NSAIDs

Question 1

LO
Historical perspectives of NSAIDs
Safety considerations and withdrawal
Best practice guidelines

Question 2

Where do all NSAIDs come from?

Answer 2

derived form natural products eg salicin (from willow tree bark)

Question 3

simialar struc drug to salicin w SE GI bleeds?

Answer 3

aspirin

Question 4

What did ibuprofen come from? drug

Answer 4

ibufenac
(had tox issues :()

Question 5

functions of COX-1 enzymes- they are constitutive and catalyse what? and for what?

Answer 5

catalyse formation of prostaglandins for normal physiological function:

• stomach mucus production
• regulation of gastric acid
• kidney water excretion

Question 6

functions of COX-2 enzymes - they are induced and used for signalling what?

Answer 6

pain and inflammatory response:

• stimulated by immune response
• by inflammatory cytokines + growth factors

Question 7

why does selectively suppressing COX2 dec chance of SEs?

Answer 7

mainly mediated through suppression of COX2

Question 8

how can COX-1 activity be decreased/inhibited?

Answer 8

traditional NSAIDs

Question 9

how can COX-2 activity be decreased/inhibited? 3

Answer 9

traditional NSAIDs
selective COX2 NSAIDs
Anti-inflammatory stimuli IL10

Question 10

how can COX-2 activity be increased

Answer 10

inflammatory stimuli IL1/ IL6/ IL8/ Trauma

Question 11

what are some examples of selective COX2 inhibitors?

Answer 11

celecoxib
(rofecoxib - withdrawn as inc CV risk, heartattack, stroke)

Question 12

celecoxib still available but has lots of SE such as…

Answer 12

angina
cough
diarrhea
GI discomfort

Question 13

what are some side effects of selective COX2 enzymes?/ how they cause SEs

Answer 13

inhibit vasodilation + vasodilator PGs (needed for normal GFR)

reduced GFR

increase risk of heart failure

Question 14

what are NSAIDs with reduced GI and stomach adverse effects?
(aka COX2 preferential inhibitors)

Answer 14

meloxicam
Etodolac
nabumetone
(nimesulide)

Question 15

COX2 preferential inhibitors indicated for what?

Answer 15

exacerbation of OA- pain and inflamm (BNF)

also inhibit osme COX1 but inc affinity for COX2

Question 16

what main 2 types of px at risk of NSAIDs?

Answer 16

renal impairment px
HF px

Question 17

forest plot explained (p520)

Question 18

what is the legal legislation for oral diclofenac use?

Answer 18

associated with small increase risk of CV side effects therefore no longer under P, required POM

Question 19

diclofenac esp at high doses may be associated w what?

Answer 19

increased risk of arterial thrombotic events eg MI/ stroke

Question 20

ibuprofen has no risk at low doses up to….

Answer 20

1200mg

(so 400mg tds)

Question 21

ibuprofen >2400mg higher risk of…

Answer 21

heart attack and strokes

Question 22

limited data for SEs/ safety of ibuprofen for which doses?

Answer 22

1200mg-2400mg
below: safe
above: not safe

Question 23

what is the MHRA and NICE recommended over the counter NSAID use?

Answer 23

ibuprofen at higher doses
or ideally naproxen

Question 24

what must be prescribed if px at risk of getting GI SE form NSAIDs?

Answer 24

gastric protection!!!

Question 25

link between NSAID and COVID19?

Answer 25

no evidence of extra harm/ disease deterioration. continue paracetamol and topical NSAIDs for localised kneww pain etc where needed

Question 26

best NSAIDs to use?

Answer 26

paracetamol or topical where possible

Question 27

avoid NSAID use in which px where possible?

Answer 27

older px.

Question 28

what to do before prescribing?

Answer 28

do full risk assessment inc gastro protection where needed

Question 29

NSAIDs SGT------------------------ which risk factors need to be considered before using an NSAID?

Answer 29

I.e. think about the lifestyle advice * Renal impairment * Older px * HF px * Any CV. Risk factors * High chance of GI AEs

Question 30

mechanism via which NSAIDs work to reduce pain?

Answer 30

NSAIDs inhibit enzyme COX: stops conversion of arachidonic acid  thromboxanes, PGs, (prostacyclins) Selective NSAID: celecoxib: high CVD risk. Weigh up risks and benefits w px. Lower PG, dec inflammation + pain Majority: Non selective

Question 31

describe events leading -> MTX toxicity

Answer 31

NSAIDs excreted renally, so is MTX. Compete for same excreted pathways if NAID wins, MTX build up can accumulate very quick and toxicity can be fatal.

Question 32

MTX tox SE/ symptoms seen?

Answer 32

* Sore throat * Fever * Cough

Question 33

What drug-drug interactions need to be considered in Rheumatoid Arthritis patients?

Answer 33

Methotrexate NSAIDs may worsen condition