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Paracetamol
NsNSAID
Selective COX-2 inhibitor
Dexamethasone
Gabanoids
Anti-neurophatic
PARACETAMOL
PARACETAMOL HISTORY
1878, synthesized by Morse
1893, introduced for medical usage
1955, reintroduced as an analgesic in US
Most popular and widely used drug for the first line
treatment of fever and pain
1985, intravenous a pro-drug preparation, propacetamol
Recent introduction to the market of a ready-to-use
intravenous formulation
Mechanism of Action :
Still under discussion
Act peripherally and/or centrally ?
Which analgesic pathway mainly affected ?
(NAFQI)
Paracetamol overdoses significant cause toxicity
Suicide attempts
Unintentional overdoses
Plasma concentration
Minimum plasma concentration for analgesia
and anti-pyresis 10-20 mg/L
Potential hepatotoxicity 150 mg/L
failure is 24 grams
Intravenous 15 mg/kg 7 mg/L and detectable in CSS
at 5 minutes
Intravenous 1 gr 14.4 mg/L in 20 minutes
Oral 1 gr large and unpredictable variability
( subtherapeutic plasma conc. in 80 min )
The Metabolism of Acetaminophen and
NAPQI production
Excessive dosing
Increased P-450 activation
ARACHIDONATE
COX-1 COX-2
prostaglandins prostaglandins
• “Constitutive” • “Inducible”
• Expressed: • Expressed:
– GI mucosa – Site of injury
– Kidneys – CNS
– Platelets
– Vascular
endothelium
NSAIDs and Renal Function
With proper selection and monitoring, the incidence of
NSAID-induced perioperative renal impairment is low
and NSAIDs need not be withheld in patients with
normal preoperative renal function (Lee A et al, 2007
Level I).
No differences between patients given diclofenac,
ketorolac, indomethacin (indometacin) or ketoprofen
(Lee A et al, 2007 Level I).
NSAIDs and Coxib have similar adverse effect on renal
function ( Level I )
NSAIDs and Bleeding
preferentially preferentially
COX-1 COX-1 Dual COX-2 COX-2
selective selective COX selective selective
inhibitor inhibitor inhibitor inhibitor inhibitor
CV Incidence
GIT Incidence
PCT, NSAIDs, COXIBs