The document discusses anti-ulcer drugs and their pharmacological treatment for peptic ulcer disease (PUD), including the anatomy and physiology of the stomach, types of gastric cells, and the causes and symptoms of peptic ulcers. It details various pharmacotherapy options, such as proton pump inhibitors, H2 receptor antagonists, and agents that enhance mucosal defense, including their mechanisms, therapeutic uses, and potential side effects. Additionally, it highlights the important role of pharmacists in managing PUD through patient education and medication management.

1. Anti-ulcer drugs
By
Pharm. (Mrs) M.M. Terhemen
Department of Pharmacology and Toxicology.
University of Benin.

2. outline
• Introduction
• Peptic ulcer
• Pharmacological treatment of peptic ulcer
• Role of pharmacist

3. Introduction
Digestive system
Stomach
• The stomach is a j-shaped
organ that digest food.
• The stomach sits on the
upper abdomen on the left
side of the body.
• The stomach expands when
full and deflates when
empty.
• Various cells in the stomach
secrete digestive enzymes
and hydrochloric acid to
break down food so the
body can absorb nutrients.

5. Types of cells in the stomach
• Surface mucous cells (foveolar cells): These cells secrete a
thick layer of mucus that covers the stomach lining and
protects it from the digestive juices.
• Parietal cells: They secrete intrinsic factor and hydrochloric
acid (HCl) via the gastric hydrogen potassium ATPase
pump. HCl breaks down food and kills bacteria and other
microorganisms that may be present in food.
• Chief cells: Secretes pepsinogen, which is converted to
pepsin in the presence of HCl to digest proteins.
• neuroendocrine cells:

6. Neuroendocrine cells
• G-cells: produce gastrin (hormone) that increase hydrochloric
acid production by stimulating ECL-like cells to release
histamine.
• ECL-like cells: These cells secrete histamine that increase HCl
production.
• D-cells: secrete an inhibitory molecule called somatostatin that
suppresses gastrin and the overall production of gastric acid.
• EC-cells: secrets serotonin that is involved in regulating
gastrointestinal motility and fluid secretion.
• P/D1 cells: secrete ghrelin (hunger hormone) that increases
appetite and promotes fat storage.

7. Gastric secretions
• The fluid secreted into the stomach is called gastric
juice or gastric acid.
• gastric juice consists of inorganic and organic
constituents together with water.
• Among the important components of gastric juice
are HCl, salts, intrinsic factor, pepsins, mucus, and
bicarbonate.
• Gastric acid secretion is a complex and continuous
process.
• Acid secreting cells in the stomach are called
parietal cells.

8. Gastric secretions contd…
• Gastric acid can be stimulated in response to the site,
smell, taste, or anticipation of food.
• The three stimulants of gastric acid secretion likely to
have physiological roles in regulation of the secretion
are acetylcholine, gastrin, and histamine.
• Somatostatins and prostaglandins (PGE2 and PGI2)
inhibit gastric acid secretion from parietal cells.
• Gastric hydrogen potassium ATPase, also known
as H+
/K+
ATPase, is an enzyme which functions to
acidify the stomach, found in parietal cells.

9. Functions of the stomach
• Storage i.e temporary reservoir for food.
• Secretion of H+ to kill microorganisms and convert
pepsinogen to pepsin.
• Secretion of intrinsic factor to absorb vitamin B12
(cobalamin).
• Secretion of mucus and bicarbonate to protect the gastric
mucosa
• Secretion of water for lubrication and to provide aqueous
suspension of nutrients
• Motor activity for mixing secretions (H+ and pepsin) with
ingested food
• Coordinated motor activity to regulate the emptying of
contents into the duodenum

11. Conditions that can affect the stomach
• Gastritis: Stomach inflammation.
• Gastroesophageal reflux disease
(GERD): When stomach contents travel up to the
esophagus, causing heartburn or coughing.
• Gastroparesis: Nerve damage that affects the
stomach’s muscle contractions.
• Indigestion (dyspepsia): causes discomfort, pain or
burning in the upper stomach.
• Peptic ulcer disease: Ulcers (sores) in either the
stomach or the first portion of the small intestine
(duodenum).
• Stomach cancer: Occurs when cancerous cells grow
uncontrollably in the stomach.

12. Peptic Ulcer disease (PUD)
• Peptic ulcers are open sores that develop on
the inside lining of the stomach and the
proximal portion of the small intestine.

13. Signs and symptoms
• Burning stomach pain
• Feeling of fullness, bloating or belching
• Intolerance to fatty foods
• Heartburn
• Nausea
• Vomiting or vomiting blood — which may appear red or black
• Dark blood in stools, or stools that are black or tarry
• Trouble breathing
• Feeling faint
• Unexplained weight loss
• Appetite changes

14. Causes of peptic ulcers

15. Helicobacter pylori
• H. pylori, a gram-negative, helical, rod-shaped
bacterium, colonizes the gastric mucosa.
• H. pylori is present in 95% of patients with
duodenal ulcers and in 70% of those with
gastric ulcers.
• It is typically transmitted via the fecal-oral
route

17. Diagnosis of peptic ulcer
Physical examination
• check for swelling in the abdomen.
• tap on the abdomen to check for tenderness or pain.
Blood test
• To check for signs of H. pylori infection.
Urea breath test
• If H. pylori is present, the bacteria will convert
swallowed urea capsule labelled with carbon atom into
carbon dioxide that is exhaled after few minutes. If the
carbon atom is detected in the exhaled breath, it
signifies the presence of H. pylori.

