NSAIDS

Question 1

Which pathway products do NSAIDs work on?

Answer 1

Arachidonic acid

Question 2

Name prostanoids

Answer 2

PGE2 
PGF2a 
PGD2
PGI2 - prostacyclin 
TXA2 - thomboxane

Question 3

Prostanoids work on what receptor type and are enhanced by?

Answer 3

GPCRs

Enhanced by local autacoids including bradykinin and histamine

Question 4

How do NSAIDs work as analgesics?

Answer 4

Reduce prostataglandin synthesis

Question 5

How do NSAIDs work as anti-inflammatorys?

Answer 5

Reduce the production of prostaglandin released during injury and therefore inhibit vasodilation in post capillary venules.

Question 6

How do NSAIDs work as antipyretics?

Answer 6

Inhibit hypothalamic COX-2, where cytokine (pyrogen) induced prostaglandin synthesis results in an increased temperature.

Question 7

Name a NSAID with high COX-2 selectivity

Answer 7

Celecoxib

Etoricoxib

Question 8

Name a NSAID with mixed COX inhibition

Answer 8

Naproxen

Diclofenac

Question 9

Name an NSAID with increased COX-1 selectivity

Answer 9

Ibuprofen

Aspirin

Question 10

What are the most common ADRs from NSAIDs?

Answer 10

Dyspepsia, nausea, peptic ulceration, bleeding and perforation.
Decreased mucus and bicarbonate secretion and mucosal blood flow .

Can exacerbate IBD and cause local irritation and bleeding in patients which administer drugs rectally.

Question 11

In which group of patients should NSAIDs be given with caution?

Answer 11

Elderly
Prolonged use
Glucocorticoid stereos 
Anticoagulants 
Smoking 
Alcohol
History of peptic ulceration 
H.pylori

Question 12

What renal ADRs do NSAIDs have?

Answer 12

Reduce GFR and renal blood flow- reversible
More likely to impair those with CKD and heart failure, where prostaglandins are needed for vasodilation and renal perfusion.
Very young and elderly are at greatest risk.

Since prostaglandins usually inhibit sodium absorption in the CD, there is an increase in Na and water- resulting in increased BP.

Question 13

What drug interactions should you be aware of when giving NSAIDs?

Answer 13

NSAIDs cause competitive displacement, therefore increasing free drug concentrations of other bound drugs, particularly highly protein bound drugs.
These drug include:
Sulfonylureas- hypoglycaemia
Warfarin - increased risk of bleeding
Methotrexate- accumulation and hepatotoxicity, leukopenia and RA.