NON STEROIDAL ANTI INFLAMMATORY DRUGS AND ANTIPYRETICANALGESIC

NON STEROIDAL ANTI INFLAMMATORY DRUGS AND ANTIPYRETICANALGESIC

INTRODUCTION

• These drugs have analgesic , antipyretic and anti-inflammatory action.

• Like morphine they do not depress CNS, do not produce physical dependence.

• They act primarily on peripherally, but also in CNS to raise pain threshold.

• They are also called nonopoidor nonnarcotic.

Classification 

1. Non selective COX inhibitors

a. Salicylate –aspirin, sodium salicylate

b. Propionic acid derivatives –ibuprofen , naproxen

c. Indole derivative –indomethacine, sulindac

d. Pyrolo-pyrol derivative –ketorolac

e. Pyrazolonederivative –phenylbutazone

f. N-aryl anthranilic acid –mefenamic acid, meclofenamate, diclofenac

g. Oxicam derivative –piroxicam

2. PreferntialCOX-2 inhibitors –

       nimesulide, meloxicam

3. Selective COX-2 inhibitors –

     celecoxib, parecoxib

4. Analgesic –antipyretic with poor anti inflammatory   action

a. Para aminophenol derivative –paracetamol , phenacetin

b. Pyrazolonederivative –metamozol, propyphenazone

c. Benzoxazocinederivative --nefopam

Aspirin

Sodium salicylate

COOH     COONa+ OCOCH3                 OH

Mefenamic acidMeclofenamate COOH               COONa CH3                 Cl R                      Cl Diclofenac COOH           CH2COOH CH3              absent R                   Cl N -ARYL ANTHRANILIC ACID

indomethacineSulindac INDOL DERIVATIVES

PROPIONIC ACID DERIVATIVES

naproxen

ibuprofen

piroxicamketorolac

OXICAM DERIVATIVESPYROLO -PYROL DERIVATIVES

PYRAZOLONE DERIVATIVES

Phenyl butazone

paracetamol

Phenacetin

ANALGESIC –ANTIPYRETIC

PARAAMINO PHENOL DERIVATIVES

Mechanism 

• NSAIDs are irreversible inhibitor of cyclooxygenase (COX-1,COX-2), which is responsible for the biosynthesis of prostaglandin.

• Prostaglandinshave cytoprotective action for restoring integrity of stomach lining and maintaining renal function • and also reduce gastric acid secretion.(PGE2)

• INDUCE platelet aggregation.(TXA2)

• Also cause utereuscontaction. (PGE2,PGF2 ALPHA)

When inflammation occur 

• Sensitize afferent nerve endings to Release pain inducing chemical and mechanical stimuli (PGI2,PGE2)

• Also cause inflammation

• It rise body temperature by reset thermostat to cause fever (PGE2)

Salicylates 

• Antipyretic action – it reset hypothalamic thermostat and also by  mobilization of water and consequent dilution of blood, cutaneous vasodilation and perspiration.

• analgesic action produced by preventing PG mediated sensitisation of nerve endings .

• It also block platelet TXA2 production –so used as antiplatelet agent in myocardial infarction and ischemic stroke.

Therapeutic uses

• Analgesic

• Antipyretic

• Anti inflammatory

• Rhumatoidarthritis, osteo arthritis

• Dysmnerrhoea

ANALGESIC ANTIPYRETIC-PARACETAMOL

• It has antipyretic analgesic  and week anti inflammatory action

• It is a poor inhibitor of prostaglandin synthesis in peripheral tissue

• And also inhibit COX 3

• Side effect are very less than others

Acute paracetamol poisoning

• Paracetmolmetabolites are O-sulfate,o-glucuronides and small amount of N-hydroxylate.

• In normal thseare detoxified by conjugation with glutathione

• But when in over dose these metabolite rearrange to form N acetyl iminoquinone,whichis reactive metabolites.

• This bind to protein in liver cell and cause necrosis.

• This toxicity is high in alcoholic individual because it induce CYP2E1, CYP3A4

{these are essential for metabolite formation}