NSAIDs and pain processing Flashcards
What are Eicosanoids and how are they produced
Play an important role in inflammation
-generated from phospholipids. Arachidonic acid is the main source
What is the rate limiting step in synthesis of Eicosanoids
The liberation of arachidonic acid from Phospholipase A2
What does the generation of eicosanoids make
Prostaglandins, thromboxanes
leukotrienes
What is the synthesis of eicosanoids driven by
many different stimuli including cell damage
What is arachidonic acid metabolised by
One of two fatty acid cycle-oxygenase enzymes
What is involved in increasing the increased expression of COX2
IL1 and TNF alpha
What is COX2 responsible for
Production of prostaglandin mediators of inflammation
Role of PGI2
Increases responses ro painful stimuli (hyperalgesic)
Vasodilator
Decrease platelet aggregation
What does PGE2 do
Hyperalgesic
Vasodilator
What does PGD2 do
Vasodilator
Decrease platelet aggregation
Role of TXA2
Thrombotic vasoconstrictor
What are the prostaglandin receptors and what do they act on
PGD2: DP receptor PGF2a: FP receptor PGI2:IP receptor TXA2: TP receptor PGE2: EP receptor
What are prostaglandins generated by
Local tissue and blood vessels
What are prostaglandins released by
PGD2
What is involved in chronic inflammation
Monocytes/macrophages release PGE2/TXA2
What do prostaglandins synergise with and what are the roles
Histamines- itch
Bradykinin- pain
What do prostaglandins potentiate the actions of
Bradykinin and histamine on blood vessels and peripheral nerves
What does bradykinin act on
Nociceptors by B1 and B2 receptor
What is the action of bradykinin
Increase prostaglandin production
Prostaglandins enhance nociceptor responses to bradykinin
What do prostaglandins do to nociceptors
Sensitise them
What happens once inflammation occurs
1- injury leads to inflammation which is associated with increased bradykinin
2- bradykinin activates sensory nerve terminals
3-sensory nerve terminals release substance P and CGRP into local tissue
4-Substance p and CGRP acts on blood vessels and increase permeability and are also vasodilatory
5) blood vessels are source of bradykinin
6) bradykinin act on sympathetic nerves which release neurotransmitters
7) in inflammation, there is also a decrease in pH which directly activate sensory nerves
role of mast cells in inflammation and how
release 5HT
-acts a receptors which are excitatory and pro inflammatory
What else can also directly activate sensory nerves
Cytokines, nerve growth factor
How are NSAIDS antipyretic (reduce body temp)
Inhibit prostaglandin production in hypothalamus
How else can you inhibit COX enzyme and what is its mode of action
Glucocorticoids - inhibit induction of enzyme
NSAIDS- inhibit enzyme
How are NSAIDs analgesic
reduce inflammation (oedema and vasodilation) which causes pain
How are NSAIDs used for chronic pain
In conjunction with opioids
Mode of action of aspirin
Irreversible inactivation of COX1 and cox2
Where do NSAIDs act
Nociceptors
