• Peptic ulcer therapy

• Antiemetics
• Laxatives
• Antidiarrheal drugs
• Peptic Ulcer - a broad term for an ulcer occurring in the
esophagus, stomach, or duodenum w/in the upper GI
tract (esophageal, gastric & duodenal ulcers).
• Duodenal ulcers 10X more frequent than gastric,
esophageal
• Release of hydrochloric acid (HCL) from the parietal
cells of the stomach influenced by histamine, gastrin &
acetylcholine

* Esophageal ulcers  reflux of acidic gastric secretion

into the esophagus d/t a defective or incompetent
cardiac sphincter
* Duodenal ulcers  hypersecretion of acid from the
stomach that passes to the duodenum
* Gastric ulcer  breakdown of GMB (gastric mucosal
barrier)
• Peptic Ulcer Disease
Imbalance between defenses and aggressive factors
• Defensive factors:
• Prevent the stomach and duodenum from self-digestion
– Mucus: continually secreted, protective effect
– Bicarbonate: secreted from endothelial cells
– Blood flow: good blood flow maintains mucosal integrity
– Prostaglandins: stimulate secretion of bicarbonate and mucus,
promote blood flow,
– suppress secretion of gastric acid
• 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
– Smoking: nicotine stimulates gastric acid production
 Mucosa protective factors

Factors Increasing
H. pylori Factors Decreasing
NSAIDs Mucus production
Acidic agents Buffers
Pepsin, histamine, Blood flow
Smoking, tobacco Prostaglandins
 Pathogenesis of Ulcers
Therapy is directed at enhancing host defense or
eliminating aggressive factors; i.e., H. pylori.

Aggressive Factors Defensive Factors

 Acid, pepsin  Mucus, bicarbonate layer
 Bile salts  Blood flow, cell renewal
 Drugs (NSAIDs)  Prostaglandins
 H. pylori  Free radical scavengers
Regulation of Gastric Acid Secretion
• Reduction of acid secretion
– H2 blockers -cimetidine, ranitidine, famotidine, roxatidine,
nizatidine
– PPI -omeprazole, lansoprazole, pantoprazole, rabeprazole,
esomeprazole
– Anticholinergics -pirenzepine, propantheline, oxyphenonium
– PG anologue- misoprostol, enprostil

• Neutralization of gastric acid

– Systemic – sod. Bicarbonate, Na citrate
– Non systemic –Mg hydroxide, mg trisilicate, al hydroxide,
calcium carbonate

• Ulcer protectives –
– sucralfate, colloidal bismuth sulfate
• Ulcer healing - carbenexolone
• Anti H. pylori drugs
– Amoxycillin, Clarithriomycin, Metronidazole, tinidazole,
Tetracycline
 H2 receptor antagonists
Cimetidine, Ranitidine, Famotidine, Nizatidine
mechanism:

block H2-R→ reduce the secretion of gastric acid →↓the

volume of gastric acid & acidity
• Competitive and selective inhibition of histamine H-2 receptor
• Suppress 24 hr gastric secretion by 70%
• Suppress all phases- basal, psychic, neurogenic, gastric
• All stimuli- Ach, gastrin, insulin, alcohol, food
• No effect on motility
• Less effective than PPI
• Caution: renal failure, pregnancy, breast feeding
• Interaction: Cimetidine binds to CYP 450 (retards oxidative drug
metabolism)
note interactions with warfarin, phenytoin, theophylline..
• Side effects
– Well tolerated, less than 3% adverse effects
– Diarrhoea, headache, drowsy, fatigue, constipation,
– CNS- confusion, restlessness
– cimetidine Antiandrogenic action- gynaecomastia, loss of libido, impotence, reduced sperm
count
– Rarely blood dyscrasias
 uses
• Duodenal ulcer
• Gastric ulcer
• Stress ulcer
• Zollinger ellison syndrome
• GERD
• Urticaria
• Ranitidine
1) Antisecretive effect is 10 times that of Cimetidine .
2)Less effect on hepatic microsomal metabolism system.
3)Longer duration and less antiandrogenic effect
 Proton pump inhibitors
 Omeprazole, Lansoprazole, Pantoprazole, Esomeprazole, Rabeprazole
 Prodrugs activated in acidic secretory canaliculi of parietal cells
 Inhibit gastric H+K+ ATPase irreversibly
 Decrease acid secretion by up to 95% for up to 48 hours
 Resting as well as stimulated
 Inactive at neutral pH
 Bioavailability is reduced by food
 Inhibition occur in 1 hr, max at 2hr and last for 3 days.
 No dose modification in elderly. Renal, hepatic disorders

