Paracetamol Nimesulide. “ Humanity has but three great enemies; Fever, Famine and War. Of these by...

Paracetamol

Nimesulide

“ 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/MacrophagesEndothelial cells and other cell type

Corticosteroid

Pyogenic cytokinesIL –1 alpha and beta

TNF,IL_6, IFNSEnhanced immunity

Archidonic Acid

PGF2

COX2

Antipyretic

Anterior hypothalamusElevation of

ThermoregulatorySet point

Increased heat productionIncreased heat conservation

Fever

MODE OF ACTION

Tissue damage, release of pyrogens and phospholipids from cell membrane

Archidonic acid

NSAID blockCOX –1*and COX –2in periphery and CNS

Paracetamol blocks COX –2 and COX –3 ?

in CNSPG3

PG3 PG3

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- 1956Well 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