antiulcer agents include all the drugs in ulcer treatmewnt with etiology and pathophsilogy and also acid secretrion and regulation of acid

1. Antiulcer drugs
PREPARED BY: SONAL PANDE
MPHARM.SEM1
DEPARTMENT: PHARMACOLOGY

2. Definition
 Ulcers are defined as a breach in the
mucosa of the alimentary tract, which
extends through the mucosa into sub
mucosa or deeper muscle.
 Peptic ulcers are chronic most often
solitary that occur in any portion of
gastrointestinal tract exposed to the
aggressive action of acid-peptic juices.

3. Acid secretion in stomach

4. Phases of gastric acid secretion

5. Regulation of Gastric acid secretion from
paritel cells

7. Region/
Location
Modified Johnson Classification of peptic
ulcers
Stomach
Duodenum
Esophagus
Meckel's Diverticulum ulcer
Type I: Ulcer along the body of the stomach,
most often along the lesser curve at incisura
angularis
Type II: Ulcer in the body in combination
with duodenal ulcers. Associated with acid
over secretion.
Type III: In the pyloric channel within 3 cm of
pylorus. Associated with acid over secretion.
Type IV: Proximal gastro-esophageal ulcer
Type V: Can occur throughout the stomach.
Associated with chronic NSAID and ASA use.

8. Sign and symptoms
 Abdominal pain, classically epigastric with severity relating to mealtimes, after around 3 hours
of taking a meal (duodenal ulcers are classically relieved by food, while gastric ulcers are
exacerbated by it);
 Bloating and Abdominal fullness;
 Waterbrash (to pour back of watery acid from the stomach);
 Nausea, and Vomiting;
 Loss of appetite and weight loss;
 Hematemesis (vomiting of blood); this can occur due to bleeding directly from a gastric ulcer, or
from damage to the esophagus from severe/continuing vomiting.
 Melena (tarry, foul-smelling feces due to oxidized iron from hemoglobin);
rarely, an ulcer can lead to a gastric or duodenal perforation, which leads to acute peritonitis. This
is extremely painful and requires immediate surgery.

10. ETIOLOGY AND RISK FACTORS
Aggressive factors
 Helicobacter pylori: Gram negative bacteria, can live in stomach and duodenum, may
breakdown mucus layer => inflammatory response to presence of the bacteria also produces
urease – forms CO2 and ammonia which are toxic to mucosa.
 Gastric Acid: needs to be present for ulcer to form => activates pepsin and injures mucosa
Decreased blood flow: causes decrease in mucus production and bicarbonate synthesis, promote
gastric acid secretion
 NSAIDS: inhibit the production of prostaglandins, These hormone-like substances help
protect stomach lining from chemical and physical injury and inhibit acid secretion
 Smoking: nicotine stimulates gastric acid production.
 Excessive alcohol consumption:
Alcohol can irritate and erode the mucous lining of stomach and increases the amount of stomach
acid that's produced.
 Stress :
Stress may aggravate symptoms of peptic ulcers and, in some cases, delay healing.

11. DEFENSIVE FACTORS
Mucus : The stomach produces a lubricant-like mucus that
coats the stomach and shields stomach tissues.
Bicarbonate : The stomach can produce a chemical called
bicarbonate that neutralizes digestive fluids and breaks them
down into less harmful substances.
Blood circulation in the lining of the stomach, as well as cell
renewal and repair, help protect the stomach.

12. PATHOPHYSIOLOGY
 Role of H. Pylori infection in the pathogenesis of peptic ulcer:
 H. pylori survive, close to the stomach's epithelial cell layer.
It produces adhesins which bind to membrane- associated lipids and carbohydrates and help it
adhere to epithelial cells.
 H. pylori produces large amounts of the enzyme urease.
 Urease breaks down urea to carbon dioxide and ammonia.
 The ammonia is converted to ammonium by taking a proton (H+) from water, which leaves
only a hydroxyl ion.
 Hydroxyl ions then react with carbon dioxide, producing bicarbonate, which neutralizes gastric
acid.
 The survival of H. pylori in the acidic stomach is dependent on urease.
 The ammonia produced is toxic to the epithelial cells, and, along with the other products of H.
pylori—including proteases, vacuolating cytotoxin A (VacA), and certain
phospholipases—damages those cells

