What are the effects of Proton Pump Inhibitors (PPIs)?

From the Guidelines

Proton pump inhibitors (PPIs) should be used with caution and at the lowest effective dose for the shortest duration necessary, as they may be associated with potential risks including reduced calcium absorption, increased risk of certain infections, vitamin B12 deficiency, and kidney problems, as well as interactions with other medications such as clopidogrel 1.

Effects of PPIs on Stomach Acid Production

PPIs work by irreversibly binding to the hydrogen-potassium ATPase enzyme in stomach parietal cells, preventing the final step of acid production. This reduction in stomach acid production can be beneficial for conditions such as gastroesophageal reflux disease (GERD), peptic ulcers, and H. pylori infections.

Potential Risks and Interactions

However, long-term PPI therapy may be associated with potential risks, including:

• Reduced calcium absorption
• Increased risk of certain infections
• Vitamin B12 deficiency
• Kidney problems Additionally, PPIs may interact with other medications, such as clopidogrel, which can reduce the effectiveness of the medication and increase the risk of adverse cardiovascular outcomes 1.

Recommendations for Use

To minimize the risks associated with PPIs, patients should:

• Take the lowest effective dose for the shortest duration necessary
• Have regular follow-ups with their healthcare provider to assess ongoing need for therapy
• Be aware of potential interactions with other medications and inform their healthcare provider of any concerns
• Consider alternative medications or therapies, such as H2 antagonists, if necessary 1.

Key Points

• PPIs are effective in reducing stomach acid production and treating conditions such as GERD, peptic ulcers, and H. pylori infections
• Long-term PPI therapy may be associated with potential risks, including reduced calcium absorption, increased risk of certain infections, vitamin B12 deficiency, and kidney problems
• PPIs may interact with other medications, such as clopidogrel, and reduce their effectiveness
• Patients should take the lowest effective dose for the shortest duration necessary and have regular follow-ups with their healthcare provider to assess ongoing need for therapy.

From the FDA Drug Label

Omeprazole delayed-release capsules can cause serious side effects, including: • A type of kidney problem (tubulointerstitial nephritis). • Diarrhea. • Bone fractures. • Certain types of lupus erythematosus.

The effects of Proton Pump Inhibitors (PPIs), such as omeprazole, include:

• Increased risk of kidney problems, such as tubulointerstitial nephritis
• Diarrhea, which may be caused by an infection (Clostridium difficile) in the intestines
• Bone fractures, particularly in people who take multiple daily doses of PPI medicines for a long period of time (a year or longer)
• Certain types of lupus erythematosus, including cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE) 2 Additionally, PPI therapy may be associated with an increased risk of osteoporosis-related fractures of the hip, wrist, or spine, and Clostridium difficile-associated diarrhea 2

From the Research

Effects of Proton Pump Inhibitors (PPIs)

• PPIs have demonstrated gastric acid suppression superior to that of histamine H2-receptor blockers 3
• They have enabled improved treatment of various acid-peptic disorders, including gastroesophageal reflux disease, peptic ulcer disease, and nonsteroidal antiinflammatory drug-induced gastropathy 3
• PPIs have minimal side effects and few significant drug interactions, and they are generally considered safe for long-term treatment 3

Therapeutic Uses of PPIs

• PPIs are the treatment of choice for acid-related diseases, including gastroesophageal reflux disease (GERD) and peptic ulcer disease 4
• They are also used for the treatment of Helicobacter pylori infection and upper gastrointestinal bleeding 5
• PPIs are effective in preventing GERD relapse when used as maintenance therapy 4

Comparison of Different PPIs

• Different PPIs have similar efficacy in many cases, but there are some differences in their clinical pharmacology 4
• Rabeprazole has a more rapid onset of H+,K+-ATPase inhibition than other PPIs 4
• Esomeprazole, rabeprazole, and lansoprazole were found to be superior to pantoprazole on the first day of treatment in terms of acid inhibitory effects 6
• Twice-daily dosing of esomeprazole effectively inhibits acid secretion in CYP2C19 rapid metabolisers compared with twice-daily omeprazole, rabeprazole or lansoprazole 7

Pharmacology and Efficacy of PPIs

• PPIs inhibit the growth of Helicobacter pylori and, when administered in combination with antibiotics, provide the best treatment for eradication of the bacterium 4
• The proton pump inhibitors omeprazole, lansoprazole, rabeprazole, and esomeprazole appear to have similar efficacy 3
• PPIs have been shown to be effective in healing duodenal ulcer, gastric ulcer, and ulcerative or erosive GERD 4