B.

PHARAMACY SEM – IV

MEDICINAL CHEMISTRY – I
(13PH0402)

Unit – 5 NON-STEROIDAL ANTI-

INFLAMMATORY AGENTS

Presented by - Ms.Chandni Padwani

Assistant professor,
Faculty of pharmacy,
Marwadi University, Rajkot
 ANTI-INFLAMMATORY AGENTS

 All drugs grouped in this class have analgesic, antipyretic and anti-inflammatory
actions in different measures. In contrast to morphine they do not depress CNS,

 They do not produce physical dependence, have no abuse liability and are weaker
analgesics (except for inflammatory pain).

They are also called;

nonnarcotic,
nonopioid or
 aspirin like analgesics.

They act primarily on peripheral pain mechanisms, but also in the CNS to raise pain
threshold. They are more commonly employed and many are over-the-counter drugs.
 CLASSIFICATION OF ANTI-INFLAMMATORY AGENTS

A. Nonselective COX inhibitors (traditional NSAIDs)

1. Salicylates: Aspirin

2. Propionic acid derivatives: Ibuprofen, Naproxen, Ketoprofen, Flurbiprofen.

3. Fenamate: Mephenamic acid.

4. Enolic acid derivatives: Piroxicam, Tenoxicam.

5. Acetic acid derivatives: Ketorolac, Indomethacin, Nabumetone

6. Pyrazolone derivatives: Phenylbutazone, Oxyphenbutazone

B. Preferential COX-2 inhibitors:

i. Nimesulide,
ii. Diclofenac,
iii. Aceclofenac,
iv. Meloxicam,
v. Etodolac.

C. Selective COX-2 inhibitors:

i. Celecoxib,
ii. Etoricoxib,
iii. Parecoxib.
D. Analgesic-antipyretics with poor anti-inflammatory action

1. Para-aminophenol derivative: Paracetamol (Acetaminophen).

2. Pyrazolone derivatives: Metamizol (Dipyrone), Propiphenazone.

3. Benzoxazocine derivative: Nefopam.

 LIST OF ANTI-INFLAMMATORY AGENTS AS PER
CURICULLUM

1. Sodium salicylate,
2. Aspirin,
3. Mefenamic acid*,
4. Meclofenamate,
5. Indomethacin,
6. Sulindac,
7. Tolmetin,
8. Zomepriac,
9. Diclofenac,
10. Ketorolac,
CLASSIFICATION OF ANTI-INFLAMMATORY AGENTS

11. Ibuprofen*,
12. Naproxen,
13. Piroxicam,
14. Phenacetin,
15. Acetaminophen,
16. Antipyrine,
17. Phenylbutazone.
Prostaglandins, prostacyclin (PG I2) and thromboxane A2 (TXA2) are
produced from arachidonic acid by the enzyme cyclooxygenase

which exists in a constitutive (COX-1) and an inducible (COX-2)

isoforms; these are present in minute quantities.

These isoforms of cyclo-oxygenase enzymes are induced by

CYTOKINES.
 CYTOKINES – are the mediators that tend to be released as an
immune reaction to the body.

Upon release of these CYTOKINES, Prostaglandins are generated –

which give the inflammation changes at the site.
 COX-2 is constitutively present at some sites in:

• brain,
•juxtaglomerular cells and
• foetus; it may serve physiological role at these sites.

 Most NSAIDs inhibit COX-1 and COX-2 nonselectively, but now some selective
COX-2 inhibitors have been produced.
Beneficial actions due to PG synthesis inhibition

Analgesia

Prevention of pain nerve ending sensitization

Antipyresis

Antiinflammatory

Antithrombotic
Shared toxicities due to PG synthesis inhibition

Gastric mucosal damage

Bleeding
inhibition of platelet function
Limitation of renal blood flow
Na+ and water retention
Delay/prolongation of labour
1. SODIUM SALICYLATE 2. ASPIRIN (Acetyl
(sodium salt of Salicylic acid) salicylic acid)
3. MEFENAMIC ACID 4. MECLOFENAMATE
5. INDOMETHACIN
 DRUG MECHANISM OF USES ADEVERSE
ACTION EFFECTS

SODIUM inhibit the activity Analgesic •tuffy nose.

SALICYLATE of the enzyme now •Sinus infection and
called Antipyretic. inflammation
cyclooxygenase •Asthma.
(COX) which leads acts as non-steroidal anti- •Diarrhea.
to the formation of inflammatory drug (NSAID), and •Gas.
prostaglandins induces apoptosis in cancer cells and •Abdominal pain.
(PGs) that cause also necrosis. •Gut inflammation
inflammation, (colitis)
swelling, pain and  It is also a potential replacement
fever for aspirin for people sensitive to it.
 MECHANISM OF ACTIONS OF ASPIRIN

 ASPIRIN disrupts the production of prostaglandins throughout the body by targeting

cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2).

Acetylsalicylic acid is considered an antipyretic agent because of its ability to interfere

with the production of brain prostaglandin E1.

 Prostaglandin E1 is known to be an extremely powerful fever-inducing agent.

Effects on platelet aggregation.

The inhibition of platelet aggregation by ASA occurs because of its interference

with thromboxane A2 in platelets, caused by COX-1 inhibition.

