Drugs used in Drugs used in peptic ulcer peptic ulcer

Drugs used in Drugs used in peptic ulcer peptic ulcer

Peptic Ulcer Peptic Ulcer

A localized loss of gastric as well as duodenal mucosa leads to the formation of peptic ulcer

Symptoms – heartburn, abdominal pain, bloating, loss of appetite and weight loss

ClassificationClassification ClassificationClassification

I. Reduction of gastric acid secretion - a) H2 receptor antagonists : Cimetidine,

Ranitidine, Famotidine

b) Proton pump inhibitors : Omeprazole, Lansoprazole, Pantoprazole

c) Anticholinergics : Pirenzepine, Telenzepine d) Prostaglandin analogue : Misoprostol

I. Reduction of gastric acid secretion - a) H2 receptor antagonists : Cimetidine,

Ranitidine, Famotidine

b) Proton pump inhibitors : Omeprazole, Lansoprazole, Pantoprazole

c) Anticholinergics : Pirenzepine, Telenzepine d) Prostaglandin analogue : Misoprostol

II. Neutralization of gastric acid

(Antacids) – a) Systemic : Sodium bicarbonate Sodium citrate

b) Nonsystemic : Magnesium hydroxide Magnesium trisilicate Aluminum hydroxide Calcium carbonate

II. Neutralization of gastric acid

(Antacids) – a) Systemic : Sodium bicarbonate Sodium citrate

b) Nonsystemic : Magnesium hydroxide Magnesium trisilicate Aluminum hydroxide Calcium carbonate

III. Ulcer protectives – Sucralfate, Colloidal bismuth subcitrate (CBS)

IV. Anti-H.pylori drugs - Amoxicillin, Clarithromycin, Metronidazole, Tinidazole, Tetracycline

III. Ulcer protectives – Sucralfate, Colloidal bismuth subcitrate (CBS)

IV. Anti-H.pylori drugs - Amoxicillin, Clarithromycin, Metronidazole, Tinidazole, Tetracycline

HISTAMINE

GR ST M?

M3H2GR

ATPase C

A

H+ K+ Cl-

Food

Gastrin G cells

SomatostatinD cells

Acetylcholine

+-

ECL cell

Parietal cellH2 blockersH2 blockersH2 blockersH2 blockers

HH22 Receptor Antagonists - Receptor Antagonists - Cimetidine, Ranitidine, FamotidineCimetidine, Ranitidine, Famotidine

HH22 Receptor Antagonists - Receptor Antagonists - Cimetidine, Ranitidine, FamotidineCimetidine, Ranitidine, Famotidine

Mechanism of action

• Competitive inhibition of H2 receptors -

Inhibits gastric acid secretion (60-70%)

• Suppresses all phases of acid secretion, mainly nocturnal acid secretion; pH ↑to

4-5

Mechanism of action

• Competitive inhibition of H2 receptors -

Inhibits gastric acid secretion (60-70%)

• Suppresses all phases of acid secretion, mainly nocturnal acid secretion; pH ↑to

4-5

Therapeutic uses

Peptic ulcer : Gastric and Duodenal ulcer

Gastroesophageal reflux disease (GERD)

Stress ulcers and Gastritis

Zollinger-Ellison syndrome

Therapeutic uses

Peptic ulcer : Gastric and Duodenal ulcer

Gastroesophageal reflux disease (GERD)

Stress ulcers and Gastritis

Zollinger-Ellison syndrome

Adverse effects Cimetidine - antiandrogenic effect

• Gynaecomastia, impotence – men

• Menstrual irregularities, galactorrhoea – women

Enzyme inhibitor - inhibits metabolism

of many co-administered drugs – toxicity

Adverse effects Cimetidine - antiandrogenic effect

• Gynaecomastia, impotence – men

• Menstrual irregularities, galactorrhoea – women

Enzyme inhibitor - inhibits metabolism

of many co-administered drugs – toxicity

HISTAMINE

GR ST M?

M3H2GR

ATPase C

A

H+ K+ Cl-

Food

Gastrin G cells

SomatostatinD cells

Acetylcholine

+-

ECL cell

Parietal cellH2 blockersH2 blockersH2 blockersH2 blockers

PPIsPPIs

PPIs: Omeprazole, PPIs: Omeprazole, Pantoprazole Pantoprazole Lansoprazole, Rabeprazole Lansoprazole, Rabeprazole

PPIs: Omeprazole, PPIs: Omeprazole, Pantoprazole Pantoprazole Lansoprazole, Rabeprazole Lansoprazole, RabeprazoleMechanism of action PPIs (prodrugs)

sulfenamide cation (activated form)

binds with sulfhydryl groups of the H+K+- ATPase - inactivate it irreversibly

Mechanism of action PPIs (prodrugs)

sulfenamide cation (activated form)

binds with sulfhydryl groups of the H+K+- ATPase - inactivate it irreversibly

Therapeutic usesTherapeutic usesTherapeutic usesTherapeutic uses

Peptic ulcer

H.pylori associated ulcers

NSAID induced ulcers

GERD

Zollinger-Ellison syndrome

Stress ulcers

Peptic ulcer

H.pylori associated ulcers

NSAID induced ulcers

GERD

Zollinger-Ellison syndrome

Stress ulcers

Adverse effects Adverse effects Adverse effects Adverse effects

Muscle & joint pain Rashes, leucopenia, headache Atrophic gastritis

Muscle & joint pain Rashes, leucopenia, headache Atrophic gastritis

Prostaglandin analoguesProstaglandin analoguesMisoprostol (PGEMisoprostol (PGE11))

