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.
The relative risk of GI side effects from NSAIDs (low to high)
Celecoxib Ibuprofen Diclofenac Naproxen Indometacin Piroxicam Azapropazone
Treatment of NSAID induced peptic ulcers
Firstly, and most importantly, the NSAID should be withdrawn. The patient is then given a full dose PPI for two months. If a test for H. pylori is positive then eradication therapy should be prescribed. If there is a gastric ulcer, this is re-scoped after two months to check healing and minimise the risk of further bleeding. If the ulcer is healed a low dose PPI prn is prescribed.
PPIs, whilst being of great value in the treatment of GI symptoms, should not be regarded as drugs with minimal risks attached. They are linked with C. difficile infections, osteoporotic fractures, pneumonia and rebound acid hypersecretion.
What to do after h.pylori is eradicated
Concordance is a major cause of treatment failure as the most common side effects are nausea and vomiting.
There is no need to continue with a PPI once H.pylori is eradicated from a patient, however it is common practice to continue for 1-2 months.
Patients with a peptic ulcer (gastric or duodenal) and H. pylori should be offered retesting for H.pylori 6-8 weeks after beginning treatment depending on the size of the lesion.
Patients with a gastric ulcer and H.pylori should be offered repeat endoscopy 6-8 weeks after beginning treatment depending on the size of the lesion.
Patients with a duodenal ulcer do not require repeat endoscopy.
Other drugs that exacerbate the GI toxicity of NSAIDs are:
SSRI’s and low dose aspirin (an NSAID itself).
How should re-testing be done?
Re-testing for H.pylori should be done using a 13C urea breath test. Due to the lack of evidence currently available to recommend the stool antigen test as a test of eradication.
If the ulcer is fully healed on re-scoping and there are no further symptoms the patient may be
prescribed a low dose PPI to be taken when required.
what therapy does NICE recommend
Whilst NICE still recommends the 7 day triple therapy regimens, a review was published in August 2015 examining the efficacy of different eradication regimens.
In this review the standard 7 day triple therapy regimen was found to be the least effective of the available regimens.
On endoscopy they find that he has a bleeding duodenal ulcer, what is the best way to treat it?
Perforated ulcers require immediate surgery. Bleeding ulcers are injected with adrenaline 1:10000 on endoscopy which causes vasoconstriction. Sclerotherapy is then used to stop the bleeding. This involves the use of a heater probe which causes thermocoagulation. Endoclips may also be used.
After treating the bleeding ulcer they want to give a PPI to Mr SJ. How should this be given in the short term (next few days) and the longer term (1 week to 2 months).
Intravenous administration of Omeprazole. A dose of 80mg is given initially over 40 to 60 minutes, this is followed by a continuous intravenous infusion of 8mg/ hour for 72 hours. Whilst this is an unlicensed indication, it is commonly used and is listed in the BNF. Following this the patient will be changed to oral therapy for 2 months, then patient should have a repeat endoscopy.
