COX inhibitors (NSAIDs)

Question 1

List 3 major therapeutic actions of COX inhibitors

Answer 1

Anti-inflammatory: Decrease in PGE2 &PGI2 reduces vasodilation & oedema
Analgesic (pain relief) : decreases in PGI2 reduces sensitisation of nociceptive nerve endings to bradykinin
Antipyretic (fever relief): Decrease in PGE2 , reduces temp ‘set point’ in the hypothalamus

Question 2

Difference between COX-1 and COX-2

Answer 2

COX-1 : constitutive enzyme so produced all the time
COX-2 : inducible enzyme- produced only under certain conditions

Question 3

where is cox-2 enzyme expressed?

Answer 3

in inflammatory cells when these cells are activated by inflammatory cytokines
-constitutively expressed in kidney, female reproductive tract & CNS

NB: Never get complete cox-2 selectivity, cox-1 will always be activated a bit too

Question 4

cox-1 expression

Answer 4

expressed in most tissues

Question 5

example of cox-1 inhibitor

Answer 5

Flurbiprofen

Question 6

example of cox-2 inhibitor

Answer 6

celecoxib

Question 7

Binding sites of cox-1 and 2

Answer 7

exists as homodimers attached to intracellular membrane
Arachidonate binds to hydrophobic tunnel
Due to a change in amino acid sequence in COX-2, there is a bulge or ‘side pocket’ associated tunnel

Question 8

Vioxx withdrawn why?

Answer 8

-COX-2 selective inhibitor but withdrawn due to concern about its effects on the cardiovascular system

Question 9

Aspirin

Answer 9

Widely used, generally as an anti-platelet drugs- by blocking COX in platelets it can interfere with platelet aggregation

Question 10

Ibuprofen

Answer 10

Weak anti-inflammatory action but with low adverse effects
Used quite widely, non-prescription drug
Used for pain & inflammation in rheumatic disease & other musculoskeletal disorders

Question 11

Naproxen

Answer 11

Very good efficacy & low incidence of adverse effects
Used for pain & inflammation in rheumatic disease & other musculoskeletal disorders
Can be given orally or rectally

Question 12

Naproxen can be combined with?

Answer 12

misoprostol

Question 13

Celecoxib

Answer 13

selective COX-2 inhibitor
Given orally for pain & inflammation in rheumatoid arthritis & osteoarthritis

Question 14

Etoricoxib

Answer 14

Selective COX-2 inhibitor
Given orally for pain & inflammation in rheumatoid arthritis & osteoarthritis
Not approved for use in USA