Pharmacology of Gastric Acid Control Flashcards
What are ulcers?
Chronic, usually solitary lesions/sores in areas of the GI tract exposed to acids/peptic juices
Display spontaneous relapse and remission
Where are ulcers most commonly found?
Duodenum
How much more common are duodenal ulcers than gastric ulcers?
4 times
What are the symptoms of ulcers? (5)
Abdominal pain - typically an epigastric burning sensation
Usually nocturnal pain
Heartburn
Bloating
Duodenal ulcer pain relieved by eating
What are the three complications which can arise from ulcers?
Penetration
Perforation
Upper GI bleeding
Does acid hypersecretion cause ulcers?
Only in Zollinger-Ellison syndrome
What is Zollinger-Ellison syndrome?
Rare, gastrin-producing tumour of pancreas or duodenum causing oversecretion of acid
Does smoking cause ulcers?
No, risk factor - interferes with healing/blood flow
By how much does smoking increase the risk of getting ulcers?
50% increase
What is the main bacteria which is associated with ulcers?
Helicobacter pylori
Does Helicobacter pylori cause ulcers?
Causes chronic gastritis which weakens the mucosal barrier allowing ulcers to form
What drugs can cause ulcers?
Aspirin and NSAIDS
What is the main type of ulcer caused by NSAIDs?
Gastric
What percentage of ulcers are idiopathic?
20%
How do NSAIDs and aspirin cause ulcers?
Inhibit prostaglandin production which weakens the mucosal barrier allowing ulcers to form
What must be balanced to prevent ulcers?
Mucosal defense
Acid/pepsin secretion
What are the usual characteristics of gastric ulcers?
Helicobacter pylori infection of gastric corpus
Low-normal levels of acid with defect in gastric mucosal defense
What are the usual characteristics of duodenal ulcers?
Helicobacter pylori infection of pyloric antrum
Increased acid/pepsin secretion causing gastric metaplasia of duodenum which allows infection by H. pylori
What type of tissue can Helicobacter pylori infect?
Gastric
What affects the progression of acute gastritis to chronic gastritis?
Host factors
Strain of Helicobacter pylori
What does antral predominant gastritis lead to?
Duodenal ulcers
What does multifocal atrophic gastritis lead to?
Gastric ulcers
Gastric cancer
Why is there often low levels of acid production with gastric ulcers?
Multifocal atrophic gastritis - ongoing inflammation causes gastric mucosa to be replaced by intestinal and fibrous tissue
Are those in the age group 20-40yo more likely to get gastric ulcers or duodenal ulcers?
Duodenal ulcers
What is Helicobacter pylori?
Spiral-shaped bacterium which causes chronic gastritis
Incidence increases with age
What does Helicobacter pylori do?
Grows on enterocyte surface beneath mucus
Increases secretion of gastrin and pepsin
May produce toxins which damage the mucosa
What is the Cag pathogenicity island?
Collection of genes coding for CagA and a type IV secretion system
Makes some strains of H. pylori especially pathogenic
What is CagA?
Cytoskeleton-disrupting protein
What does a type IV secretion system do?
Injects CagA into epithelial cells
How does Helicobacter pylori protect itself from acid?
Secretes a urease
Converts endogenous urea to HCO3 and CO2 = alkaline bubble
How do we test for H. pylori?
Test for antigens in stool samples
Test for antibodies in blood samples
How does histamine affect parietal cells?
Binds H2 receptors
Increase cAMP and phosphorylation
Increase acid production
How do ACh and gastrin affect parietal cells?
Increase intracellular Ca to increase acid production
Which prostaglandin is prominent in the mucosal defence system?
PGE2
What does PGE2 do?
Bind to EP3 receptors
- On mucus-producing cells to stimulate release of HCO3 and mucus
- On parietal cells to suppress HCl secretion
Vasodilatation
Give an example of a proton pump inhibitor.
Omeprazole
Esomeprazole
What do proton pump inhibitors do?
