NSAID Flashcards
What can Arachidonic acid be converted into and by what?
Lipoxins by 15-lipoxygenase
Prostanoids by Cyclooxygenase
Leukotrienes by 5-lipoxygenase
What are the different type of prostanoids?
Prostacyclin
Classical prostaglandins
Thromboxane
What is the effect of Prostacyclin?
Vasodilation
inhibit platelet aggregation
What is the effect of classical prostaglandins?
Increase vascular permeability and pain
What is the effect of thromboxanes?
Vasoconstriction and platelet aggregation
What are the effects of Aspirin?
- Analgesic
2.Anti-pyretic (by blocking prostaglandin)
3.Anti platelet
Explain the “analgesic ceiling” effect of Aspirin
Production of prostaglandin (which causes pain) is blocked by Aspirin. –> this sensitive the nociceptive fibres to stimulation by other inflammatory mediator, making them more sensitive to other compounds like Bradykinin and leukotrienes which can result in pain sensation
Explain why Aspirin is antiplatelet even though it inhibits production of prostacyclin (inhibits platelet aggregation)
Aspirin inhibits both Prostacyclin (which inhibits platelet aggregation) and Thromboxane A2 ( which promotes platelet aggregation)
PGI2 can be restored by synthesis of new COX enzyme which takes a few hours while TXA2 can only be restored by the formation of new platelets which takes 1-2 weeks
Net effect of inhibit platelet aggregation
Aspirin is a ____ (reversible/irreversible) COX inhibitor
Irreversible
What can aspirin be used for?
Aspirin is used at low dose as a blood thinner in cardiovascular diseases
What are the adverse effect of aspirin?
COX inhibition –> Salicylate toxicity when at high doses ( GI intolerance and tinnitus)
Always linked to Reye’s Syndrome. Children with viral infection could develop encephalitis (swelling of brain), hepatomegaly. Contraindicated in children
When is aspirin given in children?
Kawasaki Syndrome when there is high risk of cardiovascular complications including aneurysm and impaired blood flow to periphery.
What are some adverse effect of typical NSAIDS?
PGE2 (prostaglandin)
- Reduce gastric acid section
-increase mucosal blood flow
-increase secretion of mucus
- increase secretion of bicarbonate
Ulcer formation and haemorrhage risk in chronic users
Inhibition of PGE 2
- Sodium and water retention
- Peripheral edema
- Hypertension
Inhibition of PGI 2
- Suppression of renin/aldosterone secretion
- Hyperkalemia
- Acute renal failure
Other effects
- Bronchospasm in asthmatics due to excess leukotrienes due to “back damping effect
- Failure of haeomostasis, bruising
- Pseudo-allergic reaction: rashes, swelling, itching, nasal
congestion, anaphylactic shock
What are the typical NSAID and what are they used for?
Typical NSAIDS:
- Naproxen
a. More effective in women (higher free fraction) used for dysmenorrhea - Indomethacin
a. Strongly anti-inflammatory due to additional steroid-like phosphlipase A inhibition
b. But CNS adverse effects (confusion, depression, psychosis) - Diclofenac
a. Short plasma half-life, therefore low GI risk
b. Long half-life in synovial fluid, used for inflammatory joint disease
What are the main function of COX-1 and COX-2?
Constitutive COX-1: responsible for house keeping, physiological function
- production of TbA2,PGI2,PGE2
Inducible COX-2: Inflammation
- production of PGI2 and PGE2