Pharmacology of GORD Flashcards
What is the mechanism of action of NSAIDs?
What causes the therapeutic effects and what causes side effects?
NSAIDS inhibit the enzyme cyclo-oxygenase (COX) which is the rate-limiting step for the production of all prostanoids (prostaglandins & thromboxanes)
It is thought that the anti-inflammatory actions, and probably most of the analgesic & antipyretic actions, of the NSAIDs are related to inhibition of COX-2, while their unwanted effects are largely a result of inhibition of COX-1.
What are the common NSAIDs?
Ibuprofen, naproxen, diclofenac
What are NSAIDs used for?
analgesics for the relief of mild to moderate pain
antipyretics to reduce fever
anti-inflammatory drugs for chronic control of inflammatory diseases
anti-aggregatory agent to inhibit platelet aggregation in patients who are at risk of stroke or myocardial infarction.
What do NSAIDs act on the produce unwanted effects?
COX 1 enzyme
What are side effects of NSAIDs?
Gastric irritation Ulceration, bleeding and perforation Reduced creatinine clearance Nephritis; Bronchoconstriction Adverse cardiovascular effects (due to prolonged use in pts with previous CV risk) Skin rashes & other allergies Dizziness Tinnitus.
What are the main PPIs?
Omeprazole, lansoprazole
What is the mechanism of action for PPIs?
They irreversibly inhibit H+/K+ ATPase in gastric parietal cells reducing secretion of gastric acid
What are side effects of PPIs?
Headache Diarrhoea Bloating Abdominal pain Rashes
What can omeprazole inhibit and mask the effect of?
cytochrome P2C19
Has been reported to reduce the activity of e.g. clopidogrel
What is the main histamine receptor antagonist? Where can you get it?
Ranitidine
Can buy it over the counter without prescription
What is the mechanism of action of histamine receptor antagonists?
Target: Histamine H2 receptor
Location: enterochromaffin-like (ECL) cells on gastric parietal cells
Effect: inhibit gastric acid secretion by approximately 60%.
What are side effects of histamine receptor antagonists?
Diarrhoea
Dizziness
Muscle pain
Rash
What is done if a patient develops gastric side effects from NSAIDs?
Stop NSAID use if possible
Give a 4-8 week course of PPIs e.g. omeprazole 20mg oral
Why can’t PPIs be given if someone has osteoperosis? What is given instead?
PPIs increase the risk of fractures, a histamine receptor antagonist is given instead
How does Naproxen cause analgesia?
Inhibits the production of prostaglandin.
The location of this is peripheral nociceptive nerve endings.
PGs sensitise peripheral nociceptor mediators (bradykinin and histamine), so by reducing PGs we can indirectly reduce pain.
PGs also mediate inflammation so NSAIDs will reduce inflammation.
