Treatment of Gastric and Duodenal Ulcers (20.02.2020) Flashcards
Acute gastric/duodenal ulcer symptoms
- Epigastric pain
- burning sensation that occurs after meals
What are the most important tests for ulcers?
- Carbon-urea breath test – positive (suggests H. pylori presence)
- Stool antigen test – positive -> confirms H. Pylori
Diagnosis = H Pylori positive peptic ulcer
Pathophysiology of H. pylori
- Dissolves mucus layer (in small portions) -> urease enzyme
- Causes epithelial cell death (exotoxins, inflammation)
- Increased acidity -> peptic ulcer
can cause upper GI blood loss
Treatment of an acute H Pylori positive peptic ulcer (first line)
- Amoxicillin & Clarithromycin/Metronidazole – Antibiotics that are most effective against that bacterium
- Proton Pump Inhibitor (PPI) – reduces acid production (7d)
Helicobacter pylori
- causes mucous layer to dissolve
- Gram negative, motile, microaerophilic bacterium
- Resides in human GI tract – exclusively colonising gastric-type epithelium
- generally it is a commensal bacterium, found in many people
How does H pylori cause ulcers?
- Increased gastric acid formation – increased gastrin or decreased somatostatin
- Gastric metaplasia – cell transformation due to excessive acid exposure
- Downregulation of defence factors - decreased epidermal growth factor & decreased bicarbonate production
- The Urease enzyme is very problematic, a product damages epithelial cells, evokes immune response
- certain virulent strains produce cytotoxins
=> does several different things, multi front attack on the gastric epithelium
Virulence of H. pylori
- Urease – catalyses urea into ammonium chloride & monochloramine -> damage epithelial cells
- Urease – antigenic -> evokes immune response
- Certain virulent strains produce CagA (antigenic) or VacA (cytotoxic) – more intense tissue inflammation
Presentation of chronic ulcers
- Epigastric pain
- burning sensation
Had an ulcer before
Treatment of chronic peptic ulcers
- Antibiotics for H Pylori (amoxicillin & clarithromycin/metronidazole)
- Consider quinolone, tetracycline, bismuth (peptobsimol), sucralfate -> alkalating agents, create a less acidic environment in the stomach, increase pH
- Proton Pump Inhibitor (omeprazole) – 4-12 weeks
Triple therapy with AB, PPI and maybe bismuth/sucralfate or AB other option that first ones
Proton pump
H+-K+-ATPase (proton pump)
- Expressed on secretory vesicles within parietal cells
- increased [Ca2+]ic -> increased cAMP -> translocation of secretory vesicles to parietal cell apical surface -> H+ secretion
(- cAMP is directly linked to Gs proteins)
In ulcers: Increased activity of proton pump – increased H+ secretion -> reduction gastric pH
=> treat with PPIs
Are most ulcers H pylori positive or negative?
positive
What is the second most common cause of ulcers?
NSAID use
Presentation of a H. pylori negative ulcer
Epigastric pain
burning sensation
INVESTIGATIONS and diagnosis of a Hp negative ulcer
Carbon-urea breath test – negative
Stool antigen test – negative
NSAID use – positive
NSAIDS and ulcers
- Directly cytotoxic
- Reduces mucus production
- Increases likelihood of bleeding
- Increased acidity -> peptic ulcer
REWATCH THIS PART
How do you treat NSAID induced ulcers?
- removal of NSAID (this is not always possible, the patient might be taking the NSAID for their heart)
- Proton Pump Inhibitor or histamine H2 receptor antagonist (Ranitidine) – 4-8 weeks
(- H2 receptor increases acid secretion)
Ranitidine
- histamine H2 receptor antagonist
- effective for ulcers
- not used that commonly because PPIs are more effective
Give an example of an H2R antagonist
Ranitidine
- effective for ulcers
- not used that commonly because PPIs are more effective
What can cause changes in PPIs?
- Acetylcholine (ACh) released from neurones (vagus / enteric) acts on muscarinic (M3) receptors - increases [Ca2+]i
- Prostaglandins (PGs) released from local cells act on EP3 receptors - ↓ cAMP => PROTECTIVE
- Histamine released from enterochromaffin-like cells (ECL) act on H2 receptors - increase cAMP
- Gastrin released from G-cells, acts on cholecystokinin B receptors - increase [Ca2+]i
What increases / decreases PPIs?
Increases:
- ACh
- Histamine
- gastrin
Decreases
- Prostaglandin
What effects does ACh have of PPIs?
Acetylcholine (ACh) released from neurones (vagus / enteric) acts on muscarinic (M3) receptors - increases [Ca2+]i
=> increased H+ secretion
What effects does histamine have of PPIs?
Histamine released from enterochromaffin-like cells (ECL) act on H2 receptors - increase cAMP
-> increased gastric acid secretion
What effects do prostaglandins have of PPIs?
Prostaglandins (PGs) released from local cells act on EP3 receptors - ↓ cAMP
=> decreased H+ secretion
What effects does gastrin have of PPIs?
Gastrin released from G-cells, acts on cholecystokinin B receptors - increased [Ca2+]i
=> increased H+ secretion
MCQ 2: Which of the following drugs is not used in the treatment of peptic ulcers?
- amoxicillin
- aspirin
- omperazole
- ranitidine
- other AB
Aspirin
MCQ 3: activation of which receptor does not cause increased secretion of
EP3 and SS-receptor activation
LO1: Explain the underlying pathology of peptic ulcers
- Helicobacter pylori: increased gastric acid formation; gastric metaplasia; decreased defence factors
- Proton pump: H+ secretion - activated by increased Ca2+ and increased cAMP
- Histamine released from ECL cells act on H3 receptors - I increased cAMP
LO2: Identify the drugs used in the treatment of peptic ulcers and their mechanisms of action
- Antibiotics: removal of H pylori infection
- Proton pump inhibitors: e.g. omeprazole – reduce acid -production from parietal cells
- Histamine H2 antagonists: reduce acid production from parietal cells
MCQ 3: activation of which receptor does not cause increased secretion of H+?
- ACh
- EP3
- Histamine
- Gastrin R
- SS R
EP3 and SS-receptor activation
LO1: Explain the underlying pathology of peptic ulcers
- Helicobacter pylori: increased gastric acid formation; gastric metaplasia; decreased defence factors
- Proton pump: H+ secretion - activated by increased Ca2+ and increased cAMP
- Histamine released from ECL cells act on H3 receptors - increased cAMP
