By- Ritam Choudhury

B.pharm

CHEMISTRY OF ASPIRIN

Contents:Non steroidal anti inflammatory drugsClassificationMechanism of actionAspirinSynthesis of AspirinSAR of AspirinUsesDosesAdverse EffectReference

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.

Classifications :Nonselective COX inhibitors: Preferential COX-2

inhibitors:1. Salicylates :- Aspirin Nimesulide , Diclofenac ,2. Propionic acid derivatives:-Ibuprofen , Naproxen Aceclofenac3. Fenamate:-Mephenamic acid.4. Enolic acid derivatives:-Piroxicam5. Acetic aid derivatives:-Indomethacin6. Pyrazolone derivatives:-Phenylbutazone.

Selective COX 2 inhibitors: Analgesic-antipyretics with poor antiinflammatory action:

Celecoxib , Etoricoxib 1. Paraaminophenol derivatives:- Paracetamol

Paracoxib 2. Pyrazolone derivatives:-Metamizole3. Benzoxazocine derivatives:-Neofam

Mechanism Of Action : Mainly by blocking of Prostaglandins synthesis.

Cycloxygenase-1 & Cycloxygenase-2Produce from Arachidonic acid.

Most NSAIDs inhibit COX-1

NSAIDs inhibit COX-2 nonselectively.But now some selective COX-2 inhibitors have been produced.

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 C9H8O4

Molecular mass 180.157 g/mol

Physical data

Density 1.40 g/cm3

Melting point 135 °C (275 °F)

Boiling point 140 °C (284 °F) (decomposes)

Solubility in water 3 mg/mL (20 °C)

Mechanism Of Action as Analgesic :

Mechanism Of Action as Antipyresis

Mechanism Of Action as Antiplatelet Aggregatory :

Synthesis Of Aspirin

Aspirin

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

Structure activity Relationship(SAR) of

Aspirin

CONTINUED…

1) Substitution on carboxyl groups may affect the potency and toxicity.

2) Reducing the acidity of the –COOH, retains the analgesic action of salicylic acid , but it is devoid of the anti-inflammatory properties.

3) Placing the phenolic hydroxyl group , meta or para to the carboxyl group abolishes the activity .

4) Substitution of halogen atoms on the aromatic ring enhances potency and toxicity.

5) Substitution of aromatic rings at the 5 position of salicylic acid increases anti-inflammatory activity.

U S E S

As an analgesic

As an anti- pyretic

To cure acute rheumatic fever

Rheumatoid arthritis

Osteoarthritis

D O S ESymptoms/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

Adverse Effects:Side effects – Nausea, vomiting, peptic ulcer.

Hypersensitivity and idiosyncrasy – rashes, fixed drug erruption, urticaria.

Acute salicylate poisoning- vomiting, dehydration, halucination, convulsion.

References : T.L.Lemke,D.A.Williams,Foye’s principles of Medicinal Chemistry,6th Edition,Wolters Kluwer(India),Nonsteroidal anti-inflammatory drugs,Chemistry of Aspirin,Page No-965-969.

D.Sriram,P.Yogeeswari,Medicinal Chemistry,2nd Edition,Pearson,Antipyretics & Non-steroidal Anti-Inflammatory drugs,Salicyclic Acid Derivatives,Page no-230-231.

K.D.Tripathi,Essentials of Medical Pharmacology,7th edition,Jaypee,Nonsteroidal anti-inflammatory drugs,The Salicylates,Page no-179-184.