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Dr Harsha R Assistant Professor Department of Pharmacology


Dr Harsha R Assistant Professor Department of Pharmacology

Peptic ulcer disease

Peptic ulcer disease is one of the common GI disorder in clinical practice

Peptic ulcer is defined as breach in mucosa that occurs in part of GIT which is exposed to gastric acid and pepsin i.e.

Stomach and Duodenum

Peptic ulcer Disease

  • 1. Gastric ulcer

  • 2. Duodenum ulcer

  • 3. Stress ulcers

  • 4. NSAIDs induced ulcer

Peptic ulcer disease

In all these condition at the end MUCOSAL EROSION OR ULCERATION


The exact etiology for development of these ulceration is unknown.

It results probably due to imbalance between the aggressive factors and the defensive factors

Peptic ulcer disease

Gastric ulcer vs. Duodenal ulcer


Gastric ulcer

Duodenal ulcer


Acid secretion is Normal

Acid secretion is higher


Deficient mucosal defense plays a key role in gastric ulcer


H Pylori has a role NSAIDs has a role

H Pylori has a role


Gastric ulcer tend to occur later in life With peak incidence reported in 6 th decade


Peptic ulcer disease

1 st approach in treating any case of ACID PEPTIC DISEASE ( GERD, GASTRIC ULCER, DUODENAL ULCER, NSAIDs Induced ulcer, Stress ulcer, non ulcer dyspepsia) is reduction of gastric acid secretion

Classification of drugs used in APD

Drugs used to reduce gastric acid secretion

1. Drugs reducing gastric acid secretion secretory)

( Anti

  • a) Proton Pump Inhibitors( PPIs)

  • b) H 2 antihistamines

  • c) Anti-cholinergic drugs

Proton Pump Inhibitors

Most widely prescribed acid suppressing drugs world wide due to their

outstanding efficacy and safety.

PPIs have assumed a major role for the treatment of acid peptic disorders

PPIs available for clinical use

Omeprazole ( Prototype) Esomeprazole Patoprazole Rabeprazole Dexrabeprazole Lansoprazole Dexlansoprazole

Omeprazole(Prototype drug)

Mechanism of Action Uses Adverse effects

Gastric gland

Gastric gland

Gastric Parietal cell

Gastric Parietal cell

Mechanism of action

PPIs are administered as Inactive Prodrug. Inactive Prodrug is acid labile

To protect this acid labile inactive prodrug from rapid destruction- PPIs are

Enteric coated tablets Delayed release tablets

Mechanism of action

PPIs- Enteric

Mechanism of action

This active drug molecule inside the parietal cell will form a covalent

disulfide bond with H + /K + - ATPase irreversibly inactivating the enzyme.

Mechanism of action

Mechanism of action


All PPIs are administered orally in enteric coated form or in delayed release formulation. Bioavailability: Of all PPIs is reduced by Food

All PPIs should be taken in Empty stomach, followed one hour later by a meal to activate the H + /K + - ATPase.

PPB: highly bound to Plasma Proteins


  • 1. Gastro esophageal reflux disease

  • 2. Peptic ulcer disease

    • A. H pylori associated ulcer

      • B. NSAID- associated ulcer

      • C. Prevention of re-bleeding from peptic ulcer

        • 3. Non ulcer dyspepsia

        • 4. Prevention of stress releated mucosal bleeding

1. Gastro-esophageal reflux disease(GERD)

Gastro-esophageal reflux disease(GERD)

2. Peptic ulcer disease

A. Peptic ulcer disease- H pylori associated ulcer

OCA- Regimen

OCM- Regimen

OCT- Regimen

B. PUD-NSAIDs induced ulcer

NSAIDs are weak organic acids

NSAIDs induced ulcer

Aspirin and other NSAIDs inhibit

NSAIDs induced ulcer

NSAIDs induced ulcer

C. Prevention of rebleeding from peptic ulcers

3. Non ulcer dyspepsia

PPIs have modest efficacy for treatment of non ulcer dyspepsia

It benefits only 10-20% of patients having non ulcer dyspepsia

4. Prevention of stress related Mucosal bleeding

Adverse effects

PPIs are extremely safe PPIs produce minimal adverse effects

PPIs are not teratogenic in animal models

However safety during pregnancy has not been established

Adverse effects

Adverse effects

Q1-Explain why proton pump inhibitors should be administered on empty stomach?

PPIs to be taken 30 Minutes before breakfast

PPIs to be taken in empty stomach then one hour later patient is advised to take food

Q2-Explain why PPIs are administered once daily even though they have short half life ?



Half life


  • 1 Omeprazole



  • 2 Esomeprazole



  • 3 Lansoprazole



  • 4 Dexlansoprazole



  • 5 Pantoprazole



  • 6 Rabeprazole






3-4times a day


Though PPIs have a short serum half life of about 1-2hrs, acid inhibition is present

for up to 24hrs. This is due to Irreversible inactivation of the proton pump (H + /K + - ATPase)

The synthesis of new proton pump (H + /K + - ATPase) will take around 18- 24hrs. Till then action of PPIs will last

Q3-Explain why PPIs are called “hit and run” drugs?

