NSAIDs Flashcards
Hilton’s law
The nerve supplying a joint also supplies the muscles that move the joint, the skin over the joint, and the insertion of the muscles
Characteristics of somatic pain
Aching
Often constant
Dull or sharp
Worse with movement
Well localised unless deep
4 steps on the WHO analgesic ladder
Nonopioids
Weak opioids
Strong opioids
Nerve block/epidural/PCA pump/spinal stimulators
Which type of pain goes up the WHO analgesics ladder and which type goes down
Acute goes down
Chronic and cancer goes up
NSAID MOA
Inhibition of COX enzymes preventing prostaglandin formation
Which NSAIDS inhibit COX1 and COX2
Aspirin
Ibuprofen
Diclofenac
Ketoprofen
Which NSAIDS are selective COX2 inhibitors
Rofecoxib
Celecoxib
Etoricoxib
Meloxicam
MERC
How does the MOA of aspirin differ from those of ibuprofen diclofenac and ketoprofen
All inhibit COX 1+2
Ibuprofen, diclofenac, and ketoprofen also have additional mechanisms
Effects of aspirin
Analgesic
Antipyretic
Anti inflammatory
Effects of ibuprofen diclofenac and ketoprofen
Analgesic
Anti inflammatory
Most prescribed NSAID in UK
Naproxen
Function of COX enzymes
Catalyse formation of prostaglandins from Arachidonic acid
3 classes of prostaglandins
Prostaglandins D E and F
Prostacyclin
Thromboxane A
What type of molecule are prostaglandins
Tissue hormones
How far do prostaglandins travel from site of production to site of action
Work on cells within tissue that produced them
Don’t diffuse far
PGE2 actions
Vasodilation of renal art
Suppress lymphocytes
Sensitises peripheral nerve endings
Inhibits gastric acid secretion
Fever
Uterine relaxation
PGD2 actions
Vasodilation
Bronchoconstriction
PGI2 action
Vasodilation of renal artery
Inhibits platelet aggregation
Bronchodilation
Inhibit gastric secretion
Sensitise afferent nerve endings to pain
PGF alpha actions
Vasoconstriction + dilation
Bronchoconstriction
Uterine contraction
TXA2 actions
Vasoconstriction
Induce platelet aggregation
Bronchoconstriction
Uterine contraction
How many types of prostaglandin receptor are there and what receptor type are they
9
G protein coupled receptor
Which COX enzyme is physiologic and which is inducible
COX1 physiologic
COX2 inducible
What enzyme catalyses the conversion of cell membrane phospholipids to arachadonic acid
Phospholipase A2
What conditions increase COX2 in joints
OA
RA
What molecules cause COX2 increase in joints effected by OA and RA
IL1, TNF, IL17 -> stim iNOS -> induces COX2
Production of Which prostaglandin in joints can be directly activated by mechanical stress
PGE2
Which COX isoforms is predominant in the stomach
COX1
Where is COX1 and COX2 found in the stomach
1 - in crypts
2 - superficial mucosa
How is COX1 beneficial in the stomach
Produces PGE2 which protects gastric mucosa
Why are long term NSAIDs harmful to the stomach
Long term COX1 inhibition blocks PGE2 production leading to gastritis and gastric ulcers
Why are NSAIDs given as GI preparations
Decrease risk of gastric ulcers
Effects of PGE2 on gastric mucosa
Incr mucus secretion
Incr cell regeneration
Incr HCO3 release
Incr blood flow
Decr H+ secretion
Effects of PGI2/prostacyclin and thromboxane A2 on the cardiovascular system
PGI2 vasodilation, prevents platelet aggregation
Thromboxane A2 vasoconstriction, promotes platelet aggregation
Where is COX1 and COX2 found in the cardiovascular system
COX1 - platelets
COX2 - endothelium
What type of spinal cord transmission is COX2 important in
Nocioceptive
What increases COX2 in the kidney
Salt deprivation
Protective effects of PGE2 and PGI2 in the kidney
PGE2 regulates Na reabsorption
PGI2 incr K secretion by stimulating renin
Vasodilation
Which COX enzyme is more harmful
COX2
What drug type has the suffix -coxib
Selective COX2 inhibitor
What adverse effect is associated with rofecoxib diclofenac celecoxib and high dose ibuprofen
Increased cardiovascular risk
Is GI risk higher in selective COX2 inhibitors or non selective NSAIDs
Non Selective NSAIDs
How many COX enzymes do humans have
COX1
COX2
COX3 - non functional
