Peptic Ulcer and GERDs Asmaa A.

Physiology of gastric secretion

The stomach secretes roughly about 2–3 L of gastric juice/day. Thechief or peptic cells secrete pepsinogen, which is converted to pepsinby gastric acid. Parietal or oxyntic cells secrete acid and intrinsicfactor (IF). Superficial epithelial cells secrete alkaline mucus andbicarbonate ions.

Regulation of gastric acid secretion

The secretion of gastric acid by parietal cells is regulated by ACh,histamine, gastrin and prostaglandin E2 (PGE2). Binding of histamine,ACh and gastrin to their specific receptors on the parietal cell results inincreased secretion of gastric acid. In contrast, the binding of PGE2 toits receptor decreases gastric acid secretion. There are various phases ofgastric acid secretion—basal, cephalic and hormonal. A membrane-bound proton pump H+, K+ ATPase plays an important role in the finalstep of gastric acid secretion.

Damage to the mucosa and deeper tissue exposed to acid and pepsinis known as peptic ulcer. The exact cause of peptic ulcer is not clear.In most of the cases, peptic ulcers are caused by Helicobacter pyloriinfection or the use of nonsteroidal anti-inflammatory drugs(NSAIDs).

GI Disease

The major problem is one of acidity, in the form of increased acidsecretion, reflux of corrosive gastric contents or gastric damage. UpperGI problems encompass simple to serious disease:

• GERD is reflux of the gastric contents into the esophagus, whichleads to erosion (reflux esophagitis).

• Gastritis: inflammation of the stomach.

• Peptic ulceration: gastric and duodenal.

• Zollinger- Ellison syndrome (ZES): is caused by a gastrin producingtumor.

• NSAIDs induce peptic damage.

Peptic Ulcer

Ulceration lesion in the mucosa of the stomach or duodenum.

Types:

- Gastric.

- Duodenum.

Gastric Ulcer• Pain occur immediately or 1 hour after meals.

• Pain usually does not wake patients.

• Accentuated by ingestion of food.

• Risk of malignancy.

• Deep and penetrating and usually occur on the lesser curvature of the stomach.

Duodenal Ulcer• Pain occurs 2-4 hours after meals.

• Pain wakes up patients.

• Pain relieves by food.

• Very little risk for malignancy.

Symptoms

• Epigastric tenderness:

- Gastric: epigastrium: left of midline.

- Duodenal: mid to right of epigastrium.

• Sharp, burning, aching, gnawing pain.

• Dyspepsia.

• Nausea/ Vomiting.

• Belching.

• Hematemesis or melena with GI bleeding.

PUD - Diagnosis

• Endoscopy

• Barium meal – contrast x-ray

• Biopsy – malignancy

• H.Pylori:

Endoscopy cytology

Biopsy – Special stains

Culture – difficult

Urease Breath test.

Treatment

Non-pharmacological treatment:

-Life style modification:

- Discontinue NSAID.

- Smoking cessation.

- Alcohol cessation.

- Stress reduction.

Classification of drugs used in peptic ulcer

1. Drugs that inhibit gastric acid secretion

a.Proton-pump inhibitors (PPIs): Omeprazole, esomeprazole,lansoprazole, pantoprazole, rabeprazole.

b.H2-receptor antagonists (H2-blockers): Cimetidine, ranitidine,famotidine, nizatidine and roxatidine.

c.Antimuscarinic agents (Anticholinergic agents): Pirenzepine,telenzepine.

d. Prostaglandin analogues: Misoprostol.

2. Ulcer protectives

Sucralfate, colloidal bismuth subcitrate (CBS).

3. Drugs that neutralize gastric acid (antacids)

a. Systemic antacids: Sodium bicarbonate, sodium citrate.

b.Non-systemic antacids: Magnesium hydroxide, magnesium trisilicate,aluminum hydroxide, calcium carbonate.

4. Anti-H. pylori drugs

Amoxicillin, tetracycline, clarithromycin, metronidazole, tinidazole,bismuth subsalicylate, H2-antagonists and proton pump inhibitors.

Drugs That Inhibit Gastric Acid Secretion

Proton Pump Inhibitors (PPIs)

Proton pump H+, K+–ATPase is a membrane-bound enzyme that playsan important role in the final step of gastric acid secretion. Omeprazoleis the prototype drug. The other PPIs are lansoprazole, pantoprazole andrabeprazole. They are prodrugs and are activated to sulfenamide atacidic pH. As PPIs act in the final step of acid secretion, they areeffective in inhibiting acid production following any stimulation. Theactivated form binds covalently with SH group of the proton pump andirreversibly inactivates it. PPIs are the most powerful inhibitors ofgastric acid secretion.

They are administered orally about 30 min before food because foodstimulates secretion of acid, which is necessary for activation of PPIs.

PPIs are available as enteric-coated form or as powder containingsodium bicarbonate to prevent their degradation by acid in thestomach.

Parenteral (i.v.) formulations are available for esomeprazole,omeprazole, lansoprazole, pantoprazole and rabeprazole.

They are highly bound to plasma proteins; extensively metabolized inliver and their metabolites are excreted in urine.

Therapeutic uses

1. Peptic ulcer

2. Gastroesophageal reflux disease (GERD)

3.Zollinger–Ellison syndrome (Z–E syndrome)

Adverse effects

• Proton pump inhibitors are generally well tolerated. The side effects areheadache, diarrhoea and abdominal pain.

• Skin rashes and arthralgia can rarely occur.

• Long-term use of PPIs can decrease vitamin B12 absorption, increase therisk of infections (e.g. hospital acquired pneumonia) and fracture of bones.

• Chronic use also results in hypergastrinaemia, which may predispose togastric tumours.

Drug interactions

• Omeprazole can inhibit the metabolism of drugs like phenytoin,warfarin, diazepam, etc.

• Proton pump inhibitors decrease the bioavailability of itraconazole,iron salts, etc.

• Omeprazole and esomeprazole may decrease effectiveness ofclopidogrel because they inhibit CYP2C19 and prevent conversion ofclopidogrel to active metabolite.