[india-drug] Re: Omeprazole (2)

["Medicine Information Centre @ NIPER" <medinfo@niper.ac.in>]

Omeprazole (2)
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Dear Pranav,

Further to your query on Omeprazole, the answers are as follows:

 1. Do PPI block Na-K ATPase in oxyntic cells from luminal side (i.e
locally, from the stomach) or from interstitial (i.e reach the cells by
blood) side?

Answer:   The PPI are prodrugs that require activation in an acid
environment.

After absorption into the systemic circulation, the prodrugs diffuses into
the parietal cells of    the stomach and acculumates in the acidic secretory
canaliculi.  Here, it is activated by proton-catalyzed formation of a
tetracyclic sulfenamide trapping the drug so  that it cannot diffuse back
across the canalicular membrane.  The activated form then binds covalently
with sulfhydryl groups of cysteines in the  H+, K+-ATPase,  irreversibly
inactivating the pump molecules. The acid secretion resumes only after new
pump molecules are synthesized and inserted into luminal membrane.

2. If they act from the interstitial side, where do they form the charged
ions?

Answer:   Explained above.

3. What is the site of absorption of PPI?

Answer:    The site of absorption of PPI is small intestine.

4. Is the new combination rational?

Answer:    The proton pump inhibitors are degraded in acidic medium in the
gastric lumen. They are available in various form such as enteric-coated tablets, granules and  capsules and also as powdered drug combined
with sodium bicarbonate  (to prevent degradation in gastric lumen).

Therefore, omeprazole coated with alkali appears to be well thought
combination.  But this is based upon the current knowledge of the mechanism
of action as available in Goodman & Gilman's The Pharmacological Basis of
Therapeutics, 11th Ed.

I hope you find this information useful.

Thanks,

Ms. Sukhpreet
Medicine Information Centre
NIPER, S A S NAGAR (PUNJAB), INDIA
http://www.niper.gov.in/medicine.htm
Contact us via email at medinfo@niper.ac.in

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