Proton-pump inhibitor
Overview
Proton-pump inhibitors (PPIs) are a group of drugs whose main action is a pronounced and long-lasting reduction of stomach acid production. They are the most potent inhibitors of acid secretion available today. The group includes drugs such as omeprazole, lansoprazole, rabeprazole, pantoprazole, and esomeprazole.
Mechanism of Action
Proton-pump inhibitors act by irreversibly blocking the hydrogen/potassium ATPase enzyme system of the gastric parietal cell. This enzyme system is regarded as the acid (proton) pump within the gastric mucosa. The blocked enzyme prevents the movement of hydrogen ions, a component of hydrochloric acid, from the parietal cell into the stomach, thereby inhibiting acid secretion.
Clinical Uses
PPIs are used in the treatment of many conditions, such as gastroesophageal reflux disease (GERD), peptic ulcers, and Zollinger-Ellison syndrome, that are caused by stomach acid. They have largely replaced the H2 receptor antagonists for treating these conditions.
Adverse Effects
While generally safe and effective when prescribed by a physician, proton-pump inhibitors can cause adverse effects, which may vary in incidence and severity from patient to patient. Some of the common side effects include headache, nausea, diarrhea, abdominal pain, fatigue, and dizziness. Serious adverse effects include risk of fractures, infections, and deficiency states such as low levels of magnesium and vitamin B12.
Pharmacokinetics
Proton-pump inhibitors are metabolized in the liver by the cytochrome P450 system. They have a short plasma half-life, but the effect on the acid-producing parietal cells is long-lasting since the drug is bound to the enzyme system, allowing for once or twice daily dosing.
Drug Interactions
Proton-pump inhibitors can interact with other drugs due to their effect on the cytochrome P450 system, an enzyme system involved in the metabolism of many drugs. Drugs that may interact with PPIs include clopidogrel, warfarin, and phenytoin.