitors. Cleveland Clinic. https://my.clevelandclinic.org/health/articles/proton-pump-inhibitors

UpToDate. (n.d.). UpToDate. https://www.uptodate.com/contents/proton-pump-inhibitors-overview-of-use-and-adverse-effects-in-the-treatment-of-acid-related-disorders?search=ppi%20side%20effects&source=search_result&selectedTitle=1%7E150&usage_type=default&display_rank=1#H59974951