18. GI Pharmacology Flashcards
what are the two types of peptic ulceration?
Gastric and duodenal ulcers
What are peptic ulcers?
Peptic ulcers are defects in the gastric or duodenal mucosa that extend through the muscularis mucosa
What are the symptoms of peptic ulcers?
Epigastric pain after meals - location of pain not reliable guide to ulcer location
• Soon after meals (gastric ulcer
• 2-3 hours after (duodenal)
What are the complications of peptic ulcers?
- haemorrhage
- perforation (peritonitis)
- scarring and obstruction (of gastric outlet)
What are the risk factors for peptic ulcers?
• H- pylori infection
• NSAIDs - inhibit protective action of prostaglandin
• Acid essential for ulceration and inability of
normal [acid] to inhibit further acid is a significant factor
• Early gastric emptying
• Smoking and alcohol delay healing
describe the factors that affect acid secretion
- proton pump pumps H+ out of parietal cell and K+ in
- acetylcholine and gastrin, through the release of calcium ions, activate protein kinase which stimulates the proton pump
- histamine binds to g protein coupled receptors and activate adenylyl cyclase which converts ATP to cAMP which activates protein kinase
- prostaglandin inhibit action of adenylyl cyclase
What is the goal of treatment for peptic ulcers?
Eliminate underlying cause, relieve symptoms, heal ulcers and treat complications (bleeding)
what are the action of alginates and antacids?
• antacids – Buffering stomach acid
alginic acid – increase stomach content viscosity and reduce reflux
• Often taken as compound preparations
name of a drug containing alginates and antacids?
Gaviscon
give more detail on preparation of Gaviscon
Alginic acid – sodium alginate + aluminium hydroxide/magnesium carbonate - antacids
adverse effects of Gaviscon?
Magnesium salts can cause diarrhoea and aluminium salts can cause constipation
warnings, contraindications for Gaviscon?
- Na+ and K+ containing preparations should be used with caution in renal failure
- High [sucrose] in some preparations - hyperglycaemia in DM
Δ important drug interactions of gaviscon?
- Can reduce absorption of many drugs so doses should be separated
- Increased urine alkalinity can increase aspirin excretion
action of Proton pump inhibitors (PPI)?
• Irreversibly inhibit the H+/K+ ATPase in gastric parietal cells
Final stage in the pathway – very significant reduction in acid secretion
examples of Proton pump inhibitors (PPI)?
Lansoprazole
Omeprazole
adverse effects of Proton pump inhibitors (PPI)?
- GI disturbance – abdominal pain, constipation diarrhoea
- Headache, dizziness
- Drowsiness/confusion
warnings, contraindications of Proton pump inhibitors (PPI)?
- Mask symptoms of gastro-oesophageal cancer
* Osteoporosis – fracture risk - reduced absorption of calcium
Important drug interactions of Proton pump inhibitors (PPI)?
- Omeprazole CYP inhibitor – reduced clopidogrel action
* PPIs can increase effects of warfarin and phenytoin - monitor
aim when prescribing Proton pump inhibitors (PPI)?
Shortest effective duration at lowest effective dose
what is often prescribed alongside Proton pump inhibitors (PPI)?
Often prescribed along side long term NSAID (due to risk of ulceration) or steroid
Action of H2 receptor antagonists?
- Inhibition of H2 receptors – local histamine release contributes to proton pump activation
- Other routes to pump inhibition mean only partial reduction in acid secretion
example of H2 receptor antagonists?
Ranitidine
adverse effects of H2 receptor antagonists?
generally well tolerated - diarrhoea, headache
warnings, contraindications of H2 receptor antagonists?
Mask symptoms of gastro-oesophageal cancer, careful renal impairment as excreted renally
Important drug interactions of H2 receptor antagonists?
Few common DDIs – (reduced exposure to some antivirals and protein kinase inhibitors)
why is there Current large scale recall on most ranitidine containing products and what is given instead?
due to possible carcinogenic contaminant
- lansoprazole typically first alternative upon patient review
when should H pylori be considered?
Consider for all patients with duodenal or gastric ulcers not associated with NSAID or unresponsive to lifestyle PPI and antacids
how is H pylori tested?
urea breath test - given urea labelled with carbon 12. urease produced by h pylori converts urea to CO2 which is breathed out
How is H pylori treated
•One week triple therapy
PPI + two antibacterial agents
• Lansoprazole + clarithromycin + amoxicillin
OR
Lansoprazole + clarithromycin + metronidazole
where allergic to amoxicillin
what are Amionsalicylates used for?
Used as a first line treatment in ulcerative colitis (UC) - anti inflammatory action
example of Amionsalicylates ?
Mesalazine
action of Amionsalicylates ?
Release of 5-aminosalsylic acid
Topical action at the colon (enteric coated tablets limit gastric breakdown)
role of Mesalazine in rheumatoid arthritis?
• mesalazine has no role in rheumatoid arthritis
• sulfasalazine has more side effects so used infrequently for UC but sulfa group good for
rheumatoid arthritis
adverse effects of Amionsalicylates ?
GI disturbance – nausea, dyspepsia
leukopenia - rare
warnings, contraindications of Amionsalicylates ?
are salicylates like aspirin – similar hypersensitivity
Important drug interactions of Amionsalicylates ?
Enteric coated tablets may break down quicker in presence of PPI (because of ↑pH)
