NSAIDs and pain processing

Question 1

What are Eicosanoids and how are they produced

Answer 1

Play an important role in inflammation

-generated from phospholipids. Arachidonic acid is the main source

Question 2

What is the rate limiting step in synthesis of Eicosanoids

Answer 2

The liberation of arachidonic acid from Phospholipase A2

Question 3

What does the generation of eicosanoids make

Answer 3

Prostaglandins, thromboxanes

leukotrienes

Question 4

What is the synthesis of eicosanoids driven by

Answer 4

many different stimuli including cell damage

Question 5

What is arachidonic acid metabolised by

Answer 5

One of two fatty acid cycle-oxygenase enzymes

Question 6

What is involved in increasing the increased expression of COX2

Answer 6

IL1 and TNF alpha

Question 7

What is COX2 responsible for

Answer 7

Production of prostaglandin mediators of inflammation

Question 8

Role of PGI2

Answer 8

Increases responses ro painful stimuli (hyperalgesic)

Vasodilator

Decrease platelet aggregation

Question 9

What does PGE2 do

Answer 9

Hyperalgesic

Vasodilator

Question 10

What does PGD2 do

Answer 10

Vasodilator

Decrease platelet aggregation

Question 11

Role of TXA2

Answer 11

Thrombotic vasoconstrictor

Question 12

What are the prostaglandin receptors and what do they act on

Answer 12

PGD2: DP receptor
PGF2a: FP receptor 
PGI2:IP receptor
TXA2: TP receptor 
PGE2: EP receptor

Question 13

What are prostaglandins generated by

Answer 13

Local tissue and blood vessels

Question 14

What are prostaglandins released by

Answer 14

PGD2

Question 15

What is involved in chronic inflammation

Answer 15

Monocytes/macrophages release PGE2/TXA2

Question 16

What do prostaglandins synergise with and what are the roles

Answer 16

Histamines- itch

Bradykinin- pain

Question 17

What do prostaglandins potentiate the actions of

Answer 17

Bradykinin and histamine on blood vessels and peripheral nerves

Question 18

What does bradykinin act on

Answer 18

Nociceptors by B1 and B2 receptor

Question 19

What is the action of bradykinin

Answer 19

Increase prostaglandin production

Prostaglandins enhance nociceptor responses to bradykinin

Question 20

What do prostaglandins do to nociceptors

Answer 20

Sensitise them

Question 21

What happens once inflammation occurs

Answer 21

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

Question 22

role of mast cells in inflammation and how

Answer 22

release 5HT

-acts a receptors which are excitatory and pro inflammatory

Question 23

What else can also directly activate sensory nerves

Answer 23

Cytokines, nerve growth factor

Question 24

How are NSAIDS antipyretic (reduce body temp)

Answer 24

Inhibit prostaglandin production in hypothalamus

Question 25

How else can you inhibit COX enzyme and what is its mode of action

Answer 25

Glucocorticoids - inhibit induction of enzyme

NSAIDS- inhibit enzyme

Question 26

How are NSAIDs analgesic

Answer 26

reduce inflammation (oedema and vasodilation) which causes pain

Question 27

How are NSAIDs used for chronic pain

Answer 27

In conjunction with opioids

Question 28

Mode of action of aspirin

Answer 28

Irreversible inactivation of COX1 and cox2

Question 29

Where do NSAIDs act

Answer 29

Nociceptors