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Gastroesophageal Reflux Disease Essay

1014 words - 5 pages

About 40 years ago the inappropriate level of gastric acid was a very major problem.That time very few medical treatments were available for this type of Gastroesophageal reflux disease(GRED).For this type of disease Heartburn was the most common type of symptom and the peptic ulcer was one of the most common type of disease. If it was untreated then it can be life threatening. That time the only cure of the disease to administration of antacid drugs. But it had only temporary effect. With the progress of the drug chemistry new drugs came into the market for the gastric diseases which effect is for the long time.These tpe of drugs are generally targeting the different type of receptor like Histamine(H2) receptor,proton pump receptors etc. In this review they showed the development of the new antacid drug by the structure activity relationship such as Omeprazole and Esoprazole.

Development History

The breakthrough of the GRED type diseases was in the late 1970 when antisecretory drug cimetidine was developed which is the antagonist of the Histamine(H2) which has the important role in the gastric juice secretion. After that cimetidine type compounds with the same type of mechanism of action has the good potential for the GRED but the effect is temporary. But it reduces the need of surgery. In this time one of the pharmaceutical company Astra, they are trying to develope some compound which inhibits the proton pump in the acid secretion the pariental cells of the stomach which is most important in the acid secretion step. After the long screening of the molecules they ended up with the drug called Omeprazole which was first launched as Losec in Europe in 1988 and in 1990 as Prilosec in US. This type of drug is much more superior to the Histamine(H2) antagonist receptor.But the Omeprazole remains as the recimic mixture.But the S isomer is much more superior to that of the racemate Omeprazole due to the higher bio availability .

Mechanism of the action of Omeprazole

In the above process Omeprazole act as a prodrug which converted into the active form in acidic medium. As the Omeprazole is weakly basic so it is concentrated in the canaliculi of the parietal cell, where it is converted to the active form sulphonamide intermediate.Then this Intermediate interacts covalently with the Cys 813 of H+ K+ ATPase and it inhibits the activity. They confirmed the mechanism of the Omeprazole by the radio labelled isotope with the 92 kDa protein which is associated with the catalytic sub unit of H+K+ATPase enzyme.

Now Omeprazole has several characteristics that are very much important for the mechanism of the action. That are firstly it is very much lipophilic so it can penetrate through the cell membranes. Secondly it is a very weak base that means it will concentrate into the acidic compartment. Thirdly, in very acidic medium half life of the Omeprazole is very less for...

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