NSAIDs Flashcards
NSAIDs types?
- Non-selective
- COX-2 Inhibitors
- Paracetamol
(ACETAMINOPHEN)
Non-selective NSAIDs drugs?
- Aspirin
- Naproxen
- Indomethacin
- Diclofenac
Aspirin effects?
Anti-inflammatory
Analgesic
Antipyretic
Antiplatelet
Aspirin anti-inflammatory effect mechanism?
- ↓ vasodilation
* ↓ increase in vascular permeability
Aspirin Analgesic effect mechanism?
• ↓ sensitization of nociceptive fibres to stim by inflammatory mediators
o Analgesic ceiling – does not block direct nociceptive activation
Aspirin Antipyretic effect mechanism?
• Act on hypothalamus & reset thermostat
Aspirin Antiplatelet effect mechanism?
• 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
Aspirin Side effects?
• Not to be prescribed to
children with viral infections –> Reye’s syndrome (rare but life-threatening)
What happens in Reye’s syndrome?
o Encephalitis o Liver swelling o Vomiting o Delirium o Convulsions o Loss of consciousness
Naproxen plasma half life?
Long T ½ (12-24h)
Naproxen uses?
Dysmenorrhea – more effective in women
Indomethacin uses?
- Strong anti-inflammatory
* Steroid-like ↓ PLA2
Indomethacin Side effects?
• CNS: confusion, depression, psychosis
Diclofenac plasma half life?
Short T ½ (<2hrs)
Diclofenac uses?
- Less GI risk due to short T ½
* But longer T ½ in synovial fluid
GIT Side Effects of NSAIDs?
- Dyspepsia
- Nausea, vomiting
- Ulcer
GIT Side Effects of NSAIDs mechanism?
Prostaglandins have a protective function to ↓ acid, ↑ bicarbonate & mucus
Renal Side Effects of NSAIDs?
- Edema
- Hypertension
- Hyperkalemia
- Acute renal failure
Renal Side Effects of NSAIDs:
• Edema
• Hypertension
Mechanism?
- ↓ PGE2 (inhibits reabs)
* ↑ Na+ and water reabs at TAL
Renal Side Effects of NSAIDs:
• Hyperkalemia
• Acute renal failure
Mechanism?
- ↓ PGI2 (which stim RAAS)
* Suppression of renin and aldosterone secretion
Pseudo-allergic Side Effects of NSAIDs?
- Rash
- Itch
- Nasal congestion
- Anaphylaxis
Asthma Side Effects of NSAIDs?
• Bronchospasm in susceptible (excess
leukotrienes)
Pseudo-allergic and Asthma Side Effects of NSAIDs Mechanism?
- Inhibition of arachidonic acid à prostaglandins
* Shunt arachidonic acid to produce leukotrienes
Bleeding Side Effects of NSAIDs?
- Bruising
* Bleeding
Bleeding Side Effects of NSAIDs mechanism?
Due to antiplatelet activity
NSAIDs contraindications?
Avoid NSAIDs in 3rd trimester of pregnancy:
May cause premature closure of ductus arteriosus
COX-2 Inhibitors drugs?
Coxibs eg. Celecoxib
COX-2 Inhibitors Mechanism of Action?
• Selective inhibition of COX-
2 (inducible) reduces GIT side effects
• Mainly anti-inflammatory, analgesic
COX-2 Inhibitors Side Effects?
- Avoid in late pregnancy (3rd trimester)
- Renal toxicity
- Effects on ovulation
- GIT sparing incomplete
- Increase risk of thrombosis
Why avoid cox-2 inhibitors in late pregnancy (3rd trimester)?
o Premature closure of ductus arteriosus
Why do cox2 inhibitors cause Renal toxicity?
o Due to COX-2 in kidney
How do cox2 inhibitors cause effects on ovulation?
o Delayed follicular rupture
Why is GIT sparing incomplete due to cox2 inhibitors?
o Due to impairment of wound healing
Significance of cox2 inhibitors causing increased risk of thrombosis?
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
Paracetamol mechanism of action?
• CNS-selective COX inhibitor. May
also involve serotonin relays or
receptors
Paracetamol uses?
- Good analgesic
- Potent antipyretic
- Spares the GIT
- Safe for children with few side effects
- (not potent as anti-inflammatory)
Paracetamol Side Effects?
• Liver damage
o Exacerbated by chronic alcohol use
o Should not occur at therapeutic doses
in healthy individuals
- Allergy
- Nausea/vomiting
