Treatment of Peptic Ulceration and Inflammatory Bowel Disease Flashcards
Why does the digestive system need acid?
o Digestion of food o Iron absorption o Killing pathogens
What is the function of mucous secreting cells as a protective mechanism against acid?
o Trap bicarbonate ions (alkaline) o Creates gel like barrier o Important protective layer
What is the action of prostaglandins are locally produced in the stomach?
o Stimulates secretion of mucus and bicarbonate
o Dilate mucosal blood vessels
o Cytoprotective
What increases the risk of GORD and ulcers?
- If disturbance in protective layer/secretions PLUS acid
What is likely to disturb protective functions of the stomach?
- Many NSAIDs disturb these protective functions (Inhibit COX-1, enzymes responsible for synthesis of prostaglandins)
What are the 2 main cells involved in gastric acid production?
oxyntic/parietal cells chief/peptic cells
What is the action of oxyntic cells?
form HCl and release intrinsic factor
What is the function of intrinsic factor?
absorb Vitamin B12
Draw a diagram illustrating the secretion of HCl by the gastric parietal cells
What are the three endogenous secretagogues?
Gastrin, Acetylcholine and Histamine
Describe the action of Gastrin
- Gastrin is a polypeptide hormone
- Gastrin is secreted by gastrin cells; G Cells
- Located in the gastric antrum and duodenum
- Proteins in food have a strong effect in the gastrin cells
- Stimulates secretion of acid by parietal cells (through the proton pump)
- Also increases pepsinogen secretion – stimulates blood flow and increases gastric motility
Describe the function of ACh
- Released from neurons
- Stimulates muscarinic receptors on surface of parietal cells and histamine containing cells
Describe the function of histamine
- Mast cells lying close to parietal cell release histamine
- Histamine release increased by gastrin and acetylcholine
- Acts on parietal cell H2 receptors
What is a secretagogue?
substances that promote the production and secretion of acid
What are the main associations of H.pylori with stomach problems?
- Causative factors in gastric and duodenal ulcers
- Risk factor for gastric cancer (adenocarcinoma)
- Strong link with MALT (Mucosa Associated Lymphoid Tissue) Lymphoma
What are the additional associations of H.pylori with stomach problems?
- Gastro-oesophageal reflux disease
- Dyspepsia
- Atrophic gastritis
- Iron deficiency anaemia
- Idiopathic Thrombocytopenia Purpura
What type of infection can H.pylori cause?
Can cause acute infection with symptoms that include nausea, dyspepsia, malaise and halitosis
How long does acute infectoon by H pylori tend to last?
Acute infection tends to last about two weeks
What is the damage to the gastric mucosa in acute infection caused by H pylori?
Gastric mucosa is inflamed with neutrophils and inflammatory cells with marked persistent lymphocyte penetration
What does the outcome of chronic infection by H pylori depend on?
- Pattern of inflammation
- Host response
- Bacterial virulence
- Environmental factors
- Patient age
What is the pathogenesis of chronic infection caused by H pylori?
Local inflammation and gastritis
What is the first line treatment of Helicobacter pylori?
- First line = offer people (non-penicillin allergic) who test positive for H. pylori a 7-day, twice-daily course of treatment with:
- A PPI and amoxicillin and either clarithromycin or metronidazole
What are the main proton pump inhibitors and what is their action?
reduce gastric acid secretion
- Esomeprazole
- Lansoprazole
- Omeprazole
- Pantoprazole
What are the main indications for a proton pump inhibitor?
- Helicobacter pylori eradication
- Peptic ulcer disease
- Dyspepsia
- GORD
- Treatment and prevention of NSAID associated ulcers
- Reflux oesophagitis
- Zollinger-Ellison syndrome
Describe the action of omeprazole
- inhibits K+H+ATPase irreversibly (the proton pump)
- Basal and simulated gastric acid secretion reduced
- Drug is weak base and accumulates in acid environment of the canaliculi of the stimulated parietal cell
- Usually oral administration
Describe the unwanted effects of PPIs
- Relatively uncommon
- Includes:
- Headache
- Diarrhoea
- Rashes
- Dizziness
- Somnolence
- Confusion
- Impotence
- Gynaecomastia
- Pain in muscles/joints
When should proton pump inhibitors be used with caution
liver disease, pregnancy, breast feeding
What may a PPI mask the symptoms of?
gastric cancer
What are histamine H2 receptor antagonists used for?
peptic ulcers and reflux oesophagitis
What is the mechanism of action of Histamine H2 receptor antagonists?
