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Gastric Proton Pump Inhibitors:- Hand Written Notes

Description

Proton Pump Inhibitors (PPIs) are irreversible inhibitors of gastric parietal cell proton pump. This enzyme promotes the exchange of H + or K+ ions, which are required for mediating HCl secretion. PPIs induce 80 -90% inhibition of basal, nocturnal, and food stimulated acid levels after single administration.
PPIs reduce the acid production by blocking the enzyme present in the stomach wall. Reduction in the production of acid by stomach prevents the occurrence of ulcers and also facilitates the healing of ulcers already existing in the oesophagus, stomach, and duodenum.

The H+-K+-ATPase proton pump of the apical membrane of parietal cell is the
mediator of acid secretion . The newer substituted benzimidazoles have been developed as specific inhibitors because the H+-K+-ATPase proton pump is unique to parietal cells. These benzimidazoles are used in peptic ulcer.

The PPIs have a sulphinyl group in a bridge between substituted benzimidazole and pyridine rings. These agents ar e chemically stable and lipid -soluble weak bases without inhibitory activity at neutral pH. These neutral weak bases reach the parietal cells from the blood and diffuse into the secretory canaliculi.
Here the drugs become protonated and trapped. The protonated agent re-arranges for producing sulphuric acid and sulphonamide, which covalently interacts with sulphhydryl groups of cysteine at critical sites in the extra cellular domain of the -ATPase. Thus, it irreversibly inhibits gastric acid secretion.
Uses
Proton pump inhibitors are used for treatin g ulcers and haemorrhagic ulcers
caused by Helicobacter pylori as they inhibit the growth of H. pylori. They also
allow the continuous use of NSAIDs in a patient with known peptic ulcer.
Proton pump inhib itors are also used for preventing recurrent haemorrhagic
ulcers. Clot formation comprises of the processes that weaken in acidic environments, and the clot integrity is maintained in the ulcer bed by the suppression of gastric acid secretion by proton pump inhibitors.
For example, an intravenous infusion o f omeprazole maintains the intragastric
pH above 6, thus, it supports platelet aggregation and clot stability. Proton pump inhibitors are superior to H 2-receptor antagonists (like ranitidine)
for heali ng gastric and duodenal ulcers in patients who continue the use of
NSAIDs. This is because proton pump inhibitors can withstand a constant
increase in gastric pH.
Study of Individual Drugs
The following gastric PPIs are discussed below:
1) Omeprazole,
2) Lansoprazole,
3) Rabeprazole, and
4) Pantoprazole.
Omeprazole
Omeprazole inhibits the proton pump and decreases the amount of acid produced in the stomach.

Mechanism of Action
Omeprazole suppresses gastric acid secretion by inhibiting the H+
–ATPase in the gastric parietal cell. Thus, by acting specifically on the proton pump it blocks the final step in acid production, and reduces gastric acidity.
Uses
1) It is used for t reating GERD and other conditions caused by excessive
production of stomach acid.
2) It is used to promote the healing of erosive oesophagitis (damage caused to
oesophagus by the stomach acid).
3) It is used to relieve heartburn, difficulty in swallowing, and persistent cough.
4) It is used to prevent oesophageal cancer.
5) It is used along with antibiotics to treat gastric ulcer caused by H. pylori.
Lansoprazole
Lansoprazole is a substituted benzimidazole prodrug having the selective and irreversible proton pump inhibitor activity. It prevents the production of acid in the stomach.
Mechanism of Action
Lansoprazole is an anti -secretory compound. It is a substituted benzimidazole that is devoid of anticholinergic or H2-receptor antagonist properties. However, it suppresses gastric acid secretion by inhibiting the H+ -ATPase enzyme system at the secretory surface of gastric parietal cell. Since this enzyme system i s the acid (proton) pump in the parietal cell, lansoprazole is considered the gastric acid-pump inhibitor which inhibits the final step of acid production . This effect is dose -dependent and inhibits the basal as well as stimulated gastric acid secretion irrespective of the stimulus.
Uses
1) It is used for treating acid -reflux disorders ( like GERD) and peptic ulcer
disease.
2) It is used for H. pylori eradication.
3) It is used in combination with NSAIDs for preventing gastrointestinal
bleeding.

Rabeprazole
Rabeprazole is an antiulcer drug that blocks the H-ATPase of the coating
gastric cells. It also inhibits the dose -dependent oppresses basal and stimulated gastric acid secretion.
Mechanism of Action
Rabeprazole is an anti -secretory compound. It is a substituted benzimidazole proton-pump inhibitor that suppresses gastric acid secretion by inhibiting the H ATPase enzyme system at the secretory surface of gastric parietal cell. Since this enzyme system is the acid (proton) pump i n the parietal cell, rabeprazole is considered the gastric acid -pump inhibitor which inhibits the final step of acid production.
Uses
1) It is used in the treatment of Gastroes ophageal reflux disease (GERD) and
poorly responsive systemic GERD.
2) It is used in severe erosive esophagitis.
3) It is used in pathol ogic hypersecretory conditions, like Zollinger-Ellison syndrome, systemic mastocytosis, and multiple endocrine adenomas.
4) It is used for treating duodenal ulcers with or without anti -infectives for
Helicobacter pylori.
5) It is also used for curing the daytime or night time heartburn. Pantoprazole
Pantoprazole is a first generation PPI. It is also used for treating other disorders
wherein gastric acid secretion needs to be reduced . Pantoprazole is available in
many forms , such as a delayed -release oral capsule, oral suspension, and intravenous injection.
Mechanism of Action
Pantoprazole is a substituted benzimidazole derivative and a weak base. It collects in the acidic space of the pa rietal cell and then converts into active sulfenamide derivatives in the acidic environment of the canaliculi of gastric

parietal cell. The active derivatives obtained inhibit the function of gastric acid pump by making disulfide bonds with important cyste ines on the pump.
Pantoprazole binds to the sulfhydryl group of H +-ATPase (an enzyme that
accelerates the final step in acid secretion pathway ). This enzyme is inactivated and gastric acid secretion is inhibited.
Uses
1) Pantoprazole injection is given t o patients having GERD and history of
erosive esophagitis for short -term treatment (7 -10 days) . It is given as an
alternate to pantoprazole delayed-release tablets in patients who are not able to swallow the tablets.
2) It is used in the treatment of pathological hypersecretory conditions related to Zollinger-Ellison syndrome or other neoplastic conditions.
3) Pantoprazole delayed-release oral suspension is used for short-term treatment of erosive esophagitis related to GERD.
4) It is also used to promote the healing of erosive esophagitis and decrease the
relapse rates of daytime and night time heartburn symptoms in adult patients
of GERD.

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