NSAIDS Flashcards
What are the 5 signs and symptoms of inflammation
redness, swelling, pain, heat, loss of functions
synthesis of prostanoids
physical/chemical damage to membrane phospholipids > stimulation of phospholipase A > cleaves membrane phospholipids to produce arachidonic acid > arachidonic acid covered to prostanoids via cyclooxygenase (COX1&2)
what are the 5 forms of prostanoids
PGI2, PGD2, PGE2, PGF2, TXA2
what are prostanoid receptors
G-protein coupled receptors
Biological functions/roles of prostanoids
PGI - vasodilation, inhibition of platelet aggregation
PGD- mediate pain, increase vascular permeability, vasodilation, bronchoconstriction
PGE- mediate pain, increase vascular permeability, vasodilation, both bronchodilation and constriction, inhibition of gastric secretion
PGF-mediate pain, increase vascular permeability, vasoconstriction, bronchoconstriction
TXA - vasoconstriction, stimulation of platelet aggregation, bronchoconstriction
mechanism of traditional NSAIDS (aspirin)
irreversible inhibition of COX1&2, forms covalent bond with serine residue > decrease in prostanoid level
NSAIDS as anti-inflammatory drugs
block vasodilation to reduce redness and heat
block increase in vascular permeability to reduce swelling
block pain associated with inflammation
NSAIDS as analgesic (pain)
without NSAID: PGE sensitization of nociceptors enhance pain sensation
with NSAID: PGE levels decrease due to blocking of COX1&2 > gets rid of mild to moderate pain sensation but not for severe (limitations) > NSAIDS does not block the nociceptor pathway to the brain for pain sensation
NSAID as antipyretic (fever)
without NSAID: neutrophiles stimulates cytokines release triggers COX1&2 > PGE levels reset body thermostat to a higher body temperature
with NSAID: blocks COX1&2 > PGE levels decreases > body thermostat returns back to normal temperature (NSAIDS does not reduce body temperature below normal)
Aspirin as an anti platelet aggregation drugs
platelets have COX1 that are constantly active converting arachidonic acid to TXA (stimulates platelet aggregation)
endothelial cells have COX1 that are constantly active converting arachidonic acid to PGI (inhibits platelet aggregation)
balanced homeostasis
With aspirin: it blocks COX1 irreversibly. While platelets is anucleate, endothelial cells have nucleus that can regenerate faster than platelets.
this means that aspirin inhibits platelet aggregation as it reduced TXA more than PGI levels
adverse effects of traditional NSAIDS
- GI tract: PGE levels reduced > increase gastric acid secretion > gastric ulceration and upset
- Bleeding due to blood thinner
- pseduo allergic effects: anaphylatic shock and rash
- aspirin induced asthma due to COX inhibition. LOX converts arachidonic acid to leukotrienes, that mediates asthma
- kidney failure: reduce glomerular filtration, water retention, edema, acute renal failure
*all non aspirin drugs have high risk of inducing stoke and heart attack
COX 2 selective inhibitor (celecoxib) limitations
- still have some inhibitory effects on COX1 that results in gastric issues
- thrombosis due to stimulation of platelet aggregation
- COX 2 selective inhibitor impairs wound healing and exacerbate ulcers
paracetamol advantages & disadvantages
advantages
- good analgesic
- potent antipyretic
- less drug drug interaction
- less side effects
- does not damage GI tract
disadvantages
- weak anti immunity
- paracetamol overdose = hepatotoxicity (liver damage)
paracetamol overdose > destroys glutathione > glutathione protects liver from alcohol > alcohol overdose + paracetamol overdose = liver damage > N-acetyl-cysteine converts acetyl to glutathione to protect liver
the NSAID drugs that binds reversibly using hydrogen bonding is
Ibuprofen
list all NSAID drugs
aspirin, paracetamol, ibuprofen, celecoxib