- Competitively inhibit histamine actions at all H2 receptors
- Inhibit histamine, gastrin and acetylcholine stimulated acid production
- Pepsin secretion also falls with reduction in volume of gastric juice
What are the main examples of Histamine H2 receptor antagonists?
Ranitidine (approximately 50% bioavailability, half-life 2-2.5hrs, renal excretion)
Cimetidine (>60% bioavailability, half-life = 2hrs, renal excretion
What are the unwanted effects of Histamine H2 Receptor Antagonists?
- Diarrhoea
- Dizziness
- Muscle pains
- Alopecia
- Transient rashes
- Hypergastrinemia
What are the cautions of Histamine H2 receptor antagonists?
can mask symptoms and signs of gastric cancer
What are the specific unwanted effects of Cimetidine?
- Can interact with androgen receptors:
- Gynaecomastia in men
- Decreased sexual function
- Inhibits cytochrome P450
- Slows the metabolism (and potentiates action) of range of drugs e.g. oral anticoagulants and tricyclics
- Confusion in elderly
Dyspepsia =
pain or discomfort in upper abdomen exacerbated by food
GORD =
acid reflux, associated with water brash
What is the lifestyle advice when treating dyspepsia and GORD?
- Healthy eating
- Weight reduction
- Smoking cessation
What are the known precipitants of dyspepsia and GORD?
- Alcohol
- Coffee
- Chocolate
- Fatty foods
What is the main advice offered prior to pharmacological intervention for dyspepsia and GORD?
- Raise the head of the bed and have a main meal well before going to bed
- Stop NSAIDs where appropriate/applicable
What are the main iver the counter remedies for dyspepsia and GORD?
- Antacids; directly neutralise acid and inhibit activity of peptic enzymes
- Salts of magnesium and aluminium
- Alignates; increases viscosity and adherence of mucus to oesophageal mucosa
- Simeticone; antifoaming agent (helps bloating, flatulence)
What is a peptic ulcer?
gastric or duodenal ulcer
Genesis of peptic ulcers
- Can be associated with infection and gastric mucosa with H pylori
- Imbalance between:
- Mucosal-damaging and mucosal protecting
Initial treatment for peptic ulcer disease if H pylori positive
Offer H pylori eradication if peptic ulcer disease and H pylori positive
Initial treatment for NSAID associated ulcers
Stop the used of NSAIDs where possibly. Offer full-dose PPI or H2RA therapy for 8 weeks and, if H pylori is present, subsequently offer eradication therapy
Initial treatment of peptic ulcer if H pylori negative and no NSAID
Offer full-dose PPI or H2RA therapy for 4 to 8 weeks
What should people with a gastric ulcer and H pylori be offered?
repeat endoscopy after 6-8 weeks
Perform re-testing for H pylori using carbon 13 urea breath test
What should be excluded if a person has a non-healed ulcer?
non-adherence, malignancy, failure to detect H pylori, NSAID use, other ulcer inducing medication and rare causes such as Zollinger-Ellison syndrome or Crohn’s disease
What is inflammatory bowel disease an umbrella term for?
ulcerative colitis and crohn’s disease
Symptoms of inflammatory bowel disease
abdominal pain, diarrhoea, PR blood, weight loss, systemic upset, ulcers, fever
What are the main differences between UC and Crohn’s
What are the main complications of inflammatory bowel disease
- Stoma
- Anaemia
- Perforation
- Obstruction/stricture
- Fistulae
- Toxic megacolon
- Malnutrition
- Increased risk of bowel cancer
What are the main invetsigations for inflammatory bowel disease?
- RBC, CRP
- Stool MCS
- Faecal calprotein
- CT scan/MRI
- Endoscopy (sigmoidoscopy, colonoscopy) + biopsies
What are the main treatments for inflammatory bowel disease?
- Aminosalicylates e.g. mesalazine
- DMARDs e.g. azathioprine, methotrexate
- Biologics e.g. infliximab
- Corticosteroids
- Symptomatic relivers (analgesics, laxatives, “constipators”)
- Surgery
