NSAIDs work by inhibiting the enzyme cyclooxygenase, which prevents the formation of prostaglandins responsible for pain and inflammation. They have analgesic, antipyretic, and anti-inflammatory effects. Common NSAIDs include aspirin, ibuprofen, naproxen, and celecoxib. While effective at reducing pain and inflammation, NSAIDs can cause gastrointestinal irritation and bleeding. Due to their safety risks, use should be discussed with a medical provider.

1. NSAIDS
 NSAIDS: Non Steroidal Anti-inflammatory drugs.
 These are aspirin type of opioid analgesics.
 In addition, they have anti-inflammatory, antipyretic and
uricosuric properties with out addiction liability.
 MOA: during inflammation, arachidonic acid is liberated
from memberane phospholipids.
 Arachidonic acid id converted into prostaglandins by the
enzyme cyclo-oxygenase.
 These prostaglandins produce hypealgesia. They sensitize
the nerve endings to pain and other mediators of
inflammation like bradykinin and histamine.
 NSAIDS inhibits the PG synthesis by inhibiting the enzyme
cyclo-oxygenase.

2. PHOSPHOLIPIDS
ARACHIDONIC
ACID
LEUCOTRIENES
PROSTAGLANDINS
Phospholipase A2
Lipoxygenase
Cyclo-oxygenase

3. CLASSIFICATION:
 Salicylic acid derivatives: Aspirin, Sodium salicylate.
 Para-aminophenol derivatives: Paracetamol.
 Pyrazolone derivatives: Phenylbutazone.
 Indole acetic acid derivatives: Indomethacin.
 Arylacetic acid derivative: Diclofenac.
 Propionic acid derivatives: Ibuprufen.
 Anthranilic acids: Flufenamic acid.
 Oxicams: piroxicam, tenoxicam.
 Alkanones: nabumetone.
 Sufonanilide derivatives: nimesulide, celecoxib.

4. SALICYLATES:
 Salicylates are the salts of salicylic acid.
 Pharmacological actions:
 Analgesia:
 aspirin-for pain originating from integumental tissues
like muscles, bones, joints, and pain in connective
tissues is relieved.
 Pain is relieved without euphoria and hypnosis.
 There is no development of tolerance and dependance.
 But aspirin is a weak analgesic when compared to
morphine.

5.  Antipyretic:
 In fever, salicylates bring down the temperature to
normal level. But in normal individuals there is no
change in temperature
 In fever, pyrogen (a protein) circulates in body and this
increases the synthesis of PGs in hypothalamus, there by
raising the temperature. The thermostatic mechanism
in hypothalamus is thus disturbed.
 Aspirin inhibits PG synthesis in hypothalamus and
resets the thermostat at the normal level bringing down
the temperature.

6.  Anti-inflammatory action:
 PG synthesis is inhibited.
 PGs present in inflammatory tissue are responsible for
oedema, erythema and pain.
 In addition, aspirin also interferes with the formation of
chemical mediators of the kallikrein system.
 As a result, it decreases the adherence of granulocytes to
the damaged vasculature, stabilizes lysosomes and
decreases the migration of the polymorphonuclear
leukocytes and macrophages into the site of
inflammation.

7.  Respiration:
 In therapeutic doses, salicylates increase the
consumption of oxygen by skeletal muscles.
 As a result, there is increased CO2 production.
 The increased CO2 stimulates respiratory center.
 Salicylates also directly stimulates the medullary
respiratory centre.
 Both the above actions increases the rate and depth of
respiration.
 Other pharmacological effects also includes: acid-base
and electrolyte balance, metabolic effects, Gastro
intestinal tract, CVS, immunological effects, Uric acid
excretion, blood, local effects.

8.  Adverse effects: nausea, vomiting, erosive gastritis,
peptic ulcer, epigastric distress, allergic reactions
(rashes, urticaria, angio-oedema, asthma),
hepatotoxicity, nephrotoxicity, delay in onset of labor
in pregnancy.
 Precautions and contraindications: peptic ulcer, liver
diseases, bleeding tendencies, pregnancy. NSAIDS
should be stopped one week before surgery.
 Uses: used as an analgesic for head ache, back ache,
tooth ache. In fever, inflammatory conditions,
rheumatoid arthritis, osteo arthritis, post Myocardial
infraction of post stroke, to delay labor.
 Drug interactions:

9.  Drug interactions: salicylates compete for protein
binding sites and displace other drug resulting inn
toxicity with warfarin, heparin, naproxen, phenytoin,
and sulfonyl ureas.
 Inhibition of platelet aggregation may increase the risk
of bleeding with oral anticoagulants.

