Nonsteroidal anti-inflammatory drugs (usually abbreviated to NSAIDs /ˈɛnsɛd/ en-sed), also called nonsteroidal anti-inflammatory agents/analgesics (NSAIAs) or nonsteroidal anti-inflammatory medicines (NSAIMs), are a drug class that groups together drugs that provide analgesic (pain-killing) and antipyretic (fever-reducing) effects, and, in higher doses, anti-inflammatory effects.

1. NSAIDS
Lakshmi Ananth
NSAIDS 1

2. INTRODUCTION OF PAIN AND
NOCICEPTION Nociception is the mechanism whereby noxious peripheral stimuli
are transmitted to the central nervous system.
 Pain is an unpleasant sensory and emotional experience with
actual or potential tissue damage.
 Superficial:
 Stimulation of skin & mucous membranes.
 Fast response
 Deep:
 Arises from muscles, joints, tendons, heart ..etc.
 Fast response
 When tissues become injured, they release chemicals called
prostaglandins and leukotrienes that make the pain receptors
more sensitive and thus causing pain. NSAIDS 2

3. ACUTE & CHRONIC PAIN
Acute Pain Chronic Pain
Sudden onset Persistent – usually lasting
more than six months
Temporary (disappears once
stimulus is removed)
Cause unknown – may be due
to neural stimulation or a
decrease in endorphins
Physiological responses to
acute pain include increased
RR, HR, BP and reduction in
gastric motility.
Physiological responses are
less obvious especially with
adaptation. Psychological
responses may include
depression.
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4. PROSTANOIDS AND MOA OF NSAIDS
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Prostanoi
ds
Membrane
Phospholipids
Arachidonic
Acid
Leukotrienes Prostaglandins Prostacyclins Thromboxane
Phospholip
ase
Cyclooxygena
se
Corticostero
ids
NSAID
s

5. CYCLOOXYGENASE ENZYME AND
ITS ISOZYMES
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COX 1 COX 2 COX 3
Responsible for the
Physiologic production of
Prostanoids.
Expressed only in brain,
kidney & bone.
COX-3 more effects in CNS
Regulates the normal
cellular processes
 Gastric cytoprotection
 Vascular homeostasis
 Platelet aggregation
 Kidney function.
 Responsible for the
elevated production of
Prostanoids in
inflammation & disease.
 Expression at sites is
increased in
inflammation.
??
Non selective COX inhibitors eg.
Aspirine

6. CLASSIFICATION OF NSAIDS
Non-Selective COX Inhibitors. Selective COX Inhibitors.
Drugs with Analgesic & Marked Anti-
inflammatory
Celecoxib , Etoricoxib,
Meloxicam, Nimesulide.
Salicylic Acid Derivatives (Aspirin)
Pyrazolon Derivatives (Phenylbutazone)
Acetic Acid Derivatives (Diclofenac,
Sulindac)
Oxicams (Piroxicam, Tenoxicam)
Drugs with Analgesic & Moderate Anti-
inflammatory
Propionic acid derivatives (Ibuprofen,
Naproxen)
Fenamates (Meclofenamic)
Drug with Analgesic & no Anti-
inflammatory
Para aminophenol Derivative
NSAIDS 6

7. ASPIRIN PROFILE
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• As anti-inflammatory: Aspirin irreversibly acetylates both isoforms of
cyclooxygenase enzyme. There by inhibits biosynthesis of PG which helps in
modulation of inflammation.
Aspirin inhibits inflammation in Rheumatoid Arthritis but it neither arrests the
progress of disease.
• As analgesic: reduces production of PGE2 (involves in sensitizing nerve ending)
there by repress sensation of pain.
Toothache, Dysmenorhoea, used along with opioids in post operative pain.
Inhibit pain stimuli at subcortical sites -Thalamus & Hypothalamus.
• As antipyretic: Aspirin lowers raised body temperature , no effect on normal
temperature.
• As antiplatelet: In low doses Inhibit Platelet Aggregation, as TXA2 promotes
platelet aggregation.
• Dosage of Aspirin:

8. ASPIRIN PROFILE
NSAIDS 8
• Adverse effects of Aspirin
GI disturbances (Can be prevented if given with misoprostol,
enteric coated aspirin)
Impaired hemostasis
Allergy or Hypersensitivity reactions
Hyperuricemia (Retention of uric acid at low doses)
Decreased renal function
Salicylism (Vomiting, tinnitus, vertigo)
Respiratory depression in toxic doses (by affect on CNS)
Increased risk of Reye’s Syndrome (Acetaminophen or Ibuprofen
should be used)

9. ASPIRIN PROFILE
NSAIDS 9
• Contraindications
• Peptic ulcer.
• Hemophilia.
• Aspirin hypersensitivity Children with a viral illness.
• Chronic liver disease.
• Aspirin should be stopped one week before elective surgery.
• Avoid high doses in G-6-PD deficient.
• Avoid in pregnancy & lactation.
There is no antidote
till date

