pharmacological approach to peptic ulcer

1. By :
DR. NAWRAS Maher & DR. Batool
Obaid

2. DEFINITION & PATHOPHYSIOLOGY
Definition : ulcer is a break in the mucosal
surface >5 mm in size, with depth to the submucosa
penetrating the muscularis mucosa
Pathophysiology of peptic ulcer disease
P.U is the end result of an imbalance between
aggressive and defensive factors in the
Gastroduodenal mucosa

3. Factors Affecting The Incidence of Peptic Ulcer Disorder
• H. pylori infection: ( 75% of G.U & 90% of D.U)
• Drugs: NSAIDs, Corticosteroids & Reserpine
• Cigarette smoking
• Alcohol consumption
• Genetic factors :
Family history of P.U & blood group O
• Psychological stress
• Diet (pickles)
• Others : seasonal variation & regional differences

4. CLINICAL FEATURE of PUD
• History
1. Dyspepsia
2. Anorexia & weight loss ( more in GU )
3. Vomiting
4. Sudden severe generalized abdominal pain ( perforation)
5. Haematemesis & Melina ( bleeding )

5. • Physical examination : Epigastric tenderness
PUD related complications
1. Hemorrhage
2. Perforation
3. Gastric outlet obstruction
4. Gastric CA
Diagnosis
- History
- Lab studies :
1. Routine tests : CBP , iron studies
2. Serum gastrin & gastric acid analysis
3. Tests for H. pylori
- Radiographic ( barium study )
- Endoscopic (OGD) examination

6. Figure: D.U visualized by OGD

7. Classification of Treatment of P.U
Three groups of drugs
 Drugs that decrease gastric acid secretion
 Drugs that neutralize gastric acid
 Drugs that enhance mucosal defense

8. I- Drugs that decrease gastric acid secretion:
1- H2 receptor blockers
2- Anticholinergics (antimuscarinic)
3- Proton pump inhibitors

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

10. H2 - receptor blockers
Scientific
Name
Trade
Name
Relative
Potency
Daily
Dosage
Cimetidine Tagamet 1 x 800 mg H.S or
400 mg Bid
Ranitidine Zantac 4-10 x 300 mg H.S or
150 mg Bid
Famotidine Pepcid 20-50 X 40 mg H.S or
20 mg Bid
Nizatidine Axid 4-10 x 300 mg H.S or
150 mg Bid

11. INDICATION
1- G.U & D.U
2- Gastro esophageal reflex disease (GERD)
3- hypersecretory conditions :
a- Zollinger – Ellison syndrome
b- systemic mastocytosis
c- multiple endocrine neoplasia
4- pre-anesthesia: (emergency and labour) to
decrease incidence of mendelson's syndrome
5- Controlling symptoms of gastric CA
6- Hiatus hernia
7- Stress ulcer

12. SIDE EFFECT
• Sedation
• Gynaecomastia , low sperm count , and
impotence (♂) & galactorrhea (♂)
• Blood dyscrasia
• Cholestatic effect, hepatitis +/- jaundice
Associated mostly with Cimetidine, rarely with
Ranitidine, and not with Famotidine and
Nizatidine

13. PROTON PUMP INHIBITORS
Omeprazole, Lansoprazole, Pantoprazole,
Esomeprazole
Most effective drugs in antiulcer therapy
They inhibit H / K ATPase enzyme in parietal cells
Indications:
P.U, GERD & Zollinger – Ellison syndrome.
Side Effects:
Erythema Multiformis (E.M), gynaecomastia,
bronchospasm, leukopenia, thrombocytopenia,
photosensitivity & alopecia.

14. Anticholinergics:
Pirenzepine (Gastrozepin)
Octerotide:
Synthetic somatostatine analogue
inhibits gastric and pancreatic secretions
Used in Zollinger – Ellison syndrome & portal
hypertension
PROTON PUMP INHIBITORS

15. Drugs That Neutralize Gastric Acid
Antacids:
Basic substances that decrease acidity by
neutralizing HCL protecting ulcer from acid
and pepsin by increasing PH (as pepsin is
inactive when PH > 5)
MOA: They provide mucosal protection either
through stimulation of P.G production or by
binding to identified injurious substance.

16. .
Drugs That Neutralize Gastric Acid
Classification:
• Systemic: absorbable but cause metabolic alkalosis (Na
bicarbonate)
• Non -systemic: not significantly absorbed, not affecting acid –
base balance (Mg and Al salts)
Side effects :
• Al antacids → Constipation
• Mg antacids → Osmotic diarrhoea
• In renal failure Al antacids → Aluminum toxicity
&
Encephalopathy

17. Drugs That enhance enhance mucosal
defense
.
1- Bismuth chelate :
- Chelate with protein in the ulcer base forming a
coat that protects from acid, bile & pepsin
- Stimulates the production of mucous and PG
- Has antimicrobial activity against H.Pylori
Indications:
D.U & G.U (therapeutic activity equal to H2
blockers, But with less relapse of ulcer )
Side Effects:
- Darkening of tongue, teeth and stool
- Arthropathy and encephalopathy

18. Drugs That enhance enhance mucosal
defense
.
2. Sucralfate:
(sulfated sucrose and Al OH)
Sucrose becomes hydrated when contact with acid
to form viscous paste that protects ulcer from acid
and pepsin
Stimulate PG synthesis and bind to pepsin and bile
acid
Indications:
P.U, GERD, GI bleeding, stress ulcer & ulcerative
colitis
Side Effects:
Constipation, vertigo & skin rash

19. Drugs That enhance enhance mucosal
defense
.
3. Misoprostol:
Synthetic analogue of PGE1
prevents G.U in patients taking NSAIDs
inhibits acid secretion stimulated by histamine
Side Effects:
Dysmennrohea and rash
4. Zinc salts
5. Liquorice

20. Combination Therapy of Peptic Ulcer
.
• Triple Therapy:
Omeprazole plus Clarithromycin plus
Amoxicillin / Metronidazole
Given for 14 days followed by P.P.I for 4 – 6
weeks
• Quadruple Therapy:
Omeprazole plus Bismuth plus Metronidazole
plus Tetracycline
Given when Triple Therapy fails