Non Steroidal Anti-inflammatory Drugs

1. NSAIDS (NON-STEROIDAL ANTI-INFLAMMATORY DRUGS)
NSAIDS are the drugs that reduce inflammation, pain & fever
by inhibiting the synthesis of prostaglandins & related
compounds.
NSAID inhibits cyclooxygenase 1 or 2 or both enzymes.
NSAIDS have three major actions:
 Analgesic
 Antipyretic
 Anti-inflammatory
Uses:
• Postoperative Pain
• Menstrual Pain
• Myalgia/Neuralgia
• Headache/Backache
• Pyrexia(Fever)
• Osteoarthritis
• Rheumatoid Arthritis
• Anti-platelet

2. There are two forms of cyclooxygenase, cyclooxygenase-1 (COX-1)
and cyclooxygenase-2 (COX-2).
COX-1: Produced by normal cells & tissues, maintains homeostasis
COX-2: Induced by inflammed cells, mediates inflammation

4. Functions Of Prostaglandins
• Directly Cause Pain
• Enhances Pain Inducing Effects Of Bradykinin
• Induces Fever
Functions Of Thromboxanes
• Cause platelets to aggregate
• Causes vasoconstriction
• Enhances function of inflammatory cells
Functions Of Histamines
• Causes tissue congestion & swelling
• Causes bronchoconstriction
• Causes sneezing, watery eyes, itching
• Causes pressure & pain
Functions Of Leukotrienes
• Increases vessel permiability and leakiness
• Stimulates platelet aggregation

5. Pain & Fever during Inflammation
Pain: PGE2 sensitize nerve terminal to the action of
bradykinin, PG, histamine and other local
mediators released from inflamed tissue & cause
pain.
Fever: Pyrogen, Cytokine (WBC), IL and chemical
mediators are activated during inflammation,
infection and diseases condition which stimulate PG
synthesis in hypothalamus and temperature set up
point is raised.
Analgesic, Anti-pyretic & Anti-inflammatory action
is due to inhibition of inflammatory mediators;
prostaglandins, histamines, thromboxanes and
leukotrienes.

7. Inflammation is the body’s response towards
injurious stimulus. It is a protective response
involving immune cells and chemical mediators.
Inflammatory response includes calor (warmth),
dolor (pain), rubor (redness), and tumor
(swelling).
Why inflammation should be controlled?
Inflammation can exaggerate & become harmful
Extremely inconvenience to patient
To reduce the symptoms like fever & pain

8. Non-Selective COX inhibitors
• Aspirin
• Ibuprofen
• Flurbiprofen
• Naproxen
• Mephenamic acid
• Piroxicam
• Ketolorac
• Indomethacin
• Phenylbutazone

9. Preferential COX-2 Inhibitors
• Nimesulide
• Meloxicam
• Etodolac
• Diclofenac
• Aceclofenac
Selective COX-2 Inhibitors
• Celecoxib
• Etoricoxib
• Parecoxib
Analgesic but poor anti-inflamatory
• Paracetamol (Acetaminophen)
• Metamizol
• Nefopam

10. ASPIRIN (ACETYLSALICYLIC ACID)
MOA: Aspirin is non selective inhibitor of cox enzymes and
supress prostaglandin synthesis.
Indication:
• Mild to moderate pain
(headache, backache, joint pain, toothache, dysmenorrhoea)
Aspirin 600mg=Codeine 60mg=Morphine 6mg
• Antipyretic in fevers
• Anti inflammatory in acute rheumatic fever, rheumatoid
arthritis, osteoarthritis
• Antiplatelet agent in atherosclerotic diseases, post-operative,
myocardial infarction, post stroke patients
• Aspirin is prescribed in a small dose as a means to lower the
risk of heart attack (prevents clotting action of platelets)
• Dose: 300-600mg TDS analgesic, antipyretic & anti-
inflammatory action
75-150mg OD myocardial infarction/stroke

11. Adverse effects
• Gastric mucosal damage, peptic ulcer
• Hypersensitivity
• Salicylism—dizziness, tinnitus, vertigo, reversible
impairment of hearing and vision, excitement and mental
confusion, hyperventilation and electrolyte imbalance.
• Liver injury
• Acute salicylate poisoning
Contraindication
• Peptic ulcer
• Bleeding disorder
• Hypersensitivity to NSAIDs
• Under 12 children
• Liver disease
• Pregnancy and lactation
• Chickenpox of influenza infection

12. PARACETAMOL (ACETAMINOPHEN)
MOA: Paracetamol inhibits the synthesis of prostaglandins in the
CNS by inhibiting COX 1 & 2 enzymes in the brain. Thus it inhibits
prostaglandin synthesis in hypothalamus & temperature set up
point is reduced. It also increases pain threshold & reduces pain.
It has less effect on COX enzyme in peripheral tissues, which
account for their weak anti-inflammatory activity.
Indications:
Over The Counter (OTC) drug for:
• Fever
• Headache
• Musculoskeletal Pain
• Dysmenorrhoea
• Osteoarthritis
Dose: Adult 325-1000mg 4-6 hourly or SOS (650mg rectally)
Child 10-15mg/kg 4-6 hourly; Safe in Pregnancy!

