7.2 NSAIDs

Question 1

How are prostaglandins synthesised?

Answer 1

From arachidonic acid, which is cleaved from membrane phospholipids
Via COX 1 and 2 enzymes

Question 2

Which type of prostaglandin is most important in mediating an inflammatory response?

Answer 2

Prostaglandin E

Question 3

Which COX enzyme is responsible for most of the ADRs of NSAIDs?

Answer 3

COX 1
As this is expressed in many tissues for normal activity, so inhibition of these causes unwanted side effects

But the relief of inflammation is most effective by acting on COX 2 as these are expressed at the site of inflammation

Most NSAIDs act on COX 1 and 2 e.g. aspirin

Question 4

Which afferent fibres carry pain?

Answer 4

C fibres

Question 5

How do prostaglandins have a role in peripheral nociception by EP1?

Answer 5

PGs are synthesised in response to tissue injury
The PG E binds to C fibres EP1 GqPCR
The GPCRS activation acts to increase the C fibre sensitivity
(e.g. increased neurotransmitter release so increase pain fibre conduction)

Question 6

What is allodynia?

Answer 6

Painful response from stimuli which do not normal provoke pain

Question 7

What is hyperalgesia?

Answer 7

An increased response to a painful stimulus

Question 8

What happens as a result of prostaglandins binding to EP2 receptors?

Answer 8

In the dorsal horn more PGE is synthesised as a result of the sustained nociception
This binds to EP2 and reduces the binding affinity of glycine receptors, so in effect removes some inhibitory control so that pain perception is increased

Question 9

Pyrexia is due to prostaglandins binding to which receptors?

Answer 9

EP3 receptors

Question 10

The main therapeutic effects of NSAIDs is via inhibition of which enzyme?

Answer 10

COX2

Question 11

What is the most common ADR of NSAIDs?

Answer 11

GI disturbance

E.g. nausea, stomach pain, heartburn, gastric bleeding, ulceration

Question 12

How are GI ADRs with NSAIDs usually offset?

Answer 12

By prescribing then alongside a PPI

Question 13

Why can Renal side effects occur for a px on NSAIDs?

Answer 13

As prostaglandins he’ll maintain renal blood flow
If PGs are reduced due to NSAIDs then this can lead to GFR being reduced
So N/K/Cl and water retention can follow which increases the likelihood of hypertension

Question 14

What are some ADRs of NSAIDs?

Answer 14

1. GI upset
2. Renal compromise
3. Vascular increased bruising due to increase bleeding time
4. Hypersensitivity rashes

Question 15

What are the 3 steps of the WHO pain ladder?

Answer 15

1. Non-opioid e.g. paracetamol +/- NSAID
2. Mild opioid e.g. codeine, cocodamol
3. Strong opioid e.g. morphine, diamorphine, fentanyl

Can use alongside neuropathic meds

Question 16

What are the phase 1 and phase 2 steps in paracetamol metabolism?

Answer 16

Phase 1 oxidises it the NAPQI (v reactive and toxic)

Phase 2 conjugated NAPQI with glutathione

Question 17

What happens in paracetamol overdose?

Answer 17

Phase 2 metabolism is saturated and the pharmacokinetics become zero order
This leads to increased phase 1 production of the toxic NAPQI which can lead to hepatic cell death

Question 18

How can paracetamol overdose be treated?

Answer 18

If within 4 hours, activated charcoal can be used orally to reduce the uptake

Within 0-36 hours IV N-acetylcysteine can be given IV