Irreversibly block parietal cell H/K-ATPase
What is the mechanism of proton pump inhibitors? (4)
Inactive pro-drugs at neutral pH
Absorbed in SI and move via blood to accumulate in oxyntic glands
Converted to sulfenamides at pH<3
React covalently with sulfhydryl groups on ATPase
Why is only one pill of omeprazole required per day?
Proton pump inhibitors irreversibly block H/K-ATPase
Cells must make more H/K-ATPase to secrete acid
What are the adverse effects of PPIs?
Uncommon but long-term use can cause osteoporosis and increased risk of serious cardiac events
Withdrawal can cause rebound acid hypersecretion
Give an example of a H2 receptor blocker.
Famotidine
Ranitidine
Cimetidine
What do H2 receptor blockers do?
Selectively block parietal cell H2 receptors to decrease acid production
What is the adverse effect associated with cimetidine?
Inhibits multiple cytochrome P450s
Retards metabolism of a large number of widely used drugs such as nifedipine and warfarin
Why was ranitidine withdrawn in October 2019?
NDMA contamination (potential carcinogen)
Which drugs enhance mucosal protection? (3)
Bismuth chelate
Sucralfate
Misoprostil
What does bismuth chelate do? (3)
Coats ulcer to protect from gastric juices and promotes healing
Stimulates secretion of mucus, PG, HCO3
Chemotherapeutic effects against H. pylori
What is sucralfate?
Aluminium hydroxide/sulfated sucrose complex
What type of ulcers is sucralfate used for?
Duodenal ulcers not related to NSAID use
Stress ulcers
What is the mechanism of sucralfate?
Negative sulfated sucrose (dissociated from complex) binds HCl to form a viscous adhesive which binds positive groups in the ulcer crater
This buffers acid and stimulates secretion of mucus, PG and HCO3
Decreases number and adherence of H. pylori
How does sucralfate affect other drugs?
Decreases absorption of some drugs like antibiotics
What is misoprostil?
Stable PGE1 analogue which heals and prevents NSAID-induced damage (when taken with NSAID)
What are the adverse effects of misoprostil?
Diarrhoea
Abdominal cramps
Uterine contractions - avoid in pregnancy
Why is antimicrobial therapy sometimes used when treating ulcers?
Eradicate H. pylori and prevent ulcer relapse
How is antimicrobial therapy often used in ulcer treatment?
In combination with H2 blocker or PPI (increased pH to stabilise antibiotic)
2 weeks typically
What is gastro-oesophageal reflux disease?
Reflux of stomach acid back into oesophagus
What are the symptoms of GORD?
Pain (oesophageal)
Oesophagitis
Heartburn
Bad taste in mouth
What is heartburn?
Retrosternal burning pain brought on by meals or lying flat
What can increase the risk of developing GORD?
Transient lower oesophageal sphincter relaxation or atonic LOS
Increased intra-abdominal pressure due to obesity/pregnancy/heavy meals
Why does GORD often worsen during sleep?
Normal defence mechanisms less active (salivation and swallowing)
How can GORD affect the oral cavity?
Tooth erosion
How does GORD cause tooth erosion?
Acid removes pellicle protection and can easily get beneath saliva due to lower surface tension
Dished-out lesions
What lifestyle modifications might be advised for a GORD patient?
Leave at least 2 hours between meals and bedtime
Reduce fat, alcohol, coffee, chocolate intake
Elevate head during sleep
What drugs may cause GORD?
Birth control pill
Hormone replacement therapy
Ca channel blockers
What can be used to treat less severe GORD cases and how?
Antacids/alginic acid
Neutralise stomach acid
How does alginic acid work?
Detergent which forms a foam ‘raft’ on top of stomach contents
Acts as a physical barrier to reduce reflux
Why might gastric motility-stimulation agents be used with a PPI? Why don’t we use this?
Increase tone of lower oesophageal sphincter
Side effects
(Metoclopromide and domperidone)
