PUD

1. Drugs useD inDrugs useD in
peptic ulcerpeptic ulcer
Drugs useD inDrugs useD in
peptic ulcerpeptic ulcer

2. Peptic UlcerPeptic 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. ClassificationClassificationClassificationClassification
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

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?
M3H2GR
ATP
ase C
A
H+
K+
Cl-
Food
Gastrin
G cells
Somatostatin
D cells
Acetylcholine
+
-
ECL cell
Parietal cellH2 blockersH2 blockersH2 blockersH2 blockers

7. HH22 Receptor Antagonists - Cimetidine,Receptor Antagonists - Cimetidine,
Ranitidine, FamotidineRanitidine, Famotidine
HH22 Receptor Antagonists - Cimetidine,Receptor Antagonists - Cimetidine,
Ranitidine, FamotidineRanitidine, 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

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?
M3H2GR
ATP
ase C
A
H+
K+
Cl-
Food
Gastrin
G cells
Somatostatin
D cells
Acetylcholine
+
-
ECL cell
Parietal cellH2 blockersH2 blockersH2 blockersH2 blockers
PPIsPPIs

11. PPIs: Omeprazole, PantoprazolePPIs: Omeprazole, Pantoprazole
Lansoprazole, RabeprazoleLansoprazole, Rabeprazole
PPIs: Omeprazole, PantoprazolePPIs: Omeprazole, Pantoprazole
Lansoprazole, RabeprazoleLansoprazole, 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 effectsAdverse effectsAdverse effectsAdverse effects
 Muscle & joint pain
 Rashes, leucopenia, headache
 Atrophic gastritis
 Muscle & joint pain
 Rashes, leucopenia, headache
 Atrophic gastritis

14. Prostaglandin analoguesProstaglandin analogues
Misoprostol (PGEMisoprostol (PGE11))
Prostaglandin analoguesProstaglandin analogues
Misoprostol (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

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,
TelenzepineTelenzepine
Anticholinergics - Pirenzepine,Anticholinergics - Pirenzepine,
TelenzepineTelenzepine
 Selective M1 receptor blockers
 Inhibits acid secretion - heals peptic
ulcer
 Selective M1 receptor blockers
 Inhibits acid secretion - heals peptic
ulcer

17. AntacidsAntacidsAntacidsAntacids
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 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

19. Magnesium hydroxide andMagnesium hydroxide and
Aluminum hydroxideAluminum hydroxide
Magnesium hydroxide andMagnesium hydroxide and
Aluminum hydroxideAluminum 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 combinationsAntacid 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 SubcitrateColloidal Bismuth Subcitrate
Ulcer protectives –Sucralfate ,Ulcer protectives –Sucralfate ,
Colloidal Bismuth SubcitrateColloidal 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 SubcitrateColloidal Bismuth Subcitrate
(CBS)(CBS)
Colloidal Bismuth SubcitrateColloidal 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. AntiAnti H.pyloriH.pylori drugsdrugsAntiAnti H.pyloriH.pylori drugsdrugs
• Amoxicillin
• Clarithromycin
• Tetracycline
• Metronidazole/Tinidazole
• PPIs, H2 blockers, CBS
• Amoxicillin
• Clarithromycin
• Tetracycline
• Metronidazole/Tinidazole
• PPIs, H2 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 youThank you