6. Gastrointestinal Disease Flashcards
What is H.Pylori?
= Helicobacter pylori Gram negative bacteria that can live in stomach and duodenum
- Stimulates the secretion of gastrin and leads to a ‘hypergastrinemia’ state excess gastrin leads to increased gastric acid secretion, inflammation and ulceration
- Weakens protective mucous coating of the stomach and duodenum acid and H pylori irritate lining causing ulcer
- ## neutralises acid in the stomach, allowing H pylori to survive
What is the test for H.Pylori?
= Urea breath Tests
First line treatment for H.pyloi eradication?
= Triple therapy: 1 PPI and 2 antibiotics for 7 days
Eg. Esomeprazole 20mg bd (Nexium)
Clarithromycin 500mg bd (Klacid)
Amoxicillin 1g bd (Amoxil)
- If amoxicillin unsuitable replace with 400mg metronidazole bd
- High prevalence of side effects (nausea, diarrhoea, taste disturbances)
What is the role of H.Pylori eradication prior to NSAID use?
- Patients with history of ulcer disease should be tested and treated for H.Pylori infection before regular NSAID use because eradication for pylori reduces the risk of ulcer and bleeding
What is PPIs and what is their mechanism of action?
Give examples
= Protein Pump inhibitors
PPI ‘kill off’ (inactivate) the PP in parietal cells so that there is no longer acid produced
o Acid production obliterated for 24-48 hours
- digestion of some nutrients (ie B12 and calcium) is affected as they require HCl to digest, so supplements are given for digestion without HCl
Examples: Omeprazole, Lansoprazole, Esomeprazole, Rabeprazole
Risks of Long term PPI use?
Increase risk of:
o Enteric infections
o Pneumonia
o Decrease serum B12
o Fracture (due to decreased calcium carbonate absorption) and osteoporosis
It is important that treatment with PPI is reviewed regularly and where possible:
o Stop treatment
o Use intermittently when symptoms develop
o Step down to low-dose therapy
Mechanism of action H2 antagonists?
= Competitively block H2 receptors on parietal cells of stomach and so reduce acid secretion
o Available OTC
o e.g. Ranitidine
o Not P450 inhibitor
o Cimetidine
CYP P450 Enzyme
o CYP metabolise drugs
o Drugs that inhibit enzyme means that it can no longer metabolise the drugs it is meant to, so this causes an increase in that drug within the body toxicity
o Eg. Warfarin + cimetidine cimetidine inhibits P450 which metabolises warfarin warfarin toxicity (pharmacokinetic interaction)
What is GORD
= The acidic stomach contents enter the oesophagus and in some causes the throat and the mouth.
o Exposure of the oesophagus to refluxed gastric contents results in
o Heartburn, acid regurgitation
o More severe symptoms: difficulty swallowing, chest pain
o Complications include oesophageal erosions, oesophageal ulcer and narrowing of the oesophagus (oesophageal stricture)
o In some patients the normal oesophageal lining may be replaced with abnormal (Barrett’s) epithelium which is linked to oesophageal cancer
Mechanism of action GORD
- GORD is related to disturbance of normal anti-reflux mechanisms
- Lower oesophageal sphincter (LOS) tone plays an important in anti-reflux mechanisms
- Hiatus hernia (HH) may be the cause in some cases
Causes of GORD?
Lower oesophageal sphincter (LOS) tone may be reduced by:
- Muscle weakness
- Abdominal distension
- Smoking
- Alcohol
- Certain foods and medications
Consequences of GORD?
o Erosive oesophagitis
o Oesophageal stricture disease
o Barrett’ s oesophagus
What is the aim of the management of GORD?
- Relieve symptoms, heal erosions or ulcerations, decrease recurrence and prevent complications
Non-pharmacological management GORD
= life style changes
- Losing weight
- Avoiding triggering food and drunks
- Reducing portion sizes
- Avoid eating shortly before bed
- Sleep with head raised
Pharmacological management of GORD
- Step Up starry with low potency treatments and increase if necessary
o Antacid/alginate > H2RA > PPI - Step down start with high potency treatments and decrease if possible
o PPI> H2RA > Antacid/ alginate
GORD management
Antiacid/alginate ?
= a base that neutralises the acid
Antacids (eg. Mylanta, Gaviscon)
o Neutralise gastric acid
o Calcium carbonate, aluminium hydroxide, magnesium trisilicate
Adverse effects
o Constipation, diarrhoea (depending on base used)
o Symptomatic relief only and doesn’t prevent further episodes – usually have to be taken with every meal
Alginate combines with antacid to form a physical barrier (‘raft) to prevent stomach contents from flowing into oesophagus
o Gaviscon is a combination of both
EXAMPLES - Mylanta, gaviscon
GORD management
H2 Antagonist
= decrease acid production
- Competitively block H2 receptors on parietal cells of stomach and so reduce acid secretion
o Available OTC o Ranitidine o e.g. Cimetidine
Adverse effects: sleeping difficulties, headache, diarrhea
GORD management
Proton Pump Inhibitors (PPI)
= decrease acid production
- Can still have wash up into oesophagus, but now the contents are less acidic
Adverse effects: constipation, abdominal pain, headache
What is Peptic Ulcer Disease - PUD
= Occurs when ulcers are found in the stomach (gastric ulcers) or duodenum (duodenal ulcers)
Symptoms of PUD
o Burning abdominal pain, often a few hours after eating, nausea & vomiting, weight loss, blood in vomit and stools in severe cases
Cause of PUD
o Protective mucous layer of digestive tract is broken/compromised, so underlying tissue is exposed to acid
o H pylori induced ulcers and NSAID induced ulcers
Contributory factors of PUD
o Gastric acid: needs to be present for ulcer to form
o Decreased blood flow: decrease in mucous and bicarbonate production (thus decreased protection from gastric juice)
o NSAIDS: inhibit production of prostaglandins which maintain mucosal layer
o Smoking: nicotine stimulates acid production
o Helicobacter pylori bacteria
Management of PUD?
= NSAIDS
- Inhibit the synthesis of prostaglandins by inhibiting cyclo-oxygenase (COX)
o Inhibition of COX-2: anti-inflammatory and analgesic action
o Inhibition of COX-1: impaired gastric cytoprotection and antiplatelet effect - Prostaglandins synthesised by COX-1 help maintains the protective lining of the stomach by:
o Increasing bicarbonate ion secretion
o Increasing mucous secretion
o Increasing mucosal blood flow
o Reducing gastric acid secretion
