drugs mangemanta of peptic ulcer

1. Presented By
Dr. Manoj Kumar
Assistant Professor
Department of Pharmacology
Adesh Medical College & Hospital Ambala Can’t

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3. Pathogenesis
Aggressive Factors
 Acid, pepsin
 H. pylori
 Nicotine
 Alcohol
 Drugs (NSAIDs)
 Delayed gastric emptying
 Stress
Defensive Factors
 Mucus, bicarbonate layer
 Intercellular tight
junctions
 Prostaglandins
 Free radical scavengers
Therapy is directed at enhancing host defense or
eliminating aggressive factors
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4.  Stomach secretes 2-3 L of gastric juice/day
 Peptic/ Chief cells secrete pepsinogen
Pepsinogen Pepsin
ells secrete acid, IF
 Superficial epithelial cells secrete alkaline
mucous, bicarbonate ions
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Gastric acid

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9.  Increased by ACh, histamine, gastrin
◦ Activate H+K+ATPase pump
 Decreased by PGE2
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10.  Types
◦ Gastric ulcer
◦ Duodenal ulcer
◦ Zollinger-Ellison Syndrome
◦ Stress Ulcers
◦ Drug associated ulcers
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11. 1. Reduction of gastric acid secretion
◦ Proton Pump Inhibitors (PPIs)
● Omeprazole ●Lansoprazole ●Pantoprazole
◦ H2 receptor antagonists (H2 blockers)
● Cimetidine ● Ranitidine ● Famotidine
◦ Anticholinergics
● Pirenzepine, Oxyphenonium
◦ Prostaglandin analogues
● Misoprostol, Rioprostil
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12. 2. Neutralization of gastric acid (Antacids)
◦ Systemic: Sodium bicarbonate, Sodium citrate
◦ Non-systemic: Magnesium hydroxide, Aluminium
hydroxide, Calcium carbonate
3. Ulcer protectives: Sucralfate, Colloidal
Bismuth Subcitrate
3. Ulcer healing drugs: Carbenoxolone sodium
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13. 5. Anti- H.pylori drugs:
 Amoxicillin
 Clarithromycin
 Tetracycline
 Metronidazole
 Tinidazole
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14. Inhibit
secretion
Prevent
contact
Neutralize
acid
Mechanisms Example
Ranitidine
Omeprazole
Prostaglandins
Muscarinic antagonists
Sucralfate
Antacids
H+
H+
H+

15.  Omeprazole, Esomeprazole, Lansoprazole,
Pantoprazole, Rabeprazole, Dexlansoprazole
 Prodrugs
 Inhibit H+K+ATPase
◦ Irreversible inhibition
 Inhibit gastric acid secretion (80-95%)
 Oral; IV (Pantoprazole, lansoprazole,
esomeprazole)
 Dose: 20-40mg OD *4-6 weeks
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17.  Given 30 min before meals
 Acid labile: Enteric coated tablets/ capsules
 Weakly basic drugs
 Accumulate & activate in canaliculi of parietal cell
 Bind covalently to extracellular domain of H+ K+ ATPase
 Acid secretion resumes only after synthesis of
new molecules
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18.  Not all proton pumps inactivated with 1st
dose
 Reaching max potential takes up to 3–4 days
 After stopping, takes 3–4 days for full acid secretion to
return
 Advantages
◦ Rapid onset of action, Faster ulcer healing
 Microsomal enzyme inhibitor
◦ Diazepam, phenytoin, warfarin
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19.  Uses
◦ Peptic ulcer
◦ GERD, ZES
◦ Reflux esophagitis, H.pylori ulcer
◦ OTC – heartburn
 Adverse effects: well tolerated
 Nausea, abdominal pain, constipation, flatulence,
diarrhea
 Headache, skin rash
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20.  H2 blockers
 Less potent than PPIs
 Competitive blockage of H2 receptors on
parietal cell
◦ Inhibit acid secretion (70%)
 Cimetidine, Ranitidine, Famotidine,
Nizatidine, Roxatidine, Loxatidine
◦ Oral, IV (Ranitidine, Famotidine)
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21.  Very effective in inhibiting nocturnal acid
secretion (as it depends largely on
Histamine)
 Modest impact on meal stimulated acid
secretion (as it depends on gastrin, ACh,
histamine)
 Avoided in pregnancy & lactation
◦ Crosses placental barrier
◦ Secreted in breast milk
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23.  Therapeutic uses
◦ Gastritis
◦ Peptic ulcer
◦ ZES
◦ Stress ulcers (burns)
◦ Uncomplicated GERD
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24.  Diarrhoea, headache, drowsiness, fatigue,
muscular pain, constipation
 Cimetidine: Antiandrogenic
(Gynaecomastia in males, menstrual
irregularities in females)
 Microsomal enzyme inhibitor
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25.  M1 Blockers – Pirenzepine, Telenzepine
• MOA – Suppress acid production
• Disadvantages
• Poor efficacy
• Significant & undesirable anticholinergic adverse
effects
• Delay gastric emptying
• Prolong exposure of ulcer bed to acid
• Status – Not preferred these days
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26.  PGE1 analogues: Misoprostol
◦ PGE2 analogues: Enprostil, Rioprostil
 Inhibit acid production, increase mucous &
bicarbonate secretion (Cytoprotective effects)
• Adverse effects – Diarrhea, abdominal pain, cramps
(increases water & electrolyte secretions in GIT)
• Uses – Prevention & treatment of NSAID associated GI
injury, peptic ulcer
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28.  Limitations
◦ Cost
◦ Poor compliance
 Multiple dosing (t1/2: 25-30 min)
 CI: Pregnancy (Increase in uterine contractions)
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29.  Weak bases, neutralize gastric acid & raise pH
Systemic: Sodium bicarbonate, Sodium citrate
◦ Rapidly neutralize gastric acid, short DOA
 Raise gastric pH: 7.4
◦ Disadv: rapidly absorbed, Rebound Acidity, gastric
distension (CO2), Na+ load
 Used rarely
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HCl + NaHCO3 → NaCl + CO2 + H2O

