Ppi drugs
Pro Research Analysisby 
Searched over 200M research papers for "ppi drugs"
Proton Pump Inhibitors (PPIs): Efficacy, Safety, and Emerging Concerns
Introduction to Proton Pump Inhibitors (PPIs)
Proton pump inhibitors (PPIs) are among the most effective medications for reducing gastric acid secretion. They are widely prescribed for conditions such as gastroesophageal reflux disease (GERD), peptic ulcers, and for the prevention of gastrointestinal bleeding in patients on antiplatelet therapy1 2 5. Despite their widespread use and general safety, concerns about the long-term effects and potential adverse outcomes of PPIs have been increasingly reported1 2 4.
Long-term Use and Gastric Pre-malignant Lesions
The long-term use of PPIs has been scrutinized for its potential to promote gastric pre-malignant lesions. Studies have shown mixed results regarding the development of conditions such as atrophic gastritis, intestinal metaplasia, and enterochromaffin-like (ECL) cell hyperplasia. While some studies indicate an increased risk of ECL cell hyperplasia, the clinical significance of this finding remains uncertain. Importantly, no dysplastic or neoplastic changes were observed in the reviewed trials1.
Adverse Effects of PPIs
Common Adverse Effects
PPIs are generally well-tolerated, but common adverse effects include abdominal pain, diarrhea, and headache8. These side effects are typically mild and transient.
Serious Adverse Effects
Recent studies have highlighted more serious potential adverse effects associated with long-term PPI use. These include an increased risk of fractures, chronic kidney disease, Clostridium difficile infection, hypomagnesemia, vitamin B12 deficiency, and dementia2 8 10. However, most of the evidence supporting these associations comes from observational studies, which makes it difficult to establish a direct causal relationship2 8.
PPIs and Cancer
The relationship between PPIs and cancer is complex. PPIs may influence cancer development and survival through various mechanisms, including drug-drug interactions (DDIs) with cancer medications and alterations in the gut microbiome. Some studies suggest that PPIs can decrease the efficacy of certain chemotherapy agents, while others indicate potential protective effects on the renal system3. The overall impact of PPIs on cancer outcomes remains unclear, necessitating further research3.
Overprescription and De-prescribing Strategies
PPIs are often overprescribed for conditions where their benefits are not well-established, such as functional dyspepsia and primary prevention of drug-related gastroduodenal damage4 5. This overuse contributes to unnecessary healthcare costs and increases the risk of adverse effects. The American Gastroenterological Association (AGA) recommends regular review of PPI indications and de-prescribing in patients without a clear need for long-term therapy4. Strategies for de-prescribing include dose tapering or abrupt discontinuation, with consideration of patient-specific factors and potential rebound acid hypersecretion4.
Conclusion
While PPIs are highly effective for managing acid-related disorders, their long-term use should be carefully considered due to potential adverse effects and the risk of overprescription. Clinicians should regularly review the necessity of PPI therapy and consider de-prescribing when appropriate. Further high-quality studies are needed to clarify the long-term safety profile of PPIs and their impact on conditions such as cancer and chronic kidney disease.
Sources and full results
Most relevant research papers on this topic
Long-term proton pump inhibitor (PPI) use and the development of gastric pre-malignant lesions.
Long-term PPI use may not significantly increase the risk of developing gastric pre-malignant lesions, but long-term use may not be recommended for certain diseases.
Meta-Analysis
Very Rigorous Journal
Highly CitedAdverse Effects Associated With Proton Pump Inhibitors.
Proton pump inhibitors (PPIs) are associated with a number of adverse effects and are overprescribed, including chronic kidney disease.
Systematic Review
Rigorous JournalHighly CitedProton Pump Inhibitors and Cancer: Current State of Play
PPIs may interact with cancer microbiome and antineoplastic agents, potentially decreasing their efficacy and worsening side effects, but their impact on cancer survival remains unclear.
Systematic ReviewAGA Clinical Practice Update on De-Prescribing of Proton Pump Inhibitors: Expert Review.
De-prescribing PPIs is a cost-effective strategy to lower pill burden and reduce risks, but should be considered for patients with uncertain benefits and those with known complications.
Systematic ReviewHighly CitedThe appropriate use of proton pump inhibitors (PPIs): Need for a reappraisal.
The inappropriate use of proton pump inhibitors (PPIs) has increased costs and risks, necessitating educational initiatives to guide physicians and specialists to their correct use in clinical practice.
Highly CitedThe Indications, Applications, and Risks of Proton Pump Inhibitors.
Proton pump inhibitors are effective for treating gastric acid-related diseases, but their cost and potential adverse effects require only valid prescriptions for scientifically validated indications.
Systematic ReviewHighly CitedInhibitors of protein-protein interactions (PPIs): an analysis of scaffold choices and buried surface area.
Protein-protein interactions can be effectively inhibited by small molecules or peptides, depending on the scaffold used and the target interaction's surface area.
Literature ReviewHighly CitedProton Pump Inhibitors: Review of Emerging Concerns
Long-term use of proton pump inhibitors (PPIs) may increase the risk of serious adverse effects, but current evidence is insufficient to definitively link their use to serious risks.
Highly CitedSmall molecules, big targets: drug discovery faces the protein–protein interaction challenge
Protein-protein interactions can be targeted for drug discovery, with successful inhibitors reaching clinical development for certain classes.
Highly CitedAdvantages and Disadvantages of Long-term Proton Pump Inhibitor Use
Long-term proton pump inhibitor use is relatively safe and beneficial for treating acid-related diseases, but its clinical relevance remains unclear.
Rigorous JournalHighly Cited