NSAIDs

Question 1

what are the main actions of NSAIDs?

Answer 1

+ anti-inflammatory
+ analgesic
+ anti-pyretic

Question 2

what is the primary action of NSAIDs?

Answer 2

inhibit prostaglandin biosynthesis by direct action on cyclo-oxygenase enzymes

Question 3

what are the 2 mechanisms by which NSAIDs inhibit cyclo-oxygenase?

Answer 3

1. an irreversible, time-dependent inhibition of enzyme

2. a rapid, reversible competitive inhibition of enzyme

Question 4

name a drug that follows this mechanism of action: irreversible, time-dependent inhibition of enzyme

Answer 4

aspirin

Question 5

name a drug that follows this mechanism of action: rapid, reversible competitive inhibition of enzyme

Answer 5

ibuprofen

Question 6

what are prostaglandins?

Answer 6

+ PGE2, PGI2
+ PGD2 from mast cells

+ generated in tissues from a precursor (arachidonic acid) by cyclo-oxygenase enzymes

Question 7

what are the two main cyclo-oxygenase enzymes?

Answer 7

+ COX-1

+ COX-2

Question 8

what is the role of prostaglandins?

Answer 8

+ prostaglandin release accompanies inflammation

Question 9

what are features of prostaglandins (PGE2, PGI2, PGD2)?

Answer 9

+ act as potent vasodilators
+ synergise with other inflammatory mediators (histamine and bradykinin)
+ potentiate histamine and bradykinin actions on postcapillary venule permeability and pain sensory nerves

Question 10

what type of inflammation are prostaglandins important mediators of?

Answer 10

vasodilation and resultant oedema

Question 11

what is the relationship between NSAIDs and prostaglandins in regards to inflammation?

Answer 11

NSAIDs only effect aspects of inflammation in which prostaglandins play a significant part

Question 12

which local signs and symptoms of inflammation can NSAIDs reduce?

Answer 12

+ redness
+ heat
+ swelling
+ pain

Question 13

body temperature is regulated by the hypothalamus - how are prostaglandins involved?

Answer 13

+ fever occurs when hypothalamic thermostat “set point” is raised

+ bacterial endotoxins cause release of factors (interleukin 1) from macrophages

+ interleukin 1 causes generation of prostaglandins in hypothalamus (PGEs)

+ prostaglandins increase thermostat “set point”

Question 14

what is the relationship between NSAIDs and prostaglandins in regards to anti-pyretic effects?

Answer 14

NSAIDs act by preventing formation of prostaglandins and prevent the rise in temp
- no effect on normal body temp

Question 15

what is the relationship between NSAIDs and prostaglandins in regards to analgesic effects?

Answer 15

+ prostaglandins sensitise nocioceptive nerves to histamine and bradykinins

+ by preventing prostaglandin production NSAIDs prevent sensitisation to pain-producing compounds

Question 16

what are features of aspirin?

Answer 16

+ pro-drug (acetylsalicylic acid)
- can directly acetylate COX enzyme

+ also metabolised to active compound (salicylic acid) by plasma and tissue esterases

+ salicylates found in plasma within 30 mins

+ peak plasma concentrations within 1-2 hr

Question 17

what kind of unwanted effects of salicylates can occur?

Answer 17

+ stomach
- bleeding, ulcers

+ systemic
- tinnitus, dizziness, impaired hearing, nausea, vomiting, hypersensitivity

+ metabolic changes
- blood coagulation affected, action on platelets

+ CNS effects
- stimulation initially, ultimately coma and respiratory depression

+ renal
- insufficiency in susceptible patients with chronic use and overdose

Question 18

what examples of drugs are propionic acids, and what are their features?

Answer 18

+ ibuprofen and naproxen

• not prodrugs
• well absorbed
• last for 4-6 hours

Question 19

what is an example of a fenemate?

Answer 19

mefenamic acid

Question 20

what is an alternate name for paracetamol?

Answer 20

acetaminophen

Question 21

what are features of paracetamol?

Answer 21

+ good analgesic

+ good antipyretic activity

+ well tolerated in GIT

+ weak COX inhibitor
-may be selective inhibitor of CNS-specific, COX-3

+ given orally, well absorbed

Question 22

why might paracetamol have fewer side effects than other NSAIDs?

Answer 22

due to its selectivity for COX enyzmes

Question 23

what is the major issue due to overdose of paracetamol?

Answer 23

hepatotoxicity

Question 24

what are examples of COX-2 inhibitors?

Answer 24

coxibs

e.g. celecoxib

Question 25

what are features of coxibs?

Answer 25

+ used for osteoarthritis and rheumatoid arthritis
+ restricted for when traditional NSAIDs produce too severe GIT side effects
+ cardiovascular risk needs to be assessed

Question 26

what are examples that NSAIDs might be used to treat, as analgesics?

Answer 26

\+ headache
\+ dysmennorhea
\+ backache
\+ bony metastases of cancer
\+ postoperative pain

Question 27

what drugs are short-term analgesics?

Answer 27

+ aspirin
+ paracetamol
+ ibuprofen

Question 28

what are longer-lasting analgesic drugs for chronic pain?

Answer 28

+ naproxen

+ diclofenac

Question 29

for anti-inflammatory action, what is the preferred drug?

Answer 29

ibuprofen

Question 30

for anti-pyretics, what is the preferred drug?

Answer 30

paracetamol

Question 31

name products generated from arachidonic acid by COX enzymes

Answer 31

• thromboxanes
• prostaglandins
• leukotrines

Question 32

COX-1

Answer 32

• constitutive
• important in maintaining GIT integrity
• flurbiprofen (inhibitor)

Question 33

COX-2

Answer 33

• inducible
• involved in inflammatory response
• implicated in cancer development
• celecoxib (inhibitor)

Question 34

what causes inflamed regions to be painful?

Answer 34

due to histamine and bradykinin release:

• activate nocioceptive afferent nerve terminals
• register a painful stimulus