This presentation contains brie information of peptic ulcer and its treatment may helpful for academic students

1. PRESENTED BY:
PRASHANT N. AMALE
M.PHARM (PHARMACOLOGY)
DEPARTMENT OF PHARMACEUTICAL SCIENCES
RTMNU,NAGPUR

3.  Ulcers are the disorders of the GIT resulting due
to imbalance between factors associated with
protection of mucosa & factors modifying acid
secretion.
 Commonest forms of ulcers are:
a. Duodenal ulcers
b. Gastric ulcers
c. Stress induced ulcers
d. NSAID induced ulcers

4. HOSTILLE VS PROTECTIVE FACTORS
PATHOGENESIS

12.  INCREASES SECRETION
 Histamine
 Acetyl choline
 Gastrin
 INHIBITS SECRETION
 Somatostatin

13. 1. Mucus : Secreted by mucous neck cells.
2. Bicarbonate ions : Secreted by mucous neck cells.
Both Mucus & Bicarbonate form gel like protective
barrier for mucosa.
3. Prostaglandins(PGE2) :Stimulate release of mucus
& bicarbonate ions.

14. 4. Mucosal blood flow : Removes acid that might
diffuse through mucosa.
5. Competent pyloric sphincter : Prevents
regurgitation of aggressive factors ( pancreatic
enzymes) into stomach.

15. 1. Controlling gastric acidity, hypermotiliy &
promoting ulcer healing.
2. Prevention of complication & re-occurence.
3. Treatment of Helicobacter pylori infection.

16. 1. REDUCTION OF GASTRIC ACID SECRETION :
a. H2 antihistaminics : Cimetidine, Ranitidine,
Roxatidine, Famotidine.
b. Proton pump inhibitors : Omeprazole, Esomeprazole,
Lansoprazole, Pantoprazole
c. Anticholinergics : Pirenzipine, Propantheline
d. Prostaglandin analogue : Misoprostol
2. NEUTRALIZATION OF GASTRIC ACID :
a. Systemic : Sodium bicarbonate, sodium citrate
b. Non-systemic : Magnesium hydroxide, aluminium
hydroxide gel, magnesium trisilicate.

17. 3. Ulcer protective : Sucralfate, Colloidal bismuth
subcitrate.
4. Ulcer healing agent : carbinoxolone
5. Anti-Helicobacter pylori drugs : Amoxicillin,
Clarithromycin, Metronidazole, Tinidazole,
Tetracycline,

18. ProglumideACh
PGE2
Histamine
Gastrin
Adenyl
cyclase
_
+
ATP cAMP
Protein Kinase
(Activated)
Ca++
+
Ca++
Proton pump
K
K+ H+
Gastric acid
Parietal cell
Lumen of stomach
AntacidOmeprazole
Ranitidine
H2M3
Misoprostol
_
_
_
_
+
PGE
receptor
+
+
Gastrin
recepto
r
+
+
+

20. H2 BLOCKERS–SIDE EFFECTS &
INTERACTIONS
• Extremely safe drugs
• Cimetidine causes gynecomastia, galactorrhea
(as it is antiandrogenic & increases prolactin level)
• Cimetidine inhibits CYP450 & increases conc.
of Warfarin, Theophylline, Phenytoin,
Ethanol.

21. PROTON PUMP INHIBITORS
• Most effective drugs in antiulcer therapy
• Irreversible inhibitor of H+ K+ ATPase
• Prodrugs requiring activation in acid environment
• Weakly basic drugs & so accumulate in canaliculi of
parietal cell
• Activated in canaliculi & binds covalently to
extracellular domain of H+ K+ ATPase
• Acid secretion resumes only after synthesis of new
molecules

22. POTON PUMP INHIBITORS – KINETICS
• Given as enteric coated granules in capsule or
enteric coated tablets
• Pantoprazole also given intravenously
• Half life – 1.5 hrs
• Since it requires acid for activation - given 1 hr
before meals
• Other acid suppressing agents not co-
administered

23. P.P.I. – SIDE EFFECTS & INTERACTIONS
• Extremely safe drugs
• Causes hypergastrinemia which leads to
carcinod tumor in rats
• But no evidence of such tumors in man
• Inhibit CYP 450 & hence metabolsim of
warfarin, phenytoin, etc
• Pantoprazole & Rabeprazole have no
significant interactions

24. MISOPROSTOL
• PGE1 analogue
• Modest acid inhibition
• Stimulate mucus & bicarbonate secretion
• Enhance mucuosal blood flow
• Approved for prevention of NSAID induced ulcer
• Diarrhoea & cramping abdominal pain – 20 %
• Not so popular as P.P.I are more effective & better
tolerated

25. ANTACIDS
• Weak bases that neutralise acid
• Also inhibit formation of pepsin
(As pepsinogen converted to pepsin at acidic pH)
• Present day antacids :
Aluminium Hydroxide
Magnesium Hydroxide
• Not part of Physician prescribed regimen
• OTC drug for symptomatic relief of dyspepsia

26. ANTACIDS – CONT…
• Duration of action :
• 30 min when taken in empty stomach
2 hrs when taken after a meal
Side effects :
• Al3+ antacids – constipation (As they relax gastric
smooth muscle & delay gastric emptying)
• Mg2+ antacids – Osmotic diarrhoea .
• In renal failure Al3+ antacid – Aluminium toxicity
&
Encephalopathy

27. ANTACID - INTERACTIONS
• Antacid(CaCo3) with tetracycline form insoluble complexes
that are not absorb .
• Clinical importance :
Interactions can be avoided by taking antacids 2 hrs
before or after ingestion of other drugs .

28. ANSWER THIS QUESTION
• Is it rational to combine aluminium hydroxide and
magnesium hydroxide in antacid preparations ?

29. Answer
• Combination provides a relatively fast and sustained
neutralising capacity .
(Magnesium Hydroxide – Rapidly acting
Aluminium Hydroxide - Slowly acting )
• Combination preserves normal bowel function.
(Aluminium Hydroxide – constipation
Magnesium hydroxide – diarrhoea )

30. MUCOSAL PROTECTIVE AGENTS
• Sucralfate
• Colloidal Bismuth compounds

31. SUCRALFATE
• Salt of sucrose complexed to sulfated aluminium
hydroxide
• In acidic pH polymerises to viscous gel that adheres
to ulcer crater
• Taken on empty stomach 1 hr. before meals
• Concurrent antacids, H2 antagonist avoided
(as it needs acid for activation )

32. COLLOIDAL BISMUTH COMPOUNDS
• Coats ulcer, stimulates mucus & bicarbonate secretion
• Direct antimicrobial activity against H.pylori
• May cause blackening of stools & tongue
• Not used for long periods – bismuth toxicity
AVAILABLE COMPOUNDS :
Bismuth subsalicylate – in USA
Bismuth sobcitrate – in Europe
Bismuth dinitrate

33.  CARBINOXOLONE :Mechanism
1. Acts on Microsomal glycosyl transferase
2. Inhibits NAM containing mucoprotein
3. Increase mucus secretion,

35.  Amoxicillin: B-lactum antibiotic
 Clarithromycin-
 Metronidazole-
 tetracycline

36. 1. K D Tripathi, Essentials of medicinal Pharmacology,
Jaypee Publishers, 6th ed, pp.627-63
2. Goodman & gilman’s –the pharmacogical basis of
therapeutics 11th edition
3. www.google.in