Proton Pump Inhibitors: Mechanisms, Clinical Applications, and Future Perspectives

Proton pump inhibitors (PPIs) are widely prescribed for the treatment of acid-related gastrointestinal disorders, including peptic ulcers, gastroesophageal reflux disease (GERD), and Helicobacter pylori infection.Their therapeutic action is based on the irreversible inhibition of gastric H⁺/K⁺-ATPase, resulting in sustained acid suppression.Despite their application, PPIs exhibit several pharmacological limitations such as delayed onset of action, short plasma half-life, inter-individual metabolic variability, and inadequate nocturnal acid control, which can compromise therapeutic outcomes.To address these issues, potassium-competitive acid blockers (P-CABs) have emerged as promising alternatives, offering rapid, metal-independent acid suppression with improved pharmacodynamic profiles.This review explores the pharmacological mechanisms, clinical applications, and long-term safety concerns associated with PPIs, including nutrient malabsorption, increased infection risk, and idiosyncratic hepatotoxicity.This article emphasizes the role of computational drug design tools like molecular docking, QSAR modelling, and ADMET prediction in accelerating the discovery and optimization of next-generation acid suppressants.Case studies and experimental strategies are discussed to focus on the therapeutic potential of both PPIs and P-CABs.The article also addresses regulatory considerations, ethical implications, and future directions in precision drug design, emphasizing the need for a balanced approach to efficacy, safety, and individualized therapy in acid-related gastrointestinal diseases.