DRUGS FOR PEPTIC ULCER DISEASE

Introduction
• Acid-peptic diseases include
o gastroesophageal reflux
o peptic ulcer (gastric and duodenal)

• Mucosal ulcerations arise when aggressive factors (acid, pepsin, bile)

overwhelm the
protective factors(mucus, bicarbonate, prostaglandins, blood flow).

I. AGENTS THAT REDUCE

INTRAGASTRIC ACIDITY

Mechanism of Acid Secretion

• Acid is secreted from gastric parietal cells

• Ach or histamine binds to parietal cell → stimulates protein kinases→ ↑acid

secretion

from a H+,K+ ATPase (the proton pump).

Gastric acid secretion

1. ANTACIDS
• Are weak bases that react with gastric HCl to form a salt and water.
Examples:
a. Sodium bicarbonate
Reacts rapidly with HCl to produce CO2 (causes belching) and NaCl (causes fluid
retention)

b. Calcium carbonate
• Eg. Tums
• Reacts with HCl to form CO2 and calcium chloride (CaCl2).
• Excessive doses given with calcium-containing dairy products can lead to
hypercalcemia,
renal insufficiency, and metabolic alkalosis (milk-alkali syndrome).

c. Magnesium/Aluminium hydroxide
• React slowly with HCl to form magnesium chloride or aluminum chloride
and water.
• No gas is generated thus belching does not occur.
• Unabsorbed magnesium salts may cause an osmotic diarrhea
• Aluminum salts may cause constipation

Drug Interactions
• Antacids may affect absorption of other drugs by binding the drug or by
increasing
intragastric pH so that the drug's dissolution is altered.
• Thus, antacids should not be given within 2 hours of:
o Tetracyclines
o Fluoroquinolones
o Itraconazole
o Iron.

2. H2- RECEPTOR ANTAGONISTS

• Include:
o Cimetidine

o Ranitidine

o Famotidine

o Nizatidine.

Pharmacodynamics

• Competitively inhibit the parietal cell H2 receptor.

• Inhibit 60-70% of 24 hr acid secretion.

Adverse Effects

• Diarrhea, headache, fatigue, myalgia

• Cimetidine may cause gynecomastia
• Rapid IV infusion may cause bradycardia and hypotension through blockade of
cardiac H2 receptors

Drug Interactions

• Cimetidine inhibits hepatic CYP 450 enzymes hence, the half-lives of drugs
metabolized
by these pathways may be prolonged.

3. PROTON PUMP INHIBITORS

• Include:
i. Omeprazole
ii. Lansoprazole
iii. Rabeprazole
iv. Pantoprazole
v. Esomeprazole.

PPIs

• Are available in oral formulations.

• Esomeprazole and pantoprazole also have IV formulations.
• Prodrugs
• Bioavailability ↓d ≈ 50% by food; hence should be given 1 hr before a meal.

• MoA: Form a covalent disulfide bond with the H+,K+ ATPase, irreversibly
inactivating

the enzyme.
.
• Inhibit 90–98% of 24-hour acid secretion.
• PPIs provide faster symptom relief & faster ulcer healing than H2 antagonists.

• Used in triple therapy regimens for eradication of

H.pylori (PPI+Clarithromycin+Amoxicillin
or Metronidazole).
Adverse Effects
• Diarrhea, headache, abdominal pain
• Minor ↓n in Vit. B12 absorption

• May ↓ calcium absorption leading to osteoporosis

II. MUCOSAL PROTECTIVE AGENTS

1. SUCRALFATE

• Is a salt of sucrose complexed to sulfated aluminium hydroxide.

• MoA: The negatively charged sucrose sulfate binds to positively charged proteins
in the

base of ulcers, forming a physical barrier that restricts further caustic damage.

Adverse Effects
• Constipation due to the aluminium salt.

Drug Interactions
• Sucralfate may bind to other medications, impairing their absorption.

2. PROSTAGLANDIN ANALOGS

• Ex. Misoprostol, a methyl analog of PGE1.

• T ½ is < 30 minutes

• Stimulates mucus and bicarbonate secretion and enhances mucosal blood flow.
• Useful in prevention of NSAID-induced ulcers

Adverse Effects
• Diarrhea and abd cramps.

• Stimulates uterine contractions, thus should not be used during pregnancy.

3. BISMUTH COMPOUNDS
• Include:
a) Bismuth subsalicylate
b) Bismuth subcitrate potassium.

Pharmacodynamics

• Bismuth coats ulcers and erosions, creating a protective layer against acid and
pepsin.

• Stimulate PG, mucus, and bicarbonate secretion.

• Bismuth has direct antimicrobial effects against H.pylori and also binds
enterotoxins.

Adverse Effects

• Bismuth causes harmless blackening of the stool & darkening of the

tongue.

• Prolonged use may rarely lead to bismuth toxicity →encephalopathy (ataxia,

headaches,

confusion, seizures)