10. ACETAMINOPHEN PROFILE
NSAIDS 10
• Rapid absorption from GIT.
• Significant First pass metabolism in gut wall & liver.
• Used for mild to moderate pain
Toxicity:
At therapeutic doses
drug fever
mild increase in hepatic enzymes
At over doses(above 15g)
Hepatic necrosis
Renal tubular necrosis
Hypoglycemic coma
N-acetyl Cysteine is
antidote

11. SELECTIVE COX 2 INHIBITORS
• these are 10-20 times more selective to cox-2 and is
reversible.
• Celecoxib: chemically sulphonamide having half life of 11hrs.
• Meloxicam: Related to Piroxicam. Preferentially selective COX-
2 inhibitor.
• Etoricoxib: Long half life: 22 hrs, Monitoring of hepatic
functions required.
• Nimesulide: new compound less gastric irritation.
• Valdecoxib & Rofecoxib: Withdrawn due to. higher risk of
incidence of Cardiovascular thrombotic events Myocardial
Infarction & stroke.
NSAIDS 11

12. SELECTIVE COX 2 INHIBITORS
Pharmacologic Effects & advantages:
Analgesic, Antipyretic, Anti-inflammatory effects
No inhibition of platelet aggregation. Does not prolong
bleeding time.
No inhibition of protective gastric PGs No gastric
irritation.
• Adverse effects:
Potential for increasing thrombotic events Myocardial
infarction & stroke
Renal toxicities similar to non selective NSAIDs
Skin rashes for Celecoxib NSAIDS 12

13. CLINICAL USES OF NSAIDS
NSAIDS 13

14. NSAIDS 14
GENERIC NAME TRADE NAME SPECIFIC USES ADVERSE REACTIONS
Celecoxib Celebrex • Rheumatoid arthritis and
osteoarthritis.
ophthalmic changes
Diclofenac
Sodium
Voltaren* • Rheumatoid arthritis and
osteoarthritis.
• Ankylosing spondylitis
Gastric and duodenal
ulcers formation.
GI bleeding.
Fenoprofen Nalfon • Long term management to
mild to moderate pain
Visual disturbances
Jaundice
Peptic ulcers
Ibuprofen Advil, Genpril • Mild to moderate pain.
• Painful dysmenorrhea.
• Rheumatoid arthritis.
GI Disturbances
Nausea, Dizziness
GI Bleeding
Indomethacin Indocin • Rheumatoid arthritis
• Ankylosing spondylitis
• Acute gouty arthritis
Hematologic changes
Nausea, Constipation
Duodenal Ulcers
meflofenamate meflofenamate* • mild to moderate pain.
• Painful dysmenorrhea.
Rash
Bleeding
Headache, Dizziness,
Nausea, Dyspepsia

15. NSAIDS 15
GENERIC NAME TRADE NAME SPECIFIC USES ADVERSE
REACTIONS
Naproxen Aleve,
Anaprox*
• Management of
inflammatory disorders.
• Mild to moderate pain.
• Painful dysmenorrhea.
visual changes,
nausea, vomiting
GI bleeding.
Rofecoxib Vioxx • Signs and symptoms of
osteoarthritis.
• Management of acute pain
• Primary dysmenorrhea.
Visual Disturbances
Sulindac Clinoril* • Mild to moderate pain.
• Rheumatoid arthritis
• Ankylosing spondylitis
• gouty arthritis
nausea, vomiting,
Diarrhoea,
constipation,
GI bleeding. Gastric
and duodenal ulcers
formation.
Valdecoxib Bextra • osteoarthritis.
• Rheumatoid arthritis
Anemia, Headache,
Dyspepsia,

16. ADVERSE REACTIONS OF NSAIDS
• Gastrointestinal tract: nausea, vomiting, diarrhea, constipation,
epigastric pain, indigestion, abdominal distress or discomfort,
intestinal ulceration, stomatitis, jaundice, bloating, anorexia, and
dry mouth
• Central nervous system: dizziness. headache, drowsiness,
insomnia.
• Cardiovascular: decrease or increase in blood pressure, and cardiac
arrhythmias
• Renal: hematuria and acute renal failure In those with impaired
renal function
• Special senses: visual disturbances, blurred or diminished vision.
• Hematologic: anemia NSAIDS 16

17. CONTRAINDICATIONS & INTERACTIONS
• Contraindicated in patients with known hypersensitivity and in
third trimester of pregnancy and during lactation.
•If a patient is allergic to one NSAID, there is an increased risk of
an allergic reaction with any other NSAID (Cross sensitivity)
• Cautiously in patients with bleeding disorders, renal disease,
cardiovascular disease, or hepatic impairment.
• Increased risk of Ulcers in patients of age 65 and above.
• Prolong bleeding time and increase the effects of
anticoagulants.
• May decrease the effects of diuretics or antihypertensive drugs.
NSAIDS 17

18. IN BRIEF….
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Advantage
s
disadvantag
es

19. NSAIDS
NSAIDS 19