Inflammation 1 Flashcards
How are prostaglandins normally produced
Phospholipids are metabolised by phospholipase A2 to form arachidonic acid - this is then metabolized by COX enzymes to form prostaglandins
What are NSAIDs
Non-steroidal anti-inflammatory drugs - all are inhibitors of COX enzymes
Describe COX-1
Ubiquitous and always active
Why is COX-2 a more desirable target for anti-inflammatories?
Only turned on during the inflammatory response
inhibiting COX-2 doesn’t normal function and lead to side effects seen in COX-1 inhibition
Where is COX-3 found?
CNS and kidneys - not expressed in the gut - target for paracetamol
Why are NSAIDs said to be anti-inflammatory
Because the inhibit the production of prostaglandins
How do NSAIDs reduce oedema
Prostaglandins are vasodilators - inhibition of this
How are NSAIDs analgesic
Reduction of sensitization of nociceptors by prostaglandins
How are NSAIDs antipyretic
In normal infection - Cytokine Il-1 induces the production of E-type prostaglandins through the action of COX-2 enzymes
By inhibiting this it therefore acts to lower raised temperatures
Where are COX enzymes found
The endoplasmic reticulum
Where is Arachidonic produced
At the plasma membrane - diffuses through the cytoplasm into the rough ER where it binds to the catalytic site of COX enzymes
How does aspirin interact with COX enzymes
Covalently binds to serine residue in the COX enzyme
How does aspirin interact with COX
Suicidal inhibition - once bound it is permanent - lasting effects of aspirin dependent on the time it takes for new COX enzymes to be produced - normally around four hours
What are the main side effects of NSAIDs
- Stomach pain
renal failure
liver damage
bronchospasm
Why is nausea so common with the use of NSAIDs
Prostaglandins in the gut inhibit acid secretion and protect the gut mucosa - by inhibiting you get reduced mucous secretion
What use does misoprostol have
Administered in conjunction with NSAIDs - it is a prostaglandin analogue who’s action is restricted to just the stomach so can alleviate some of the GI tract problems
How do NSAIDs affect renal blood flow
Reduced prostaglandins = reduced renal blood flow - stronger NSAIDs can cause renal failure
How do NSAIDs affect the liver
Especially true for paracetamol - metabolism in the liver produces a toxic intermediate that kills off liver cells - normally quickly converted but in overdose can have an overwhelming effect
