PHARMA L1

PEPTIC ULCER DISEASE

Gastric ulcer an ulcer in the stomach.
Duodenal ulcer an ulcer in the first part of the intestine.

THE MOST COMMON SYMPTOMS:

- Upper abdominal pain (epigastric pain)

- Belching.
- Vomiting.
- Poor appetite and Weight loss.
Complications may include
- Bleeding and perforation of the stomach

CAUSATIVE FACTORS ARE RECOGNIZED:

- Infection with gram-negative Helicobacter pylori.

- Use of nonsteroidal anti-inflammatory drugs (NSAIDs).
- Increased HCl secretion.
- Tumors (rare)
Zollinger–Ellison syndrome (Tumor increases gastrin→↑ Hcl)
- Inadequate mucosal defense against gastric acid.

TREATMENT APPROACHES INCLUDE:

1. Eradicating the H. pylori infection (Antimicrobial agents)

2. Reducing secretion of gastric acid (PPIs or H2-receptor antagonists).
3. Protect the gastric mucosa from damage (misoprostol and sucralfate).
4. Neutralizing gastric acid (antacids).

A- ANTIMICROBIAL AGENTS
To document infection with H. pylori:
- Endoscopic biopsy of the gastric mucosa.
- Serologic tests.
- Urea breath tests
Triple therapy
(PPI + either metronidazole or amoxicillin + clarithromycin).
Quadruple therapy
(PPI + metronidazole + bismuth subsalicylate+ tetracycline )
 They are administered for a 2-week course.
  Treatment with a single antimicrobial drug is less effective, results in antimicrobial
resistance, and is absolutely not recommended

B- H2-RECEPTOR ANTAGONISTS

1. Cimetidine
2. Ranitidine
3. Famotidine
4. Nizatidine
 The use of these agents has decreased with the advent of PPIs.

Therapeutic uses :
a. Peptic ulcers :
All four agents are equally effective in promoting the healing of duodenal and gastric
ulcers.
b. Acute stress ulcers : These drugs are typically given as an intravenous infusion
c. Gastroesophageal reflux disease (GERD) :
Cimetidine is the prototype H2-receptor antagonist.
However, its utility is limited by its adverse effect and drug–drug interactions.

C. PPIS: INHIBITORS OF THE H+/K+-ATPASE PROTON PUMP

 ( ---prazole )
- Omeprazole and lansoprazole
are available over the counter for short-term treatment of GERD.
- Dexlansoprazole
- Esomeprazole.
- Pantoprazole
- Rabeprazole

Therapeutic uses
- The PPIs are superior to the H2 antagonists in suppressing acid production and
healing ulcers.
- They are the preferred drugs for the treatment of GERD, erosive esophagitis,
duodenal ulcer, and Zollinger-Ellison syndrome.
- PPIs reduce the risk of bleeding
- PPIs are also used for stress ulcer prophylaxis and management.
- Finally, PPIs are combined with antimicrobial regimens used to eradicate H. pylori.

For maximum effect, PPIs should be taken 30 to 60 minutes before

breakfast or the largest meal of the day.
D. PROSTAGLANDINS

Prostaglandin E, produced by the gastric mucosa:

1. Inhibits secretion of HCl .
2. Stimulates secretion of mucus and bicarbonate (cytoprotective effect).

A deficiency of prostaglandins is thought to be involved in the pathogenesis of peptic

ulcers.

Misoprostol :
- Analog of prostaglandin E1.
- Used for the prevention of gastric ulcers induced by NSAIDs

Although misoprostol has cytoprotective actions, it is clinically effective only at higher doses
that diminish gastric acid secretion.

Like other prostaglandins, misoprostol produces uterine contractions, dislodging

of the fetus, and is contraindicated during pregnancy.

E. ANTACIDS

- Antacids are weak bases that react with gastric acid to form water and a salt to
diminish gastric acidity.
- Antacids also reduce pepsin activity.

Commonly used antacids such as:

1- Aluminum hydroxide ( Al(OH)3 )
2- Magnesium hydroxide [ Mg(OH)2 ].
3- Combination of ( Al(OH)3 ) + [ Mg(OH)2 ].
4- Calcium carbonate [CaCO3] + HCl → CO2 + CaCl2
5- Sodium bicarbonate [NaHCO3]
 Systemic absorption of sodium bicarbonate [NaHCO3]→metabolic alkalosis.
Therefore, this antacid is not recommended for long-term use.

Therapeutic uses:
1- Aluminum- and magnesium-containing antacids are used for symptomatic relief of
peptic ulcer disease and GERD, and they may also promote healing of duodenal
ulcers.
2- 2- [Note: Calcium carbonate preparations are also used as calcium supplements for
the treatment of osteoporosis.]
Adverse effects:
- Aluminum hydroxide → constipation.
- magnesium hydroxide → diarrhea.
(Preparations that combine these agents aid in normalizing bowel function)
The binding of phosphate by aluminum-containing Antacids → hypophosphatemia.
- sodium bicarbonate → systemic alkalosis AND liberates CO2, causing flatulence.

F. MUCOSAL PROTECTIVE AGENTS

1. Sucralfate:
- complex of aluminum hydroxide + sulfated sucrose .
- binds to positively charged groups in proteins of both normal and necrotic mucosa.
- It also stimulates prostaglandin release as well as mucus and bicarbonate output,
- and it inhibits peptic digestion

sucralfate effectively heals duodenal ulcers

sucralfate should not be administered with : PPIs, H2 antagonists, or antacids.
2. Bismuth subsalicylate:
- Preparations of this compound effectively heal peptic ulcers.
- In addition to their antimicrobial actions.
- They inhibit the activity of pepsin.
- increase secretion of mucus.
- interact with glycoproteins in necrotic mucosal tissue to coat and protect the ulcer
crater.