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Resistance to treatment with PPIs, including Esomeprazole, has been speculated among Barrett’s Esophagus (BE) patients who did not indicate any symptomatic improvement after being placed on a standard PPI drug dose [20]. No contributory mutations causing PPI resistance have been found [20]. It is speculated that the high acid exposure in BE patients may be due to “reflux diathesis” rather than resistance to gastric acid secretion [21]. Other possible reasons for PPI failure include Helicobacter pylori infection, rapid metabolism, and bioavailability; reasons of clinical significance include delayed gastric emptying and visceral hypersensitivity [20]. More studies need to be conducted to understand the mechanisms underlying the development of resistance to PPIs [20].
Resistance to treatment with PPIs, including Esomeprazole, has been speculated among Barrett’s Esophagus (BE) patients who did not indicate any symptomatic improvement after being placed on a standard PPI drug dose [20]. No contributory mutations causing PPI resistance have been found [20]. It is speculated that the high acid exposure in BE patients may be due to “reflux diathesis” rather than resistance to gastric acid secretion [21]. Other possible reasons for PPI failure include Helicobacter pylori infection, rapid metabolism, and bioavailability; reasons of clinical significance include delayed gastric emptying and visceral hypersensitivity [20]. More studies need to be conducted to understand the mechanisms underlying the development of resistance to PPIs [20].


== References ==
== Notes & References ==
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<references />
1. Mayo Clinic. Esomeprazole (Oral Route). http//www.mayoclinic.com/health/drug-information/DR603283 (accessed November 11, 2013).
2. National Institutes of Health: DailyMed. NEXIUM (Esomeprazole magnesium) capsule, delayed release [A-S Medication Solutions LLC]. http//dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=9af7a792-d38a-4b2a-b5d6-855d2183b029 (accessed November 11, 2013).
3. Drug Information Online. Esomeprazole. http//www.drugs.com/ingredient/esomeprazole.html (December 4, 2013).
4. Sachs, G.; and Shin, J.M. Pharmacology of Proton Pump Inhibitors. Curr. Gastroenterol Rep. 2008, 10(6), 528-534.
5. Abcam Biochemicals. Esomeprazole sodium (ab120500). http//www.abcam.com/Esomeprazole-sodium-ab120500.html (accessed November 21, 2013).
6.Nexium (Esomeprazole). https//www.youtube.com/watch?v=pEKFVBbhABE (accessed December 1, 2013)
7. Shin, J.M.; Munson, K; and Sachs, G. The gastric HK-ATPase: structure, function, and inhibition. Eur. Journ. Physio. 2009, 457 (3), 609-622.
8. Sachs, G.; Shin, J. M.; and Howden, C.W. Review article: the clinical pharmacology of proton pump Inhibitors, Aliment Pharmacol Ther. 2006, 26 (7), 2-8.
9. Acid secretion in stomach. https//www.youtube.com/watch?v=Wgs6d919kl0 (accessed December 1, 2013).
10. MTAP - Gastric Acid Secretion and Medicines used in the Treatment of Peptic Ulcers https//www.youtube.com/watch?v=fuG03VDV0N8 (accessed December 1, 2013).
11. Caplan, M.J.; Dunbar, L.A.; Ion Pumps in Polarized Cells: Sorting and Regulation of the Na+,K+- and H+,K+-ATPases. Journal of Bio. Chem. 2001, (276) 29617-29620.
12. Abe, K; Tani, K; Nishizawa, T; and Fujiyoshi, Y; Inter-subunit interaction of gastric H+,K+-ATPase prevents reverse reaction of the transport cycle. EMBO. 2009, (28) 1637 – 1643.
13. Pharmacogenomics Knowledge for Personalized Medicine (PharmGKB). Proton Pump Inhibitor Pathway, Pharmacodynamics. http//www.pharmgkb.org/pathway/PA152530845#PGG (accessed November 24, 2013).
14. MTAP - Gastric Acid Secretion and Medicines used in the Treatment of Peptic Ulcers https//www.youtube.com/watch?v=fuG03VDV0N8 (accessed December 1, 2013).
15. Kendall, M.J.; Review article: Esomeprazole, the first proton pump inhibitor to be developed as an isomer. Aliment Pharmacol Ther. 2003, 17, 1-4.
16. Sachs, G.; Shin, J.M.; and Cho, Y.M. Chemistry of covalent inhibition of the gastric (H+, K+)-ATPase by proton pump inhibitors. J Am Chem Soc. 2004 126(25), 7800-11.
17. Sachs, G.; Besancont, M.; Shin, T.M.; Mercier,F.; Munson, K.T.; Miller, M.; and Hershey, S.G.; Membrane Topology and Omeprazole Labeling of the Gastric H+, K+- Adenosinetriphosphatase. Biochemistry 1993, 32, 2345-2355.
18. Abe, K.;Tani, K.; and Fujiyoshi, Y. Conformational rearrangement of gastric H(+),K(+)-ATPase induced by an acid suppressant. Nat.Commun. 2011, 2, 155.
19. Yan, D.; Yuan-Dong, H.U.; and Mao-Sheng, C.; A model of 3D structure of H+, K+-ATPase catalytic subunit derived by homology modeling. Acta Pharmacol Sin. 2004, 25(4), 474-479.
20. Fass, R.; Shapiro, M.; Dekel, R.; and Sewell, J.; Systematic review: proton-pump inhibitor failure in gastro-oesophageal reflux disease – where next? Aliment Pharmacol Ther. 2005, 22, 79–94.
21. Spechler, S.J.; Sharma, P.; Traxler, B.; Levine, D.; Falk, G.W. Gastric and esophageal pH in patients with Barrett's esophagus treated with three esomeprazole dosages: a randomized, double-blind, crossover trial. Am J Gastroenterol. 2006, 101(9), 1964-71.
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