Gastric Proton Pump Inhibitor

Medicinal chemistry - II
B. pharmacy, third year
semester Vth

1. Gastric Proton Pump Inhibitor B. Pharm Third Year By- S. K. Dhawale D. K. Patil Institute of Pharmacy, Sayal road loha , Nanded .

2. Introduction Proton pump is an integral membrane protein in parietal cell of stomach. It pumps proton in stomach Hydrogen ions are generated within the parietal cells from dissociation of water. Hydroxyl ions formed in this process rapidly combines with CO2 to form bicarbonate ions (HCO3) Bicarbonate is transported out of basolateral membrane in exchange of chloride. Hydrogen ion is pumped out of cell in lumen in exchange for potassium through the action of proton pump. By using ATP an acidic hydrogen ion replaces a non acidic potassium ion through the action of proton pump.

3. Ulcer Ulcer is kind of open wound followed by inflammation. Occurs both on outer skin of internal epithelium like surface of stomach or inside mouth. It occurs due to Infection of H. Pylori Due to increased concentration of stomach acid. Due to pressure on skin. Clinical Uses of Proton pump Inhibitors Dyspepsia( reduction in thrust) Peptic ulcer disease Gastrointestinal reflux disorder Stress induced gastritis Zollinger Ellison Syndrome (tumors form in pancreas/ small intrestine )

4. Antiulcer Drug Drugs which are used to treat various kind of gastric ulcer, peptic ulcer or duodenal ulcer. In gastric mucosa, Oxyntic glands are present which stimulate parietal cells to secret about 2-3 liters of HCl in stomach. Gastric parietal cells do not store HCl . H+ ions and Cl- Ions are secreted separately into the stomach. The working of proton pump is controlled by various regulators. Histamine at H1 receptor. Gastrin at G receptor. Acetylcholine at M2 receptor. Prostaglandine . Somadostatin .

5. Antiulcer drugs Classification 1)Reduction of gastric acid secretion H2 Antihistamine- Cimetidine, Ranitidine, Famotidine, Roxantidine Proton pump inhibitors – Omeprazole, Pantoprazole, Rabeprazole , Esmoprazole Anticholinergics – Piperazines , Propanthaline , Oxyphenonium Prostaglandine Analogues – Misoprostol, Enprostil , Rioprostil . 2) Neuralization of gastric acid Systemic – Sodium Bicarbonate, Sodium Citrate Non- Systemic- Magnesium hydroxide, Aluminium Hydroxide, Calcium Carbonate. 3) Ulcer Protective Sucralfate , Collidal bismuth subcitrate . 4) Ulcer beating drugs Carbenoxolone sodium.

6. Some IMP structures of PPI Lanseprazole Pantoprazole

7. Omerazole The absorption of omeprazole takes place in the small intestine and completed within 3-6hrs. Distribution of the drug is wide and about 95% of the drug is bound to proteins The plasma half life of drug is 0.5-1hr Mechanism of action: Omeprazole belongs to category of anti secretory compound that act primarily by suppressing the gastric acid secretion. This action is achieved by inhibiting the H+/K+ ATPase enzyme selectively at the secretory surface of the gastric parietal cells.

8. Synthesis of Omeprazole

9. Omerazole Adverse Reaction: CNS manifestation CVS Manifestation Endocrinal Manifestation Gastrointestinal Manifestation Omeprazole have less side effects than other drugs in this class, so used commonly in treating gastric disorders.