13. NSAIDS

14. DIAGONOSIS
 Upper gastrointestinal (GI) series -- You will drink a chalky liquid called
barium and then undergo a series of x-rays to check for an ulcer.Endoscopy –
The doctor will carefully insert a thin tube with a tiny camera at the end
(called an endoscope) down your throat, through the esophagus to the
stomach and duodenum. The endoscope lets the doctor examine your
digestive tract and take a sample of tissue to test for H. pylori, if needed.
Laboratory tests
 Gastric acid secretory studies
 Tests for Helicobacter pylori
a blood test checking for antibodies to this organism,
a breath test after drinking a substance called urea, and
a stool test looking for the bacteria.
Other diagnostic tests

15. TREATMENT
1.Reduction of gastric acid secretion
(a)H2 antihistamines: Cimetidine, Ranitidine, Famotidine, Roxatidine
(b) Proton pump inhibitors: Omeprazole, Esomeprazole, Lansoprazole,
Pantoprazole, Rabeprazole, Dexrabeprazole
(c) Anticholinergic drugs: Pirenzepine, Propantheline, Oxyphenonium
(d) Prostaglandin analogue: Misoprostol
2.Neutralization of gastric acid (Antacids)
(a) Systemic: Sodium bicarbonate, Sod. citrate
(b) Nonsystemic: Magnesium hydroxide, Mag. trisilicate, Aluminium hydroxide
gel, Magaldrate, Calcium carbonate

16. 3.Ulcer protectives: Sucralfate, Colloidal bismuth
subcitrate (CBS)
4. Anti-H. pylori drugs: Amoxicillin, Clarithromycin,
Metronidazole, Tinidazole, Tetracycline

17. H2 BLOCKERS
MECHANISM OF ACTION
 Cimetidine and all other H2 antagonists block histamine-induced gastric
secretion
 H2 receptor antagonists inhibit acid production by reversibly competing
with histamine for binding to H2 receptors on the basolateral membrane of
parietal cells
 Block histamine from stimulating the acid-secreting parietal cells of the
stomach.
 Reversible competitive inhibitors of H2 receptor.
 Highly selective for H2 receptors.
 Very effective in inhibiting nocturnal acid secretion ( as it depends largely
on Histamine )

18. Comparison of H2 blockers
Cimetidine Ranitidine Famotidine Nizatidine
Bioavailibility 80 50 40 >90
Relative
potency
1 5-10 32 5-10
Half life(hrs) 1.5-2.3 1.6-2.4 2.5-4 1.1-1.6
Duration of
action(hrs)
6 8 12 8
Dose 400 150 20 400
Inhibiton of
CYP 450
1 0.1 0 0

19. Pharmacokinetics
 Absorbed rapidly and completely except for famotidine; food and antiacids may
reduce absorption; distributed widely throughout the body; metabolized by the
liver; excreted primarily in the urine.
• cimetidine RanitidineBioavailability 80 50Relative Potency 1 5 -10Half life (hrs)
1.5 - 2.3 1.6 - 2.4Duration of 6 -8action (hrs)Inhibition of 1 0.1CYP 450Dose
mg(bd) 400 150
 Used therapeutically to:
1. Promote healing of duodenal and gastric ulcers.
2. Provide long-term treatment of pathological GI hypersecretory conditions.
3. Reduce gastric acid production and prevent stress ulcers.
Therapeutic Uses

20. Adverse effect
Headache, Dizziness, Bowel upset, Cimetidine causes gynecomastia,
galactorrhea(as it is antiandrogenic & increases prolactin level)
Interaction
Inhibits CYP-450 leads to inhibits the metabolism of many drugs so that they
accumulate to toxic level. e.g. theophylline, warfarin, phenytoin, quinidine.
Contraindication
Renal impairment Hepatic failure

21. Proton Pump Inhibitors (PPIs)
 Disrupt chemical binding in stomach cells to reduce acid production,
lessening irritation and allowing peptic ulcers to heal.
 These drugs include:Omeprazole Rabeprazole Pantoprazole
Lansoprazole Esomaprazole
MECHANISM OFACTION OF PPIs.
 Block the last step in the secretion of gastric acid by combining with
hydrogen, potassium, and adenosine triphosphate in the parietal cells of
the stomach.
 Most effective drugs in antiulcer therapy. Irreversible inhibitor of H+ K+
ATPase to apical membrane of the parietal cell.

