21.drugs used in peptic ulcer

drugs used in peptic ulcer

1. Drugs useD in Drugs useD in
peptic ulcer peptic ulcer
Drugs useD in Drugs useD in
peptic ulcer peptic ulcer

2. 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

3. ClassificationClassification ClassificationClassification
I. Reduction of gastric acid secretion -
a) H
2
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) H
2
receptor antagonists : Cimetidine,
Ranitidine, Famotidine
b) Proton pump inhibitors : Omeprazole,
Lansoprazole, Pantoprazole
c) Anticholinergics : Pirenzepine, Telenzepine

d) Prostaglandin analogue : Misoprostol

4. 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

5. 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

6. HISTAMINE
GR
ST M
?
M
3
H
2
GR
ATP
ase C
A
H
+
K
+
Cl
-
Food
Gastrin
G cells
Somatostatin
D cells
Acetylcholine
+
-
ECL cell
Parietal cellH2 blockersH2 blockersH2 blockersH2 blockers

7. HH
22 Receptor Antagonists - Cimetidine, Receptor Antagonists - Cimetidine,
Ranitidine, FamotidineRanitidine, Famotidine
HH
22 Receptor Antagonists - Cimetidine, Receptor Antagonists - Cimetidine,
Ranitidine, FamotidineRanitidine, Famotidine

Mechanism of action
•Competitive inhibition of H
2
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 H
2
receptors -
Inhibits gastric acid secretion (60-70%)
•Suppresses all phases of acid secretion,
mainly nocturnal acid secretion; pH

↑to 4-5

8. 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

9. 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

10. HISTAMINE
GR
ST M
?
M
3
H
2
GR
ATP
ase C
A
H
+
K
+
Cl
-
Food
Gastrin
G cells
Somatostatin
D cells
Acetylcholine
+
-
ECL cell
Parietal cellH2 blockersH2 blockersH2 blockersH2 blockers
PPIs
PPIs

11. PPIs: Omeprazole, Pantoprazole PPIs: Omeprazole, Pantoprazole
Lansoprazole, Rabeprazole Lansoprazole, Rabeprazole
PPIs: Omeprazole, Pantoprazole PPIs: Omeprazole, Pantoprazole
Lansoprazole, Rabeprazole Lansoprazole, Rabeprazole
Mechanism 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

12. 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

13. Adverse effects Adverse effects Adverse effects Adverse effects
Muscle & joint pain
Rashes, leucopenia, headache
Atrophic gastritis
Muscle & joint pain
Rashes, leucopenia, headache
Atrophic gastritis

14. Prostaglandin analoguesProstaglandin analogues
Misoprostol (PGEMisoprostol (PGE
11))
Prostaglandin analoguesProstaglandin analogues
Misoprostol (PGEMisoprostol (PGE
11))
 “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

15. 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

16. Anticholinergics - Pirenzepine, Anticholinergics - Pirenzepine,
Telenzepine Telenzepine

Anticholinergics - Pirenzepine, Anticholinergics - Pirenzepine,
Telenzepine Telenzepine
Selective M
1
receptor blockers
Inhibits acid secretion - heals peptic
ulcer
Selective M
1
receptor blockers
Inhibits acid secretion - heals peptic
ulcer

17. 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.

18. Sodium bicarbonateSodium bicarbonateSodium bicarbonateSodium bicarbonate
Reacts rapidly with HCl – produces CO
2
and
NaCl
Demerits
 Distension and belching
 Metabolic alkalosis
 Fluid retention
 Acid rebound
Reacts rapidly with HCl – produces CO
2
and
NaCl
Demerits
 Distension and belching
 Metabolic alkalosis
 Fluid retention
 Acid rebound

19. 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

20. 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

21. 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

22. Use – duodenal and gastric ulcers
Adverse effects – constipation, dry
mouth & hypophosphatemia


Use – duodenal and gastric ulcers
Adverse effects – constipation, dry
mouth & hypophosphatemia

23. 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

24. 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

25. Anti Anti H.pyloriH.pylori drugs drugsAnti Anti H.pyloriH.pylori drugs drugs
•Amoxicillin
•Clarithromycin
•Tetracycline
•Metronidazole/Tinidazole
•PPIs, H
2
blockers, CBS
•Amoxicillin
•Clarithromycin
•Tetracycline
•Metronidazole/Tinidazole
•PPIs, H
2
blockers, CBS

26. Drug regimens - triple therapyDrug regimens - triple therapyDrug regimens - triple therapyDrug regimens - triple therapy

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)

27. Thank you Thank you