Lansoprazole

 

Overview

Lansoprazole is an acid proton pump inhibitor. Lansoprazole is a benzimidazole sulfoxide derivative and produces long lasting inhibition of gastric acid secretion. Lansoprazole is a chiral compound with one chiral center, synthsized as a racemic mixture and both enantiomers are active. Chemically Lansoprazole is identified as 2-[[[3-methyl-4-(2, 2, 2-trifluoroethoxy)-2-pyridinyl] methyl] sulfinyl ]-1H-benzimidazole. Lansoprazole is effective in the treatment of duodenal or gastric ulcer, gastroesophageal reflux disease and in the treatment of zollinger-ellison syndrome. Lansoprazole is administered orally.

Primary Characteristics

It is of Synthetic origin and belongs to Sulphinyl Benzimidazole. It belongs to H/K Atpase proton pump inhibitor pharmacological group on the basis of mechanism of action and also classified in Antacids pharmacological group. The Molecular Weight of Lansoprazole is 369.00.

Its pKa is 8.85.

 

Indications

Lansoprazole is primarily indicated in conditions like Acid-related dyspepsia, Benign gastric ulcer, Duodenal ulcer, Duodenal ulcer associated with h. Pylori, Esophagitis, Gastric ulcer, Gastro-esophageal reflux disease, Heart burn, Helicobacter pylori positive duodenal ulcer, NSAID-associated gastric and duodenal ulcers, NSAID-associated gastric and duodenal ulcers (prophylaxis), NSAID-associated gastric or duodenal ulcers, Peptic ulcer, Resistant ulcers, Zollinger-ellison syndrome, and can also be given in adjunctive therapy as an alternative drug of choice in GI bleeding.

 

Pharmacokinetics

Oral absorption of Lansoprazole is found to be 40% ±40. Volume of distribution is found to be 24 ± 8 liter and plasma proteins binding is 97-99%. and metabolism is reported Hepatic(extensively). Renal Excretion accounts for 30% and plasma half life is 1-2 hr.

Pharmacodynamics

Lansoprazole decreases gastric acid secretion by targeting H+,K+-ATPase, which is the enzyme that catalyzes the final step in the acid secretion pathway in parietal cells.  Conveniently, lansoprazole administered any time of day is able to inhibit both daytime and nocturnal acid secretion. The result is that lansoprazole is effective at healing duodenal ulcers, reduces ulcer-related pain, and offers relief from symptoms of heartburn  Lansoprazole also reduces pepsin secretion, making it a useful treatment option for hypersecretory conditions such as Zollinger-Ellison syndrome.

Mechanism of action

As a PPI, lansoprazole is a prodrug and requires protonation via an acidic environment to become activated.  Once protonated, lansoprazole is able to react with cysteine residues, specifically Cys813 and Cys321, on parietal H+,K+-ATPase resulting in stable disulfides. PPI’s in general are able to provide prolonged inhibition of acid secretion due to their ability to bind covalently to their targets.

 

 Side Effects

The severe or irreversible adverse effects of Lansoprazole, which give rise to further complications include Atrophic gastritis, Epidermal necrolysis.

The symptomatic adverse reactions produced by Lansoprazole are more or less tolerable and if they become severe, they can be treated symptomatically, these include Headache, Nausea, Diarrhea, Constipation, Rashes, Pruritus.

 

Interference in Pathology

• Elevations of SGPT and SGOT
• Abnormal LFTs
• Increased Alkaline Phosphatase Levels
• Elevation in ALT or AST
• Increased in serum creatinin