Peptic Ulcers Flashcards
What is a peptic ulcer?
An area of damage to the inner lining of the stomach (gastric ulcer) or the upper part of the duodenum (duodenal ulcer)
How can gastric ulcers and duodenal ulcers be distinguished
based on timing of symptoms:
Gastric ulcer causes pain at meal times when the acid is secreted and a duodenal ulcer causes pain to be relieved by a meal as the pyloric sphincter closes (pain starts after 2-3 hrs)
What are examples of protective factors of the GI barrier
- mucus from gastric mucosa to make GI mucosal barrier
- HCO3- ions are trapped in the mucous and generate a protective pH of 6-7 at the mucosal surface
- locally produced prostaglandins stimulate mucus and bicarb production (paracrine action) and inhibit gastric acid secretion and facilitate a good blood supply to the stomach
Why is are protective factors needed in the GI barrier
Lubricate the food and protect the mucosal surface
What are factors that convert the food into chyme that can damage the mucosal barrier?
- parietal cells that secret acid from the oxyntic glands in the gastric mucosa
- chief cells that are pepsinogens that erode the mucus layer
What are factors that contribute to mucosal damage?
- increased acid, decreased HCO3-
- Decreased thickness of mucosal layer
- Increased pepsin layer 1
- Decreased mucosal blood flow
- Infections with H pylori
- risk factors eg genetics, stress, diet (alcohol, smoking)
What are types of drugs that are used to treat peptic ulcers
- antibiotics
- inhibitors of gastric acid secretion
- cytoprotective drugs
- antacids
- triple therapy
What is triple therapy? What drugs are used for peptic ulcers
Clarithromycin, amoxicillin, proton pump inhibitor (omeprazole) - antibiotics more than one type bc there is some small resistance and some drugs reduce gastric acid secretion and some promote healing
What are examples of inhibitors of gastric acid secretion
- proton pump inhibitors; omeprazole
- H2 receptor antagonists; cimetidine, ranitidine
- anti muscarinics
What are the target sites or situations for gastric acid secretion inhibitors
- presence/smell of food can trigger
- fundus acid secreting parietal cells.
- PNS can act on H cells to stimulate histamine production - antrum amino acids can trigger g cells to secrete gastrin
- Gastrin triggers more histamine release or can simply trigger more acid production directly (CCKb receptors)
What happens when acid is produced in the stomach
Acid is produced by a H+/K+ exchanger, and histamine acts on H2 receptors on patietal cells to trigger activation of these exchangers via cAMP pathway. Superficial epithelial cells procide the protective bicarb secretion which mixes with the mucus to protect
What is the MoA of omeprazole?
IRREVERSIBLE INHIBITOR OF H+/K+ ATPASE EXCHANGER
that becomes inactive at neutral pH therefore limiting action on other PP around the body
Where does omeprazole accumulate and why
At the canaliculi because is a weak base so concentrates action here
What are the uses of omeprazole
- peptic ulcers resistant to the H2 receptor antagonist
- triple therapy component
- GERD and oesophagitis
- prophylaxis of peptic ulvers in intensive care, high risk patient prescribed aspirin, NSAIDs, antiplatelets and anti coagulants
How is omeprazole administered?
Oral in an enteric coating
What are side effects of omeprazole? Why do they not usually happen
Enteric infections eg c difficile, community acquired pneumonia, hip fracture
Rare because short term treatment
What is the moA of cimetidine and ranitidine?
Competitive H2 receptor antagnoists
Administration, acting length of cimetidine and ranitidine?
Oral and Ranitidine acts longer
What are side effects of cimetidine and ranitidine
Headaches, dizziness and fever side effects of ranitidine (available OtC)
Why are H2 receptor antagonists used in triple therapy
relapses are likely after withdrawal from treatment
Why aren’t muscarinic drugs used to treat peptic ulcers
Anti ulcer drugs are more effective in combination therapies so they aren’t used a lot
What are examples of cytoprotective drugs used in peptic ulcers?
Sucralfate, bismuth chelate, misoprostol
What is the moA of sucralfate?
In an acid environment it needs a strong neg charge as it binds to the positive groups in large molecules resulting in gel like complexes. This coats and protects the ulcer, limiting H+ diffusion and pepsin degradation of mucus
What do cytoprotective drugs do in peptic ulcers
Enhance the mucosal protection and/or build a physical barrier over the ulcer
What are the side effects of sucralfate
Mostly orally administered sucralfate remains in the GIT so can cause constipation or reduced absorption of other drugs eg digoxin and antibiotics
What is the moA of bismuth chelate/pepto bismol
Acts like sucralfate - makes gel like complezes that increase prostaglandin, mucus and HCO3- production and decreases number of H pylori
What is the moA of misoprostol?
Mimics action of prostaglandins to maintain mucosal barrier - prostaglandin analogue
What is the use of misoprolol
Co-prescribed with NSAIDs when used chronically as NSAID block the COX enzymes required for PG synthesis from arachidonic acid
What are side effects of misoprostol?
Diarrhoea, abdominal cramps, uterine contractions (so don’t give to pregnant women)
What is the moA of antacids
Neutralise acid, raise gastric pH, reduce pepsin activity
What is the speed of action of different antacids
Sodium bicarbonate has rapid effects whilst aluminium hydroxide and magnesium trisilicate have slower actions.
What are examples of antacids
Salts of Na+, Al3+, Mg2+
What are antacids usually used for?
Non ulcer dyspepsia eg rennie (OTC)
What are examples of drugs used in triple therapy
Example 1:
o Metronidazole / amoxicillin. (Anaerobic bacteria or protozoa / broad-spectrum.)
o Clarithromycin. (Macrolide antibiotic – inhibits translocation of bacterial tRNA.)
o Proton pump inhibitor.
Example 2:
o H2-receptor antagonist.
o Clarithromycin.
o Bismuth.
What are problems with triple therapy
- compliance
- antibiotic resistance
- adverse response to alcohol (metronisazole)
What is GORD/GERD, OTC?
Patients experience heart burn so OTC medication - antacids and H2 antagonists
What is the benefit of triple therapy
the inclusion of antibiotics along with inhibitors of gastric acid secretion or cytoprotective agents in the treatment of gastric acid secretion or cytoprotective agents in the treatment of peptic ulcers reduces relape rates from>90% to <15%
What is chronic GORD called and what is used to treat it
Barrett’s oesophagus and PPIs or H2 antagonists are used to treat it (latter is less effective but used in patients that are resistant to PPIs)