13. Paracetamol is Safe and Well Tolerated!
Adverse Effects
Over doses causes:
• Liver & kidney damage
• Gastric irritation, mucosal erosion & bleeding
• Rashes
• Nausea, Vomiting and Sweating
Contraindication
• Hypersensitivity
• Peptic ulcer
• Abuse of alcohol

14. NIMESULIDE
MOA: Nimesulide is an anti-inflammatory, analgesic,
and antipyretic that selectively inhibits COX-2 and
weakly inhibits PG synthesis.
Indications:
Short-lasting painful inflammatory conditions/sports injuries
• Sinusitis
• Dental surgery
• Bursitis
• Fever
Dose: 100mg BD
• Low backache
• Dysmenorrhoea
• Postoperative pain
• Osteoarthritis

15. Adverse Effects
• Gastrointestinal (epigastralgia, heart burn,
nausea, loose motions)
• Dermatological (rash, pruritus)
• Central (somnolence, dizziness)
• Hepatic Failure
Contraindication
• Liver toxicity/ Hepatic failure on long term use
• Pregnancy & Breastfeeding
• Children under 12 years of age

16. IBUPROFEN
MOA: Ibuprofen inhibits the COX enzymes and supresses the
synthesis of prostaglandins which are mediators of pain,
inflammation, and fever. It also inhibits the thromboxane
A2 which stimulates platelets aggregation & formation of
blood clot.
Indications: Over The Counter (OTC) Drug
• Fever
• Dysmenorrhoea
• Osteoarthritis
• Rheumatoid arthritis
• Musculoskeletal disorders
• Headache, Backache, Toothache
• Postpartum and Postoperative pain
Dose: 400-800mg TDS (children 20mg/kg/day)

17. Adverse Effects:
• Gastric discomfort, nausea and vomiting
• Gastric erosion and occult blood loss
• Dizziness, blurring of vision, tinnitus
• Rashes, itching and other hypersensitivity
Contraindication:
• Peptic ulcer
• Pregnancy & Lactation
• Children under 7 years
• Hypersensitivity

18. DICLOFENAC SODIUM
MOA: Diclofenac inhibits the synthesis of prostaglandins by
inhibiting COX enzymes and leucocyte migration. It is
somewhat COX-2 selective so it has better anti-inflammatory
action. It is also a potent analgesic preferred in mild to
moderate pain.
Indications:
• Quick relief of pain and edema, Toothache
• Rheumatoid arthritis, Osteoarthritis
• Dysmenorrhoea (menstrual pain)
• Bursitis (pain in shoulder, hip and elbow)
• Ankylosing spondylitis (inflammation in vertebra)
• Postoperative or post-traumatic pain and inflammation
• Ocular inflammation and pain
Dose: 50mg TDS, 75mg deep i.m

19. Adverse effects:
• Epigastric pain, nausea, headache, dizziness
• Rashes
• Gastric ulceration and bleeding
• Hepatic and Renal damage
Contraindications:
• Peptic ulcer
• Children under 7 years of age
• Kidney disease
• Liver disease
• Inflammatory bowel disease
• Patients with bleeding disorder
Aceclofenac: Similar in action with Diclofenac with fewer side
effects and better tolerability. Dose: 100mg BD

20. NSAIDS USES DOSE
Ketorolac Postoperative pain, inflammation 15-30mg i.m or
i.v
Indomethacin Acute GOUT, Rheumatoid arthritis,
Ankylosing spodylitis
25-50mg TDS
Naproxen Rheumatoid arthritis, Ankylosing
spodylitis
250-500mg BD
Piroxicam Osteoarthritis, Rheumatoid arthritis,
Ankylosing spodylitis
10-20mg OD
Mefenamic
acid
Muscle, Joint, Tissue Pain
Dysmenorrhoea, Rheumatoid
arthritis, Osteoarthritis
250-500mg
TDS
Celecoxib Selective COX-2 Inhibitors
Anti-inflammatory
”
100-200mg
OD-BD
Etoricoxib 60-120mg OD