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Presented by: Mohd akhtar M.Pharm. (Pharmacology)
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Page 1: Peptic ulcer (defination, cause, tratment)

Presented by:Mohd akhtar

M.Pharm. (Pharmacology)

Page 2: Peptic ulcer (defination, cause, tratment)

Anatomy of Stomach Acid Peptic Disorders Peptic ulcer disease Comparison of Gastric & Duodenal ulcers Risk factors Symptoms Physiology of Acid secretion Treatment of peptic ulcer Summary

Page 3: Peptic ulcer (defination, cause, tratment)

MuscularisSerosa

MucosaSubmucosa

Fundic Fundic regionregion

Esophagus

Duodenum

AntrumAntrum

Layers

Parietalcells

BodyBody

Pyloricsphincter

Chief cells

Gastric pit

Page 4: Peptic ulcer (defination, cause, tratment)

Peptic Ulcers• Gastric ulcer• Duodenal Ulcer

Gastro Esophageal Reflux Disease (GERD) Dyspepsia Stress Ulcers Gastric Cancers

Page 5: Peptic ulcer (defination, cause, tratment)

Peptic ulcer refers to an erosion of the mucosal layer anywhere in the GI tract; however, it usually refers to erosions in the stomach or duodenum.

Over 80% of peptic ulcers are caused by Infection with the bacterium Helicobacter pylori.

Page 6: Peptic ulcer (defination, cause, tratment)

Pathophysiology of Peptic Ulcer Pathophysiology of Peptic Ulcer Disease (PUD)Disease (PUD)

Mucosal Defenses

• Bicarbonate

• Mucus

• Prostaglandin

• Growth factor

• Mucosal regeneration

Luminal Aggressors

• H. pylori

• NSAIDs

• Acid

• Pepsin

Page 7: Peptic ulcer (defination, cause, tratment)

DUODENAL GASTRIC

INCIDENCE More common Less common

ANATOMY First part of duodenum – anterior wall

Lesser curvature of stomach

DURATION Acute or chronic Chronic

MALIGNANCY Rare Benign or malignant

Page 8: Peptic ulcer (defination, cause, tratment)
Page 9: Peptic ulcer (defination, cause, tratment)

HELICOBACTER PYLORI Infection Non Steroidal Anti-inflammatory Drugs Steroid therapy Smoking Excess alcohol intake Genetic factors Zollinger Ellison syndrome – rare syndrome caused by

gastrin-secreting tumour Blood group O Hyperparathyroidism

Page 10: Peptic ulcer (defination, cause, tratment)

Nausea – Vomiting – Anorexia Epigastric pain after meal and during meal Intolerance of fatty food Heartburn Loss of weight Oral flatulence, bloating Pain radiating to the back

Page 11: Peptic ulcer (defination, cause, tratment)

Feldman: Sleisenger & Fortran’s Gastrointestinal and Liver Disease, 7 th ed.

Page 12: Peptic ulcer (defination, cause, tratment)

Gastrointestinal hemorrhage Chronic iron deficiency anemia

Pyloric stenosis Perforation

peritonitis

Page 13: Peptic ulcer (defination, cause, tratment)

Bacteria Gram Negative spiral bacterium 40% of patients >60 years are +ve for H.pylori Transmitted: possibly person to person Most common cause of antral gastritis

Mechanism of gastric injury Adherence to epithelial cells Infects mucosa of stomach > inflammatory response >

gastritis > increased gastrin secretion > gastric metaplasia > damage to mucosa > ulceration

Cytotoxin

Page 14: Peptic ulcer (defination, cause, tratment)

Inhibits prostaglandin synthesis (COX inhibition)

Disrupts functional mucosal integrity

↓ mucosal blood flow ↓ cell regeneration Direct GI irritation Antiplatelet effect

(causing bleeding) ↑ acid (basal and

maximal stimulation) secretion

Page 15: Peptic ulcer (defination, cause, tratment)
Page 16: Peptic ulcer (defination, cause, tratment)

ProglumideACh

PGE2

Histamine Gastrin

Adenyl cyclase

_+

ATP cAMP

Protein Kinase (Activated)

Ca++

+

Ca++

Proton pump

K+ H+

Gastric acid

Parietal cell

Lumen of stomach

AntacidOmeprazole

Ranitidine

H2M3

Misoprostol

_

__

_

+

PGE receptor

+

+

Gastrin receptor+

+

+

Cl- K+

Page 17: Peptic ulcer (defination, cause, tratment)
Page 18: Peptic ulcer (defination, cause, tratment)

Promotion of ulcer healing.Symptomatic relief of pain.

Prevention of recurrence (relapse).Prevention of complications

Page 19: Peptic ulcer (defination, cause, tratment)

I. Gastric hyposecretory drugs Proton pump inhibitors H2 receptor blockers Muscarinic receptor blockers

II. Eradication of H. pylori infections To prevent relapse

III. Mucosal cytoprotective agents Sucralfate Colloidal bismuth Prostaglandin analogues

IV. Neutralizing agents (antacids)

Page 20: Peptic ulcer (defination, cause, tratment)

1. Proton pump inhibitors2. H2 receptor blockers3. Muscarinic receptor blockers

Page 21: Peptic ulcer (defination, cause, tratment)

Mechanism of actionIrreversible inhibition of proton pump (H+/ K+ ATPase) that is responsible for final step in gastric acid secretion from the parietal cell.

PP inhibitors include: Omperazole Lansoprazole Pantoprazole Rabeprazole

Page 22: Peptic ulcer (defination, cause, tratment)

They are prodrugs – taken orally. Are given as enteric coated capsules

They are activated in the acidic medium of the secretory parietal cell canaliculus.

They are inactivated if (combined with H2 receptor blockers).

