Anti-Ulcer Drugs Flashcards
What are the two types of peptic ulcer?
Gastric ulcer
Duodenal ulcer
Describe how gastric ulcers and duodenal ulcers can be distinguished based on their symptoms.
Gastric ulcer – pain at meal times when gastric acid is secreted
Duodenal ulcer – pain relieved by a meal as the pyloric acid closes –pain -3 hours after a meal
Which type of peptic ulcer is more common?
Duodenal (4:1)
What are the protective factors that protect the stomach lining from damage?
Mucous lining the stomach
Bicarbonate produced by cells in the stomach
Prostaglandins facilitate a good blood flow in the stomach, increasemucous and bicarbonate production and inhibit acid secretion
Which cells produce stomach acid?
Parietal cells
Which cells produce pepsinogens?
Gastric chief cells
State some factors that could contribute to the pathogenesis of ulcers.
Increase in acid production Decrease in bicarbonate production Decreased thickness of mucosal layer Increase in pepsin Decreased mucosal blood flow Increase in H. pylori
What is the aim of antibiotics treatment with regards to ulcers?
90% eradication of H. pylori within 7-14 days
What is a simple way of testing for the presence of helicobacter in a subject?
Give a urate mixture that contains a distinctive isotope of carbon
H. pylori has enzymes that can break down the urate mixture and liberate the carbon isotope
This carbon isotope is then incorporated into carbon dioxide and is breathed out – this can then be detected to confirm high levels of H. pylori
What treatments can be put together to form the best practice ‘Triple Therapy’?
Antibiotics
Drugs that reduce gastric acid secretion
Drugs that promote healing
Where are parietal cells found in the stomach?
Fundus
Which cells in the stomach produce histamine?
H cells
Explain how the parasympathetic nervous system affects gastric acid production.
The parasympathetic nervous, via the vagus nerve, stimulates histamine production by H cells
Histamine then stimulates an increase in acid production by parietal cells
Which cells in the stomach produce gastrin and where are these cells found?
G cells
Located in the antrum
What triggers gastrin release from G cells?
The breakdown of food in the stomach and the liberation of amino acids stimulate gastrin release
What are the effects of gastrin?
They trigger the release of histamine from H cells
They also directly trigger acid production by the parietal cells
What do D cells release?
Somatostatin
What are the effects of somatostatin?
It is inhibitory – it decreases the release of histamine and gastrin
What type of ion transporter is the proton pump found in parietal cells?
H+/K+ ATPase
Which cells produce bicarbonate?
Superficial epithelial cells
Give an example of a proton pump inhibitor.
Omeprazole
What is the mechanism of action of PPIs?
Irreversible inhibitors of H+/K+ ATPase
What are the effects of PPIs?
Inhibits basal and stimulated gastric acid secretion from the parietal cells by >90%
What features of PPIs limits its action on other proton pumpsaround the body?
Inactive at neutral pH
It is a WEAK BASE so it accumulates in the cannaliculi of the parietal cells – this concentrates its actions in the cannaliculi
What are some uses of PPIs?
Peptic ulcers
GERD
Prophylaxis of ulcers in the intensive care setting, and among high-risk patients being prescribed aspirin, NSAIDs, anti-platelets and anticoagulants
Describe the pharmacokinetics of omeprazole.
Orally active
Enteric-coated slow release formulation
What are the unwanted effects of omeprazole?
Rare with short-term use
Long-term and high-dose use is associated with enteric infections, community acquired pneumonia, hip fracture
Give two examples of histamine receptor antagonists.
Cimetidine
Ranitidine
What are the effects of histamine receptor antagonists?
Inhibits gastric acid secretion from the parietal cells by about 60%
Describe the pharmacokinetics of histamine receptor antagonists.
Orally active
Ranitidine is longer acting than cimetidine
What are the unwanted effects of histamine receptor antagonists?
Rare – dizziness, headache
Ranitidine has fewer side effects
Give three examples of cytoprotective drugs.
Sucralfate
Bismuth Chelate
Misoprostol
What is sucralfate composed of?
It is a polymer containing aluminium hydroxide and sucrose octa-sulfate
Describe the mechanism of action of sucralfate.
It acquires a strong negative charge when in an acidic environment
It binds to positively charged groups in large molecules (proteins, glycoproteins) resulting in gel-like complexes
The gel-like complexes coat and protect the ulcer, limit H+ diffusion and pepsin degradation of mucus
It also increases prostaglandin synthesis and reduces H. pylori
What are the unwanted effects of sucralfate?
Most of the orally administered sucralfate remains in the GI tract and this may cause constipation or reduced absorption of other drugs
How does bismuth chelate work?
Same as sucralfate
What is misoprostol?
It is a prostaglandin analogue (PGE1)
What are the uses of misoprostol?
May be co-prescribed with oral NSAIDs when used chronically
What are the unwanted effects of misoprostol?
Diarrhoea Abdominal cramps Uterine contractions (not to be given during pregnancy)
Give three examples of antacids and their speed of onset.
Sodium bicarbonate (FAST) Aluminium hydroxide (slow) Magnesium trisilicate (slow)
What is the drug of choice for gastroesophageal reflux disease?
Proton pump inhibitors e.g. omeprazole
What other type of drug could be given with PPIs to reduce the risk of reflux?
Drugs that increase gastric motility and gastric emptying e.g. dopamine receptor antagonists
Why is it important to treat GERD?
Chronic GERD can progress to pre-malignant mucosal cells that can potentially lead to oesophageal adenocarcinoma
