Topic 34 - NSAIDs Flashcards
What things must you consider before prescribing NSAIDs?
- Drug interactions
- Patient factors which affect safety of prescribing the drug
What are NSAIDs prescribed for and what qualities do they have that are suited to this?
They’re prescribed for mild-mod pain.
Analgesic and anti-pyretic and anti-inflammatory.
What is the mode of action (anti-inflammatory, analgesic) of NSAIDs?
NSAIDs inhibit COX-1 and COX-2 enzymes which are found in living tissue (cyclo-oxygenase). Because of this, prostaglandin synthesis is reduced. Prostaglandins make nociceptors which are receptors for pain and they respond to stimuli like bradykinin at low concentrations. Because of this, NSAIDs are particularly effective at treating mild-mod pain.
COX-2 enzymes also cause less vasodilation (so less redness and flushing), cause less tissue oedema as capillaries are less leaky (which means less sweating) and cause less sensitisation of nociceptors (analgesia).
What are prostaglandins?
Inflammatory mediators
Why are there side effects of using NSAIDs?
The problem is their mode of action means they have wide-reaching effects, and there’s lots of potential side effects and drug interactions that you must be aware of as a dentist.
COX-2 enzymes are mainly responsible for side effects.
What are the types of COX enzymes and where are they found?
COX-1 is found in many tissues such as liver, stomach, platelets and blood vessels. It’s constitutionally active and is predominantly responsible for the adverse side effects produced by NSAIDs.
COX-2 is induced by inflammatory cells when there’s tissue inflammation.
What kind of pains does NSAIDs work for best?
Mild-moderate pain. Not as useful for severe inflammatory pains.
It’s also more useful in integumentary system or muscle pain rather than deep visceral pain.
E.g. headaches, toothache, post-op.
Why are NSAIDs effective against headaches?
They ensure less prostaglandins are produced, so less cerebral vasodilation (which can cause an increase in pressure in the head therefore pain).
What is the anti-pyretic mode of action of NSAIDs?
They inhibit COX-2 metabolised prostaglandin synthesis at the level of the hypothalamus, which makes the body temperature rise to above 38 in infection. With the body temperature returned to 37 degrees, this is below optimal for bacteria to reproduce and grow. They’re less able to produce pyrogens like LPS that would be produced from Gram -ve bacteria like E.coli and klebsiella so no inflammatory reaction.
Describe the 5 types of NSAIDs, what they bind to and what their side effects are relative to each other.
- Salicylates e.g. aspirin - used for anti-platelet function in pts with thromboembolic events in UK, and can be used for pain relief. Weakly cox-1 selective and the effects are irreversible so the effect lasts long after the drug has been taken.
- Paracetamol - used for pain relief and anti pyretic function. Is a reversible non-competitive COX inhibitor. Is much safer than the other NSAIDs and doesn’t produce GI/bleeding side effects, and has no effect on acid-base balance (unless recommended dose ignored). It is not as effective in anti-inflammatory causes as other NSAIDs because it can’t bind to the COX enzymes at the inflammatory site due to the high number of peroxides there.
- Propionic acid derivates e.g. ibuprofen and naproxen.
Has less GI effects than aspirin.
Naproxen has a half life of 14 hrs while ibuprofen’s 2 which is why they’re used differently and ibuprofen can be purchased OTC. Ibuprofen is weakly selective COX-1 inhibitor. - Selective COX-2 inhibitors e.g. celecoxib.
These are prescribed in rheumatology for inflammatory joint disease. Less risky for GI.
Celecoxib - moderately COX-2 selective
Etoricoxib. - strongly COX-2 selective. - Enoic acids include things like diclofenac. This is weakly COX-2 selective and is called volterol by brand name.
What are some side effects of NSAIDs?
Can children use aspirin?
GI bleeding, peptic ulcers, nausea, oral ulceration, dyspepsia
Bleeding because of anti-platelet activity which can exacerbate GI bleeding and increase risk of thromboembolic events.
Bronchospasm (acute exacerbation) in asthmatic patients (ask if they’ve had bad reaction before), macular rashes, oral lichenoid reactions, direct irritant effect when people attempt to use tablet topically.
Reye’s syndrome describes when a person takes aspirin and this results in renal failure and cephalitis. This is why it’s not administered to children under 16.
What happens in paracetamol overdose?
Over 10-15g paracetamol. Paracetamol overdose can result in liver failure and death because we don’t have enough glutathione to remove toxic metabolites. Send pts who have paracetamol to A&E and they’ll be given oral methionine and N-acetylcysteine to increase glutathione in our bodies.
Toxic metabolite is called N-acetyl-p-benzoquinone.
