NSAIDS Flashcards
Pain vs nociception
Pain is a subjective experience. Nociception detects and signals presence of noxious stimuli
How do steroids and NSAIDS affect cyclooxygenase synthesis
Steroids inhibit phospholipids A2, preventing break down of phospholipids to arachidonic acid
NSAIDS inhibit formation of cyclooxygenase from arachidonic acid
Cyclooxygenase forms 3 prostanoids what are they
Prostacyclin
Prostaglandin
Thromboxane
What are the effects of prostacyclin
Vasodilatation, inhibit platelet aggregation
What are the effects of prostaglandin
Vasodilation
Vascular permeability
Pain
What are the effects of txa2 (cox 1 only vs cox 1 and 2 for pgi2 and pge2)
Vasoconstriction and platelet aggregation
Effects of aspirin
Anti inflammatory
Analgesic
Anti pyretic
Anti platelet
How does aspirin exert anti inflammatory effect
Block vasodilation
Block increase in vascular permeability
How does aspirin exert analgesic mechanism
Blocks production of prostaglandins which sensitise nociceptive fibres to stimulation by other inflammatory mediators eg bradykinin and leukotrienes
Ie block sensitisation rather than direct nociceptive activation hence nsaids have analgesic ceiling
Additional analgesics action in the cns. Crosses the blood brain barrier to affect pain modulataion and processing
How does aspirin exert anti pyretic effect
Inhibit cox formation, no pge2 forms. Pge2 responsible for fever
How does aspirin exert anti platelet function
Platelets tend to have cox1 which produce txa2, promoting aggregation. Endothelial cells have cox which forms pgi2 which inhibits aggregation.
Aspirin is an irreversible cox inhibitor. Platelets have no nucleus, unable to make new COX; takes 1-2 weeks to make COX to make txa2 to promote aggregation
Endothelial cells can recover in 3-4h to restore inhibition of platelet aggregation
Side effects of aspirin (due to salicylate chemical structure)
GI bleeding, tinnitus (sign of overrode), hypoprothrombinaemia (excessive lack of thrombosis, prone to bleeding)
Why is aspirin contraindicated in children
Reye’s syndrome. Increased risk when children with viral infections are exposed to salicylate eg aspirin.
Leads to encephalitis and liver swelling. Increased pressure on brain can cause delirium, convulsions, personality changes, loss of consciousness
What are the first gen nsaids
Aspirin, naproxen, indomethacin, diclofenac
What is naproxen used for
First gen nsaids used for dysmenorrhea because more effective in women and long half life of 12-14h
What is indomethacin used for
Rheumatoid arthritis, gout, closes ductus arteriosus in fetus
Compare indomethacin to other nsaids
More potent than other nsaids. Strongly inflammatory as it is a phospholipase a2 inhibitor (more steroid like)
Has cns adverse effects such as hallucination, depression
What is diclofenac used for
1st gen nsaid (cox2>cox1)
Low GI risk because short plasma half life
Longer half life in synovial fluid and accumulates in synovial joint fluid hence useful for inflammatory joint diseases eg rheumatoid arthritis
What are the adverse gastrointestinal effects of NSAIDS
Decrease prostaglandin synthesis; prostaglandins responsible for decreasing gastric acid synthesis, increasing bicarbonate secretion, increasing mucosal blood flow and mucus secretion
NSAIDS result in dyspepsia, nausea, vomiting, ulcer formation, hemorrhage risk in chronic users
How to avoid hemorrhage risk in chronic users of NSAIDS
Use for less than 7 days and use with other drugs eg antacids
But taking an antiplatelet eg aspirin will increase hemorrhage risk if preexistinf ulcer
What are the renal side effects of NSAIDS (esp naproxen due to long duration of action 12-14h)
Inhibition of pge2:
Sodium and water retention leading to peripheral edema and hypertension
Act at ascending limb (25%)
Inhibition of pgi2
Suppresses renin and aldosterone secretion
Hyperkalemia that can result in acute renal failure
Act at DCT (1-2%)
How do nsaids cause pseudoallergic reaction and asthma
Inhibit cox, push arachidonic acid to 5-lipoxygenase (eicosanoids). Excess leukotrienes lead to bronchospasm (asthma patients susceptible) and allergic reaction like symptoms es rashes, swelling, nasal congestion
How do first gen nsaids cause bruising
Inhibit cox. Less thromboxane which promotes platelet aggregation, less haemostasis
What are Coxibs
Gen 2 cox 2 selective inhibitors
First gen vs second gen nsaids
Second gen nsaids are cox 2 selective
Cox 1 constitutive effects
Cox 2 is inducible in response to inflammatory stimulus, hence cox 2 selective inhibitors avoid adverse effects
(But constitutive in CNS, kidney, female reproductive tract, synovium)
What are the adverse effects of Coxibs
Cox 2 still constitutive in kidney. Still have renal toxicity but less severe adverse effect
Delay follicular rupture, affecting ovulation to decrease chance of pregnancy
Premature close of ductus arteriosus in third trimester hence ALL NSAIDS CONTRAINDICATED IN 3RD TRIMESTER
Impair wound healing and exacerbate ulcers (not cause)
Increase thrombosis risk because relative shift to TXA2 (cox 1 only so not affected vs pgi2 and pge2) hence favour platelet aggregation
What are the cox1>2 and cox2>1 nsaids
Cox1>2: Kaley please i am not idiotic Ketoprofen Piroxicam Indomethacin Aspirin Naproxen Ibuprofen
Cox2>1: DM me cute pictures Evan Diclofenac Mefenamic acid Meloxicam Celecoxib Parecoxib Etoricoxib
As cox 2 selectivity increases, drug effect becomes more
Anti inflammatory
Stronger analgesic property
More prothrombotic with the exception of aspirin
Can i use nsaids in pregnancy
Contraindicated in third trimester
Why does paracetamol not have adverse GI effect
Cns selective cox inhibitor, does not inhibit peripheral cox
What are the uses of paracetamol
Analgesics, antipyretic
Weak anti inflammatory effect
How does paracetamol cause hepatotoxicity
Metabolised to NAPQI. CYP2E1 (induced by alcohol) metabolised NAPQI to toxic metabolite
Glutathione converts toxic metabolite to non toxic. Glutathione is depleted by overdose and alcohol abuse, replenished by n acetylene cysteine
