Pharmacology of Gastro-Oesophageal Reflux Disease (GORD) / Peptic Ulcer Disease Flashcards
Non-steroidal anti-inflammatory drugs (NSAIDs) Proton pump inhibitors (PPIs) Histamine (H2) receptor antagonists Acetaminophen
What are non-steroidal anti-inflammatory drugs (NSAIDs) used for?
Used as:
- Analgesics for relief of mild to moderate pain
- Antipyretics to reduce fever
- Anti-inflammatory for chronic control fo inflammatory disease
An NSAID is used to treat:
- Rheumatoid arthritis
- Osteoarthritis
- Ankylosing spondylitis
- Polyarticular juvenile idiopathic arthritis
- Tendinitis
- Bursitis
- Acute gout
- Primary dysmenorrhea
- Mild to moderate pain
What is the primary drug target of non-steroidal anti-inflammatory drugs (NSAIDs)?
- Cyclo-oxygenase (COX) enzyme
What is the drug target type of non-steroidal anti-inflammatory drugs (NSAIDs)?
- Enzyme inhibitor
What are the locations of action of non-steroidal anti-inflammatory drugs (NSAIDs)?
- Nerve endings (COX-2)
- Intestinal mucosa (COX-1)
What is the mechanism of action of non-steroidal anti-inflammatory drugs (NSAIDs)?
- NSAIDs are non-selective COX inhibitor
- Inhibits the activity of COX-1 & COX-2
- Inhibition of COX-1 is thought to cause some of the side effects of NSAIDs
- Inhibition of COX-2 decreases the synthesis of prostaglandins
- Inhibition of the pain, fever, swelling and inflammation
What are the main adverse effects of non-steroidal anti-inflammatory drugs (NSAIDs) (10)?
-
Common:
- Gastric irritation
- Ulceration
- Bleeding
-
Rare:
- Perforation
- Reduced creatine clearance
- Allergies
- Possible nephritis
- Bronchocostriction
- Skin vasles
- Dizziness
- Tinnitus
-
Cardiovascular effects (may occur after prolonged use or in patients with pre-existing CV risk):
- Hypertension
- Stroke
- MI
- Chronic renal failure (associated with prolonged analgesic abuse)
Give 4 examples of non-steroidal anti-inflammatory drugs (NSAIDs).
- Ibuprofen
- Diclofenac
- Naproxen
- Aspirin
What is the main adverse effect of aspirin (special non-steroidal anti-inflammatory drugs (NSAIDs))?
- Rare but serious post-viral encephalitis in children
What is the main action of aspirin different from the rest of non-steroidal anti-inflammatory drugs (NSAIDs)?
- Anti-aggregatory agent to inhibit platelet aggregation in patients who are at risk of stroke or MI
What is the action of the cyclo-oxygenase (COX) enzyme?
- Production of prostanoids (prostaglandins & thromboxanes) from the parent arachidonic acid
- Prostanoids act through a large number of prostanoid receptors to produce a highly complex array of actions
What are proton pump inhibitors (PPIs) used for?
Proton pump inhibitors are used to:
- Help gastrointestinal ulcers heal
- Treat symptoms of gastroesophageal reflux disease (GORD)
- Eradicate Helicobacter pylori
- Treat hypersecretory conditions such as Zollinger-Ellison Syndrome
What is the primary drug target of proton pump inhibitors (PPIs)?
- H+/K+ ATPase (Proton pump)
What is the drug target type of proton pump inhibitors (PPIs)?
- Ion channel antagonist
What is the mechanism of action of proton pump inhibitors (PPIs)?
- Weak bases that accumulate in the acid environment of the canaliculi of the pariteal cells
- This concentrates their action there and prolongs their duration of action
- Inhibit basal and stimulated gastric acid secretion by >90%
What is the location of action of proton pump inhibitors (PPIs)?
- Gastric parietal cells
What are the main adverse effects of proton pump inhibitors (PPIs) (7)?
-
Uncommon:
- Headache
- Diarrhoea
- Bloating
- Abdominal pain
- Rashes
- Omeprazole is an inhibitor of cytochrome P2C19 and has been reported to reduce the activity of other drugs
- PPIs may mask the symptoms of gastric cancer
Give 2 examples of proton pump inhibitors (PPIs).
- Omeprazole
- Lansoprazole
Why are proton pump inhibitors (PPIs) generally administered orally as capsules containing enteric-coated granules?
- PPIs are pro-drugs which, at low pH, are converted into 2 reactive species which react with sulphydryl groups in the H+/K+ ATPase responsible for transporting H+ ions out of the parietal cells, however they degrade rapidly at low pH.
What are histamine (H2) receptor antagonists used for?
- Histamine (H2) antagonists are used to treat duodenal ulcers, Zollinger-Ellison syndrome, gastric ulcers, GORD, and erosive esophagitis
What is the primary drug target of histamine (H2) receptor antagonists?
- Histamine (H2) receptor
What is the mechanism of action of histamine (H2) receptor antagonists?
- Histamine (H2) receptor antagonists inhibit histamine (H2) receptors in the gastric parietal cells of the stomach
- Gastrin does not bind on the histamine (H2) receptor reducing the gastric acid secretion by approximately 60%
What is the drug target type of histamine (H2) receptor antagonists?
- Receptor antagonist
What is the location of action of histamine (H2) receptor antagonists?
- ECL cells on the gastric parietal cells
What are the main adverse effects of histamine (H2) receptor antagonists (3)?
- Diarrhoea
- Dizziness
- Muscle pains
