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.