chemistry of aspirin
TRANSCRIPT
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.