Prostaglandin analoguesProstaglandin analoguesMisoprostol (PGEMisoprostol (PGE11))

“Cytoprotective action” - increases mucus &

bicarbonate secretion, increases mucosal blood flow

Therapeutic use NSAID induced ulcers

“Cytoprotective action” - increases mucus &

bicarbonate secretion, increases mucosal blood flow

Therapeutic use NSAID induced ulcers

Adverse effects Diarrhea, abdominal cramps,

uterine contractions & bleeding

Multiple daily dosing – poor patient compliance

Adverse effects Diarrhea, abdominal cramps,

uterine contractions & bleeding

Multiple daily dosing – poor patient compliance

Anticholinergics - Anticholinergics - Pirenzepine, Pirenzepine, Telenzepine Telenzepine

Anticholinergics - Anticholinergics - Pirenzepine, Pirenzepine, Telenzepine Telenzepine

Selective M1 receptor blockers

Inhibits acid secretion - heals peptic ulcer

Selective M1 receptor blockers

Inhibits acid secretion - heals peptic ulcer

AntacidsAntacids AntacidsAntacids

Basic substances which

neutralize gastric acid and raise

pH of gastric contents.

Basic substances which

neutralize gastric acid and raise

pH of gastric contents.

Sodium bicarbonateSodium bicarbonateSodium bicarbonateSodium bicarbonate

Reacts rapidly with HCl – produces CO2

and NaCl Demerits Distension and belching Metabolic alkalosis Fluid retention Acid rebound

Reacts rapidly with HCl – produces CO2

and NaCl Demerits Distension and belching Metabolic alkalosis Fluid retention Acid rebound

Magnesium hydroxide and Magnesium hydroxide and Aluminum hydroxide Aluminum hydroxide

Magnesium hydroxide and Magnesium hydroxide and Aluminum hydroxide Aluminum hydroxide

Reacts slowly with HCl No belching No metabolic alkalosis

Mg salts diarrhea , Al salts constipation

so both are administered together

Reacts slowly with HCl No belching No metabolic alkalosis

Mg salts diarrhea , Al salts constipation

so both are administered together

Antacid combinationsAntacid combinations Antacid combinationsAntacid combinations

Magnesium hydroxide – fast acting

Aluminum hydroxide – slow acting

Mg salts – diarrhea

Al salts – constipation

Dose reduction – reduced toxicity

Magnesium hydroxide – fast acting

Aluminum hydroxide – slow acting

Mg salts – diarrhea

Al salts – constipation

Dose reduction – reduced toxicity

Ulcer protectives –Sucralfate ,Ulcer protectives –Sucralfate , Colloidal Bismuth Subcitrate Colloidal Bismuth Subcitrate

Ulcer protectives –Sucralfate ,Ulcer protectives –Sucralfate , Colloidal Bismuth Subcitrate Colloidal Bismuth Subcitrate

Sucralfate

MOA – • At acidic pH < 4, it undergoes

extensive polymerization – forms a sticky gel over the ulcer base – protects it

Sucralfate

MOA – • At acidic pH < 4, it undergoes

extensive polymerization – forms a sticky gel over the ulcer base – protects it

Use – duodenal and gastric ulcers

Adverse effects – constipation, dry mouth & hypophosphatemia

Use – duodenal and gastric ulcers

Adverse effects – constipation, dry mouth & hypophosphatemia

Colloidal Bismuth Subcitrate Colloidal Bismuth Subcitrate (CBS)(CBS)

Colloidal Bismuth Subcitrate Colloidal Bismuth Subcitrate (CBS)(CBS)

• Detaches H.pylori from surface of mucosa Use – Eradication of H.pylori infection Adverse effects – blackening of stool & tongue

• Detaches H.pylori from surface of mucosa Use – Eradication of H.pylori infection Adverse effects – blackening of stool & tongue

Helicobacter

pylori

• Gram –ve bacilli

• Attaches beneath the mucus

• Cause back diffusion of H+ ions

• Present in 90% of cases with peptic ulcers

Helicobacter

pylori

• Gram –ve bacilli

• Attaches beneath the mucus

• Cause back diffusion of H+ ions

• Present in 90% of cases with peptic ulcers

Anti Anti H.pyloriH.pylori drugs drugsAnti Anti H.pyloriH.pylori drugs drugs

• Amoxicillin• Clarithromycin• Tetracycline• Metronidazole/Tinidazole

• PPIs, H2 blockers, CBS

• Amoxicillin• Clarithromycin• Tetracycline• Metronidazole/Tinidazole

• PPIs, H2 blockers, CBS

Drug regimens - triple Drug regimens - triple therapytherapy

Drug regimens - triple Drug regimens - triple therapytherapy

Lansoprazole 30 mg + Amoxicillin 1000 mg

+ Clarithromycin 500 mg

(All twice daily for 2 weeks)

Lansoprazole 30 mg + Amoxicillin 1000 mg

+ Clarithromycin 500 mg

(All twice daily for 2 weeks)

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