After few hours of administration of PPIs , they are removed from the body but their effect( Acid supressing effect) continues


It is the S-enantiomer of omeprazole Claimed to have higher oral bioavailability Claimed to have better acid supression effect


It is similar in potency and clinical efficacy to omeprazole

More acid stable Higher bioavailability It is also available for IV administration


This newer PPI is claimed to cause fastest acid suppression

Potency and efficacy similar to omeprazole

H2 blockers

Write a note on H 2 – Receptor Antagonist Explain disadvantage of cimetidine Rantidine is preferred over cimetidine in peptic ulcer. Rantidine is preferred over cimetidine in clinical practice . Give reasons. How does cimetidine differ from ranitidine?

H 2 – Receptor Antagonist

H 2 – Receptor Antagonist commonly referred as H 2 blockers

Before the advent of PPIs H 2 blockers were the first line of drugs in treating APD

Four H 2 blockers are in clinical use Cimetidine ( Prototype) Ranitidine Famotidine Nizatidine : Roxatidine

Cimetidine( Prototype drug)

MOA Cimetidine vs Rantidine Uses Adverse effects


Because of structural similarity to histamine , these drugs act selectively by competitive blockade of parietal cell H 2 Receptor.

Tolerance : due to down regulation of H 2 receptor

Rebound phenomenon: May occur




When given in usual prescription dose all

H 2

– Receptor Antagonist inhibit 60-70% of total 24hr acid secretion H 2 – Receptor Antagonist are specially effective at inhibiting Nocturnal acid secretion ( which depends largely on histamine) Modest impact on meal- stimulated acid secretion ( which depends on Ach, Gastrin, and histamine)

Q1-Rantidine vs Cimetidine

Rantidine is 5 times more potent than Cimetidine

Rantidine has longer duration of action with greater 24hrs acid supression

No Anti- androgenic effect. Cimetidine has Anti- androgenic effect it causes gyanecomastia and reduced sperm count and impotence

Less Central nervous system effects:

Rantidine does not cross BBB , hence incidence of CNS effects very less

Leeser drug interaction with Rantidine when compared with cimetidine

Q2-Explain why cimetidine but not rantidine prolong half life of concurrently administered drugs ?

Cimetidine inhibits several Cytochrome P-450 isoenzymes- Drug metabolising enzymes like CYP1A2, CYP2C9, CYP2D6.

Thus it can inhibit the metabolism of various other drugs whose metabolism is depended on these enzymes and increase their concentration leading to toxicity.

Q2-Explain why cimetidine but not rantidine prolong half life of concurrently administered drugs

Drug interaction seen with cimetidine Phenytoin Phenobarbitone Sulfonylureas Carbamazepine Metronidazole



Peptic ulcer disease ( gastric ulcer, duodenal ulcer, NSAIDs induced ulcer, H- plylori associated ulcer)

Non ulcer dyspepsia

Prevention of bleeding from stress related gastritis


Write a note on non systemic antacids? As antacids magnesium trisilicate and aluminium hydroxide are used in combination. Give reason Rationale for combination of antacids in peptic ulcer therapy

Why are antacids not given along with sucralfate in peptic ulcer?


Antacids are weak bases that react with gastric HCL to form salt and water


Antacids are defined as basic substances which neutralizes gastric acid and rises gastric Ph


Raising gastric Ph although is possible with antacids , it is difficult to maintain it continuously, because antacids acts for only 30-60min

In spite of their limitation ( Short duration of action), antacids are valuable as they produce considerable, immediate symptomatic relief in patients with APD

Antacid- classification

Non systemic antacid

  • 1. Aluminium hydroxide

  • 2. Magnesium hydroxide

  • 3. Magnesium trisilicate

  • 4. Calcium carbonate

. Systemic antacid

Non systemic antacids

Non systemic antacids
Non systemic antacids

Non systemic antacids

Non systemic antacids

Non systemic antacids

Non systemic antacids

Q1-Rationale for using combination of two or more antacid







( magnesium hydroxide + aluminum hydroxide )

Onset of





Effect on



Will nullify each others


action: Bowl movement least affected




Will nullify each others


action: gastric emptying least affected


Can be


Adverse effect minimal



Q2-Rationale for withholding drugs for two hours after administration of antacids

Non systemic antacids forms complexes( weak bases+ acid= non absorbablecomplex)

These complexes may decrease the absorption of many drugs to varying extent

Tetracyclins Diazepam Phenytoin Isoniazide Ethambutol Iron salts


Write a note on sucralfate

Rationale for using sucralfate in peptic ulcer disease

Explain the interaction between sucralfate and antacids

Ulcer protective agents – Sucralfate

Is an octasulfate

Sucrose + Aluminium hydroxide ( Sucr+ alfate)

In acidic environment ,the drug undergoes extensive cross- linking to produce a viscous, sticky, polymer that adheres to epithelial cell

It thus creates a physical barrier on the ulcer base and prevent the ulcer from the damaging effects of the acid .


Sucralfate action is entirely local Sucralfate has no acid neutralising effect Surcalfate is minimal absorbed after oral administration

Ulcer healing dose of sucralfate is 1g to be taken in empty stomach one hour before three major meal and at bed time for 4-8 weeks

Q1-Explain the interaction between sucralfate and antacids



Rationale for using prostaglandin analogue in peptic ulcer

Uses of misoprostol



Misoprostol (PGE1) Enprostil (PGE2) Rioprostil (PGE2)

Rationale for using prostaglandin analogue in peptic ulcer