Drugs used in Gastro

Oesophageal reflux disease

(GORD)& peptic ulcer

Dr Anuradha Dassanayake
Senior Lecturer in Pharmacology
University of Kelaniya
 Definition
• GORD is a normal phenomenon and
occurs <4% of the time in normal people
• It becomes abnormal if it is frequent or the
patient becomes symptomatic
• It is one of the most common diseases in
the Western world
 Pathogenesis
Anti reflux mechanisms
• LOS
• Diaphragm
• Intra abdominal oesophagus

• Main problem is acid related

 GORD current trends
• The current perception is that reflux
disease is an entirely acid mediated
condition.
• PPI’ s are the treatment of choice for the
erosive and non erosive reflux disease.
Anti reflux mechanism
 Pathogenesis
Factors that increase gastro-esophageal
Reflux

• Pregnancy , obesity
• Foods (Fat, Dairy products)
• Smoking, alcohol
• Drugs Ca channel blockers, Nitrates
• Hiatus hernia
Reflux
 Complications
• Barrett’s
• Carcinoma
• Stricture
• Aspiration
Barrett’s
 Management of GORD
Life style modifications
• Weight reduction
• Smoking
• Alcohol
• Food
• Clothing
• Sleeping posture
 Peptic Ulcer
• Gastric ulcer/Duodenal ulcer
• Gastritis/Erosions
• Increased acidity/reduced resistance of
the mucosal barrier
• Helicobacter pylori associated
• NSAIDS
• Zollinger - Ellison Syndrome
 Management of GORD
Life style modifications
• Weight reduction
• Smoking
• Alcohol
• Food
• Clothing
• Sleeping posture
 Drugs used in GORD

• Proton pump inhibitors

• Prokinetic agents
Domperidone,Metachlopramide,
Mosapride
• Antacids
H2 receptor blockers
Cimetidine, Ranitidine
H2-receptor antagonists
• Competitively inhibit all H2 receptors
- Inhibit histamine & gastrin stimulated
acid secretion
- Reduce Ach induced acid secretion
• Reduce basal/food induced acid secretion
• Examples: Cimetidine, ranitidine,
famotidine
 Do they have a role to play in the
era of PPI
• Yes
• Mild GORD
• Symptomatic relief
• Shorter duration of action is the problem
H2-receptor antagonists
Unwanted effects – rare and reversible
Cimetidine:
Gynaecomastia & impotence
CNS disturbances – elderly
Inhibits cytochrome P450
Ranitidine and Famotidine have less adverse effects
 Proton pump inhibitors
• Most widely prescribed drugs
Proton pump inhibitors -
Omeprazole
• Irreversibly inhibits H+/K+ pumps – final step
• Markedly inhibits basal/stimulated acid
• It is a weak base – accumulates in acidic
environment of parietal cells

Others:Lanzoprazole,Pantoprazole,
Rabeprazole, Esomeprazole
Proton pump inhibitors

Clinical uses:
• Peptic ulcer
• Reflux oesophagitis
• H. pylori infection
• Zollinger-Ellison syndrome
 Proton pump inhibitors
Pharmacokinetics
• Given orally – omeprazole is given as an
enteric coated granules
• Half-life – 1 hour (effect lasts 2-3 days)
• A single dose of 20 mg reduces gastric
output by 90% over 24 hrs..
• Eliminated by metabolism
 Unwanted effects
Not very common
Nausea,headache
Rashes, Constipation
 Which proton pump inhibitor Is
more effective?
Esomeprazole 40 mg daily has been
compared with
Omeprazole 40
Pantprazole 40
Lanzaprazole 30

Healing rates are superior with esomeprazole.

 Treatment duration

• Esomeprazole 40mg daily

• GORD with erosions - 2months
• GORD without erosions -1 month

• Maintanece 20mg daily.

Do PPI reduce Biliary reflux?
The role of bile in GERD or gastritis not very
well documented
Bile reflux may play a part in the reflux
symptoms in patients with normal
eosophageal pH
PPI ‘s do not have a demonstrable effect on
Bile induced reflux symptoms
PPI’s donot have gastric prokinetic properties.
 When to give PPI
– Best is at night! In GORD
• Followed by a meal
• Prevents nocturnal acid
breakthrough(NAB) responsible for severe
Erosive Oesophagitis.
• Rabeprazole.
• Pehlivanov et al- APT 18 880-890
Antacids
• Act by neutralizing gastric acid – raises
pH
• Controls mild reflux symptoms when taken
regularly after meals and as necessary
• Salts of Magnesium and Aluminium
• Aluminium can cause constipation and
magnesium can cause diarrhoea.
 Antacids cont-
• Alginate produces a viscous floating gel
which blocks reflux and protectively coats
the oesophagus.
• Alginic acid combination may be more
useful
Eradication of H. pylori
H. pylori is implicated in pathogenesis of:
• Peptic ulcers (mainly duodenal)
• Gastric cancer (risk factor)

• Role in GORD not yet clear

Triple therapy:
• Proton pump blocker – Omeprazole
• Amoxycllin (Clarithromycin)
• Metronidazole (Tinidazole)
 Domperidone
Is a Dopamine receptor antagonist
Has anti emetic and gastric prokinetic
properties
Not as effective as proton pump inhibitors
Unlike PPI’s do not have firm evidence for
its benefit.
Unwanted effects are common
Adverse effects - Domperidone
• Extra pyramidal reactions
– Tremors
– Dystonic reactions
• Galactorrhoea & Amenorrhoea
• Reduced libido, Gynaecomastia
• Raises prolactin
 Cisapride
• Action on 5HT-4 receptors
• Gastric prokinetic agent
• QT prolongation and fatalities reported
• Now withdrawn from the market in most
countries.
 Mosapride
• A novel prokinetic agent
• A 5 HT 4 receptor agonist
• Increases ACH activity
• Gastric prokinetic activity
• May be contributing to functional dyspepsia.
• No QT prolongation reported
• No extrapyramidal effects reported.
 Mosapride cont-
• A small study Ruth etal APT in 1998 in 21
patients
• RCT trial 25 patients
– Huge dose
• Reduced reflux symptoms
• Reduced oesophageal PH
• No evidence of major side effeects
 Conclusion
• Proton pump inhibitors are the mainstay in the
treatment of GORD - Long term treatment may
be necessary and appears to be safe.
• No firm evidence for Gastric prokinetic agents or
H-pylori eradication
• Antacids and H 2 receptor blockers have role to
play in mild GORD and symptomatic relief.