Proton Pump Inhibitor (Omeprazole)

Omeprazole is the prototype member of a new class of substitued benzimidazoles which inhibit the final common step in gastric acid secretion. The only significant pharmacological action of omeprazole is dose dependent suppression of gastric acid secretion; without anticholinergic or H2 blocking action. It is a powerful inhibitor of gastric acid: can totally abolish Hcl secretion, both resting as well as that stimulated by any of the secretagogues, without much effect on pepsin, intrinsic factor, juice volume and gastric motility.

Omeprazole is inactive at neutral pH, but at pH <5 rearrange to two charged cationic forms that react covalently with the SH groups of the H+ K+ ATPase enzyme and inactivate it irreversibly, specially when two molecules of omeprazole react with one molecule of the enzyme. Pharmacology

The oral absorption of omeprazole is ~50%, but as the gastric pH rises a higher fraction(upto 3/4) may be absorbed. It is highly plasma protein bound, rapidly metabolised in liver(plsma half life t1/2 is ~1 hour) and metabolites excreted in urine.

No dose modification is required in elderly or in renal impairment. Because of tight binding to its target enzyme- it can be detected in the gastric mucosa long after its disappearance from plasma. As such, inhibition of Hcl secretion occurs within 1 hour, reaches maximum at 2 hour, is still half maximal at 24 hour and lasts 3 days.

Side effects

Because of marked and long lasting acid suppression, compensatory hypergastrinemia has been observed. This has been found to induce proliferation of parietal cells and gastric carcinoid tumours in rats, but not in human beings. However, it may appear prudent to be apprehensive of prolonged hypergastrinemia and if possible avoid long term use of proton pump inhibitors.

Dose

20 mg OD or BD for one or two weeks