Chemistry of Aspirin

presentation is based on mainly the chemistry of aspirin,A little bit introduction about nsaid is also here.The uses,doses and side effects are also in these presentation.

1. By- Ritam Choudhury B.pharm CHEMISTRY OF ASPIRIN

2. Contents: Non steroidal anti inflammatory drugs Classification Mechanism of action Aspirin Synthesis of Aspirin SAR of Aspirin Uses Doses Adverse Effect Reference

3. Non Steroidal Anti-inflammatory Drugs These are a group of drugs which have an anti pyretic , anti- inflammatory and analgesic effect . They do not depress CNS. They do not produce physical dependence They act primarily on peripheral pain mechanisms but also in the CNS to raise pain threshold. They are commonly employed over the counter drugs (OTC). They are also known as nonnarcotic , nonopioid , or aspirin like analgesics.

4. Classifications : Nonselective COX inhibitors: Preferential COX-2 inhibitors: Salicylates :- Aspirin Nimesulide , Diclofenac , Propionic acid derivatives :-Ibuprofen , Naproxen Aceclofenac Fenamate :- Mephenamic acid. Enolic acid derivatives :- Piroxicam Acetic aid derivatives :- Indomethacin Pyrazolone derivatives :- Phenylbutazone . Selective COX 2 inhibitors: Analgesic-antipyretics with poor antiinflammatory action: Celecoxib , Etoricoxib 1. Paraaminophenol derivatives :- Paracetamol Paracoxib 2. Pyrazolone derivatives :- Metamizole 3. Benzoxazocine derivatives :- Neofam

5. Mechanism Of Action : Mainly by blocking of Prostaglandins synthesis. Cycloxygenase-1 & Cycloxygenase-2 Produce from Arachidonic acid. Most NSAIDs inhibit COX-1 NSAIDs inhibit COX-2 nonselectively . But now some selective COX-2 inhibitors have been produced.

6. aSPIRIN Pharmacokinetic  data Bioavailability 80–100 % Protein binding 80–90 % Biological half-life Dose-dependent; 2–3 hours for low doses, 15–30 hours for large doses . Excretion Urine (80–100%), sweat, saliva, feces Chemical data Formula C 9 H 8 O 4 Molecular mass 180.157 g/mol Physical data Density 1.40 g/cm 3 Melting point 135 °C (275 °F) Boiling point 140 °C (284 °F) (decomposes) Solubility in water 3 mg/ mL (20 °C)

7. Mechanism Of Action as Analgesic :

8. Mechanism Of Action as Antipyresis

9. Mechanism Of Action as Antiplatelet Aggregatory :

10. Synthesis Of Aspirin Aspirin Aspirin is synthesized by the acetylation of salicylic acid using acetic anhydride or acetyl chloride.

11. Structure activity Relationship(SAR) of Aspirin

12. CONTINUED… Substitution on carboxyl groups may affect the potency and toxicity. Reducing the acidity of the –COOH, retains the analgesic action of salicylic acid , but it is devoid of the anti-inflammatory properties. Placing the phenolic hydroxyl group , meta or para to the carboxyl group abolishes the activity . Substitution of halogen atoms on the aromatic ring enhances potency and toxicity. Substitution of aromatic rings at the 5 position of salicylic acid increases anti-inflammatory activity.

13. U S E S As an analgesic As an anti- pyretic To cure acute rheumatic fever Rheumatoid arthritis Osteoarthritis

14. D O S E Symptoms/Therapeutic use Dose For the relief of minor aches & mild to moderate pain 325-650 mg every 4 hrs. For arthritis 3.2 gm - 6 gm/day For reducing the risk of ischemia 1.3 gm /day For myocardial infraction prophylaxis 40 mg – 325 gm /day

15. Adverse Effects: Side effects – Nausea, vomiting, peptic ulcer. Hypersensitivity and idiosyncrasy – rashes, fixed drug erruption , urticaria . Acute salicylate poisoning - vomiting, dehydration, halucination , convulsion.

16. References : T.L.Lemke,D.A.Williams,Foye’s principles of Medicinal Chemistry,6 th Edition,Wolters Kluwer (India), Nonsteroidal anti-inflammatory drugs, Chemistry of Aspirin,Page No-965-969. D.Sriram,P.Yogeeswari,Medicinal Chemistry,2 nd Edition,Pearson , Antipyretics & Non-steroidal Anti-Inflammatory drugs,Salicyclic Acid Derivatives,Page no-230-231. K.D.Tripathi,Essentials of Medical Pharmacology,7 th edition,Jaypee , Nonsteroidal anti-inflammatory drugs,The Salicylates,Page no-179-184.