TREATMENT OF PEPTIC ULCER

By :DR. NAWRAS Maher & DR. Batool

Obaid

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

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

Don’t be anger u `ll get PU

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 )

• 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

Figure: D.U visualized by OGD

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

I- Drugs that decrease gastric acid secretion:

 1 -H2 receptor blockers

2 -Anticholinergics (antimuscarinic) 3- Proton pump inhibitors

ProglumideAChHistamine Gastrin

Adenyl cyclase

_ +

ATP cAMP

Protein Kinase (Activated)

Ca++

+

Ca++

Proton pump

KK+ H+

Gastric acid

Parietal cellLumen of stomach

Ranitidine

H2M3

__

+

PGE receptor

+

+

Gastrin receptor+

+

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

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 CA6- Hiatus hernia7- Stress ulcer

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

PROTON PUMP INHIBITORS

Omeprazole, Lansoprazole, Pantoprazole, Esomeprazole

Most effective drugs in antiulcer therapy

They inhibit H / K ATPase enzyme in parietal cellsIndications: P.U, GERD & Zollinger – Ellison syndrome.Side Effects: Erythema Multiformis (E.M), gynaecomastia,

bronchospasm, leukopenia, thrombocytopenia, photosensitivity & alopecia.

Anticholinergics:Pirenzepine (Gastrozepin)

Octerotide:Synthetic somatostatine analogueinhibits gastric and pancreatic secretions Used in Zollinger – Ellison syndrome & portal hypertension

PROTON PUMP INHIBITORS

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.

.

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

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.PyloriIndications: 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

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

colitisSide Effects: Constipation, vertigo & skin rash

Drugs That enhance enhance mucosal defense

.

3. Misoprostol: Synthetic analogue of PGE1 prevents G.U in patients taking NSAIDsinhibits acid secretion stimulated by histamine

Side Effects: Dysmennrohea and rash

4. Zinc salts

5. Liquorice

Combination Therapy of Peptic Ulcer

.

• Triple Therapy: Omeprazole plus Clarithromycin plus Amoxicillin / MetronidazoleGiven for 14 days followed by P.P.I for 4 – 6

weeks

• Quadruple Therapy: Omeprazole plus Bismuth plus Metronidazole

plus TetracyclineGiven when Triple Therapy fails