Proton Pump Inhibitors (PPIs) – Hazardous Group of Medicines

 

Proton Pump Inhibitors (PPIs) – Hazardous Group of Medicines

(Dr. Guru Prasad Mohanta, Professor, Department of Pharmacy, Annamalai University, Annamalai Nagar – 608 002, Tamil Nadu, E. mail: gpmohanta@hotmail.com)

The recent US FDA’s instruction to write warning on the label of all Proton Pump Inhibitors about ‘increased risk of fracture on long term use’ is an eye opening for all concerned with medicine use. These groups of medicines are often considered harmless by physicians, pharmacists and the patients as well. They are perhaps one of the most over used drugs category unmindful of risks involved.

As the name implies, the PPIs block the hydrogen-potassium adenosine triphosphatase system (proton pump) of gastric parietal cells and inhibit gastric acid secretion. The PPIs are indicated for the treatment of gastric ulcers, gastro-esophageal reflux disease (GERD) with severe symptoms and prevention of upper gastrointestinal bleeding commonly associated with NSAIDs. Unfortunately, they are even used as first choice for mild cases of heartburn (GERD). The available PPIs in the market are: Omeprazole, Lansprazole, Dexlansoprazole, Esmoprazole, Pantoprazole, Rabeprazole and Llaprazole. Esmoprazole is functionally no different from Omeprazole and so as Dexlansoprazole and Lansprazole. But they have significant difference in prices.

The studies have shown several risks associated with the use of PPIs: modest increase in hip, spine and wrist fracture; dependence on PPIs (rebound acid hyper secretion risk even after four weeks of use); infection risk (Clostridium difficile caused diarrhoea and community acquired pneumonia); and Magnesium deficiency risk.  The acid secretion in the stomach is based on a delicate hormonal balance gastrin and somatostatin. Any disruption on this balance and consequent normal physiology, as caused by PPIs, would have long term complications.  The inhibition of gastric acid secretion might interfere with absorption of calcium and interference with activity of osteoclasts, which could lead to a decrease in bone resorption. This is the possible hypothesis of increased risk of fracture. After use of one month of PPIs, upon withdrawal there is a rebound hypersecretion of acid, requiring higher doses and in consequences acid secretion would not be controlled by PPIs causing long term dependence. The presence of normal quantity of gastric acid acts as barrier for bacteria. The bacteria that get entry are killed by the acidity of the stomach. Clostridium difficile infection (CDI) commonly seen in hospitals causing diarrhoea is strongly associated with use of PPIs. H₂ Blockers do not disturb gastric secretion as do PPIs and do not allow CDI.  The PPIs induce bacterial over growth (less acidity in the stomach) in upper gastrointestinal tract and these infected secretions when aspirated especially by elderly people leads to pneumonia.

Though there are unquestionable utility of PPIs when indicated, being hazardous they should be used carefully especially in the common heartburn. Diet, life style changes, and use of safer and cheaper gastric antacids and H₂ blockers are recommended as alternative to PPIs in GERD. Eating smaller meals, not lying down for at least three hours after eating, reducing weight if desirable and avoiding alcohol are known strategies that help the GERD patients. Even when PPIs are recommended they should not be given for long term use.