Antisecretory agent PDF / PPT

Antisecretory agent 1



Antisecretory agent

• H2-receptor antagonist

– Mechanism

– Pharmacological action



– Uses 2



Antisecretory agent

• Proton pump inhibitors

– Mechanism

– Pharmacological action



– Uses 3



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 4


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 5



• 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 6


H2 receptor antagonist cont..

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 7


H2 receptor antagonist cont..

Pharmacological actions

• 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 8


H2 receptor antagonist cont..


• 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 9


H2 receptor antagonist cont..


• Headache, dizziness, bowel upset, dry mouth,rashes

• CNS effects like confusional state, restlessness,convulsions and coma

have occurred infrequently in elderly patients

• Release histamine 10


H2 receptor antagonist cont..

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 11


H2 receptor antagonist cont..

• Ranitidine has a furan ring H2 blocker, it has several desirable

features compared to cimetidine About 5 times more potent than


• 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 12



• Ranitidine is a competitive, reversible inhibitor of the action of

histamine at the histamine H2 receptors found in gastric parietal


• This results in decreased gastric acid secretion and gastric volume,

and reduced hydrogen ion concentration 13


H2 receptor antagonist cont..

• 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 14


H2 receptor antagonist cont..
Therapeutic uses

• Duodenal ulcer

• Gastric ulcer

• Stress ulcers and gastritis

• Zollinger-Ellison syndrome

• Gastroesophageal reflux disease (GERD)

• Prophylaxis of aspiration pneumonia 15


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 16


Ranitidine Vs Cimetidine cont..

• 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 17


Proton pump inhibitors

a) Reversible

Omeprazole(OMEZ) , Rebaprazole

b) Irreversible

Lansoprazole, Pantoprazole, Laminoprazole 18


Proton pump inhibitors cont..

• 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 19



• 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 20


Proton pump inhibitors cont..


• 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 21


Proton pump inhibitors

Therapeutic uses

• Peptic ulcer

• Gastroesophageal reflux disease (GERD)

• Zollinger-Ellison syndrome

• Stress ulcers

• Bleeding peptic ulcer

• Aspiration pneumonia 22


Proton pump inhibitors cont…
• Nausea
• Loose stools
• Headache
• Abdominal pain
• Muscle and joint pain
• Dizziness
• Leucopenia
• Hepatic dysfunction
• Gynaecomastia and erectile dysfunction 23


Proton pump inhibitors cont…

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 24


Proton pump inhibitors cont…

• 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. 25


Proton pump inhibitors cont…


• 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 26



• H2 blockers competitively blocks the binding of histamine to H2


• 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 27



• 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 28


Thank You

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