NSAIDs Flashcards
What are the types of cyclooxygenase (COX) inhibitors and their reversibility?
Non-selective COX inhibitors, which may be reversible or irreversible
COX-2 selective which are reversible
CNS-selective COX inhibitors which are reversible
What is the pain pathway?
Primary afferent neuron –> dorsal root ganglion –> dorsal horn of spinal cord –> ascends to the brain via the lateral spinothalamic tract
What step of the pain pathway to NSAIDs and opioids work on?
NSAIDs: primary afferent neurone
Opioids: CNS
How do steroids reduce inflammation?
By mimicking endogenous cortisone
which suppresses phospholipase A2
reducing inflammation
What mechanisms do NSAIDs block and what symptoms do they cause?
Decreases vasodilation which usually contributes to heating, redness and swelling
Blocks increase in vascular permeability –> reduces swelling
Reduces pain associated with inflammation
Why do NSAIDs have an analgesic ceiling?
Because they block prostaglandins, which sensitize nociceptive fibers to stimulation by inflammatory mediators
Therefore NSAIDs reduce sensitivity of the fibers but don’t block them directly. Other inflammatory mediators can still cause effects `
What is an irreversible, non-selective COX inhibitor that blocks prostaglandin synthesis?
Aspirin
What are the effects of action of aspirin?
Anti-inflammatory, analgesic, anti-pyretic and anti-platelet
What is the mechanism of action for the anti-inflammatory effects of aspirin?
Decreased vasodilation and decreased vascular permeability
What is the mechanism of action for the analgesic effects of aspirin?
By decreased sensitization of nociceptive fibers to inflammatory mediators (by decreasing prostaglandin levels)
What is the mechanism of action for the antipyretic effect of aspirin
Acts on the hypothalamus to reset the body temperature (but does not alter the normal body temp!)
What is the mechanism of action for the antiplatelet action of aspirin?
It inhibits both thromboxane A2 (which causes platelet aggregation) and prostaglandin I2 (which inhibits platelet aggregation)
However inhibition of thromboxane A2 > that of prostaglandin I2
What is another typical NSAID but with a long half-life of 12-24 hours? What is it used for?
Naproxen
More effective in women
Used for dysmenorrhea
What is a typical NSAID which is steroid-like and strongly anti-inflammatory?
What are its side effects?
Indomethacin
has CNS effects: confusion, depression, psychosis
What is a typical NSAID with a short half life of <2h? What is its GI risk?
Diclofenac
Lower risk of GI effects due to short half life
What are the GIT side effects of NSAIDs and their mechanisms?
nausea, vomiting, dyspepsia, ulcers and increased risk of bleeding
prostaglandins usually decrease stomach acid production, increase bicarb and mucus production and increase mucosal blood flow
but nsaids decrease prostaglandin production
One of the most common vasculitides of childhood that aspirin is prescribed for is:
Kawasaki syndrome
What are the non-RAAS renal effects of NSAIDs and their mechanisms?
Edema and hypotension
Prostaglandin E2 usually inhibits reabsorption of Na and water. Decrease in PG E2 leads to increased reabsorption and edema/hypotension
What are the pseudo-allergy side effects of NSAIDs and their mechanisms?
Rashes, itching, nasal congestion, anaphylaxis
Inhibition of COX leads to shunting of arachidonic acid down the 5-LOX and 15-LOX pathway, leading to the production of leukotriene and lipoxins respectively, which are inflammatory mediators
What are the RAAS renal effects of NSAIDs and their mechanisms?
Prostaglandin I2 usually stimulates RAAS
Decreased PG I2 –> decreased renin and aldosterone
This can’t be offset by increased Na and water reabsorption as the effect of lower PGE2 –> less Na reaching the DCT where aldosterone acts
What are the asthmatic side effects of NSAIDs and their mechanisms?
Bronchospasms in those who are already susceptible
5-LOX present > 15-LOX present
leukotrienes > lipoxins
leukotrienes are linked to asthma
What are the haematopoietic effects of NSAIDs and their mechanisms?
Bruising and bleeding
Due to anti-platelet effects
What are the symptoms of kawasaki syndrome?
Higher fever for at least 5 days
Bilateral bulbar conjunctivitis
Erythema of palms/soles
Oedema of the hands and feet
Polymorphous rash
cervical lymphadenopathy
Why should aspirin not be prescribed to children with viral infections?
It can result in Reye’s syndrome, which can result in:
Encephalitis, liver swelling, vomiting, confusion, delirium, convulsions or loss of consciousness
What are examples of selective COX-2 inhibitors?
Celecoxib or other coxibs
What is the effect of selective cox-2 inhibitors?
Selective inhibition of COX 2, reduction of GIT side effects
Mainly anti-inflammatory and analgesic, less anti-pyretic
What are the renal effects of selective COX-2 inhibitors?
Nephrotoxicity due to the expression of COX 2 in the kidney
What are the effects of selective COX 2 inhibitors on ovulation?
Delayed follicular rupture
Can NSAIDs be taken during pregnancy?
Not during the third trimester, it may cause a premature closing of the ductus arteriosus
What is the effect of selective COX-2 inhibitors on wound healing?
Impairment of wound healing
May also exacerbate ulcers
What are the haematopoietic effects of selective COX-2 inhibitors?
Thrombosis
COX 2 usually produces Prostaglandin I2 which inhibits platelet aggregation, but not thromboxane 2 which promotes platelet aggregation and clotting.
When COX-2 is inhibited, the balance between PG I2 and TXA2 is disrupted.
TXA2 now > PG I2 and platelet aggregation is favoured –> thrombosis
What is a CNS-selective COX inhibitor?
Paracetamol
What is the proposed MOA of paracetamol?
The metabolite AM404 may modulate pain transmission by inhibiting cannabinoid reuptake, or inhibiting transient receptor potential vanilloid 1 or COX
What are the effects of paracetamol?
Good analgesic and potent anti-pyretic, but weak anti-inflammatory effects.
Safe in children
Has few side effects, spares GI and has few drug-drug interactions
What are possible side effects of paracetamol?
hepatotoxicity in high doses, can be exacerbated by chronic alcoholism
Allergic skin reactions may sometimes occur
Nausea/vomiting may sometimes occur
