Anti-inflammatory Agents

Question 1

What are the actions of NSAIDS?

aspirin?

Answer 1

analgesic
anti-pyretic
anti-inflammatory
anti-platelet

NSAIDs provide only ‘symptomatic relief’
- they do not cure the underlying cause of inflammation

Question 2

Why is paracetamol not classified as an NSAID? What is its mechanism of action?

Answer 2

is an analgesic without anti-inflammatory effects
- little inhibition of COX-1 or COX-2 in peripheral tissue

have anti-pyretic action
- bacterial endotoxins produced during infections stimulate macrophages to release interleukin-1
- IL-1β acts on the hypothalamus to cause PGE2 release via COX 2
- PGE2 elevates set point temperature = onset of fever
- NSAIDs block PGE2 production so set point is lowered back to normal value and fever dissipates
= anti-pyretic but not anti-inflammatory

NSAIDS have no effect on normal body temperature

Question 3

What is the analgesic mechanism of action of NSAIDS?

Answer 3

• PGs (prostaglandins) sensitise and stimulate nociceptors
• oedema produced by inflammation also directly activates nociceptive nerve fibres
• PGs interact synergistically with other pain producing substances (e.g. kinins, 5-HT, histamine) to produce hyperalgesia (increase sensitivity to pain)
• blockade of PG production breaks this cycle and leads to pain relief

Question 4

What is the anti-inflammatory mechanism of action of NSAIDS?

Answer 4

PGE2 and PGI2 have powerful acute inflammatory effects:
- arteriolar dilatation ( blood flow)
- increase permeability in post-capillary venules
= both processes increase influx of inflammatory mediators into interstitial space (histamine, heparin)

inhibition of their formation reduces redness and swelling

Question 5

How do NSAIDS act on the cardiovascular?

Answer 5

can block synthesis of thromboxane

• reduces platelet aggregation
• increases bleeding time

Question 6

What is the mechanism of action of aspirin? What is the difference between aspirin acting on endothelial cells nd platelets?

Answer 6

aspirin can inhibit cyclo-oxygenase 2

• blocks synthesis of thromboxane = inhibits platelet aggregation, vasoconstriction
• blocks synthesis of prostaglandins = promotes platelet aggregation, vasodilation

endothelial cells can regain their function
- have a nucleus and can synthesis more COX 2 = can be induced/stimulated
platelet
- no nucleus = no new protein synthesis so inhibition of platelet aggregation remains

Question 7

How do NSAIDS act on the GI tract?

Answer 7

PGs (PGE2/PGI2) are important in protecting the gastric mucosa
- stimulate mucus secretion
- inhibit gastric acid secretion
= decrease these cytoprotective mechanisms bleeding and ulceration can result

reduced mucus secretion
reduced carbonate secretion
increased acid secretion
increased leukotriene production = follows lipoxygenase pathway = not good for asthmatics = bronchoconstriction, thick mucus

Question 8

What are examples of COX 2 inhibitors?

Answer 8

etoricoxib

- reduce PGIs

Question 9

How do NSAIDS act on the genital tract?

Answer 9

PGs cause pain and smooth muscle spasm during menstruation - NSAIDs used as treatment

PGs (PGE2 and PGF2α) - important in uterine contractions in childbirth, thus NSAIDs delay contractions

Question 10

How do NSAIDS act on the kidney?

Answer 10

Vasodilator PGs (PGE2/PGI2) regulate renal blood flow
- reduces blood flow

PG1
- mediate renin release

is counter regulated by PGE
PGE
- reduce sodium reabsorption

Question 11

What is the mode of action of naproxen?

Answer 11

inhibits COX1/COX2 levels which lowers PG levels - targets mediators engaged at the onset of inflammation

• exhibits analgesic, anti-inflammatory and antipyretic activity
• inhibits platelet aggregation (inhibits platelet TXA2).