NSAIDs Flashcards
LO
Historical perspectives of NSAIDs
Safety considerations and withdrawal
Best practice guidelines
Where do all NSAIDs come from?
derived form natural products eg salicin (from willow tree bark)
simialar struc drug to salicin w SE GI bleeds?
aspirin
What did ibuprofen come from? drug
ibufenac
(had tox issues :()
functions of COX-1 enzymes- they are constitutive and catalyse what? and for what?
catalyse formation of prostaglandins for normal physiological function:
- stomach mucus production
- regulation of gastric acid
- kidney water excretion
functions of COX-2 enzymes - they are induced and used for signalling what?
pain and inflammatory response:
- stimulated by immune response
- by inflammatory cytokines + growth factors
why does selectively suppressing COX2 dec chance of SEs?
mainly mediated through suppression of COX2
how can COX-1 activity be decreased/inhibited?
traditional NSAIDs
how can COX-2 activity be decreased/inhibited? 3
traditional NSAIDs
selective COX2 NSAIDs
Anti-inflammatory stimuli IL10
how can COX-2 activity be increased
inflammatory stimuli IL1/ IL6/ IL8/ Trauma
what are some examples of selective COX2 inhibitors?
celecoxib
(rofecoxib - withdrawn as inc CV risk, heartattack, stroke)
celecoxib still available but has lots of SE such as…
angina
cough
diarrhea
GI discomfort
what are some side effects of selective COX2 enzymes?/ how they cause SEs
inhibit vasodilation + vasodilator PGs (needed for normal GFR)
reduced GFR
increase risk of heart failure
what are NSAIDs with reduced GI and stomach adverse effects?
(aka COX2 preferential inhibitors)
meloxicam
Etodolac
nabumetone
(nimesulide)
COX2 preferential inhibitors indicated for what?
exacerbation of OA- pain and inflamm (BNF)
also inhibit osme COX1 but inc affinity for COX2
what main 2 types of px at risk of NSAIDs?
renal impairment px
HF px
forest plot explained (p520)
what is the legal legislation for oral diclofenac use?
associated with small increase risk of CV side effects therefore no longer under P, required POM
diclofenac esp at high doses may be associated w what?
increased risk of arterial thrombotic events eg MI/ stroke
ibuprofen has no risk at low doses up to….
1200mg
(so 400mg tds)
ibuprofen >2400mg higher risk of…
heart attack and strokes
limited data for SEs/ safety of ibuprofen for which doses?
1200mg-2400mg
below: safe
above: not safe
what is the MHRA and NICE recommended over the counter NSAID use?
ibuprofen at higher doses
or ideally naproxen
what must be prescribed if px at risk of getting GI SE form NSAIDs?
gastric protection!!!
link between NSAID and COVID19?
no evidence of extra harm/ disease deterioration.
continue paracetamol and topical NSAIDs for localised kneww pain etc where needed
best NSAIDs to use?
paracetamol or topical where possible
avoid NSAID use in which px where possible?
older px.
what to do before prescribing?
do full risk assessment inc gastro protection where needed
NSAIDs SGT————————
which risk factors need to be considered before using an NSAID?
I.e. think about the lifestyle advice
- Renal impairment
- Older px
- HF px
- Any CV. Risk factors
- High chance of GI AEs
mechanism via which NSAIDs work to reduce pain?
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
describe events leading -> MTX toxicity
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.
MTX tox SE/ symptoms seen?
- Sore throat
- Fever
- Cough
What drug-drug interactions need to be considered in Rheumatoid Arthritis patients?
Methotrexate
NSAIDs may worsen condition
