PROTON PUMP INHIBITOR.ppt

Proton pump inhibitors (PPIs) block the gastric H,K-ATPase, inhibiting gastric acid secretion. This effect enables healing of peptic ulcers, gastroesophageal reflux disease (GERD), Barrett's esophagus, and Zollinger-Ellison syndrome, as well as the eradication of Helicobacter pylori as part of combination regimens.Proton-pump inhibitors (PPIs) are a class of medications that cause a profound and prolonged reduction of stomach acid production. They do so by irreversibly inhibiting the stomach's H+/K+ ATPase proton pump.[1]

They are the most potent inhibitors of acid secretion available.[2] Proton-pump inhibitors have largely superseded the H2-receptor antagonists, a group of medications with similar effects but a different mode of action, and antacids.[3]

PPIs are among the most widely sold medications in the world. The class of proton-pump inhibitor medications is on the World Health Organization's List of Essential Medicines.[4][5] Omeprazole is the specific listed example.[4][5]
Mechanism of action

The activation of PPIs
Proton pump inhibitors act by irreversibly blocking the hydrogen/potassium adenosine triphosphatase enzyme system (the H+/K+ ATPase, or, more commonly, the gastric proton pump) of the gastric parietal cells.[71] The proton pump is the terminal stage in gastric acid secretion, being directly responsible for secreting H+ ions into the gastric lumen, making it an ideal target for inhibiting acid secretion.[citation needed]Because the H,K-ATPase is the final step of acid secretion, an inhibitor of this enzyme is more effective than receptor antagonists in suppressing gastric acid secretion.[72] All of these drugs inhibit the gastric H,K-ATPase by covalent binding, so the duration of their effect is longer than expected from their levels in the blood.[73]

Targeting the terminal step in acid production, as well as the irreversible nature of the inhibition, results in a class of medications that are significantly more effective than H2 antagonists and reduce gastric acid secretion by up to 99%.[2

1. GASTRIC PROTON PUMP
INHIBITOR
MEDICINAL CHEMISTRY
By
Miss. Waghhrutuja
ASSISTANT PROFESSOR
LOKMANYA TILAK INSTITUTE OF PHARMACEUTICAL SCIENCES, PUNE.

2. GASTRIC PROTON PUMP INHIBITOR
•Proton-pumpinhibitors(PPIs)areaclassofmedicationsthat
causeaprofoundandprolongedreductionofstomach
acidproduction.
•Theydosobyirreversiblyinhibitingthe
stomach'sH
+
/K
+
ATPaseprotonpump.
•Theyarethemostpotentinhibitorsofacidsecretionavailable.
•Proton-pumpinhibitorshavelargelysupersededtheH
2-
receptorantagonists,agroupofmedicationswithsimilar
effectsbutadifferentmodeofaction,andantacids

3. COVALENT
COMLEX WITH PPI
AND PROTON
PUMP

4. MECHANISM OF ACTION

5. MECHANISM OF ACTION

6. MECHANISM OF ACTION
•Proton pumpinhibitors act by irreversibly blocking thehydrogen/potassiumadenosine
triphosphataseenzymesystem (theH
+
/K
+
ATPase, or, more commonly, the gastric proton pump) of
the gastricparietal cells.
•The proton pump is the terminal stage in gastric acid secretion, being directly responsible for
secreting H
+
ions into the gastric lumen, making it an ideal target for inhibiting acid secretion.
•Because the H,K-ATPase is the final step of acid secretion, an inhibitor of this enzyme is more
effective than receptor antagonists in suppressing gastric acid secretion.
•All of these drugs inhibit the gastric H,K-ATPase by covalent binding, so the duration of their effect is
longer than expected from their levels in the blood.
•The PPIs are given in an inactive form, which is neutrally charged (lipophilic) and readily crossescell
membranesinto intracellular compartments (like the parietal cell canaliculus) with acidic
environments.
•In an acid environment, the inactive drug is protonated and rearranges into its active form.
•As described above, the active form willcovalentlyand irreversibly bind to the gastric proton pump,
deactivating it.