10. PARA-AMINOPHENOL DERIVATIVES:
PARACETAMOL: (Acetamenophen)
 It has analgesic, antipyretic and weak anti-
inflammatory properties.
 Due to weak PG inhibitory activity in periphery, it has
poor anti-inflammatory actions.
 Paracetamol is active against cyclo-oxygenase in brain
because of which it acts as an antipyretic.
 In the presence of peroxides which are present at the
site of inflammation, Paracetamol has poor ability to
inhibit cyclo-oxygenase.

11.  Adverse effects:
 nausea and rashes may occur.
 In large doses, acute Paracetamol poisoning may occur.
 It is hepatotoxic and causes severe hepatic damage.
 A small portion of paracetamol is metabolised to a toxic
compound- N-acetyl-benzoquinone-imine which is
generally destroyed by conjugation with glutatione.
 But when larger doses are given, hepatic glutathione gets
used up and the levels of toxic compounds increase. It
causes hepatic necrosis.
 Uses: used as antipyretic in fever, as an analgesic in
painful conditions like toothache, headache and
myalgia.

12. PYROZOLONE DERIVATIVES:
 Phenylbutazone has a good anti-inflammatory effect. But has
poor analgesic and antipyretic activity.
 Adverse effects:
 Can cause congestive cardiac failure, oedema. It is more toxic than
aspirin and is poorly tolerated.
 Nausea, dyspepsia, vomiting, peptic ulceration, diarrhea and
epigastric distress.
 Hypersensitivity reactions like rashes, serum sickness, hepatitis,
nephritis, dermatitis and jaundice can occur.
 It may inhibit iodine uptake by thyroid resulting in hyper
thyroidism. Causes sodium and water retention.
 CNS effects like insomnia, vertigo, blurred vision etc.
 Used in rheumatoid arthritis, osteoarthritis, gout and other
muscloskeletal disorders

13. INDOLE ACETIC ACID DERIVATIVES:
 Indomethacin is a potent anti-inflammatory agent,
anti-pyretic and good analgesic.
 Adverse reactions:
 Gastrointestinal irritation and bleeding, nausea,
vomiting, diarrhea, and peptic ulcers.
 CNS effects include headache, dizziness, ataxia,
confusion, hallucinations, depression and psychosis.
 Hypersensitivity reactions like skin rashes, leukopenia
and asthma are common.
 It may also cause bleeding due to decreased platelet
aggregation and oedema due to salt and water retention.

14.  Drug interactions:
 It affects the diuretic action of furosemide, and
antihypersensitivity reactions of thiazides, furosemide, β-
blockers and ACE inhibitors by causing salt and water
retention.
 Diclofenac is an analgesic, antipyretic and anti-
inflammatory agent. Its tissue permeability is good and
attains good concentration in synovial fluid which is
maintained for long period of time.
 Adverse effects are less.
 Used in chronic inflammatory conditions like rheumatoid
arthritis and osteoarthritis, acute musculoskeletal pain.
Also post operatively for relief of pain and inflammation

15. PROPIONIC ACID DERIVATIVES:
 Ibuprofen is better tolerated than aspirin.
 Analgesic, antipyretic and anti-inflammatory effects
are slightly lower than aspirin.
 It is 99% bound to plasma proteins.
 Adverse effects are very less. May cause vomiting,
gastric discomfort, CNS effects, hypersensitivity
reactions, fluid retention.
 Used as an analgesic, in fever, in soft tissue injuries,
fractures, tooth extraction, to relieve post operative
pain, osteoarthritis and in gout.

16. ANTHRANILIC ACID DERIVATIVES:
 Fenamates are less efficaceous, more toxic and contra
indicated in children. Should not be used for more than
one week.
OXICAMS:
 Piroxicam is a long acting oxicam derivative.
 Has good analgesic, anti-inflammatory and anti-pyretic
activity.
 No clinically significant drug interactions are seen.
 Better tolerated as it is less ulcerogenic
 Used for rheumatoid arthritis, osteoarthritis, acute
musculo skeletal pain, post operative pain.
 Other oxicams are very much similar to Pyroxicam.

17. ALKANONES:
 Nabumetone is an anti-inflammatory agent with
significant efficacy in rheumatoid arthritis and
osteoarthritis.
 Relatively low incidence of side effects, comparatively
less ulcerogenic.
 It is a prodrug and also selectively inhibits COX-2 (so
causes less gastric irritation)

18. SULFONILIDE DERIVATIVES:
 Nimesulide a sulfonamide compound is a weak inhibitor
of PG synthesis with a higher affinity for COX-2 than
COX-1.
 Has anti-histaminic and anti-allergic properties.
 Has analgesic, antipyretic and anti-inflammatory actions
like other NSAIDs.
 Adverse effects are vomiting, nausea, epigastric pain,
rashes, drowsiness, dizziness.
 It is now banned because it can cause serious
hepatotoxicity.
 Used in headache, tooth ache, myalgia, post operative
pain and arthritis.