Have long duration of action (> 18 -24 hr). Bioavailability is reduced by food. Given 1 hr before meal.

Page 23: Peptic ulcer (defination, cause, tratment)

PPIs are quite safe but may occur:GIT disturbances: nausea, vomiting, diarrhoea

Achlorhydria: increase the risk of enteric infections due to Shigella, salmonella

Hypergastrinaemia Gastric hyperplasia

Page 24: Peptic ulcer (defination, cause, tratment)

Mechanism of actionThey competitively and reversibly block to H2 receptors on the parietal cells thus reduce gastric secretion. They include:

H2 Receptor inhibitors include: Cimetidine Ranitidine

Famotidine Nizatidine

Page 25: Peptic ulcer (defination, cause, tratment)

Good oral absorption Plasma half life (1-3 h). Duration (4-12 h). First pass metabolism (50% Except Nizatidine

100 % bioavailability). Given before meals. Metabolized by liver. Excreted mainly in urine. Cross placenta & excreted in milk

Page 26: Peptic ulcer (defination, cause, tratment)

These are extremely safe drugs but may occur: nausea, vomiting, bradycardia and hypotension (rapid

I.V.) Gynecomasteia, impotence in male Galactorrhea in female on long term use

of cimitidine Decrease metabolism of oral anticoagulant,

phenytoin, benzodiazepines.

Page 27: Peptic ulcer (defination, cause, tratment)

Acid (control)H2 BlockPPI

Page 28: Peptic ulcer (defination, cause, tratment)

Mechanism of action Blocks M3 receptors on the parietal cells. Selectively inhibit gastric acid secretion Decreased gastric motility Delayed gastric emptying

Muscarinic blockers: Oxyphenonium Dicyclomine Pirenzepine Telenzepine

Page 29: Peptic ulcer (defination, cause, tratment)

TreatmentCombined therapy is usually used.

Clarithromycin, tetracycline, amoxicillin Proton pump inhibitors or H2 receptor

blockers Bismuth compounds Metronidazole

Resistance may develop to antibiotics so the better eradication is obtained using proton pump inhibitors, clarithromycin & Amoxicillin.

Page 30: Peptic ulcer (defination, cause, tratment)

The BEST among all the Triple therapy regimen is

Omeprazole/Lansoprazole - 20/30 mg bd

Clarithromycin - 500 mg bd

Amoxycillin/Metronidazole -1gm/500 mg bd

Given for 14 days followed by P.P.I for 4 – 6 weeks.

Short regimens for 7 – 10 days not very effective.

Page 31: Peptic ulcer (defination, cause, tratment)

REGIMEN DOSE DURATION

BismuthMetronidazole

Tetracycline

525 mg qid250 mg tid500 mg qid

2 weeks

omeprazoleMetronidazole

Clarithromycin

20 mg bid500 mg bid500 mg bid

1 week

omeprazoleAmoxacillin

Clarithromycin

20 mg bid500 mg qid500 mg bid

1 week

omeprazoleBismuth

MetronidazoleAmoxacillin or /

Tetracycline

20 mg bid525 mg qid500 mg qid500 mg qid

week

Page 32: Peptic ulcer (defination, cause, tratment)

1. Sucralfate2. Prostaglandin analogs3. Colloidal bismuth

Bismuth subcitrate Tripotassium dicitrato bismuthate

Page 33: Peptic ulcer (defination, cause, tratment)

Sucralfate (aluminum hydroxide + sucrose) Form a sticky like gel over ulcer crater to

protect gastrointestinal mucosa and stimulates prostaglandin synthesis

It promote mucosal repair and ulcer healing It has no acid neutralising action and delay

gastric emptying Dose: 1 g QID

Page 34: Peptic ulcer (defination, cause, tratment)

Misoprostol is a prostaglandin E1 analog that stimulates the secretion of mucus and bicarbonates and inhibits acid secretion to a minor degree.

The drug has significant side effects, primarily mild to moderate diarrhoea

Is too costly to be used by most patients.

Page 35: Peptic ulcer (defination, cause, tratment)

Drugs used to relief gastric pain associated with hypersecretion of HCL and neutralize the gastric acid.

Mechanism of ActionNeutralization of HCL

Inhibition of pepsin (inactive at PH 5)

1. Systemic AntacidsSodium bicarbonate Calcium Carbonate

2. Non Systemic AntacidsAluminum Hydroxide GelMagnesium Trisilicate

Page 36: Peptic ulcer (defination, cause, tratment)

Sodium bicarbonate Calcium Carbonate

NaHCO3 + HCL → NaCL + CO2

Disadvantages Rebound hyperacidity Stomach distension due to CO2 liberation

→ pain sensation

Sodium load → salt and water retention

( # in cardiac patients) Systemic alkalosis

Page 37: Peptic ulcer (defination, cause, tratment)

Aluminum Hydroxide Gel Magnesium Trisilicate

Al (OH)3 + HCL → HCL3 + H2O

Advantages Longer duration of action. Gradual neutralization of HCL → No rebound

hyperacidity. Adsorbs pepsin. No stomach distention

Page 38: Peptic ulcer (defination, cause, tratment)

Due to the benign nature of duodenal ulcers When patients with duodenal ulcers require

surgery, it is usually one of three procedures:

Vagotomy,Vagotomy with antrectomy,Pyloroplasty

Page 39: Peptic ulcer (defination, cause, tratment)

A peptic ulcer is a break in superficial epithelial cells penetrating down to muscularis mucosa

Duodenal > gastric ulcers H pylori is a predominant risk factor H pylori diagnosed by c urea breath test, stool

antigen or if validated serology, treated with PAC500 or PMC250 regimen

Complications of PUD can lead to acute emergency of upper GI bleed

Page 40: Peptic ulcer (defination, cause, tratment)