Omeprazole pharmacology
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Omeprazole Mechanism of Action and Pharmacological Effects
Omeprazole is a proton pump inhibitor (PPI) that works by irreversibly binding to and inhibiting the H+-K+-ATPase enzyme (the gastric proton pump) in the parietal cells of the stomach. This action leads to a strong and long-lasting reduction in gastric acid secretion, making omeprazole highly effective for treating acid-related gastrointestinal disorders such as gastroesophageal reflux disease (GERD), peptic ulcers, and Zollinger-Ellison syndrome 123. Omeprazole reduces both basal and stimulated acid secretion, regardless of the stimulus, and is considered superior to H2-receptor antagonists for healing ulcers and esophagitis .
Pharmacokinetics: Absorption, Distribution, Metabolism, and Excretion
Omeprazole is acid-labile, so it must be protected from stomach acid when taken orally, typically through enteric-coated formulations. After oral administration, omeprazole is rapidly absorbed, with peak plasma concentrations occurring within 0.5 to 3 hours depending on the formulation 45. Its bioavailability increases with repeated dosing, rising from about 35% after a single dose to around 60% with daily use 45. The drug is quickly eliminated from plasma, with a half-life of less than one hour, but its effect on acid secretion lasts much longer due to irreversible enzyme inhibition .
Omeprazole is extensively metabolized in the liver, mainly by cytochrome P450 enzymes (CYP2C19 and CYP3A4), and its metabolites are excreted primarily in the urine and to a lesser extent in bile . The main plasma metabolites, sulphone and hydroxyomeprazole, do not contribute to its acid-suppressing effects .
Clinical Use and Dosing Considerations
A typical oral dose of 20–40 mg once daily achieves near-maximal acid suppression, and this regimen is effective for most patients 13. Omeprazole is used for both short-term healing and long-term maintenance therapy in acid-related disorders, with studies showing good tolerability and low rates of serious side effects even with prolonged use 23.
Pharmacokinetics in Special Populations
Children require higher doses of omeprazole per kilogram of body weight compared to adults, especially younger children, due to higher metabolic capacity and faster drug clearance . In patients with certain conditions, such as ulcerative colitis, omeprazole metabolism may be slower, leading to higher plasma concentrations and reduced clearance, likely due to decreased activity of hepatic CYP450 enzymes .
Drug Interactions and Influencing Factors
Omeprazole can interact with other drugs by inhibiting their oxidative metabolism, particularly those metabolized by CYP2C19 and CYP3A4. Notable interactions include increased plasma levels of diazepam and phenytoin, while interactions with drugs like propranolol and theophylline are minimal 149. Omeprazole can also affect the absorption of drugs that require an acidic environment, such as certain antifungals and iron supplements 29.
Some substances, such as St John’s wort, Ginkgo biloba, and certain antiretrovirals, can induce omeprazole metabolism, reducing its effectiveness . Dietary factors, like the consumption of grape juice, can also decrease omeprazole’s systemic exposure by inducing drug-metabolizing enzymes and transporters, potentially requiring dose adjustments 610.
Adverse Effects and Long-Term Safety
While omeprazole is generally well tolerated, long-term use can be associated with gastrointestinal disturbances, nutrient deficiencies, kidney issues, and increased risk of infections . Slight hyperplasia of stomach cells has been observed with prolonged use, but no evidence of serious cell changes or tumors has been found in humans .
Conclusion
Omeprazole is a highly effective and widely used proton pump inhibitor for acid-related gastrointestinal disorders. Its pharmacological action is based on irreversible inhibition of the gastric proton pump, leading to potent and sustained acid suppression. Omeprazole’s pharmacokinetics are influenced by formulation, dosing frequency, age, disease states, drug interactions, and dietary factors. While generally safe, careful consideration of potential drug interactions and adverse effects is important, especially with long-term use or in special populations.
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