Omeprazole: It is the prototype member of substituted benzimidazoles which inhibit the final common step in gastric acid secretion. The proton-pump- inhibitors (PPIs) have overtaken H2 blockers for acid-peptic disorders. The only significant pharmacological action of omeprazole is dose dependant 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 food or any of the secretagogues, without much effect on pepsin, intrinsic factor, juice volume and gastric motility.
Uses
- Peptic ulcer: Omeprazole 20 mg OD is equally or more effective than H2 Relief of pain is rapid and excellent. Faster healing has been demonstrated with 40 mg/day: Some deudenal ulcers heal even at 2 weeks and the remaining (over 90%) at 4 weeks. Gastric ulcer generally requires 4-8 weeks. It has caused healing of ulcers in patients not responding to H2 blockers. Continued treatment (20 mg daily or thrice weekly) can prevent ulcer relapse. PPIs are integral component of anti-H. Pylori therapy. PPIs are the drugs of choice for NSAID (diclofenic, ibuprofen).induced gastric/duodenal ulcers. Healing may occur despite continued use of the NSAID (Diclofenic, ibuprofen).
However, higher doses given for longer periods are generally required. When the NSAIDs (diclofenic, ibuprofen) cannot be stopped, it is advisable to switch over to a COX-2 selective NSAIDs inhibitors (celecoxib, etoricoxib, parecoxib).Maintenance PPI treatment reduces recurrence of NSAID associated ulcer.
- Bleeding peptic ulcer: Acid enhances clot dissolution promoting ulcer bleed. Suppression of gastric acid has been found to facilitate clot formation reducing blood loss and re-bleed. High dose i.v. PPI therapy (pantoprazole 40-120 mg/day or rabeprazole 40-80 mg/day) profoundly inhibits gastric acid and has been shown to reduce re-bleeding after therapeutic endoscopy. Even in case where the bleeding vessel could not visualized, i.v. followed by oral PPI reduces recurrence of bleeding and need for surgery.
- Stress ulcers: Intravenous pantoprazole/rabeprazole is effective prophylactic(if not more) for stress ulcers as i.v. H2
- Gastroesophageal reflux diseases (GERD): Omeprazole produces more complete round-the-neck inhibition of gastric acid resulting in rapid symptom relief and is more effective than H2 blockers in promoting healing of esophageal lesions. PPIs are the drug of choice. Higher doses than for peptic ulcer or twice daily administration is generally needed.
- Zollinger–Ellison syndrome: Omeprazole is more effective than H2 blockers in controlling hyperacidity in Z-E syndrome.However,60-120 mg/day or more (in 2 divided doses) is often required for healing of ulcers. Inoperable cases have been treated >6 years with sustained benefit and no adverse effects. Other gastric hypersecretory states like systemic mastocytosis, endocrine adenomas, etc. Also respond well.
- Aspiration pneumonia: PPIs are an alternative to H2 blockers for prophylaxis of aspiration pneumonia due to prolonged anesthesia.
Adverse effect: PPIs produce minimal adverse effects. Nausea, loose stools, headache, abdominal pain, muscle and joint pain, dizziness, are complained by 3-5%.Rashes (1.5% incidence), leucopenia and hepatic dysfunction are infrequent. On prolonged treatment atrophic gastritis has been reported occasionally.
No harmful effects of PPIs during pregnancy are known. Though manufactures advise to avoid, PPIs have often been used for GERD during pregnancy.
Because of marked and long-lasting suppression,compensatory hypergastrinemia has been observed.This induces proliferation of parietal cells and gastric carcinoid tumors in rats,but not in humans.Though patients have been treated continuously for >11 years without any problems, it may appear prudent to be apprehensive of prolonged achlorhydria and hypergastrinaemia; and if possible, avoid long-term use of PPIs.
Lately, few reports of gynaecomastia and erectile dysfunction (possibly due to reduced testosterone level) on prolonged use of omeprazole have appeared. Accelerated osteoporosis among elderly patients (possibly due to reduced calcium absorption) has been recently associated with high dose long-term use of PPIs for GERD.
Interactions: Omeprazole inhibits oxidation of certain drugs: diazepam,phenytoin and warfarin levels may be increased.It interferes with activation of clopidogrel by inhibiting CYP2C19.Reduce gastric acidity decreases absorption of ketokonazole and iron salts. Clarithromycin inhibits omeprazole metabolism and increases its plasma concentration.
Other Common PPIs obtained in pharmacy are; Esomeprazole, Lansoprazole, Pantoprazole and rabeprazole.
