Nexium: Mechanism of action

Nexium (esomeprazole) is a proton pump inhibitor (PPI) for the treatment of acid-related diseases. Nexium works by binding to, and inhibiting, the acid pumps of a particular type of cell lining the stomach wall to stop the production of stomach acid. Esomeprazole suppresses gastric acid secretion by specific inhibition of H+/K+ ATPase, proton pumps, in the gastric parietal cell. By acting on the proton pump, Nexium blocks the final step in acid production, thus reducing gastric acidity. This effect is dose-related up to a daily dose of 20–40 mg and leads to inhibition of gastric acid secretion.[7]

Why is Acid Control Important?

The level of acid control is critical in the management of GERD and acid-related diseases because excessive gastric acid secretion leads to symptoms that can disrupt the physical, social and emotional wellbeing of many patients. If the disease is left untreated, it can also lead to more serious health issues.

GERD occurs when the stomach contents reflux into the esophagus.[1] Refluxed acid not only plays a key role in causing typical GERD syndromes (such as the typical reflux syndrome characterized by heartburn and regurgitation or the typical syndrome with oesophageal injury as reflux esophagitis), it is also associated with a number of other atypical syndromes (such as reflux asthma) that affect the activities of daily life and are difficult to treat.[2]

Complications of GERD include stricture of the esophagus, ulceration, bleeding and Barrett’s esophagus  (the lining of esophagus is replaced by a type of tissue similar to that normally found in the intestine) which may be associated with cancer.

Nexium’s mechanism of action results in decreased levels of acidity in the stomach. Nexium also helps to heal erosions in the esophagus or ulcers in the duodenum.[3] It is important to note that control of gastric acid secretion using Nexium does not affect the digestion of food – there is still plenty of acid left in the stomach for it to carry out its normal functions.

Nexium – the S-isomer

Isomers are one of two or more compounds that have the same molecular formula but different structures (that is, different arrangements of atoms in the molecule). Omeprazole has two optical isomers – an S-isomer and an R-isomer – the S-isomer being esomeprazole (Nexium).

As the S-isomer, Nexium provides more effective and longer-lasting acid control compared with omeprazole alone[4],[5] on the basis of advantageous metabolism. This translates into significant proven clinical benefits over omeprazole.

Nexium is also less variable between individual patients, providing a higher level of predictability that healing of reflux esophagitis will occur.[4],[6]

References

1. Malfertheiner P, Hallerbäck B. Clinical manifestations and complications of gastroesophageal reflux disease (GERD). Int J Clin Pract 2005;59:346–55
2. Vakil N, Van Zanten SV, Kahrilas P, Dent J, Jones R and the Global Consensus Group. The Montreal Definition and classification of gastroesophageal reflux disease: a global evidence-based consensus. Am J Gastroenterol 2006;101:1900–20
3. AstraZeneca data on file
4. Lind T et al. Esomeprazole provides improved acid control vs omeprazole in patients with symptoms of gastro-oesophageal reflux disease. Aliment Pharmacol Ther 2000;14:861–7
5. Röhss K et al. Effect of esomeprazole 40 mg vs omeprazole 40 mg on 24-hour intragastric pH in patients with symptoms of gastroesophageal reflux disease. Dig Dis Sci 2002;47:954–8
6. Andersson T et al. Pharmacokinetics and pharmacodynamics of esomeprazole, the S-isomer of omeprazole. Aliment Pharmacol Ther 2001;15:1563–9

7. Source: AstraZeneca.com