Pharmacology of the upper GI tract Flashcards
What drugs may lead to peptic ulcers
NSAIDs
What bacteria is the main cause of peptic ulcers
H.Pylori
What is dyspepsia
Dysfunction of the upper GI tract
How do Calcium channel inhibitors affect GERD
Promote the opening of the lower oesophageal sphincter which makes the acid come up into the oesophagus
What conditions can cause GERD
Obesity
Pregnancy
Because they increase intra-abdominal pressure
Where is peptic ulceration more common
Duodenum
What is Zollinger-Ellison syndrome
Cells that secrete gastrin (D and/or G cells in pancreas) have a tumour. Gastrin promotes acid secretion
What Is gastritis
Inflammation of the stomach
What are signs and symptoms of peptic ulceration
Epigastric pain
-Pain is variable in relation to food
Hunger pain, which is relieved by eating
Night pain which is relieved by food, milk or antacids
Waterbrash (more salivating than normal because you have acid in your throat)
Nausea and less frequently vomiting
Vomiting blood- haematemesis
What can a H.Pylori infection lead to
Chronic inflammation and gastric damage leading to ulceration
What are the tests done to see if there is H.Pylori
Urea breath test (13C)
Biopsy for urease activity
H.Pylori antigens/antibodies in blood, saliva and stools
Warning signs of peptic ulceration which indicate complications
- Over the age of 55 as it might be stomach cancer
- Weight loss
- Anaemia
- Dysphagia (can be associated with oesophageal cancer)
- Haematemesis (vomiting blood)
- Malaena
- Upper abdominal masses
- Persistent symptoms with repeat requests for OTC remedies
- Onset of new symptoms
What increases acid secretion
Histamine via H2 receptors
Gastrin
Acetylcholine via M-receptors - M3 on parietal cells
What decreases acid secretion
Prostaglandins (released by Cox) (E2 and I2)
Cytoprotective via bicarbonate and mucus release
Goals of treatment for GERD
- Avoidance of causative drugs
- Avoidance of causative foods
- Propping up bed, removing belt
What do antacids do
Raise pH
What are examples of antacids
Sodium bicarbonate and magnesium hydroxide
What are alginates and examples of them
Gaviscon
- Alginic acid when combines with saliva forms a viscous foam
- This floats on the gastric contents forming a raft which protects the oesophagus during reflux
What are Histamine H2 antagonists used for
Low dose OTC for short term relief
What is the mechanism of action of histamine H2 receptors
Coupled via adenylyl cyclase to increase cAMP which actives the proton pump
If histamine H2 antagonists don’t help, and if the patient is over 45 yo, what should the pharmacist do
Refer to doctor to rule out stomach cancer
When are histamine H2 antagonists best given
at night
What is a caution for cimetidine
INhibtis cp450 and therefore the metabolism of other drugs, resulting in important drug interactions e.g. oral anticoagulants
Which histamine H2 antagonist does not inhibit the metabolism of other drugs
Ranitidine
How do proton pump inhibitors work
Irreversible inhibition of the proton pump (H+/K+-ATPase)
Why are PPIs very well tolerated
Because they are very selective to the stomach (activated by acidic pH)
Which cells to PPIs act on
Parietal cells
What are the side effects of PPIs
Inhibit H+ secretion by >90% so may lead to achlorhydia
Increases risk of campylobacter infection (particularly in older patients) which is food poisoning
How is a helicobacter pylori infection eradicated
Triple therapy
2 antibiotics from:
- clarithromycin
- amoxicillin
- metranidazole
plus
PPI and/or H2 antagonist
Triple therapy for 1 week then PPI alone
Which antibiotics should you not have alcohol with
Metronidazole
What is the second line therapy for helicobacter
Quadruple therapy
Combination of metronidazole and tetracycline and omeprazole
Bismuth subcitrate potassium may be useful
IN the absence of H pylori dyspepsia, what is the treatment
PPI/H2RA
What is the arachidonic acid pathway
Membrane gets chopped up by PLA2 and forms arachidonic acid. The arachidonic acid then forms leukotrienes and prostaglandins
How do steroids affect the arachidonic acid pathway
They form lipocortin which inhibits PLA2 so stops the pathway
How do NSAIDs affect the arachidonic acid pathway
They inhibit COX which is used to form prostaglandins. Prostaglandins are protective in the stomach so you lose that protection when having NSAIDs
IF the patient is over the age of 65, and the patient is taking NSAIDs, what is a preventative measure to minimise GI damage
Prescribe PPIs
Give in combination with misoprostol (acts on prostanoid receptors to inhibit gastric H+ secretion)
Who should misoprostol not be given to
Females of child bearing age because it can cause abortions
Does taking NSAIDs with food prevent stomach ulcers
No. It only helps with reducing irritation
