Session 11 - GI Pharmacology Flashcards
What is GORD?
Symptoms or complications resulting from the reflux of gastric contents into the oesophagus or beyond.
Types of GORD.
Erosive
Non-erosive
Symptoms/Signs of GORD.
Heart burn
Cough
Laryngitis
Astha
Dental erosion
Complications of GORD
Oesophagitis
Ulceration
Haemorrhage
Stricture formation
Barrett’s oesophagus
Risk factors of GORD.
Older age
Hiatus hernia
Obseity
Pregnancy
Smoking
Alcohol consumption
Give examples of medications that can exacerbate GORD.
Alpha-blockers
Anticholinergics
Benzodiazepines
Beta-blockers
CCBs
Corticosteroids
NSAIDs
Give examples of lifestyle options in order to manage GORD.
Weight loss
Avoiding trigger foods
Smaller meals
Reduce alcohol and caffeine intake
Stop smoking
Medication pathway for GORD.
Proton pump inhibitor to start with.
In case it’s not enough add in H2 Receptor antagonist.
If that is not enough surgery (fundoplication)
Give examples of PPis
Omeprazole
Esomeprazole
Rabeprazole
Pantoprazole
Lansoprazole
What is gastritis?
Inflammatory changes in the gastric mucosa.
Can be either erosive or non-erosive.
Can be either acute or chronic.
Symptoms of gastritis.
Usually asymptomatic but:
Burning epigastric pain
Nausea
Vomiting
Complications of gastritis
GI tract bleeding
Risk factors of gastritis
H pylori infection
Chronic NSAID use
Bile refluxe
Treatment of erosive causes of gastritis, such as NSAIDs, alcohol or bile.
Reduce or stop the irritants
Give PPi or H2 RA.
Treatment of non-erosive gastritis such as H. pylori.
Triple therapy with PPi and 2x antibiotics
Quadruple therapy with PPi, bismuth and 2x antibiotics.
Treatment of autoimmune gastritis.
Cyanocobalamin treatment to treat the atrophy
State which drugs are used in triple therapy of non-erosive H. pylori gastritis.
PPi such as omeprazole
Amoxicillin
Clarithromycin or Metronidazole
What is peptic ulcer disease?
Defects in the gastric or duodenal mucosa that extend through the muscularis mucosa.
Symptoms of peptic ulcer.
Epigastric pain after meals
Soon after if gastric ulcer
2-3 hours after if duodenal.
Complications of peptic ulcers.
Perforation leading to peritonitis
Risk factors of peptic ulcers.
H. pylori
NSAIDs
Treatment of peptic ulcer if H. pylori negative
Stop NSAIDs and give COX-2 inhibitor instead such as celecoxib.
Give PPi and consider H2 RA if PPi is not effective.
Consider misoprostol if NSAIDs need to be given.
Treatment of peptic ulcer if H. pylori positive.
PPi
Amoxicillin
Clarithromycin or metronidazole
How is H. pylori tested for?
Carbon-13 urea breath test
Stool antigen test
Laboratory based serology
Luminal defences of the GI tract.
Acid to reduce bacterial invasion
Mucus to lubricate to reduce physical damage, traps bacteria, barrier against pepsin etc…
Epithelial defence of GI mucosa.
Apical membrane of parietal and chief cells hare highly resistant to acid
Renewable every 2-4 days.
Blood flow defence of GI mucosa
If epithelium is destroyed rapid repair can occur.
Give examples of gastric prostaglandins and their effects.
PGE2
PGI2
They are potent vasodilators that decrease acid secretion and stimulate mucus and bicarbonate secretion in stomach.
Also reduce permeability of epithelium to back flow acid.
Reduce the release inflammatory mediators that may contribute to mucosal injury.
Promotes ulcer healing by increasing blood flow.
Explain parietal cells in their resting/non secreting state and the transformation into secreting/stimulated state.
The proton pumps (H+/K+-ATPase) are located in membrane bound compartments called tubulovesicles. They lack K+ permeability and block proton pump activity.
The apical membrane of the parietal cell has K+ channels and involutions.
The tubulovesicles then fuse with the canalicular membrane and moves the proton pumps to a position where they can exchange H+ for K+.
PPis are prodrugs. How are they activated?
Pro drugs that are activated by the acidic conditions of the parietal cell caniculi.
The PPis are weak bases and will accumulate in the acidic space.
Oral forms of PPis can be activated prematurely in the stomach.
How is this prevented?
By an enteric coating of the PPi
Mechanism of action of PPis.
Bind covalently to gastric proton pumps, irreversibly and block the function.
This leads to prologed and nearly complete suppression of acid secretion and needs de novo synthesis of pump enzyme to produce more acid
Pharmacokinetics of PPis
Metabolised by CYP2C19 and CYP3A4
The metabolites are then excreted by the kidneys.
ADRs of PPis
Headache
Nausea
GI tract issues
Abdo pain
Can lead to increased levels of gastrin and therefore parietal cell and ECL hyperplasia. This may leead to increased risk of gastric carcinoid tumours.
Increase risk of hip fractures
Can lead to increased risk of various infections
How will PPIs react with clopidogrel?
May decrease the effectiveness of clopidogrel as both use CYP2C19. And clopidogrel use that enzyme to activate.
Mechanism of action of H2 RAs.
Competitively and reversibly inhibit binding of histamine to H2 receptors.
Indirectly block the effects of gastrin and ACh on parietal cells and therefore less H+ secretion.
They are rapidly absorbed in the small intestine and then excreted by the liver and kidneys.
Give an example of a H2 receptor antagonist.
Cimetidine
ADRs of H2 RAs.
Diarrhoea
Constipation
Muscle ache
Fatigue
DDIs of cimetidine.
Inhibits several cytochrome P450 enzymes leading to decreased metabolism of lidocaine, phenytoin, theophylline and warfarin and can potentially lead to toxic levels of these drugs.
Give an example of a prostaglandin analogue.
Misoprostol
Explain the action of misoprostol.
Acts of PGE2 and via the prostaglandin will inhibit seceretion of more H+.
It is used to treat NSAID induced ulcers.
ADRs of misoprostol.
Diarrhoea
Abdo pain
Contraindications of misoprostol.
In pregnant women it can cause uterine contractions and possible abortion.
Mechanism of action of antacids.
Neutralise HCL by reacting with the acid to form water and salt.
Give examples of antacids.
Aluminium hydroxide
Magnesium hydroxide
Sodium bicarbonate
Calcium bicarbonate
ADRs of Aluminium hydroxide.
Can cause constipation
Can bind phosphate and result in low phosphate levels leading to malaise and weakness.
In the presence of renal failure it can cause neurotoxicity
ADRs of magnesium hydroxide.
Diarrhoea
Can lead to increased magnesium levels in renal failure
When to avoid sodium bicarbonate?
Since it forms water, CO2 and salt when it reacts with HCL it needs to be avoided in hypertension and fluid overload.
How does H. pylori cause damage to GI mucosa?
Can attach to gastgric epithelia and produce urease.
It also produces a strong immune response and produces ammonium hydroxide that is toxic to gastric epithelia.
It also has endotoxins which are directly toxic.
