Omeprazole
Omeprazole
Generic Name
Omeprazole
Mechanism
- Selective, irreversible inhibition of the H⁺/K⁺‑ATPase (proton pump) on the gastric parietal cell luminal surface.
- Blocks proton translocation, rendering the pump unable to recycle H⁺ into the stomach lumen.
- Leads to a dose‑dependent decrease in intragastric pH, maintaining pH ≥ 5 for 18–24 hrs with once‑daily dosing.
- Activity commences after pro‑drug conversion in acidic pH (swallowing the capsule in a fasting state enhances absorption).
Pharmacokinetics
| Parameter | Value | Comments |
| Absorption | <10 % oral bioavailability; pH‑dependent | Higher GI pH → better absorption |
| Distribution | Moderate; ~30 % protein‑bound | Volume of distribution ≈ 200 L |
| Metabolism | CYP2C19 (major) → *omeprazole* → acetyl‑, sulfone‑, and sulfate‑derivatives; CYP3A4 minor | Genetic polymorphisms in CYP2C19 influence serum levels |
| Elimination | Hepatic → urinary excretion of metabolites | Half‑life ≈ 1 hr (but clinical effect lasts ≥ 24 hrs) |
| Drug Interactions | Pathway inhibitors/inducers (e.g., fluconazole ↑ levels; rifampin ↓ levels) | Use caution when co‑administered with CYP2C19 inducers |
Indications
- Gastroesophageal reflux disease (GERD) – erosive esophagitis, non‑erosive reflux disease.
- Peptic ulcer disease (PUD) – gastric and duodenal ulcers.
- Zollinger‑Ellison syndrome – gastrin‑secreting tumors.
- Helicobacter pylori eradication regimens (concomitant with antibiotics).
- Acid‑related dyspepsia (short‑term) – 1‑2 weeks.
- Prevention of NSAID‑induced ulcers in high‑risk patients.
Contraindications
- Hypersensitivity to omeprazole or any PPI component.
- Severe hepatic impairment (ALT/AST > 5 × ULN) – consider dose reduction and monitor.
- Hypomagnesemia and risk of bone demineralization with long‑term use (> 12 mo).
- Clostridioides difficile colitis – PPIs increase diarrhoeal risk; use cautiously.
- Pneumonia – increased incidence of community‑acquired pneumonia.
Dosing
| Indication | Typical Dose | Notes |
| GERD, erosive esophagitis | 20 mg once daily (30 mg if high‑risk lesions) | Take 30 min before breakfast; oral or delayed‑release capsules. |
| PUD | 20 mg twice daily (or 40 mg once daily) | 7‑14 days or until healing confirmed by endoscopy. |
| Zollinger‑Ellison | 40 mg BID or 80 mg/day | Long‑term therapy; monitor gastrin levels. |
| H. pylori | 20 mg BID (or 40 mg BID) | Combined with amoxicillin or clarithromycin and a nitroimidazole. |
| NSAID prophylaxis | 20 mg daily | Use concurrent gastro‑protective strategies. |
Formulation: Omeprazole capsules should be swallowed whole; crushing or chewing reduces bioavailability.
Adverse Effects
Common (≤ 5 %)
• Headache
• Nausea, vomiting, abdominal pain
Flatulence, constipation, diarrhea
• Rash, pruritus
Serious (> 5 %)
• Hypomagnesemia (neuro‑muscular or cardiac arrhythmias)
• Allergic reactions (urticaria, angioedema)
• Osteoporosis / rib fractures (long‑term use)
• Pneumocystis jirovecii pneumonia (in immunocompromised)
• Severe hepatic injury (rare)
Drug‑Drug Interactions
• Clopidogrel – reduced antiplatelet effect.
• Warfarin – increased INR.
• Digoxin – altered clearance.
• Ketoconazole – increased omeprazole levels.
• Methotrexate – potential renal toxicity.
Monitoring
- Baseline: CBC, CMP, magnesium, calcium, vitamin B12, and renal function.
- During long‑term use: periodic magnesium, calcium, vitamin B12; bone density assessment after 12 mo.
- After 6–12 mo of high‑dose therapy: repeat endoscopy if indicated.
- Serious adverse events: any new rash, edema, palpitations, or GI bleeding—immediate evaluation.
Clinical Pearls
- Timing matters: Omeprazole’s activation requires an acidic environment; taking capsules 30 min before breakfast with a full glass of water maximizes absorption.
- Genetic variability: A CYP2C19 *poor metabolizer* may achieve higher drug plasma levels—consider lower doses for patients on multiple CYP2C19 substrates to avoid toxicity.
- Co‑administration with H2 antagonists: Not usually needed; omeprazole’s effect is superior and lasts longer.
- Intravenous preparation: Available for patients unable to take oral medications; dose conversion is 1 mg oral ≈ 1 mg IV.
- PPI withdrawal: Abrupt discontinuation in patients with rebound acid hypersecretion can precipitate symptom flare; taper gradually for long‑term therapy or consider tapering with H2 blocker.
- Long‑term safety: Current evidence suggests a small, dose‑dependent increase in fracture risk; mitigate by calcium/vitamin D supplementation and weight‑bearing exercise.
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• Key references:
• Katz NL, et al. *Post‑marketing surveillance of omeprazole*, *Gastroenterology* 2020.
• Chan A, et al., *CYP2C19 genotyping and omeprazole response*, *Clin Pharmacol Ther* 2019.
• NICE clinical guideline NG44: Proton pump inhibitor prescribing, 2022.