Proton Pump Inhibitors (PPI) are one of the most widely sold drugs globally alongside statins, beta-2 agonists, atypical antipsychotics and synthetic thyroid medications. It is a commonly prescribed drug due to its potent action of reducing gastric acid production.

Proton Pump Inhibitors Background

This drug is most commonly distributed under the brand name Nexium (esomeprazole), the first PPI in the gastric mucosa, namely on the proton pump. This pump pumps hydrogen ions out of the cell and into the lumen in exchange for potassium ions. PPIs cause irreversible blockage of the proton pump, leading to the inhibition of acid secretion.

It is usually given to patients suffering from gastroesophageal reflux disease, peptic ulcers or Zollinger-Ellison syndrome, among others. This drug is not advisable to be taken with food, as its absorption is decreased by this. PPIs have a half-life of 60 to 90 minutes but their effect of inhibiting the secretion of gastric acid can last up to 24 hours. Due to its 24 hour effectiveness, this drug is usually given once a day.

Gut Flora and PPI Use

The stomach has low to zero bacteria present, unlike the intestines which have a low population of the potentially pathogenic microbe Clostridium difficile. The reason for the lack of bacteria in the stomach is due to the low pH/acidic environment which is unfavorable for bacterial growth. In the case of long-term PPI use, which averages from as short as 4 months up to 12 months minimum, individuals develop an achloryhdric stomach. Achlorydria is when gastric secretions lack or have an absence of hydrochloric acid. A study by Moayyedi et. al entitled “Changing Patterns of Helicobacter pylori Gastritis in Long-Standing Acid Suppression” concluded that there is a greater bacterial colonization of H. pylori, seen in the stomach after long-term PPI acid suppression. Alongside bacterial growth, an increase in cytokine levels and a higher risk for atrophic gastritis was noted.

Several studies have linked an increased risk of developing diarrhea and enteric infections, namely Clostridium difficile related. The predisposition to these infections have been observed in PPI users due to a change in the normal gut flora. The so called good bacteria have decreased in numbers in comparison to the harmful ones.

PPI Use: Prescription and Over-the-counter

PPIs can easily be picked up at the local pharmacy by individuals without the need for a doctor’s prescription. Due to the broad marketing of the drug and its well-known mechanism of action, individuals take PPIs in cases of heart burn or other hyperacidity related problems. It tends to be overused or used inappropriately which sits them in the same boat as the long-term PPI users.


The presence of the potential adverse long term effects of PPI treatment has been commonly overlooked in clinical practice as well as the general patient population. Though PPIs are considered relatively safe drugs, especially since their beneficial effects still largely outweigh the harmful effects, the aforementioned are still outcomes that need to be heeded.

It is recommended to use these drugs only when there is a clear medical indication like in the cases of peptic ulcers, Gastroesophageal reflux disease, dyspepsia, active upper gastrointestinal bleeding, Barret’s esophagus and similar cases. Clinical guidelines, for the hospital and ambulatory settings, are being established and implemented on when GI prophylaxis in the form of PPIs is appropriate. MIMS