1. Dr.M.Krishna Vasudev Dept of General Medicine Peptic Ulcer
Disease
2. Peptic Ulcer Disease Condition characterized by Erosion of
GI mucosa resulting from digestive action of HCl and pepsin
3. Peptic Ulcer Disease Ulcer development Lower esophagus
Stomach Duodenum 10% of men, 4% of women
4. Types Acute Superficial erosion Minimal erosion Chronic
Muscular wall erosion with formation of fibrous tissue Present
continuously for many months or intermittently
5. Peptic Ulcers: Gastric & Dudodenal
6. Classification Stomach (called gastric ulcer) Duodenum
(called duodenal ulcer) Oesophagus (called Oesophageal ulcer) Types
of Gastric ulcer(Modified johnson criteria): Type I: Ulcer along
the lesser curve of stomach Type II: Two ulcers present - one
gastric, one duodenal Type III: Prepyloric ulcer Type IV: Proximal
gastroesophageal ulcer Type V: Anywhere(NSAID induced)
7. Gastric Ulcers Commonly found on lesser curvature in close
proximity to antral junction Less common than duodenal ulcers
Prevalent in women, older adults, persons from lower socioeconomic
class
8. Gastric Ulcers Characterized by A normal to low secretion of
gastric acid Back diffusion of acid is greater (chronic)
9. Gastric Ulcers Critical pathologic process is amount of acid
able to penetrate mucosal barrier H. pylori is present in 50% to
70%
10. Gastric Ulcers H. pylori is thought to be more destructive
when noxious agents are used, or patient smokes
11. Gastric Ulcers Drugs can cause acute gastric ulcers
Aspirin, corticosteroids, NSAIDs, reserpine Or known causative
factors Chronic alcohol abuse, chronic gastritis
12. Duodenal Ulcers Occur at any age and in anyone Between ages
of 35 to 45 years Account for ~80% of all peptic ulcers
13. Duodenal Ulcers Associated with HCl acid secretion H.
pylori is found in 90-95% of patients Direct relationship has not
been found
14. Duodenal Ulcers Diseases with risk of duodenal ulcers COPD,
cirrhosis of liver, chronic pancreatitis, hyperparathyroidism,
chronic renal failure Treatments used for these conditions may
promote ulcer development
15. Peptic Ulcer Disease Clinical Manifestations Common to have
no pain or other symptoms Gastric and duodenal mucosa not rich in
sensory pain fibers Duodenal ulcer pain Burning, cramplike Gastric
ulcer pain Burning, gaseous
16. SYMPTOMS An early sense of fullness with eating frequent
burping or hiccupping Stomach pain wakes you up at night low blood
cell count (anemia) Blood in the stools Vomiting Melena Appetite
changes hematemesis (vomiting of blood) Unexplained weight loss
Water brash Nausea Bloating Burning pain
17. DUODENAL ULCER Classic symptoms of a duodenal ulcer include
burning, gnawing, aching, or hunger-like pain, primarily in the
upper middle region of the abdomen below the breastbone (the
epigastric region). Pain may occur or worsen when the stomach is
empty, usually two to five hours after a meal. Symptoms may occur
at night between 11 PM and 2 AM, when acid secretion tends to be
greatest. Feel better when you eat or drink and then worse 1 or 2
hours later (duodenal ulcer) GASTRIC ULCER Symptoms of a gastric
ulcer typically include pain soon after eating. Symptoms are
sometimes not relieved by
18. Peptic Ulcer Disease Complications 3 major complications
Hemorrhage Perforation Gastric outlet obstruction Initially treated
conservatively May require surgery at any time during course of
therapy
19. Peptic Ulcer Disease Diagnostic Studies Endoscopy procedure
most often used Determines degree of ulcer healing after treatment
Tissue specimens can be obtained to identify H. pylori and to rule
out gastric cancer
20. Peptic Ulcer Disease Diagnostic Studies Tests for H. pylori
Noninvasive tests Serum or whole blood antibody tests Immunoglobin
G (IgG) Urea breath test Invasive tests Biopsy of stomach Rapid
urease test
21. Peptic Ulcer Disease Diagnostic Studies Barium contrast
studies Widely used X-ray studies Ineffective in differentiating a
peptic ulcer from a malignant tumor
22. Peptic Ulcer Disease Diagnostic Studies Gastric analysis
Identifying a possible gastrinoma Determining degree of gastric
hyperacidity Evaluating results of therapy
24. AIMS OF ULCER TREATMENT Promotion of ulcer healing.
Symptomatic relief of pain. Prevention of recurrence (relapse).
