Esomeprazole
Esomeprazole
Generic Name
Esomeprazole
Mechanism
- Target: The *gastric H⁺/K⁺‑ATPase* (proton pump) located on parietal cells.
- Binding: Esomeprazole’s sulfenamide moiety covalently attaches to *cysteine* residues (Cys292/Cys344) on the enzyme, leading to irreversible inhibition.
- Kinetics: Inhibits 70–80 % of the pump at therapeutic concentrations; maximal effect occurs 1–2 hrs after dosing.
- Result: Sustained inhibition of acid secretion for 24 hrs with each dose, even in the presence of pepsinogen‑stimulated secretion.
Pharmacokinetics
| Feature | Data |
| Absorption | Oral bioavailability ~45 % (pH‑dependent; better uptake when taken before meals). |
| Metabolism | Extensive hepatic oxidation via CYP2C19 and CYP3A4; generates inactive metabolites (metabolite N‑oxide, 5‑hydroxy). |
| Half‑life | Effective half‑life ~1 hr, clinical residence time 4–10 hrs due to irreversible binding. |
| Distribution | 96 % protein‑bound (primarily to albumin). |
| Excretion | Primarily biliary; 2–8 % renal. |
| Drug Interactions | Strong CYP2C19 inhibitors (e.g., fluconazole) ↑ plasma levels; rifampin ↓ levels. |
Indications
- Gastro‑oesophageal reflux disease (GERD): erosive esophagitis, non‑erosive reflux disease (NERD).
- Peptic ulcer disease: healing and maintenance of ulcers (gastric, duodenal, NSAID‑related).
- Helicobacter pylori eradication: in triple or quadruple therapy regimens.
- Zollinger–Ellison syndrome: control of hyper‑secretory gastrinomas.
- Pre‑operative acid suppression: reduce aspiration risk in elective surgeries.
Contraindications
- Contraindications: Hypersensitivity to esomeprazole or other PPIs.
- Warnings:
- *Long‑term use* (>12 mo): ↑ risk of *osteoporosis*, *Clostridioides difficile* colitis, *electrolyte disturbances* (hypomagnesemia).
- *Pregnancy*: Category B – limited human data; use only if benefits outweigh risks.
- *Pediatric*: <12 yrs – use with caution; data are limited.
- *Renal impairment*: dose adjustments not required; monitor for signs of hepatic dysfunction.
Dosing
| Indication | Adult Dose | Pediatric (if applicable) | Notes |
| GERD | 20 mg PO once daily | 1 mg/kg PO (max 20 mg) | Dose on an empty stomach, 30 min before food. |
| Peptic ulcer | 20 mg PO once daily | — | 4–8 weeks for healing; maintenance 20 mg qd. |
| H. pylori | 20 mg PO twice daily | Same | Combined with clarithromycin + amoxicillin/metronidazole. |
| Zollinger–Ellison | 40 mg PO twice daily | 1 mg/kg q12h | May require titration to 80–120 mg/day. |
• Capsules or tablets; chewable forms available for gastro‑retentive delivery.
• For IV: 40 mg over 30 min, then 20 mg q12h for 1–3 days.
• *Switching* from other PPIs: give esomeprazole 1 day before next dose to maintain acid suppression.
Adverse Effects
- Common (≤10%)
- Headache, abdominal pain, flatulence, constipation, diarrhoea, nausea, dyspepsia.
- Serious
- *Clostridioides difficile* colitis, electrolyte disturbances (hypomagnesemia), *severe* cutaneous reactions (SJS/TEN).
- *Cardiovascular*: rare reports of QT prolongation.
- *Renal*: interstitial nephritis, acute tubular necrosis (rare).
Monitoring
- Baseline: CBC, CMP, ESR/CRP, Vit‑B12 (long‑term use).
- Periodic:
- Serum magnesium (every 3–6 mo).
- Bone density scan (if >5 yrs therapy).
- Renal function (if at risk).
- Follow‑up: Symptom resolution; endoscopy for GERD/ulcer after 4 weeks of therapy.
Clinical Pearls
- First‑bite advantage: Esomeprazole (the S‑enantiomer of omeprazole) exhibits higher plasma concentrations and longer acid‑inhibition duration compared with its racemate.
- Rapid onset: Absorbed quickly; peak plasma levels are reached in ~1 hr—ideal for acute reflux episodes.
- CYP2C19 genotype matters: *Poor metabolizers* achieve 2–3× higher drug exposure → consider lower doses or monitor for toxicity.
- Avoid PPIs with antacids: Antacids raise gastric pH, reducing esomeprazole absorption; if needed, separate administration by ≥1 hr.
- Switching pitfalls: Transitioning from a strong CYP inhibitor (e.g., ketoconazole) to esomeprazole can cause drug accumulation → dose‐adjust if needed.
- Post‑operative prophylaxis: A single 20 mg dose pre‑induction significantly reduces gastric acid‑related aspiration events in high‑risk patients.
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• *For detailed references, consult the latest clinical guidelines and peer‑reviewed pharmacology texts (e.g., "Goodman & Gilman's The Pharmacological Basis of Therapeutics," UpToDate.*