 Use: Ulcers, GORD, Zollinger-Ellison Syndrome, reflux oesophagitis

 Side effects
 Generally well tolerated
 mc Gastrointestinal, headache, headache dizziness
 Atrophic gastritis, Hypergastrinemia
 May increase risk of GI infections (reduced acidity)
 Note:
Give high dose PPI in active GI bleed (eg Omeprazole 8mg/hr for 72 hrs)
 Misoprostol
 PGE1 analogue
 Stimulates Gi pathway (↓cAMP and ↓gastric acid)
 ↑ blood flow and ↑ mucus and bicarbonate secretion, ↓
gastrin secretion

Use: prevention of NSAID induced injury

Side effects: diarrhoea, pain, cramps (30%)
Can cause exacerbation of IBD
Contraindication: pregnancy, caution in women of
childbearing age
can induce labour!
Antacids
– Mg and Al hydroxides Alk
– Do not decrease acid production
– Systemic antacids- alkalosis, Na
overload
– May chelate other drugs (avoid
concomitant administration of other
drugs)
– Side effects: diarrhoea (Mg),
constipation (Al) Acid
– Milk alkali syndrome (alkalosis, renal
insufficiency, hypercalcemia)
– Ca salts- gas, constipation, renal
stones – combined with simethicone
– Drug interactions
 Sucralfate

– Al salt of sulfated sucrose

– Polymerizes at pH < 4 and Forms sticky polymer in
acidic environment. It adheres to ulcer base
– Inhibits hydrolysis of mucous proteins by pepsin
– No acid neutralising action
– Minimally absorbed, local action
– 1 g bd to 1g qds
– Antacid interfere with polymerization
– SE: constipation, aluminium absorption (avoid in
severe renal impairment due to risk of
encephalopathy)
 Colloidal Bi salts
 ↑ mucus and bicarbonate secretion
 CBS and mucus form glycoprotein –Bi
complex Which coats ulcer act as diffusion
barrier
 Kill H pylori
• when combined with antibiotics
(metronidazole and tetracycline), ulcer
healing rates of up to 98% have been seen.
 H. pylori eradication
 Eradication increases ulcer healing
 Reduces recurrence

Triple therapy
For 7 (14) days twice daily eg
 full dose PPI +
 Amoxicillin +
 Clarithromycin/Metronidazole
Amox 750 + tini 500 + omeprazole 20 BD
Amox 750 + tini 500 + lansoprazole 30 BD
Amox 1000+ clarithromycin 500 + lansoprazole 30 BD

Effective in 80-85%
 The
The Mechanism
Mechanism &
& Side
Side Effects
Effects of
of Various
Various Acid
Acid
Suppressive
Suppressive Medications
Medications
Drug Mechanism Common side effect
Antacid Neutralize acid Mg - diarrhea
Al - constipation
Ca – constipation

H2 receptor Block histamine receptor Cytochrome 450 altered

antagonists metabolism of drugs

Prostaglandins Agonist Diarrhea, cramps,

abortion

H+/K+ ATPase Block acid pump Hypergastrinemia

inhibitors enterochromaffin cell
(ECL)
hyperplasia
Sucrafate Coat ulcerated mucosa Constipation