Non-steroidal anti-inflammatory drugs (NSAIDs) & paracetamol Flashcards
What is the function of phospholipase A2 (PLA2)?
to cleave fatty acids from the membrane phospholipids
PLA2 generates the most widely used fatty acid precursor: arachidonic acid
What kind of fatty acid is arachidonic acid?
a polyunsaturated omega-6 fatty acid
20:4(w-6)
What do lipoxygenases (LOX) do?
convert arachidonic acid into eicosanoids which are further modified to leukotrienes
What does prostaglandin-H synthase (PGHS) do?
convert arachidonic acid into endoperoxides (PGG2 and PGH2) which can then be modified into cell-specific prostanoids
Name some endoperoxides
PGG2 and PGH2
What is the ‘class action’ of NSAIDs?
inhibit COX-1 domain activity in prostaglandin-H synthase preventing generation of the precursor endoperoxides PGG2 and PGH2
What effect does PGE2 have on A-delta and C nociceptive neurons?
sensitises them to serotonin, bradykinin and ‘Substance P’
NSAID’s can inhibit this process
What enzyme is PGE2 derived from?
PGHS-2
What kind of pain relief would be given to someone suffering from moderate pain?
paracetamol and a weak opiod (codeine phosphate)
What kind of pain relief would be given to someone in mild pain?
paracetamol and/or NSAID
When are NSAIDs contra-indicated?
if pregnant
if already on a NSAID
do not use aspirin if younger than 16
if sensitised to salicylates/NSAID allergic
What syndrome is associated with giving aspirin to under 16’s?
Reye’s Syndrome
What are glycero-phospholipids?
fatty acids found in the cell membrane ‘fatty acid reservoir’
What are the two domains of the PGHS enzyme?
cyclo-oxygenase domain (COX)
peroxidase domain
What type of receptor do prostaglandins bind to on target cell membranes?
G protein-coupled receptors
Why are NSAIDs not as potent at reducing inflammation as steroids?
steroids inhibit enzyme phospholipase A2 which prevents formation of arachidonic acid (AA)
greater effect than NSAIDs because AA is a precursor for inflammatory mediators so has a wider ranging response
NSAIDs just block COX domain preventing formation of certain prostaglandins
What is the mechanism of action of ibuprofen?
competes with AA for the COX domain active site of PGHS 1&2
it is a reversible competitive inhibitor
What are the two adverse drug reactions associated with NSAID use that we should know about?
potential for gastric ulceration
compromised renal function
Why do NSAIDs have a potential for gastric ulceration?
gastric mucosa protects itself from gastric acid with a layer of mucus
the secretion of this mucus is stimulated by prostaglandins
blocking the COX domain inhibits formation of prostaglandins and gastric mucus thins leaving the stomach vulnerable to peptic ulcers
How do NSAIDs cause comprimised renal function?
What are the signs and symptoms of Reye’s Stage 1?
rash on palms and feet
heavy vomiting
lethargy
confusion
nightmares
pyrexial and headaches
What is the mechanism of action of aspirin?
irrerversible inhibition of the cyclo-oxygenase domain of prostaglandin-H synthase
other NSAIDs are reversible inhibitors
What are the signs and symptoms of Reye’s Stage IV?
deepening coma
hepatic dysfunction
mydriasis (dilation of pupil) with minimal response to light
What are the signs and symptoms of Reye’s Stage III?
more stage I and II symptoms
potential for coma, cerebral oedema, occasionally respiratory arrest
What are the signs and symptoms of Reye’s Stage II?
encephalitis-induced stupor
hyperventilation
fatty liver (steatosis)
hyperactive reflexes
What does the perioxidase domain of prostaglandin-H-synthase do?
converts prostaglandin G to prostaglandin H2
What is the precursor endoperoxide that all prostanoids originate from?
PGH2