22.  Prodrugs requiring activation in acid environment.
 React covalently with –SH groups of the H+ K+ ATPase enzyme.
 Weakly basic drugs & so accumulate in canaliculi of parietal cell.
 Activated in canaliculi & binds covalently to extracellular domain of
H+ K+ ATPase.
 Acid secretion resumes only after synthesis of new molecules.
Pharmacokinetic:
Bioavailability : ~50% (instability at acidic pH)
Metabolism : In Liver (CYP2C19 and CYP3A4).
Excretion : Metabolites excreted through renally
Onset action : ½-1 hour
Duration of action : 24 hours
Adverse effect: Hepatic dysfunction, Dizziness, Nausea, Headache.
Interaction: Inhibits oxidation of certain drugs : diazepam, phenytoin,
warfarin

23. These are the basic substances which neutralize gastric acidity.
Acid neutralizing capacity:
no.of mEq of 1N HCl that brought to pH 3.5 in 15 min. by a unit dose of
the antacid preparation.
Systemic antacid :
 Sodium bicarbonate, water soluble, acts i.v. duration of action is short.
 Potent neutralizer, pH may rises above 7.
 Produces CO2 in stomach leads to distention, discomfort.
 Increases sodium load leads to worsen in CHF with edema.
 Large dose produces alkalosis.
ANTACID

24. Characteristic of antacid
Features Sodium
bicarbonate
Calcium Magnesium
hydroxide
Aluminum
hydroxide
Onset of action Rapid Intermediat
e
Rapid Slow
Duration of
action
Short Moderate Moderate Moderate
Systemic
alkalosis
Yes - No No
Effect on stool - Constipatio
n
Laxative Constipatio
n

25. Non-systemic antacid:
These are insoluble and poorly absorbed basic compound. React in
stomach with acid to form respective chloride salts. This again reacts
with bicarbonate is not spared for absorption, hence no acid –base
disturbance.
Aluminium hydroxide gel:
The Al+³ ions relaxes smooth muscle leads to delay in gastric
emptying. This causes constipation. Mucosal astringent reaction also
leads to constipation.

26. ULCER PROTECTIVES – SUCRALFATE
 Sucralfate is aluminum salt of sucrose octasulfate.
 In an acid environment(pH <4), some of aluminum ions dissociate and the
resulting negative charged molecules polymerize to from a viscous paste like
substance;
 This substance adheres strongly to gastric and duodenum mucosa and adhere
even more strongly to partially denatured proteins such as those found at the
basal of ulcer.
 This compound does not decrease the concentration or total amount of acid in
the stomach ; it protects the gastric and duodenal mucosa from the acid/pepsin
attack.

27. Since it is activated by acid, sucralfate should be taken on an empty
stomach 1 hour before meals.
The use of antacids within 30 minutes of a dose of sucralfate should be
avoided.
The usual dose of sucralfate is 1 g four times daily (for active duodenal
ulcer) or 1 g twice daily (for maintenance therapy).

28. Anti H.pylori drugs
Amoxicillin, clarithromycin, metronidazole.
Single drugs rapidly develops resistance (metronidazole).

29. Combination must be used
Bismuth (PeptoBismol®) – disrupts cell wall of H. pylori
• Clarithromycin – inhibits protein synthesis
• Amoxicillin – disrupts cell wall
• Tetracyclin – inhibits protein synthesis
• Metronidazole – used often due to bacterial resistance to
amoxicillin and tetracyclin, or due to intolerance by the patient
Standard treatment regimen for peptic ulcer:
Omeprazole + amoxicillin + metronidazole