NSAIDs

Question 1

NSAIDs types?

Answer 1

1. Non-selective
2. COX-2 Inhibitors
3. Paracetamol
   (ACETAMINOPHEN)

Question 2

Non-selective NSAIDs drugs?

Answer 2

1. Aspirin
2. Naproxen
3. Indomethacin
4. Diclofenac

Question 3

Aspirin effects?

Answer 3

Anti-inflammatory
Analgesic
Antipyretic
Antiplatelet

Question 4

Aspirin anti-inflammatory effect mechanism?

Answer 4

• ↓ vasodilation

* ↓ increase in vascular permeability

Question 5

Aspirin Analgesic effect mechanism?

Answer 5

• ↓ sensitization of nociceptive fibres to stim by inflammatory mediators
o Analgesic ceiling – does not block direct nociceptive activation

Question 6

Aspirin Antipyretic effect mechanism?

Answer 6

• Act on hypothalamus & reset thermostat

Question 7

Aspirin Antiplatelet effect mechanism?

Answer 7

• Block TXA2 (platelet agg) > Block PGI2 (platelet inhibition)

o Blocks both but PGI2 restored faster by new COX
synthesis

o TXA2 restored only by new platelet formation

o Low dose aspirin à useful as a blood thinner

Question 8

Aspirin Side effects?

Answer 8

• Not to be prescribed to

children with viral infections –> Reye’s syndrome (rare but life-threatening)

Question 9

What happens in Reye’s syndrome?

Answer 9

o Encephalitis
o Liver swelling
o Vomiting
o Delirium
o Convulsions
o Loss of consciousness

Question 10

Naproxen plasma half life?

Answer 10

Long T ½ (12-24h)

Question 11

Naproxen uses?

Answer 11

Dysmenorrhea – more effective in women

Question 12

Indomethacin uses?

Answer 12

• Strong anti-inflammatory

* Steroid-like ↓ PLA2

Question 13

Indomethacin Side effects?

Answer 13

• CNS: confusion, depression, psychosis

Question 14

Diclofenac plasma half life?

Answer 14

Short T ½ (<2hrs)

Question 15

Diclofenac uses?

Answer 15

• Less GI risk due to short T ½

* But longer T ½ in synovial fluid

Question 16

GIT Side Effects of NSAIDs?

Answer 16

• Dyspepsia
• Nausea, vomiting
• Ulcer

Question 17

GIT Side Effects of NSAIDs mechanism?

Answer 17

Prostaglandins have a protective function to ↓ acid, ↑ bicarbonate & mucus

Question 18

Renal Side Effects of NSAIDs?

Answer 18

• Edema
• Hypertension
• Hyperkalemia
• Acute renal failure

Question 19

Renal Side Effects of NSAIDs:
• Edema
• Hypertension

Mechanism?

Answer 19

• ↓ PGE2 (inhibits reabs)

* ↑ Na+ and water reabs at TAL

Question 20

Renal Side Effects of NSAIDs:
• Hyperkalemia
• Acute renal failure

Mechanism?

Answer 20

• ↓ PGI2 (which stim RAAS)

* Suppression of renin and aldosterone secretion

Question 21

Pseudo-allergic Side Effects of NSAIDs?

Answer 21

• Rash
• Itch
• Nasal congestion
• Anaphylaxis

Question 22

Asthma Side Effects of NSAIDs?

Answer 22

• Bronchospasm in susceptible (excess

leukotrienes)

Question 23

Pseudo-allergic and Asthma Side Effects of NSAIDs Mechanism?

Answer 23

• Inhibition of arachidonic acid à prostaglandins

* Shunt arachidonic acid to produce leukotrienes

Question 24

Bleeding Side Effects of NSAIDs?

Answer 24

• Bruising

* Bleeding

Question 25

Bleeding Side Effects of NSAIDs mechanism?

Answer 25

Due to antiplatelet activity

Question 26

NSAIDs contraindications?

Answer 26

Avoid NSAIDs in 3rd trimester of pregnancy: May cause premature closure of ductus arteriosus

Question 27

COX-2 Inhibitors drugs?

Answer 27

Coxibs eg. Celecoxib

Question 28

COX-2 Inhibitors Mechanism of Action?

Answer 28

• Selective inhibition of COX- 2 (inducible) reduces GIT side effects • Mainly anti-inflammatory, analgesic

Question 29

COX-2 Inhibitors Side Effects?

Answer 29

1. Avoid in late pregnancy (3rd trimester) 2. Renal toxicity 3. Effects on ovulation 4. GIT sparing incomplete 5. Increase risk of thrombosis

Question 30

Why avoid cox-2 inhibitors in late pregnancy (3rd trimester)?

Answer 30

o Premature closure of ductus arteriosus

Question 31

Why do cox2 inhibitors cause Renal toxicity?

Answer 31

o Due to COX-2 in kidney

Question 32

How do cox2 inhibitors cause effects on ovulation?

Answer 32

o Delayed follicular rupture

Question 33

Why is GIT sparing incomplete due to cox2 inhibitors?

Answer 33

o Due to impairment of wound healing

Question 34

Significance of cox2 inhibitors causing increased risk of thrombosis?

Answer 34

o ↑ CVS death - COX2 produces prostacyclin (inhibits clotting) but not TXA2 (promotes clotting) - COX2 block > shunt more arachidonic acid to COX1 > produce more TXA2 > prostacyclin

Question 35

Paracetamol mechanism of action?

Answer 35

• CNS-selective COX inhibitor. May also involve serotonin relays or receptors

Question 36

Paracetamol uses?

Answer 36

* Good analgesic * Potent antipyretic * Spares the GIT * Safe for children with few side effects * (not potent as anti-inflammatory)

Question 37

Paracetamol Side Effects?

Answer 37

• Liver damage o Exacerbated by chronic alcohol use o Should not occur at therapeutic doses in healthy individuals * Allergy * Nausea/vomiting