Antisecretory agent

Antisecretory agent


Antisecretory agent

        H2-receptor antagonist


      Pharmacological action




       Proton pump inhibitors


      Pharmacological action





At the end of this lecture, student will be able to

       Explain the pharmacology of H2-receptor antagonist

       Describe the pharmacology of proton pump inhibitors

H2 receptor antagonist

E.g.  Cimetidine, ranitidine, nizatidine, famotidine

       First class of highly effective drugs for acid-peptic disease

       The H2 antagonists are competitive antagonists of histamine at the parietal cells H2 receptor

       They suppress the normal secretion of acid by parietal cells and the meal-stimulated secretion of acid


       Inhibits gastric acid secretion, as well as pepsin and gastrins output

        It also blocks the activity of cytochrome P-450 which might explain proposals for use 

       Cimetidine binds to an H2-receptor located on the basolateral membrane of the gastric parietal cell, blocking histamine effects

        This competitive inhibition results in reduced gastric acid secretion and a reduction in gastric volume and acidity

Pharmacological actions:

       Cimetidine and all other H2 antagonists block histamine-induced gastric secretion, cardiac stimulation

       The only significant in vivo action of H2 blockers is marked inhibition of gastric secretion

       The H2 blockers have antiulcerogenic effect

        Gastric ulceration due to stress and drugs (NSAIDs,cholinergic, histaminergic) is prevented uterine relaxation (in rat) and bronchial relaxation

       Cimetidine  has antiandrogenic action (displaces dihydrotestosterone from its cytoplasmic receptor), increases plasma prolactin and inhibits degradation of estradiol by liver

       High doses given for long periods have produced gynaecomastia

       Loss of libido

       Decrease in sperm count


       Cimetidine is adequately absorbed orally

       Absorption is not interfered by presence of food in stomach

       Crosses placenta reaches milk

       2/3 of a dose is excreted unchanged in urine


       Headache, dizziness, bowel upset, dry mouth,rashes

       CNS effects like confusional state, restlessness,convulsions and coma have occurred infrequently in elderly patients

       Release histamine

Drug Interactions

       Isoenzymes and reduces hepatic blood flow

       Inhibits the metabolism of many drugs so that they can accumulate to toxic levels, e.g. theophylline,phenytoin, carbamazepine

       Antacids reduce absorption of all H2 blockers

       Ketoconazole absorption is decreased by cimetidine


Ranitidine has a furan ring H2 blocker, it has several desirable features compared to cimetidine About 5 times more potent than cimetidine

       Pharmacokinetic profile and t½ of 2–3 hr is similar to cimetidine

       No antiandrogenic action, does not increase prolactin secretion

       Lesser permeability into the brain


       Ranitidine is a competitive, reversible inhibitor of the action of histamine at the histamine H2 receptors found in gastric parietal cells

       This results in decreased gastric acid secretion and gastric volume, and reduced hydrogen ion concentration


       Famotidine, thiazole ring containing H2 blocker which binds tightly to H2 receptors

       Longer duration of action elimination t½ of 2.5–3.5 hr 5–8 times more potent than ranitidine

       Antiandrogenic action is absent

       The oral bioavailability of famotidine is 40–50% and it is excreted by the kidney

Therapeutic uses

       Duodenal ulcer

       Gastric ulcer

       Stress ulcers and gastritis

       Zollinger-Ellison syndrome

       Gastroesophageal reflux disease (GERD)

       Prophylaxis of aspiration pneumonia

Ranitidine Vs Cimetidine

       Ranitidine, a new H2-receptor blocking antihistamine

        Pharmacokinetically similar to cimetidine, but its potency is about eightfold greater

        The clinical response to ranitidine is more prolonged, largely because of potency and not kinetic advantage

        Ranitidine for 6 to 25 months is not associated with hepatic or hematologic toxicity or alterations of serum gastrin levels

       Ranitidine can adequately inhibit acid secretion in patients with gastric hypersecretory disorders

       Safe at high doses, does not cause the antiandrogen side effects frequently seen with high doses of cimetidine

Proton pump inhibitors

a)      Reversible

           Omeprazole(OMEZ) , Rebaprazole

b)      Irreversible

         Lansoprazole, Pantoprazole, Laminoprazole


       Omeprazole It is the prototype member of substitute benzimidazoles which inhibit the final common step in gastric acid secretion inactive at neutral pH

       React covalently with SH groups of the H+K+ATPase enzyme and inactivate it


       Omeprazole is a selective and irreversible proton pump inhibitor

       It suppresses stomach acid secretion by specific inhibition of the H+/K+-ATPase system found at the secretory surface of gastric parietal cells

       The duration of inhibition is up to 72 hours


       Oral absorption of omeprazole is ~50%,

       Bioavailability of all PPIs is reduced  by food

       Metabolised in liver by CYP2C19 and CYP3A4

       No dose modification

       Antisecretory action increases on daily dosing to reach a plateau after 4 days

Therapeutic uses

       Peptic ulcer

       Gastroesophageal reflux disease (GERD)

       Zollinger-Ellison syndrome

       Stress ulcers

       Bleeding peptic ulcer

       Aspiration pneumonia



       Loose stools


       Abdominal pain

       Muscle and joint pain



       Hepatic dysfunction

       Gynaecomastia and erectile dysfunction

Drug interaction

        Clarithromycin inhibits omeprazole metabolism and increases its plasma concentration

       Omeprazole inhibits oxidation of certain drugs: diazepam, phenytoin and warfarin levels may be increased


        It is the S-enantiomer of omeprazole

       Higher oral bioavailability and to produce better control of intragastric pH than omeprazole in GERD patients because of longer t½


       More potent than omeprazole but similar in properties. Inhibition

       of H+ K+ ATPase by lansoprazole

       It has higher oral bioavailability, faster

       Onset of action and slightly longer t½ than omeprazole.


        Newer H+ K+ ATPase inhibitor, similar in potency and clinical efficacy to omeprazole

        More acid stable and has higher oral bioavailability.

       Available for i.v. Administration

       Lower affinity for cytochrome P450 than omeprazole

       Risk of drug interactions is minimal


       H2 blockers competitively blocks the binding of histamine to H2 receptors.

       H2 blockers, are a class of medications that block the action of histamine at the histamine H2 receptors of the parietal cells in the stomach

        Decreases the production of stomach acid H2antagonists can be used in the treatment of dyspepsia peptic ulcer and gastroesophageal reflux disease

       PPIs irreversibly inhibits the H+/K+ ATPase (the proton pump), the terminal step in the acid secretory pathway

       Both basal and stimulated gastric acid secretion  is reduced

       Oral administration is the most common route of administration, although some injectable preparations are available


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