Ulcer

Peptic ulcer is the condition in which imbalance of aggressive factor and defensive
factors occours.

Peptic ulcers are localized erosions of the mucous membranes of the stomach or
duodenum. The pain associated with ulcers is caused by irritation of exposed
surfaces by the stomach acids.

Aggressive factors: Gastric acid, gastrin, pepsin.

Defensive factors: Prostaglandin, mucosa, bicarbonate.

Aggressive Factors Defensive Factors

Acid, pepsin Mucus, bicarbonate layer

Bile salts Blood flow, cell renewal

Drugs (NSAIDs) Prostaglandins

H.pylori Phospholipid

The secretion of gastric acid by parietal cells of the oxyntic gland in the gastric
mucosa, producing 2 to 3 L of gastric juice per day, pH 1 in HCL .

Chief cells / peptic cells pro-rennin , pepsinogen ;

Parietal / oxyntic cells - HCl

Mucus secreting cells Mucus

Two sphincter muscles:

- Cardiac - located at the upper portion of the stomach - prevents reflux of acid
into the esophagus.

- pyloric - located at the lower portion of the stomach - prevents reflux of acid into
the duodenum.
* Esophageal ulcers reflux of acidic gastric secretion into the esophagus d/t a
defective or incompetent cardiac sphincter

* Duodenal ulcers hypersecretion of acid from the stomach that passes to the
duodenum

* Gastric ulcer breakdown of GMB (gastric mucosal barrier).

Pathology: 2 types:
1) Those associated with organisms H-pylori.
2) Those associated with the use of aspirin, NSAIDS.

Causes for ulcer

1) Presence of a bacterium called Helicobacter pylori .In many cases,hyper-

secretion of gastric acid appears to be associated with Helicobacter pylori(gram -
ve) infection.

2) Use of non steroidal anti inflammatory agents (NSAIDS) .Agents such as aspirin
inhibits the enzyme CYCLOOXYGENASE 1 (COX-1)As COX-1 is responsible
for synthesis of prostaglandins that inhibit acid secretion and protect the gastric
mucosa.

3) Increased HCl secretion. 4) Inadequate mucosal defence against gastric acid.

5) Tumors (rare). 6) Stress , alcohol , diet etc.

Symptoms

1) Abdominal pain, classically epigastric with severity relating to meal times,

after around 3hours of taking a meal. 2) Loss of appetite and weight loss.
3) Nausea, and vomiting.

Complications: Gastrointestinal bleeding is the most common complication.

Sudden large bleeding can be life-threatening.

Perforation (a hole in the wall) often leads to catastrophic consequences. Erosion

of the gastro-intestinal wall by the ulcer leads to spillage of stomach or intestinal
content into the abdominal cavity.

Scarring and swelling due to ulcers causes narrowing in the duodenum and
gastric outlet obstruction. Patient often presents with severe vomiting.

Diagnosis:
1) Endoscopy 2) Radiology. 3) H-pylori detection. 4) Serological
test.
5) Urea breathe test. 6) Stool antigen test.

Treatment:

1) H2 Receptors Antagonists:

Cimetidine Ranitidine Famotidine Nizatidine Roxatidine

Competitively block the histamine (H2) receptor of acid-producing parietal cells.

Rendering cells less responsive to not only histamine but also to the stimulation of
acetylcholine and gastrin.

Therapeutic effects:
1 Promote the healing of gastric and duodenal ulcers 2 Gastro-esophageal
reflux

3 Upper GI bleed 4 May be effective in stress ulcers & peptic

esophagitis

Side effect: CNS: headache, lethargy confusion, depression hallucinations

ENDO Impotence increased prolactin gynecomastia

HEME: Thrombocytopenia.

2) Muscarinic Antagonists : Atropine

Block the M1 class receptors & reduce acid production. abolish gastrointestinal
spasm .Relatively unpopular as a first choice because of high incidence of
anticholinergic side effects (dry mouth and blurred vision).

3 Proton Pump inhibitor:

H+,K+-ATPase (Proton Pump) inhibitor

Omeprazole Lansoprazole Pantoprazole Rabeprazole

Irreversibly binds to H+/K+ ATPase & Prevents H+ ion production & secretion

Block all acid secretion & to return to normal must synthesize new H+/K+ ATPase
& Inhibit H. pylori.

Therapeutic uses: 1 Gastroesophageal reflux disease. [GERD] 2 Peptic

ulcer.

3 Infection with H. pylori plus.

4 Upper GI bleed.

Adverse effects:

Bone fractures (on long term therapy) Enzyme inhibitor On prolonged therapy
these agents suppress gastric acid results in less absorption of vit B12,and calcium
carbonate products. Diarrhea GI disturbances
4) Mucosal Protective Agents

Prostaglandins: Pg E produced by gastric mucosa, Inhibits gastric acid secretion

& stimulates secretion of mucus and bicarbonate (cytoprotective effect). The
only available pgE analogue is misoprostal.

Uses : 1) NSAIDs induced ulcers 2) duodenal ulcers unresponsing to H2

antagonists 3) as cervical ripening agent for induction of labour. Misoprostal

Adverse effects: Shows abortifacient properties, causes uterine contraction.so

contraindicated during pregnancy. diarrhea nausea.

5) Mucoprotectives:

1) Sucralfate complex of sulfuric acid ester of sucrose & aluminium hydroxide.

MOA : by forming complex gels with epithelial cells,it creats a physical barrier
and prevents degradation of mucus by pepsin and acid ; stimulates PG ;inhibits
peptic digestion.

USES : - duodenal ulcers- to prevent recurrence, stress ulcerations

Adverse effects : should not given with agents which decreases HCl does not
prevent NSAID induced ulcer does not heal gastric ulcers.

2) Bismuth

Bismuth preparations : Action is similar to sucralfate Uses Peptic ulcer Inhibits

secretion of pepsin Increases secretion of mucus.

6 Antacids: to neutralize the released HCl . These are weak bases those react with
gastric acid to form water and salt to diminish gastric acidity.

Uses : - GERD- peptic ulcer (symptomatic relief)- duodenal ulcers- calcium

containing preparations used for osteoporosis also .

Adverse effects:1) NaHco3 transient metabolic alkalosis ;flatulence and belching

.2) Al(OH)3 - constipation ;hypophosphatemia .

3) Mg(OH) diarrhea.