pharmacology of peptic ulcer disease

1. Peptic ulcer disease
Dr. Haji Bahadar PharmD, PhD
Assistant Professor Khyber
Medical University-Peshawar

2. What is peptic ulcer?
• Peptic ulcers are open sores that develop on
the inside lining of stomach and the upper
portion of small intestine.
• Gastric ulcer: open sores that develop on the
inside lining of stomach
• Duodenal ulcer: open sores that develop on
the inside lining of the upper portion of small
intestine.

4. Causes of peptic ulcer
• Helicobacter pylori bacteria (H. pylori): H. pylori is
the most common cause of gastric and duodenal
ulcers. This bacterium damages the mucus that
protects your stomach and small intestine,
allowing for stomach acid to burn
• nonsteroidal anti-inflammatory drugs (NSAIDs)
• Zollinger-Ellison Syndrome (ZES) is a rare
condition that affects the digestive tract. It’s
characterized by the formation of tumors, called
gastrinomas. Gastrinomas produce excessive
amounts of a hormone called gastrin. Gastrin
triggers an overproduction of gastric acid.
• Stress??:

5. What is Gastrin?
• Gastrin is a peptide hormone that stimulates
secretion of gastric acid (HCl) by the parietal
cells of the stomach and aids in gastric
motility. It is released by G cells in the pyloric
antrum of the stomach, duodenum, and
the pancreas. The G cell is a type of cell in
the stomach and duodenum that
secretes gastrin. G cells are found deep
within the pyloric glands of
the stomach antrum, and in the pancreas.
A gastrinoma is a tumor in the pancreas or duodenum that secretes excess
of gastrin leading to ulceration in the duodenum, stomach and the small
intestine

6. Diagnosis of ZES
• Blood tests. A sample of blood is analyzed
to see elevated gastrin levels. While
elevated gastrin. Serum gastrin levels have a
reference range of 0-100 pg/mL.
• the secretin test is the most sensitive and
specific for the diagnosis of gastrinoma. If
gastrin levels rise 120 pg within 15 minutes of
secretin injection, the test has a sensitivity
and specificity for Zollinger-Ellison syndrome
of greater than 90%.
secretin stimulation test self,

7. The pathophysiology of PG-dependent NSAID-induced
stomach injury
• PGs play a critical role in maintaining
gastric mucosal defense system, the
inhibition of COX leading to decreased
mucosal PGs is considered as the most
important in the pathogenesis of NSAID-
induced gastric damage. Aspirin inhibits
COX irreversibly

10. Complications
• Bleeding (anemia)
• Perforation

11. DIAGNOSIS
• ???????

12. Gastric acid(HCl) production is regulated by
acetylcholine and hormones gastrin and
histamin. They stimulate the parietal cell to
produce gastric acid. Acetylcholine and
gastrin act directly on parietal cells and
indirectly enterochromaffine-like cells(ECL)
to secrete histamin
Gastrin releasing peptide stimulates the release of Gastrin from the G cells of the
stomach.
Regulation of Gastric acid secretion

13. Mechanism of acid secretion

14. Gastric Acid Secretion
 Hydrogen ions generation: Hydrogen ions
are generated from CO2 and H2O to form
H+ and HCO3 ions (carbonic anhydrase)
 Bicarbonate ions are transported out in
exchange for chloride
 Hydrogen ion is pumped out of the cell,
into the lumen, in exchange for potassium
through the action of the proton pump
(H+K+-ATPase pump)

16. Drugs used peptic ulcer
1. Drugs which neutralize acid(Antacids): Antacids neutralize
stomach acids. These drugs typically contain a base such as carbonate or
hydroxide combined with aluminum, magnesium, or calcium. The base
combines with excess hydrogen ions (H) in the stomach and thus
increases the pH

17. 2. Drugs which provide physical barrier
• Sucralfate (Carafate, Sulcrate). Sucralfate is a
disaccharide that exerts a cytoprotective effect
on the stomach mucosa. Sucralfate may form
a protective gel within the stomach that
adheres to ulcers and shields them from the
contents of the stomach.

18. 3. Drugs which decrease acid secretion
1.Proton Pump Inhibitors
• Omeprazole(Risek)
• Esomeprazole (Nexium),
• Lansoprazole
• Rabeprazole
• Pantoprazole
• Dexlansoprazole
2. H2 receptor blockers

19. Histamine stimulates specific receptors on stomach parietal
cells to increase gastric acid secretion. These histamine
receptors are classified as H2 receptors. H2 antagonists, or
blockers, prevent the histamine activated release of gastric
acid.
Side effects:
• headache
• nausea
• diarrhea
• abdominal pain
• dizziness,
• Constipation
• Cimetidine has been associated with gynaecomastia (breast
enlargement in men)and anti androgenic properties.
H2 receptor blockers

20. Mechanism of action of PPIs
• PPIs drug inhibit the H, K -ATPase enzyme
responsible for secreting acid from gastric parietal
cells of the stomach.
• Side effects: The most common side effects of proton pump
inhibitors are:
• Headache.
• Diarrhea.
• Constipation.
• Abdominal pain.
• Flatulence.
• Fever.
• Vomiting.
• Nausea.

21. Treatment of
H. Pylori
bid: bis in die or two times a day
tid:ter in die (three times a
day)
qid:quater in die( four times a
day)
Stat: urgent
sos: si opus sit, if needed