Dr. D.Y.
Patil College Of Pharmacy, Akrudi
Continuous Assignment-2
Submitted by : Rajani Bhati (67)
Suchita Mane (99)
Proton Pump Inhibitors
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.
General structure of proton pump inhibitots:
The drugs of this class are as following :
1) Omeprazole
2) Lansoprazole
3) Dexlansoprazole
4) Esomeprazole
5) Pantoprazole
6) Rabeprazole
7) Ilaprazole
Dexlansoprazole
Molecular formula : C₁₆H₁₄F₃N₃O₂S
Molecular weight : 369.36 g·mol−¹
Mechanism of action :
o Dexlansoprazole inhibits the H/K ATPase enzyme, which is involved in
the secretion of hydrochloric acid, hydrolyzing ATP and exchanging H+
ions from the cytoplasm for K+ ions in the secretory canaliculus, which
results in HCl secretion into the gastric lumen.
o Dexlansoprazole inhibits this effect of H/K ATPase by demonstrating a
high degree of activation in the acidic environment.
o After passing through the liver and reaching the gastric parietal cells
activated by a meal, PPIs undergo protonation in the acidic pH
environment, followed by conversion to sulphenamide which
represents the active form of the drug. Sulphenamide inhibits the
activity of the proton pump and hence the transport of hydrogen ions
into the gastric lumen via covalent binding to the SH groups of the
cysteine residues of H/K ATPase 2.
o The delivery technology of dexlansoprazole MR is designed to release
the drug in two separate pH-dependent phases, the first in the
proximal duodenum (25% of total drug dose) and the second (75% of
total drug dose) in the more distal small intestine.
o Dexlansoprazole reduces both basal and stimulated gastric acid
secretion.
Pharmacodynamics :
Dexlansoprazole is a proton pump inhibitor (PPI) and is included in the drug class
of antisecretory compounds. It blocks the final step of gastric acid secretion by
specific inhibition of the (H+, K+)-ATPase at the secretory surface of the parietal
cells on gastric mucosa.
Adverse Effects :
o severe stomach pain, diarrhea that is watery or bloody;
o a seizure (convulsions);
o sudden pain or trouble moving your hip, wrist, or back;
o kidney problems-- fever, rash, nausea, loss of appetite, joint pain , urinating less
than usual, blood in your urine, weight gain;
o low magnesium--dizziness, fast or irregular heart rate, tremors (shaking) or jerking
muscle movements, feeling jittery, muscle cramps, muscle spasms in your hands
and feet, cough or choking feeling; or
o new or worsening symptoms of lupus--joint pain, and a skin rash on your cheeks
or arms that worsens in sunlight.
Therapeutic Uses :
o Help gastrointestinal ulcers heal
o Treat symptoms of gastroesophageal reflux disease (GERD)
o Eradicate Helicobacter pylori
o Treat hypersecretory conditions such as Zollinger-Ellison Syndrome
o Reduce the amount of acid in your stomach
Esomeprazole
Molecular formula : C₁₇H₁₉N₃O₃S
Molecular weight : 345.42 g·mol−¹
Mechanism of action :
o Esomeprazole exerts its stomach acid-suppressing effects by preventing the
final step in gastric acid production by covalently binding to sulfhydryl
groups of cysteines found on the (H+, K+)-ATPase enzyme at the secretory
surface of gastric parietal cells.
o This effect leads to inhibition of both basal and stimulated gastric acid
secretion, irrespective of the stimulus.
o As the binding of esomeprazole to the (H+, K+)-ATPase enzyme is irreversible
and new enzyme needs to be expressed in order to resume acid secretion,
esomeprazole's duration of antisecretory effect that persists longer than 24
hours.
Pharmacodynamics :
Esomeprazole is a compound that inhibits gastric acid secretion and is indicated in
the treatment of gastroesophageal reflux disease (GERD), the healing of erosive
esophagitis, and H. pylori eradication to reduce the risk of duodenal ulcer
recurrence. Esomeprazole belongs to a new class of antisecretory compounds, the
substituted benzimidazoles, that do not exhibit anticholinergic or H2 histamine
antagonistic properties, but that suppress gastric acid secretion by specific
inhibition of the H+/K+ ATPase at the secretory surface of the gastric parietal cell.
By doing so, it inhibits acid secretion into the gsatric lumen. This effect is dose-
related and leads to inhibition of both basal and stimulated acid secretion
irrespective of the stimulus.
Adverse Effects :
o headache
o diarrhea
o nausea, stomach pain, gas, constipation
o dry mouth
o seizure (convulsions)
o kidney problems-- fever, rash, nausea, loss of appetite, joint pain, urinating less
than usual, blood in your urine, weight gain
o low magnesium--dizziness, fast or irregular heart rate, tremors (shaking) or
jerking muscle movements, feeling jittery, muscle cramps, muscle spasms in
your hands and feet, cough or choking feeling
o new or worsening symptoms of lupus--joint pain, and a skin rash on your
cheeks or arms that worsens in sunlight.
Therapeutic Uses :
o Treatment of gastroesophageal reflux disease
o treatment and maintenance of erosive esophagitis,
o treatment of duodenal ulcers caused by H. pylori,
o prevention of gastric ulcers in those on chronic NSAID therapy,
o treatment of gastrointestinal ulcers associated with Crohn's disease.
Ilaprazole
Molecular formula : C₁₉H₁₈N₄O₂S
Molecular weight : 366.44 g·mol−¹
Mechanism of action :
The mechanism of ilaprazole’s action to suppress gastric acid secretion is almost
the same as omeprazole, in which the protonated substituted benzimidazoles
suppress gastric acid secretion through inhibition of the H+/K+-ATPase at the
secretory surfaces of gastric parietal cells.
Adverse Effects :
o Headache
o Dizziness
o Diarrhoea
o Constipation
o Nausea, vomiting, flatulence
o Weakness
o Flu-like symptoms
o Back pain, aches,
o Infection
o Difficulty sleeping
o Cough, sore throat and runny nose
Therapeutic Uses :
o Treatment of Gastroesophageal reflux disease (GERD),
o Treatment of Duodenal ulcer,
o Treatment of Peptic ulcer,
o Treatment of Dyspepsia.