30.  Aluminium hydroxide
 Magnesium hydroxide
 Calcium carbonate
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31.  Causes constipation
◦ Formation of Al phosphate in intestine
◦ Smooth muscle relaxation
◦ Mucosal astringent effect
 Binds to phosphate in GI, prevent
absorption
◦ Causes hypophosphataemia
◦ Useful in hyperphosphataemia, phosphate stones
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by Al+3

32.  Mg(OH)2, CaCO3
 Powerful, fast onset, Raise gastric pH>7
CaCO3
◦ Belching due to CO2, constipation
◦ Rebound acidity (sudden rise in pH)
◦ Milk-alkali syndrome with milk
 Hypercalcaemia, renal insufficiency, metabolic alkalosis
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33. Combination useful: less dose, less adverse effects
 Mg(OH)2: Faster acting, Laxative action (osmotic
diarhoea)
 Al(OH)3: Slowly acting , Relax gastric smooth
muscle – cause constipation & delayed gastric
emptying
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34.  Adverse effects
◦ Al salts: constipation
◦ Mg salts: diarrhea, hypermagnesemia,
◦ Ca salts: constipation, milk alkali syndrome,
rebound acidity
 DI
◦ Al, Mg decreases absorption of digoxin,
tetracycline, iron salts
◦ Taken 2 hrs apart
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35.  Simethicone (Activated dimethicone)
◦ Antifoaming agent, reduces flatulence, prevents
hiccups
◦ Also used in topical skin preparations to prevent
bed sores
 Sodium alginate
◦ Forms a viscous gel (raft) with gastric acid
◦ Floats, acts as mechanical barrier
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36. • Sucralfate, Colloidal Bismuth Subcitrate (CBS),
Ranitidine Bismuth Subcitrate
Sucralfate
◦ Forms a sticky viscous gel that adheres to ulcer
base (Cytoprotective): Acts as a acid-resistant
physical barrier
◦ Promotes ulcer healing, delays gastric empting
◦ Uses: peptic ulcer, stress ulcer (1g QID)
◦ Requires pH<4 for activation
 Not given along with antacids, PPIs, H2 blockers
◦ Adverse effects: Constipation, dry mouth, headache,
itching
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37. ◦ Blackening of stool, tongue
◦ Bismuth toxicity: osteodystrophy, encephalopathy
Carbenexolone
 Ulcer healing drug
 Increases mucous, promotes healing, increases
endogenous PG levels
 Disadv: (mineralocorticoid) retains water & salt,
high BP.
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38.  H.pylori: gram -ve bacillus, urease producing
◦ Sensitive to amoxicillin, tetracycline, clarithromycin,
metronidazole
 Single drug: not used
◦ High chances of resistance
 Triple/ quadruple therapy
◦ Prevents resistance, relapse
◦ Promote ulcer healing
◦ Eradicate H.pylori infection
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39. PPI (Omeprazole 20
mg/Lansoprazole 30 mg) BD
+
Amoxicillin 1 g BD
Clarithromycin 500 mg BD
Metronidazole 400 mg BD
Total duration 14 days
Sequential therapy:
Day 1-5: Ome/lanso+amox;
Day 6-10: Ome/lanso+ Clarith +
Tinida
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Any two

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41. Proglumide
ACh
PGE2
Histamine
Gastrin
Adenyl
cyclase
_
+
ATP cAMP
Protein Kinase
(Activated)
Ca++
+
Ca++
Proton pump
K
K+ H+
Gastric acid
Parietal cell
Lumen of stomach
Antacid
Omeprazole
Ranitidine
H2
M3
Misoprostol
_
_
_
_
+
PGE
receptor
+
+
Gastrin
receptor
+
+
+

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