GI therapeutics Flashcards
Pathology - 3 areas
Absorption - Crohn’s Disease, Diarrhoea, Coeliac Disease, short bowel syndrome
Secretion - Peptic Ulcer Disease, Gastro-oesophageal reflux disease, Zollinger-Ellison syndrome
Motility - Diarrhoea, Constipation, Inflammatory Bowel
Disease, Irritable Bowel Syndrome, Bowel CA,achalasia
The oesophagus can respond to the reflux of stomach contents in three different ways:
- Endoscopy negative reflux disease (50% of cases)
- Erosive oesophagitis (40% of cases)
- Barrett’s columnar lined oesophagus (10% of cases)
Endoscopy negative reflux disease
If a patient is referred for endoscopy to investigate their symptoms there will be no changes visible to oesophageal mucosa if they have endoscopy negative reflux disease. It is thought however that the mucosa becomes highly sensitive to acid reflux which results in a high burden of both typical and non-typical symptoms. It often doesn’t respond fully to treatment with proton-pump inhibitors (PPIs) and can be associated with irritable bowel syndrome.
Erosive oesophagitis
In patients with erosive oesophagitis there will be inflamed and possibly ulcerated mucosa visible on endoscopy. Patients will usually present with typical symptoms (e.g. heartburn).
Greater acid production will increase the severity of disease. Erosive oesophagitis generally responds well to PPI with full healing of mucosa but there is a risk of stricture with severe disease
Barrett’s columnar lined oesophagus
This is where normal squamous epithelium is replaced by columnar intestinal epithelium. The length of oesophagus affected increases with increased exposure to acid and the mucosa is often exposed to acid for long periods. In patients with Barrett’s often the symptoms are not severe as columnar epithelium is insensitive to acid. There is an associated increased risk of developing oesophageal cancer in patients with Barrett’s.
There are many effective treatments for GORD available to the community pharmacist. These include:
1. Simple antacids (more suitable for younger patients) • E.g. Rennies, Settlers 2. Alginates • E.g. Gaviscon, Peptac 3. H2-receptor antagonists • Ranitidine 75 mg • Famotidine 10 mg 4. Proton Pump Inhibitors • Omeprazole 10mg • Esomeprazole 20mg • Pantoprazole 20mg If symptoms are severe enough to consider PPI, the patient really ought to be referred.
Managing uninvestigated dyspepsia - Patients with dyspepsia should be offered
Patients with dyspepsia should be offered H. pylori ‘test and treat’. Patients should not take a PPI for two weeks prior to testing for H. pylori with a breath test or stool antigen test.
Patients should be offered empirical full dose PPI therapy for 4 weeks if they have dyspepsia and test negative for H. pylori.
Treatment post-endoscopy - Endoscopy negative oesophagitis and erosive oesophagitis
Full dose PPI for four to eight weeks. If symptoms recur then the lowest dose of a PPI which controls the patient’s symptoms should be prescribed for a limited number of
repeat prescriptions. If necessary the patient can then be maintained on a prn dose of a PPI.
Alginates are often useful for symptom relief
Barrett’s columnar lined oesophagus treatment
Taken from the British Society of Gastroenterology guidelines (2005):
Long term PPI. The dose of this may be increased to the maximum licensed dose if inadequate acid suppression occurs
If inadequate acid suppression occurs at maximal doses of a PPI, then a H2-receptor antagonist may be added at night along with a prokinetic agent.
Peptic Ulcer Disease
A peptic ulcer is defined as a breach in the lining of the stomach or duodenum. They are often > 5mm in diameter and they develop when there is an imbalance between mechanisms that attack and protect the epithelial layer of the stomach or duodenum.
Factors affecting the peptic mucosa - destructive and protective
Protective
Mucus layer
Bicarbonate secretion above the epithelium
Epithelial cell barrier
Prostaglandins (↑ mucus and bicarbonate secretion, ↓ acid secretion). Synthesised by COX-1
Destructive Gastric Acid Pepsin Drugs Bacteria
Testing for H. pylori infection
Non-invasive tests include: 13C urea breath test, stool antigen test and serology (antibody presence in serum).
Invasive tests include: rapid urease test (CLO test), histology, culture.
It is important that treatment with PPIs must be discontinued two weeks before a test for H. pylori to prevent a false negative result occurring.
Helicobacter pylori infection
30-50% of the population of Western Europe have H. pylori. It is present in 100% of patients with duodenal ulcers who are not taking NSAIDs and 85% of gastric ulcer patients. H. pylori can ↑ gastrin production and can also produce enzymes which damage the mucosa (urease vacA, haemolysins)
Treatment of H. pylori associated ulcers
Antibiotics and PPIs are the mainstay of treatment. Patients should be offered a one week course of PPI and amoxicillin and either clarithromycin or metronidazole, e.g. PAC500
o Amoxicillin 1 g BD
o Clarithromycin 500 mg BD
o Omeprazole 20 mg BD
The choice of regimen should take into account lowest acquisition cost and previous exposure
to clarithromycin or metronidazole.
If the patient is penicillin allergic they should be offered a one week course of PPI and clarithromycin and metronidazole, e.g. PMC250 o Metronidazole 400 mg BD o Clarithromycin 250 mg BD o Omeprazole 20 mg BD
NSAIDs inhibit
NSAIDs inhibit prostaglandin synthesis by inhibiting COX (cyclo-oxygenase). This results in decreased mucus and bicarbonate production and an increase in acid production. COX-2 inhibitors were thought to have fewer GI side effects however trial evidence for this supposition is poor. Rofecoxib has been withdrawn due to its cardiovascular side effects.
