7.1 NSAIDs Flashcards Preview

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Flashcards in 7.1 NSAIDs Deck (29):
1

What are the 3 main actions of NSAIDs?

Antipyrexic
Anti-inflammatory
Analgesia

2

What are autocoids?

Autocoids are biological factors which are released in response to inflammation.
They have a short half life and act as local hormones

3

What are some examples of autocoids?

Cytokines
Histomine
Serotonin
Bradykinin
NO

Neuropeptides
Leukotrines
Eicosanoids

4

What are eicosanoids?

20C phospholipid signalling molecules
e.g. prostaglandins

5

How are eicosanoids made?

They come from the cell membrane, the arachidonic acid
The synthesis is catalysed by COX enzymes

6

What are the types of prostaglandin?
Which is the main one? Why?

In order of being made - G, H, D E F I
They require specific enzymes to produce each one

E, most important in monitoring the inflammatory response

7

What does Prostaglandin E do?

Vasodilate
Hyperalgesia
Fever
Immunomodulation

8

What are the types of COX Enzyme?
WHat is their distribution

COX1 - always expressed in all tissues, short half life, constant production needed
COX2 - released from noxious stimuli e.g. tissue damage

9

What are the types of COX Enzyme?
What is their distribution?
What is the difference in stucture?

COX1 - always expressed in all tissues, short half life, constant production needed
COX2 - released from noxious stimuli e.g. tissue damage
COX 1 is tight, 2 is loose
Only small drugs e.g. Aspirin can effect COX 1

10

What is the function of COX1

It is cytoprotective e.g. in gastric mucosa
It increases tissue perfusion

11

What is the function of COX2

Stimulates inflammation by converting prostaglandins e.g Pg E
It is mainly in the brain and kidneys

12

Which COX enzyme do NSAIDs give most effects through?

COX 2

13

What are the receptors that prostaglandins act on?
What GPCR is it?
Their action?

EP1 - Gq (increase nociception)
EP2 - Gs (vasodilate)
EP3 - Gi (pyrexia)

14

What is EP1?

Prostaglandin Receptor
Increases C fibre activity and activate silent C fibres (lowers threshold)

Inhibits K+ channel, Increases Na+ sensitivity and bradykinin sensitivity, Increases Ca2+ for more NTs

15

How does central sensititsation occur?

The increase in peripheral nociception leads to an increase in cytokines in the dorsal horn.
This increases COX-2 and PgE synthesis
PgE acts on EP2 to increase cAMP/PKA to increase pain perception
Inhibits glycine inhibition

16

What is EP3?

IL2 --> PGE2
PGE2 acts on the Gi receptor, to increase heat production

17

How do NSAIDs work?

They selectively inhibit COX enzymes
Most effect comes from inhibiting COX 2

18

What are some properties of NSAIDs?

Highly protein bound
GI Effects (reduce PG in stomach --> ulcers/reflux)
Increase bleeding risk
Typically oral preparations

19

What is Celecoxib?

A selective COX2 inhibitor
Tried to overcome the COX 1 side effects, but increases CVS risk

20

What is Asprin?

A COX inhibitor
Cardioprotective

21

Why is Asprin special?

It is the only one to irreversibly bind to COX

22

Properties of Asprin?
Half Life
Order

Short Half Life
Wide Spread
1st order at low doses, high=zero order

23

What is Paracetamol?

NOT an NSAID
It is a NOAD (non-opiod analgesic drug)

24

What does Paracetamol do?

NO anti-inflammatory action
Prevents pain

25

Why use paracetamol?

Has fewer ADRs

26

Why have you got to be careful with paracetamol?

Low TI
Overdose! --> toxic to hepatocytes
NAPQI toxic metabolite from phase 1 conjugation

27

How do you treat paracetamol overdose?

<4hrs - activated charcoal to prevent uptake
0-36hrs - N-acetylcystine or methionine orally

28

What are some ADRs of NSAIDS?

GI
Renal (when compromised)
Increase bleeding risk
Hypersensitivity (Asthma, rashes)
Reyers Syndrome

29

Examples of NSAIDS?

Aspirin
Ibuprofen
Celocoxib