Prevention of complications
25. DRUG TREATMENT OF PEPTIC ULCER I. Gastric hyposecretory
drugs. H2 receptor blockers Muscarinic receptor blockers Proton
pump inhibitors II. Eradication of H. pylori infections To prevent
relapse
26. DRUG TREATMENT OF PEPTIC ULCER III. Mucosal cytoprotective
agents. Sucralfate Colloidal bismuth Prostaglandin analogues IV.
Neutralizing agents (antacids).
27. Gastric hyposecretory drugs H2 receptor blockers Muscarinic
receptor blockers Proton pump inhibitors Decreasing gastric acidity
can reduce absorption of ketoconazole & iron preparation,
digoxin.
28. Proton Pump Inhibitors Mechanism of action Irreversible
inhibition of proton pump (H+/ K+ ATPase) that is responsible for
final step in gastric acid secretion from the parietal cell. PP
inhibitors include: Omeprazole Lansoprazole Pantoprazole
Esomeprazole
29. Illustration of Gastric secretion by parietal cells
30. Pharmacokinetics: They are prodrugs taken orally. are given
as enteric coated capsules They are rapidly absorbed from the
intestine. They are activated in the acidic medium of the secretory
parietal cell canaliculus. They are inactivated if (combined with
H2 receptor blockers).
31. Have long duration of action (> 12 h-24 h). Once daily
dose is sufficient Bioavailability is reduced by food. Given 1 h
before meal. Are metabolized in the liver by CytP450. They are more
potent than H2 receptor blockers Inhibits basal and stimulated-acid
secretion. Dose reduction is required in severe liver failure.
32. USES 1. Zollinger Ellison syndrome (First choice). 2.
Resistant severe peptic ulcer ( 4-8 weeks). 3. Reflux esophagitis.
4. Eradication of H. pylori.
34. H2 receptor blockers Mechanism of action They competitively
and reversibly block to H2 receptors on the parietal cells thus
reduce gastric secretion. They include: Cimetidine Ranitidine
Famotidine Nizatidine
35. Pharmacokinetics Good oral absorption Plasma half life (1-3
h). Duration (4-12 h). First pass metabolism (50% Except Nizatidine
100 % bioavailability). Given before meals. Metabolized by liver.
Excreted mainly in urine. Cross placenta & excreted in
milk
38. Adverse Effects of H2 blockers: 1. GIT disturbances:
nausea, vomiting 2. CNS effects: Headache, dizziness, confusion
(elderly renal or hepatic dysfunction). 3. CVS effects Bradycardia
and hypotension (rapid I.V.)
39. Cimetidine has other adverse effects: 4. Endocrine effects
Antiandrogenic actions (gynecomasteia impotence) Galactorrhea in
women. 5. Cytochrome P450 inhibitor: decrease metabolism of oral
anticoagulant, phenytoin, benzodiazepines.
40. Precautions 1. Maintenance dose (Relapse may occur). 2.
Dose reduction in severe renal or hepatic failure and elderly.
41. ANTICHOLINERGIC DRUGS 1. Non selective muscarinic blockers:
Oxyphenonium, dicyclomine Decreased gastric motility Delayed
gastric emptying - Heart burn - Atropine like side effects.
42. 2. Selective muscarinic blockers: Pirenzepine - Telenzepine
Blocks M1 receptors on the parietal cells. Selectively inhibit
gastric acid secretion No effect on gastric motility Less side
effects of cholinergic blockade. No effect on CNS. Dose : 50 mg bid
for 4-6 weeks Uses 1.Adjuvants to H2 receptor blockers. 2. decrease
nocturnal pain in peptic ulcer.
43. Eradication Of H Pylori Is a bacteria that causes chronic
inflammation of the inner lining of the stomach. Produce enzymes
(tissue damage), inflammation ulcer. Duodenal ulcer - Gastric ulcer
Risk factor for esophagus and stomach cancers. Eradication is
important to prevent recurrence of ulcer.
