NSAIDS Flashcards
What are the 3 main actions of NSAIDS?
1) Anti-inflammatory
2) Analgesic
3) Anti-pyretic
What is the primary baseline action NSAIDS?
To inhibit prostaglandin biosynthesis by direct action on cyclo-oxygenase enzymes
What 2 mechanisms do NSAIDS inhibit cyclo-oxygenase (COX)
- An irreversible, time-dependent inhibition of the enzyme
- A rapid, reversible competitive inhibition of the enzyme
Give an example of NSAID which causes an irreversible time-dependent inhibition of the enzyme and how it works?
e.g. aspirin
- inactivates the enzyme
- aspirin acetylates the a-amino group of the terminal serine of the enzyme forming a covalent bond
- further synthesis of prostaglandins requires synthesis of new enzyme
Give an example of an NSAID which causes a rapid, reversible competitive inhibition of the enzyme?
e.g. ibuprofen
- binds reversibly to the enzyme
- competes with natural substrate, Arachidonic Acid
list some products of arachidonic acid metabolism
prostaglandins, thromboxanes, leukotrienes
what are the two main cyclo-oxygenase enzymes?
COX - 1
COX - 2
What is the function of COX-1
- Constitutive (present in most body tissues)
- Important in maintain GIT integrity
What is the function of COX -2 ?
- Inducible (induced during an inflammatory response)
- Involved in inflammatory response
- Implicated in cancer development
where do NSAIDS inhibit the prostaglondin biosynthetic pathway
By inhibiting COX enzymes, NSAIDs prevent the conversion of arachidonic acid into prostaglandins and thromboxanes, thereby reducing inflammation, pain, and fever.
When are prostaglandins released?
prostaglandins are always released and accompany the inflammatory response
Which prostaglandins are released?
Predominantly PGE2 are released as well as PGI2
PGD2 are released from mast cells
What do prostaglandins act as?
they act as potent vasodilators
What actions do prostaglandins carry out?
they synergise (combine) with other inflammatory mediators (e.g histamine and bradykinin)
as well as potentiate (make more effective) histamine and bradykinin actions on postcapillary venule permeability and pain sensory nerves
In what two ways are prostaglandins important mediators of inflammation?
Prostaglandins are important mediators of inflammation particularly causing vasodilation and resultant oedema (swelling), they cause a lesser effect on cellular accumulation or migration
What do NSAIDS effect and reduce?
- NSAIDS only effect aspects of inflammation in which prostaglandins play a significant part
- NSAIDS reduce many of the local signs and symptoms of inflammation
What are the signs and symptoms of inflammation which are reduced?
signs and symptoms: redness, heat, swelling, pain
What is body temperature regulated by?
The hypothalamus
What are the 4 steps of the anti-pyretic effect?
1) Fever occurs when the hypothalamic thermostat “set point” is raised
2) Bacterial endotoxins cause release of factors (e.g. interleukin 1) from macrophages
3) Interleukin 1 causes generation of prostaglandins in the hypothalamus (PGEs)
4) Prostaglandins ↑ the thermostat “set point”
How do NSAIDS prevent the anti-pyretic effect?
NSAIDs act by preventing the formation of prostaglandins and prevent the rise in temperature and so there is no effect on normal body temperature
Why are inflamed regions painful?
inflamed regions are painful due to histamine and bradykinin release
What do histamine and bradykinin do?
activate nociceptive afferent nerve terminals and register a painful stimulus
How do NSAIDS cause an anti-inflammatory response?
prostoglandins sensitise nocioceptive nerves to these bradykinin and histamin. So by preventing prostaglandin production, NSAIDS therefore prevent sensitisation to pain-producing compounds (histamine + bradykinin)
What is an example of salicylates?
Aspirin is an example of salicylates
