Anti-inflammatory drugs Flashcards
Name 2 inflammatory mediators
Prostoglandins and thromboxanes
What does NSAID mean?
Non steroidal anti inflammatory drug
Whats the chemical name for aspirin?
Acetylsalicylic acid
Name three NSAIDs
Aspirin, Paracetamol, Ibuprofen
Generally what do NSAIDs do?
Inhibit production of inflammatory mediators
Prostaglandin and thromboxane
What is a COX enzyme and why is it important for NSAIDs?
Cyclo- oxygenase
Target of NSAID is COX enzymes to inhibit production of inflammatory mediators
What is an important property of prostaglandin and thromboxanes in immune response?
They are chemoattractants for immune cells
When there is inflammation immune cells will rapidly flow to it
Which reaction does NSAID stop by inhibiting COX enzymes
Arachidonate -> (cox enxymes) -> Cyclic endoperoxides
Cyclic endoperoxides are converted into prostagladins and thromboxanes
What are NSAIDs ineffective against and why?
Ineffective against mediators associated with tissue damage from chronic inflammatory conditions (rheumatoid arthritis)
Why can NSAIDs be considered analgesic?
They reduce production of prostaglandins in inflamed tissues
Prostaglandins sensitise nociceptors (pain receptors) to inflam. meds.
What is the property of anti-inflammatorys that lowers temperature?
Anti-pyretic
Interleukin-1 induces the expression of Cox2 which stimulates the hypothalamic production of prostaglandin E2 (PGE) which bind to receptors that work to increase temperature
How many Cox enzymes are there?
3
Which cox enzyme is inducible and how?
Cox 2
Induced by cytokines, growth factors or tumour promoters
Induced when responding to immune compromise
Where in the cell are the cox enzymes found and how many subunits do they have?
Embedded in the ER membrane
Two identical subunits with two active sites
Peroxisome site and cox site
What is the structural difference between cox 1 and cox 2 and why?
Cox 2 has a smaller channel than cox 1
Cox 2 has an isoleucine residue and cox 1 has a valine
Valine is much smaller than isoleucine therefore cox 1 channel = larger
Why is the difference between cox 1 and 2 helpful?
Larger drugs can be used to selectively target cox 1 and not cox 2 due the difference in pore size
Why can aspirin disrupt the mucus lining and what does this lead to ?
Prostaglandins secreted by cox 1 are important for maintaining mucus layer in the GI tract
Aspirin will inhibit cox 1 and prostaglandin production will stop
Mucus production will then halt, exposing the epithelial cells lining the tract
May cause ulcers
Why can using an NSAID cause increased bleeding?
Cox 1 important for platelet expression
When inhibited less platelets expressed
Increased bleeding - more with GI ulcers
How does aspirin work?
Suicide drug
Permenantly covalent bond between aspirin and Ser residue on cox enzyme
Prevents arachidonic acid from reaching the cyclooxygenase site
Prevents conversion to inflammatory mediator
Why does it take roughly 4 hours for aspirin to wear off?
Takes 4 hours to make a new enzyme (suicide drug)
Pros and cons of using cox 1 selective NSAID
pros - For stroke patients (anti-thrombolic)
Prevents blood clot formation
Cons- For blood thinning disorders can be dangerous
Gastrotoxicity
Pros and cons of using cox 2 selective NSAID
Pros- anti inflammatory, analgesia
Cons- Some can increase risk of cardiovascular diseases
increases blood pressure and salt retention -> heart attack