44. Helicobacter pylori in association with gastric mucosa
45. Treatment Combined therapy is usually used. Clarithromycin,
tetracycline, amoxicillin Proton pump inhibitors or H2 receptor
blockers. Bismuth compounds Metronidazole. Resistance may develop
to antibiotics. Better eradication is obtained using proton pump
inhibitors & clarithromycin.
46. Treatment The standard first-line therapy is "triple
therapy" consisting of proton pump inhibitors as omeprazole and the
antibiotics clarithromycin and amoxicillin.
49. Sucralfate Sucrose octaphosphate + aluminium hydroxide
Mechanism of action 1. In acidic pH, sucralfate dissociates into
its components. 2. The negatively charged sucrose octaphosphate
binds with positively charged protein molecules found in damaged
mucosa (Coat over the ulcer). 3. Promote ulcer healing. 4.
Inhibition of pepsin.
50. 3. Stimulation of mucosal protective mechanisms (mucous and
bicarbonates secretion). Kinetics Orally, poor systemic absorption.
Duration (6 h). Excreted in feces. Avoid co-administration of
antacid or H2 blocker. Bette taken on empty stomach.
51. Therapeutic Uses Benign gastric and duodenal ulcer. Chronic
gastritis. Adverse effects Constipation and dry mouth. Interferes
with absorption of some drugs tetracycline, theophyline, Tricyclic
antidepressant.
52. 2. Misoprostol Prostaglandin Analogues (PGE1 ) HCL
secretion. Promote tight junction of gastric cells prevent back
diffusion of HCL. mucous and bicarbonate secretion. blood flow of
mucosa improve healing of ulcer. Kinetics Orally, 30 min. is
converted into active metabolite. Excreted in urine- must be taken
3-4 times/day.
54. 3. Colloidal Bismuth compounds Bismuth subcitrate
Tripotassium dicitrato bismuthate. Mechanism of Action 1. It forms
a precipitate with mucous cover the ulcer with a protective coat
that prevent effect of HCl. 2. Promote healing of ulcer. 3.
Bactericidal effect against campylobacter pylori . 4. Decrease
activity of pepsin 5. Mucous & bicarbonate secretion.
55. Adverse Effects 1. Black stool. 2. Teeth discoloration. 3.
Encephalopathy (in renal dysfunction). USES 1. Triple therapy for
eradication of H. pylori. 2. Benign gastric & duodenal ulcer.
3. Travellers diarrhea
56. Drugs That Neutralize HCL (Antacids) Drugs used to relief
gastric pain associated with hypersecretion of HCL. Mechanism of
Action Neutralization of HCL. Inhibition of pepsin (inactive at PH
5). Therapeutic Uses 1. relief pain of peptic ulcer. 2.
Dyspepsia.
57. I - Systemic Antacids Sodium bicarbonate NaHCO3 + HCL NaCL
+ CO2. Disadvantages 1. Rebound hyperacidity. 2. Stomach distension
due to CO2 liberation pain sensation. 3. Sodium load salt and water
retention ( # in cardiac patients). 4. Systemic alkalosis.
58. Calcium Carbonate CaCO3+HCL CaCl2 + H2O + CO2 Disadvantages
1. Liberation of CO2 stomach distension 2. 10% is absorbed
hypercalcemia. 3. Rebound hyperacidity. 4. Milk alkali syndrome
(hypercalcemia, renal failure).
59. II Non Systemic Antacids 1. Aluminum Hydroxide Gel 2.
Magnesium Trisilicate Al (OH)3 + HCL HCL3 + H2O. Advantages 1.
Longer duration of action. 2. Gradual neutralization of HCL No
rebound hyperacidity. 3. Adsorbs pepsin. 4. Minimal change in acid
base balance. 5. No stomach distention
60. Disadvantages Al (OH)3 1. Constipation. 2. Drug
interaction: absorption of tetracycline, digoxin, iron. Magnesium
Trisilicate 1. Diarrhea 2. CNS depression (renal failure).
61. Alginates (Gaviscon) Combine with antacids in reflux
esophagitis to increase adherence of mucus to esophageal
mucosa.