Transcript Paracetamol - Pediatric Oncall

Nimesulide
Paracetamol
“ Humanity has but three great enemies;
Fever, Famine and War. Of these by far
the most terrible , is fever.”
( Sir William Osler )
Pathogenesis of fever
Infectious agents or toxin ( Endo/Exo)
Mediators of inflammation
Monocyte/Macrophages
Endothelial cells and other cell type
Fever
Increased heat production
Increased heat conservation
Corticosteroid
Pyogenic cytokines
IL –1 alpha and beta
TNF,IL_6, IFNS
Enhanced immunity
COX2
Antipyretic
Archidonic
Acid
PGF2
Anterior
hypothalamus
Elevation of
Thermoregulatory
Set point
MODE OF ACTION
Tissue damage, release of pyrogens and phospholipids from
cell membrane
Archidonic acid
NSAID block
COX –1*and COX –2
in periphery and CNS
PG3
PG3
PG3
Paracetamol blocks
COX –2 and COX –3 ?
in CNS
Fever and Pain
COX –1* is critical to maintain the integrity of
platelets,renal function and gastric mucosa.
Choice of antipyretic is highly debatable
Which should the choice
Safety.
Wide therapeutic window.
Short duration of action.
Side effect: Over dosing either intentional or
accidental.
Choice of antipyretic
According to WHO paracetamol is the drug of first choice* .
Ibuprofen is a useful 2nd line drug.
No other NSAID including Nimesulide should be prescribed
for children with high grade fever and used with caution has
been cleared by US FDA for using as antipyretic.
* WHO 1990
PCM was first used clinically by
Von Mering in 1893.
Marketed in US - 1950.
in UK- 1956
Well tolerated . Rarely produce
side effects of any kind when
administered in recommended doses.
Paracetamol approved FDA (USA)
OTC – status since 1955.
Consider safer in asthmatic
patients.
Pharmacokinetics:
PCM bio availability above 80% .
Peak plasma concentration occur between
15 mins and 2 hours after ingestion.
It has few Pharmacokinetics drug interaction.
Adverse effects.
Excellent safety records at therapeutic doses.
Excellent safety in patient of all age.
PCM no associated risk of major upper
GI bleed or mucosal damage.
Side Effect
Haemostasis
Meth- haemoglobinaemia.
Thrombocytopenia.
Anaemia.
Agranulocytosis.
Hepatotoxicity.
Nephrotoxicity
Contraindication and precaution
Apart from hypersensitivity, No absolute
contraindication.
Suitable in all areas with a wide range of medical conditions
 Children
 Elderly
 Patients with mild to moderate liver disease ,
renal disease,GI problems.
 Asthmatics
PCM overdose
 Excellent
safety and tolerability.
 Effective antidote for PCM available.
 Therapeutic overdose is rare.
 Acute toxic dose – 150 mg/kg or 10 times the
recommended dose.
 Over dose is usually suicidal and appropriate
over a period of time.
Nimesulide :Long duration of action.
Small therapeutic window.
Easy Overdosing – negligence or ignorance.
Serious infection may be missed.
May cause hypotension occasionally.
Many countries have withdrawn
Nimesulide
NSAID with selective COX2 inhibitory action.
Peak 1 – 4hrs after intake.
Marginal better than paracetamol.
Patient in long term use must be monitored for
side effect.
Side effects of Antipyretic
Adverse effect
PCM
NSAID
GI side effect
Rare
++
Skin Rash
Rare
++
RO bleeding
Nil
++
Bronchial hyper-reactivity Nil
+
Hepato-toxicity
++
++
( overdose)
( Overdose)
Nephrotoxicity
+
++
National Kidney foundation USA, PCM – Safe.
Seizure
Nil
+
Hypothermia
Nil
+
Pregnancy
Safe
unsafe
< 6 month
Recommended
Not recommended