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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
PathogenesisFactors 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 40Pantprazole 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. pyloriH. 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.