NSAIDs

Question 1

List the 3 major effects of NSAIDs.

Answer 1

Antipyretic, anti-inflammatory and analgesic.

Question 2

How do NSAIDs exert their analgesic and anti-inflammatory effects?

Answer 2

Inhibition of prostaglandin producing enzyme, COX.

Question 3

Describe briefly the arachidonic acid pathway.

Answer 3

Arachidonic acid (AA) is liberated from membrane phospholipids by enzyme phospholipase A2. COX enzyme converts AA to Prostaglandin G2. This is converted to Prostaglandin H2 by COX enzyme. PGH2 can then be metabolised by different enzymes to form different PG molecules which have potent biological effects.

Question 4

What controls the body temperature?

Answer 4

Centre in the hypothalamus.

Question 5

Describe how the antipyretic effect of NSAIDs work.

Answer 5

Infection causes bacterial endotoxins from LPS from the cell wall of bacteria to activate macophages. These release pro-inflammatory cytokines called interleukin 1 (IL1) which affects hypothalamus. Prostaglandin E is produced at hypothalamus causing deviation of body temp. from set point. NSAID inhibits PG-E production here = body temp. returns to set point.

Question 6

Give examples of short acting NSAIDs and the general half life.

Answer 6

Ibuprofen, diclofenac, ketoprofen, indomethacin.

T1/2 = 6 hours.

Question 7

Give examples of long acting NSAIDs and the general half-life.

Answer 7

Naproxen, celecoxib, meloxicam, piroxicam.

T1/2 = over 6 hours.

Question 8

What 7 drugs do NSAIDs interact with?

Answer 8

Methotrexate
ACE inhibitors
Angiotensin II antagonists
Lithium
Oral anticoagulants
Hypotensive agents
Diuretics

Question 9

Inhibition of COX by NSAID can prevent action of PGE2 and PGI2. What is their function and what does inhibition result in?

Answer 9

Both maintain blood flow of gastric mucosa and increases thickness of mucus barrier.
Inhibition renders GI tract to damage.

Question 10

Inhibition of COX by NSAID can prevent action of PGE2 in the kidney. What is its function and what does inhibition result in?

Answer 10

PGE2 maintains renal function - maintains renal cortical blood flow and electrolyte balance.
Inhibition causes kidney dysfunction.

Question 11

Inhibition of eicosanoid TXA2 by NSAID has effects. What is its normal function and what does inhibition result in?

Answer 11

TXA2 aids platelet function and allows for increased platelet aggregation.
Inhibition prevents TXA2 formation = increases bleeding time.

Question 12

List 5 NSAID side effects.

Answer 12

GI complications.
Reversible renal failure.
Platelet dysfunction.
Bronchospasm.
Skin reactions.

Question 13

NSAIDs can cause major GI side effects. There’s 2 main ones. List and describe them.

Some serious effects can cause bleeding and death.

Answer 13

Nuisance symptoms - heartburn, nausea, abdominal pain, dyspepsia.
Mucosal lesions - ulcers, perforated ulcers, bleeding.

Question 14

There are two COX isoenzymes. COX1 and COX2. Describe them and where they are found.

Answer 14

COX-1 - constantly present and found in all tissues and cells - responsible for basal PG production.
COX-2 - induced by inflammatory stimuli and suppressed by steroids - responsible for other prostaglandin synthesis.

Question 15

COX-2 enzyme can be found at basal levels in certain parts of body. Where are they found and what functions do they have?

Answer 15

Found in brain, kidney and ovarian tissues.
Functions:
- development of kidney
- salt and water regulation 
- ovulation and parturition

Question 16

Which NSAIDs have lowest, intermediate and highest risks for GI effects?

Answer 16

Lowest risk - ibuprofen.
Intermediate risk - naproxen, indomethacin, diclofenac
Highest risk - ketoprofen, piroxicam

Question 17

Name COX1 specific inhibitor.

Answer 17

Low dose aspirin.

Question 18

Name 2 non-specific COX inhibitors (inhibit COX1 and 2).

Answer 18

Diclofenac

Ibuprofen

Question 19

Name 2 preferential COX2 inhibitors.

Answer 19

Meloxicam

Etodolac

Question 20

Name 2 COX2 specific inhibitors.

Answer 20

Celecoxib (first generation).

Etoricoxib, Parecoxib (second generation)

Question 21

What factors contribute to increased risk of GI side effects when taking NSAIDs?

Answer 21

History of GI problems
Age >65
Concomitant use of corticosteroids and/or anticoagulants
Smoking
Alcohol consumption
Comorbid illness e.g. CV disease

Question 22

Which NSAID is the safest from a CV perspective?

Answer 22

Naproxen.

Question 23

Describe the general advice on the safe use of NSAIDs.

Answer 23

1. Preferably use ibuprofen due to lowest GI effects.
2. Start at lowest recommended dose.
3. Use for shortest duration necessary.
4. Do not use more than one NSAID concurrently.
5. All NSAIDs contraindicated with peptic ulcers.
6. Use with aspirin - increases GI side effects - only use if necessary - low dose aspirin.