18. Diagnosis of peptic ulcer contd…
Stool test
Upper gastrointestinal (GI) endoscopy and biopsy
• Endoscope (a flexible tube with a camera) is used
to see the lining of the upper GI tract, including
the esophagus, stomach, and duodenum.
Upper GI series
• X-ray and a chalky liquid that is swallowed
(barium) is used to view the upper GI tract.

19. Pharmacotherapy of peptic ulcer
Goal of therapy
• To decrease gastric acidity.
• To enhance mucosal defence
The drugs are;
• Proton pump inhibitors
• H2 receptor antagonist
• Agents that enhance mucosal defence
• Antacids
• Others e.g simethicone, antibiotics, antispasmodic such as
buscopan, anticholinergics such as pirenzepine, etc

20. Proton pump inhibitors (PPIs)
• Omeprazole, esomeprazole, lansoprazole,
dexlansoprazole, rabeprazole, pantoprazole.
Mechanism of action
• Blocks gastric acid secretion by irreversibly binding
to and inhibiting the hydrogen/potassium adenosine
triphosphate enzyme system (H⁺/K⁺ ATPase or
proton pump) that resides on the luminal surface of
the parietal cell membrane in the stomach.

21. PPIs
Therapeutic uses
• Gastric and duodenal ulcer
• Used together with anti-biotics to eradicate
Helicobacter pylori
• NSAID induced ulcer
• Gastric oesophageal reflux disease (GERD)
• Zollinger-Ellison syndrome
• Dyspepsia

22. PPIs
Adverse effects
• Nausea, vomiting, abdominal pain, constipation,
flatulence, diarrhoea, headache, skin rash, itching.
Pharmacokinetic
• The rate of absorption is decreased by concomitant
food intake. Take on an empty stomach.

23. H2 receptor antagonist
• Cimetidine, ranitidine, famotidine, nizatidine
Mechanism of action
• Reversibly compete with histamine for binding
on H2 receptors on the basolateral membrane
on parietal cells in the stomach.

24. H2 receptor antagonist
Therapeutic uses
• Promotes the healing of gastric and duodenal ulcer
• Uncomplicated GERD
• Prevents the occurrence and reoccurrence of stress
induced ulcer
• Dyspepsia
Adverse effects
• Diarrhoea, constipation, fatigue, muscular pain,
headache.
• CNS effects such as slurred speech, hallucination,
confusion are less common.

25. Agents that enhance mucosal defence
a. Misoprostol:- synthetic analogue of prostaglandin E1
(PGE1).
Replaces prostaglandins that are inhibited by NSAIDs
Mechanism of action
• Binds to EP3 receptors on parietal cells and stimulates
the Gi pathway thereby decreasing intracellular cAMP to
decrease gastric acid secretion.
• Stimulation of mucin and bicarbonate secretion and
mucosal blood flow to prevent gastric injury.

26. Misoprostol
Therapeutic uses
• Inhibit basal acid secretion
Adverse effects
• Diarrhoea with or without cramps, can
increase uterine contraction

27. Agents that enhance mucosal defence
b. Sucralfate:- This is a sulfated polysaccharide to
which aluminium hydroxide was added.
Mechanism of action
• Inhibits mucosal hydrolysis by pepsin by forming
a vicious sticky polymer that adhere to epithelial
cells and ulcer crates.
• Stimulates the production of PGs and epidermal
growth factors.

28. Sucralfate
Therapeutic uses
• Stress induced ulcer
• Duodenal ulcer
Adverse effects
• constipation

29. Agents that enhance mucosal defence
c. Bismuth
This agent has multiple ulcer-healing mechanisms
• antibacterial activity against H pylori, inhibition of
pepsin activity, and the increase of prostaglandin,
mucus, and bicarbonate production.
Adverse effects
• blackened tongue and stools

30. Antacids
• Sodium bicarbonate, calcium carbonate,
aluminium hydroxide, magnesium hydroxide
Mechanism of action
• Acid neutralization
Therapeutic uses
• Gastric acid reflux, laxative, diarrhoea

31. Antacids
Adverse effects
• Carbonate containing antacids may cause belching,
nausea, abdominal distension, and flatulence.
• Calcium can induce rebound acid secretion.
• Magnesium hydroxide can cause diarrheoa because
magnesium acts rapidly.
• Aluminium hydroxide can cause constipation because
aluminium is slow reacting.
Note: To achieve a balanced acid neutralizing effect, it is
better to combine aluminium and magnesium
hydroxide together.

32. Antibiotics
• Amoxicillin, clarithromycin, metronidazole, and tetracycline all
have antimicrobial activity against H. pylori.
• Amoxicillin is a beta-lactam antibiotic that inhibits bacterial
cell wall synthesis, resulting in bactericidal activity against
susceptible organisms.
• Clarithromycin is a macrolide antibiotic that binds to the 50S
ribosomal subunit of susceptible organisms, inhibiting RNA-
dependent protein synthesis and resulting in bacteriostatic
activity.
• Metronidazole is a nitroimidazole antibiotic that disrupts the
helical DNA structure and causes strand breakage, leading to
inhibition of protein synthesis and cell death of susceptible
organisms. It is also considered bactericidal.

35. Role of pharmacist
Pharmacists play an important role in the
management of patients with PUD.
• Provide patient education and emphasizing the
importance of adherence .
• Review medication history and make
recommendations for appropriate antibiotic and
NSAID use.
• Counseling on proper administration of drug
therapy.