Peptic ulcer disease
What is PEPTIC ULCER?????
Breaks in mucosal surface
>5mm in size
Depth till submucosa
In any part of GI tract exposed to aggressive
action of acid pepsin juices.
Can be acute or chronic
Both can penetrate muscularis mucosae..
SITES
Gastric and duodenal – 98 %
Ratio of 1:4
Duodenum:1st part >95% :ant & post walls
Gastric :junction b/w antrum &acid secr. mucosa :lesser curvature
Why Peptic ulcer occurs
?
Imbalance between Aggressive factors and
Defensive factors
Regulation of gastric acid secretion
ETIOLOGY
Predisposing factors
– Age :young in DU and GU.
– Sex :GU commoner in males
Causes
– [Link]
– NSAID
– Infection: herpes simplex,etc..
– Other drug/toxin: bisphosphonates ,glucocorticoids
Pathogenetic factors not related to
[Link] & NSAID
Smoking
Genetic : blood group O
Stress
Diet : alcohol and caffeine
Associations
Systemic mastocytosis
Nephrolithiasis
Hyperparathyroidism
Cirrhosis
Alpha antitrypsin deficiency
Pancreatitis, polycythaemia vera
Pathogenesis
Related with NSAIDs
NSAIDs migrate across lipid membrane of epithelial cells.
Trapped in an ionized form
Related with NSAIDs Cell injury
Topical NSAIDs.
Alter surface mucous layer.
Peronits back diffusion of H+ & Pepsin.
Further cell damage.
Figure shows machanisms by which
NSAIDs may induce mucosal injury :
Risk factors for NSAID – induced
Gastroduodenal ulcers
Established Possible
Advanced age. Concomitant infection with H. pylori.
History of ulcer. smoking.
Concomitant use of glucocorticoids. Alcohol consumption.
High dose of NSAIDs.
Multiple NSAIDs.
Concomitant use of anticoagulants
serious or multi system disease.
Phathogenesis of [Link]
Types of peptic ulcer
Acute peptic ulcer
Chronic peptic ulcers
- Gastric ulcers
- Duodenal ulcer
Acute peptic ulcer
Ingestion of Aspirin or butazolidin.
By stress (Stress ulcer):-
May be following endotoxic
shock :
-Hypotension,
-Hemorrhage or
-Cardiac infarction
Acute peptic ulcer
Sepsis.
After trauma or neurosurgical operations (Curling’s ulcers).
After burns (curling’s ulcers).
Patient on steroids
The size of peptic ulcer (Steroids ulcers).
CHRONIC PEPTIC ULCERS
GASTRIC ULCERS
. Decrease mucosal resistance.
. Pyloroduodenal reflex.
. Deficient mucous barriers.
. Mucosal trauma.
. Local Ischaemia.
. Antral stasis.
. NSAIDs.
. Helicobacter pylori.
DUODENAL ULCER
Acid hyper secretion.
. Genetics factor.
. Endocrine organ dysfunction.
. Liver abscess.
. Emotional factors.
. Diet & smoking.
. Helicobacter pylori.
. Decrease in bicarbonate production.
Pathophysiology Gastric ulcer Duodenal ulcer
Major causes [Link] & NSAID [Link] & NSAID
Gastric acid decreased increased
Gastric emptying delayed rapid
Abnormal resting & stimulated Bicarbonate secretion remarkably
Pyloric sphincter pressure decreased
Clinical features
Abdominal pain*
•Epigastric
•Burning or discomfort
•Awakes from sleep
Nausea
Weight loss
Dyspepsia if not relieved by antacids —penetrating ulcer
Treatment ?
H2 ANTAGONISTS
Mechanism of action
Competitively block H2 receptors on parietal
cell & inhibit gastric acid production
Suppress secretion of acid in all phases but
mainly nocturnal acid secretion
Also reduce acid secretion stimulated by
Ach, gastrin, food, etc.
Pharmacokinetics
Absorption is not interfered by food
Can cross placental barrier and reaches milk, Poor CNS
penetration
The serum half-lives range from 1.1 to 4 hours;
Cleared by a combination of hepatic metabolism, glomerular
filtration, and renal tubular secretion.
