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  1. 1. Dolonerv NSAID s
  2. 2. Dolonerv film tablets <ul><li>composition: </li></ul><ul><li>1 film tablet contains: </li></ul><ul><li>Paracetamol 500mg </li></ul><ul><li>Thiamin nitrate(vit.B1) 50 mg </li></ul><ul><li>Pyridoxine hydrochloride(vit.B6) 100mg </li></ul><ul><li>Cyanocobalamin(vit.B12) 0.5mg </li></ul>
  3. 3. “ Humanity has but three great enemies; Fever, Famine and War. Of these by far the most terrible , is fever.” ( Sir William Osler )
  4. 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. 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.
  6. 6. <ul><li>Choice of antipyretic is highly debatable </li></ul><ul><li>Which should the choice </li></ul><ul><ul><li>Safety. </li></ul></ul><ul><ul><li>Wide therapeutic window. </li></ul></ul><ul><ul><li>Short duration of action. </li></ul></ul><ul><ul><li>Side effect: Over dosing either intentional or </li></ul></ul><ul><li>accidental . </li></ul>
  7. 7. <ul><li>Choice of antipyretic </li></ul><ul><li>According to WHO paracetamol is the drug of first choice* . </li></ul><ul><li>Ibuprofen is a useful 2 nd line drug. </li></ul><ul><li>No other NSAID including Nimesulide should be prescribed </li></ul><ul><li>for children with high grade fever and used with caution has </li></ul><ul><li>been cleared by US FDA for using as antipyretic. </li></ul><ul><li>* WHO 1990 </li></ul>
  8. 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 .
  9. 9. <ul><ul><li>Paracetamol approved FDA (USA) </li></ul></ul><ul><ul><li>OTC – status since 1955. </li></ul></ul><ul><ul><li>Consider safer in asthmatic </li></ul></ul><ul><ul><li>patients. </li></ul></ul>
  10. 10. <ul><li>Pharmacokinetics: </li></ul><ul><li>PCM bio availability above 80% . </li></ul><ul><li>Peak plasma concentration occur between </li></ul><ul><li>15 mins and 2 hours after ingestion. </li></ul><ul><li>It has few Pharmacokinetics drug interaction. </li></ul>
  11. 11. <ul><li>Adverse effects . </li></ul><ul><li>Excellent safety records at therapeutic doses. </li></ul><ul><li>Excellent safety in patient of all age. </li></ul><ul><li>PCM no associated risk of major upper </li></ul><ul><li>GI bleed or mucosal damage. </li></ul>
  12. 12. <ul><li>Side Effect </li></ul><ul><li>Haemostasis </li></ul><ul><li>Meth- haemoglobinaemia. </li></ul><ul><li>Thrombocytopenia. </li></ul><ul><li>Anaemia. </li></ul><ul><li>Agranulocytosis. </li></ul><ul><li>Hepatotoxicity. </li></ul><ul><li>Nephrotoxicity </li></ul>
  13. 13. <ul><li>Contraindication and precaution </li></ul><ul><li>Apart from hypersensitivity, No absolute </li></ul><ul><li>contraindication. </li></ul><ul><li>Suitable in all areas with a wide range of medical conditions </li></ul><ul><ul><li>Children </li></ul></ul><ul><ul><li>Elderly </li></ul></ul><ul><ul><li>Patients with mild to moderate liver disease , </li></ul></ul><ul><ul><li>renal disease,GI problems. </li></ul></ul><ul><ul><li>Asthmatics </li></ul></ul>
  14. 14. <ul><li>Dolonerv overdose </li></ul><ul><li>Excellent safety and tolerability. </li></ul><ul><li>Effective antidote for Dolonerv available. </li></ul><ul><li>Antidote N-acetyl-cysteine within 10 hours. </li></ul><ul><li>Therapeutic overdose is rare. </li></ul><ul><li>Acute toxic dose – 150 mg/kg or 10 times the </li></ul><ul><li>recommended dose. </li></ul><ul><li>Over dose is usually suicidal and appropriate </li></ul><ul><li>over a period of time. </li></ul>
  15. 15. <ul><li>Nimesulide :- </li></ul><ul><ul><li>Long duration of action. </li></ul></ul><ul><ul><li>Small therapeutic window. </li></ul></ul><ul><ul><li>Easy Overdosing – negligence or ignorance. </li></ul></ul><ul><ul><li>Serious infection may be missed. </li></ul></ul><ul><ul><li>May cause hypotension occasionally. </li></ul></ul><ul><ul><li>Many countries have withdrawn </li></ul></ul>
  16. 16. <ul><li>Nimesulide </li></ul><ul><li>NSAID with selective COX 2 inhibitory action. </li></ul><ul><li>Peak 1 – 4hrs after intake. </li></ul><ul><li>Marginal better than paracetamol. </li></ul><ul><li>Patient in long term use must be monitored for </li></ul><ul><li>side effect. </li></ul>
  17. 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. 18. Thank you