1. Dolonerv NSAID s

3. “ Humanity has but three great enemies; Fever, Famine and War. Of these by far the most terrible , is fever.” ( Sir William Osler )

4. Pathogenesis of fever Infectious agents or toxin ( Endo/Exo) Mediators of inflammation Monocyte/Macrophages Endothelial cells and other cell type Corticosteroid Pyogenic cytokines IL –1 alpha and beta TNF,IL_6, IFNS Enhanced immunity Archidonic Acid PGF2 COX2 Antipyretic Anterior hypothalamus Elevation of Thermoregulatory Set point Increased heat production Increased heat conservation Fever

5. 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 Paracetamol blocks COX –2 and COX –3 ? in CNS PG 3 PG 3 PG 3 Fever and Pain COX –1* is critical to maintain the integrity of platelets,renal function and gastric mucosa.

8. 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 .

17. 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

18. Thank you