Dose reduction needed in moderate to severe renal
insufficiency
Comparison of H2 antagonists
H2 antagonists - Uses
Promote the healing of gastric and duodenal ulcers
Duodenal ulcer – 70 to 90% at 8 weeks
Gastric Ulcer – 50 to 75%
NSAID ulcers induced ulcers
Stress ulcer and gastritis
GERD
Zollinger-Ellison syndrome
Prophylaxis of aspiration pneumonia
Adverse effects
Headache, dizziness, bowel upset, dry mouth
CNS: Confusion, restlessness
Bolus IV – release histamine –
bradycardia, arrhythmia, cardiac arrest
Cimetidine has antiandrogenic actions
Proton Pump Inhibitors
Most effective drugs in antiulcer therapy
Prodrugs requiring activation in acid environment
Activated forms binds irreversibly to H+K+ATPase and
inhibit it
Omeprazole
Pantoprazole
Lansoprazole
Esomeprazole
Mechanism of Action
Prodrugs inactive at neutral pH
At pH < 5 rearranges to two charged
cationic forms (sulfenamide + sulphenic acid)
that bind covalently with SH groups of H⁺K⁺
ATPase and inactivate it irreversibly
Also inhibits gastric mucosal
carbonic anhydrase
Pharmacokinetics - PPI
Available as enteric coated tablets
They should be given 30 minutes to 1 hour
before food intake
half life is very short and only 1-2 Hrs
Still the action persists for 24 Hrs to 48 hrs
after a single dose
Action lasts for 3-4days even after stoppage of
the drug
Therapeutic uses:
1. Gastroesophageal reflux disease (GERD)
2. Peptic Ulcer - Gastric and duodenal ulcers
3. Bleeding peptic Ulcer
4. Zollinger Ellison Syndrome
5. Prevention of recurrence of nonsteroidal antiinflammatory drug (NSAID)
- associated gastric ulcers in patients who continue NSAID use.
6. Reducing the risk of duodenal ulcer recurrence associated with H.
pylori
infections
7. Aspiration Pneumonia
Adverse Effects
Nausea, loose stools, headache abdominal
pain, constipation,
Muscle & joint pain, dizziness, rashes
Rare :
Gynaecomastia, erectile dysfunction
Leucopenia and hepatic dysfunction
Osteoporosis in elderly on prolonged use
Hypergastrinemia
Drug interactions
Omeprazole inhibits the metabolism
of warfarin, phenytoin, diazepam, and
cyclosporine.
However, drug interactions are not a
problem with the other PPIs.
PPI – Dosage schedule
Omeprazole - 20 mg o.d.
Lansoprazole - 30 mg o.d.
Pantoprazole - 40 mg o.d.
Rabeprazole - 20 mg o.d.
Esomeprazole - 20-40 mg o.d
Proton Pump Inhibitors
Lansoprazole :
Partly reversible, more potent, slightly more against
[Link], Higher BA, rapid onset.
Pantoprazole:
More acid stable, I.V, CYP450 less affinity
Rabeprazole:
claimed to most rapid
Es-omeprazole
Better intragastric pH , higher healing rates.
Antacid - Interactions
Absorb drugs and form insoluble complexes that are
not absorbed
Clinical importance : Interactions can be avoided
by taking antacids 2 hrs before or after ingestion of
other drugs .
Now answer this question
Is it rational to combine Aluminium
hydroxide and Magnesium hydroxide
in antacid preparations ?
Systemic antacids
• Soluble instant short duration
• But cause systemic alkalosis
• So other uses
– Metabolic acidosis
– Alkalinisation of urine
– Antipruritic lotion,eye wash,mouth wash
Adverse effects
constipation,
hypophosphatemia
• Other uses
–Bile reflux Gastritis Stomatitis
–Prophylaxis of stress ulcers
US FDA Approved Regimen
• Lansoprazole 30mg
• Amoxicillin 1000mg
• Clarithromycin 500mg
Twice daily Two weeks
Quadruple Therapy
Given when Triple Therapy fails
CBS - 120 mg qid
Omeprazole / Lansoprazole - 20 / 30 mg bd
Metronidazole - 400 mg TDS Tetracycline - 500 mg
qid
Thank
You