7. Medical Uses
These medications are used in the treatment of many conditions, such as:
•Dyspepsia
•Pepticulcerdiseaseincludingafterendoscopictreatmentforbleeding
•AspartofHelicobacterpylorieradicationtherapy
•Gastroesophagealrefluxdisease(GERDorGORD)includingsymptomaticendoscopy-
negativerefluxdisease
[10]
and associatedlaryngopharyngeal
refluxcausinglaryngitis
[11]
andchroniccough
[12]
•Barrett'sesophagus
•Eosinophilicesophagitis
•Stressgastritisandulcerpreventionincriticalcare
•Gastrinomasandotherconditionsthatcausehypersecretionofacid
includingZollinger–Ellisonsyndrome(often2–3xtheregulardoseisrequired)

8. CLASSIFICATION
1.OMEPRAZOLE
2.LANSOPRAZOLE
3.RABEPROZOLE
4.PANTAPRAZOLE

10. OMEPRAZOLE
•White to off white crystalline powder, very slightly soluble in water.
•Omeprazoleis amphotericcompound and consistent with the proposed mechanism
of ationof the substituted benzimidazole,isacid labile.
•Hence it is an delayed release capsule containing enteruccoated granules.
•Absolute bioavailability is 30% to 40% related to first pass metabolism. where it is
95% bound to plasma protein.
Uses:
1.HERTBURN, GERD, DUODENAL ULCER, EROSIVE ESOPHAGITIS, GASTRIC ULCER
AND PATHOLOGICAL HYPERSECRETORY CONDITION.

11. LANSOPRAZOLE
•It is white to brownish white, odourlesscrystalline powder that is practically
insoluble in water.
•It is a weak base.
•Its is a prodrugand form active metabolite that irreversiballyinteract with target
ATPaseof the pump..
•In the fasting time ,about 80% of a dose reaches to systemic circulation, where it is
97% bound to plasma protein.
Uses:
1.HERTBURN, GERD, DUODENAL ULCER, EROSIVE ESOPHAGITIS, GASTRIC ULCER
AND PATHOLOGICAL HYPERSECRETORY CONDITION.
2.Zollingerellisonsyndrome.

12. rabeprazole
•It is a white to slightly yellowish white solid
•It is very soluble in water and methanol, freely soluble in ethanol, chloroform and
ethyl acetate and insoluble in etjherand hexane.
•In the fasting time ,about 52%of a dose reaches to systemic circulation, where it is
96% bound to plasma protein.
Uses:
1.EROSIVE AND ULCERATIVE GERD, DUODENAL ULCER, EROSIVE ESOPHAGITIS,
GASTRIC ULCER AND PATHOLOGICAL HYPERSECRETORY CONDITION.
2.H.PYROLI ERADICATION.

13. PANTOPRAZOLE
•White to off white crystalline powder, freely soluble in water,
practically insoluble in n hexane.
•Pantaprazolehave rapid absorption..
•In the fasting time ,about 77% oral bioavailability, where it is
98% bound to plasma protein.
Uses:
1.EROSIVE ESOPHAGITIS, GASTRIC ULCER AND PATHOLOGICAL
HYPERSECRETORY CONDITION.
2.Zollingerellisonsyndrome.

14. SIDE EFFECT
•The range and occurrence ofadverse effectsare similar for all of the PPIs, though
they have been reported more frequently withomeprazole.
•Common adverse effects includeheadache,nausea,diarrhea,abdominal
pain,fatigue, anddizziness.
•Infrequent adverse effects includerash,itch,flatulence,constipation,anxiety,
anddepression.
•Also infrequently, PPI use may be associated with occurrence ofmyopathies,
including the serious reactionrhabdomyolysis.

15. Thank you