Thromboxane A2 is an important lipid responsible for platelet aggregation, which can

lead to clot formation and future risk of heart attack or stroke.
DRUG USES ADEVERSE EFFECTS

ASPIRIN Analgesic • stomach ulcers,

Antipyretic. •stomach bleeding, and

Pericarditis •worsening asthma

rheumatic fever •Bleeding risk is greater among

those who are older,
Anti-coagulant drink alcohol
 DRUG MECHANISM USES ADEVERSE EFFECTS
OF ACTION

MEFENAMIC it inhibits both  relieve mild to • headaches, nervousness,

ACID isoforms of the moderate pain, including and vomiting.
enzyme cyclooxyge headaches, dental pain,
nase (COX- osteoarthritis and •Potentially serious side
1 and COX-2). rheumatoid arthritis. effects may
This prevents include diarrhea, gastrointe
formation  It has a role as an stinal perforation, peptic
of prostaglandins, analgesic, an ulcers, hematemesis (vomiti
which play a role in antirheumatic drug, ng blood), skin reactions
pain sensitivity, (rashes, itching, swelling
inflammation and a non-steroidal anti-
fever inflammatory drug, an
antipyretic
SYNTHESIS OF MEFENAMIC ACID
 DRUG MECHANISM USES ADEVERSE
OF ACTION EFFECTS

MECLOFENA- They act by  sodium salt for the treatment • vomiting.

MATE blocking the of dysmenorrhoea (painful •heartburn.
synthesis of periods), •dizziness.
prostaglandins •drowsiness.
by inhibiting osteoarthritis and rheumatoid •diarrhea, and.
cyclooxygenase, arthritis. •headache.
which converts
arachidonic acid  It has a role as a non-
to cyclic steroidal anti-inflammatory drug,
endoperoxides, an antirheumatic drug, an
precursors of antineoplastic agent, an
prostaglandins anticonvulsant, an analgesic, an
antipyretic
 DRUG MECHANISM OF USES ADEVERSE EFFECTS
ACTION

INDOMETHACIN mediated through potent  Most commonly used • Edema

and nonselective inhibition in rheumatoid arthritis, •Hyperkalemia (high
of the enzyme potassium levels)
cyclooxygenase (COX), spondylitis,
which is the main enzyme •Hypernatremia (high sodium
responsible for catalyzes osteoarthritis, levels)
the rate-limiting step in
prostaglandin acute shoulder pains, •Hypertension
and thromboxane biosynth and
esis via the arachidonic •Elevations of
acid (AA) pathway  acute gouty arthritis serum creatinine and more
serious renal damage such as
acute kidney failure,
chronic nephritis
6. SULINDAC 7. TOLMETIN
8. ZOMIPRIAC 9. DICLOFENAC
10. KETOROLAC
 DRUG MECHANISM OF USES ADEVERSE EFFECTS
ACTION

SULINDAC inhibition of both  anti-inflammatory • coma,

COX-1 and COX-2 •diminished urine output
which leads to the Analgesic and
inhibition of •hypotension
prostaglandin synthesis Antipyretic

TOLMETIN inhibits prostaglandin long term •lethargy,

synthetase, thereby management of •drowsiness,
inhibits release of osteoarthritis, • nausea,
inflammatory rheumatoid arthritis •vomiting, and
mediators •epigastric pain
 DRUG MECHANISM OF USES ADEVERSE EFFECTS
ACTION
ZOMIPRIAC blocking the synthesis of  management of • urogenital symptoms
prostaglandins by mild to severe pain such as dysuria and
inhibiting  antipyretic, and pyuria
cyclooxygenase, which anti-inflammatory
converts arachidonic activity
acid to precursors of
prostaglandins
DICLOFENAC inhibits COX-1 and arthritis,  indigestion, gas,
COX-2 with relative menstrual pain, nausea, vomiting,
equipotency migraines  stomach pain;
(Equally it inhibits diarrhea, constipation
COX-1 and COX-2 Treat pain headache, dizziness,
enzymes. ) Swelling drowsiness
 DRUG MECHANISM USES ADEVERSE
OF ACTION EFFECTS
KETOROLAC inhibition of  management of • stomach bleeding,
prostaglandin mild to severe pain
synthesis by •kidney failure,
competitive antipyretic, and
blocking of the •heart attacks,
enzyme anti-inflammatory
cyclooxygenase activity •bronchospasm,
(COX)
•heart failure
11. IBUPROFEN 12. NAPROXEN
13. PIROXICAM 14. PHENACETIN
15. ACETAMINOPHEN 16. ANTIPYRIN
(PARACETAMOL)
17. PHENYLBUTAZONE
 DRUG MECHANISM OF ACTION USES ADEVERSE EFFECTS

IBUPROFEN is a non-selective inhibitor of  Antipyretic • Feeling dizzy

an enzyme called Analgesic
cyclooxygenase (COX),  To relieve minor •Feeling sick
which is required for the aches and pain
synthesis of prostaglandins via from headaches, • Indigestion
the arachidonic acid Muscle aches,
Arthritis

NAPROXEN Relatively inhibits COX-1 arthritis,  Heartburn, and stomach

and COX-2  menstrual pain, pain.
 Gout  Severe side effects include
Antipyretic an increased risk of heart
disease, stroke, gastrointestin
al bleeding
 DRUG MECHANISM OF USES ADEVERSE EFFECTS
ACTION
PIROXICAM inhibition of • gas.
cyclooxygenase (COX-1 Analgesic •headache.
and COX-2) OesteoArthritis •dizziness.
Rheumatoid •ringing in the ears
Arthritis

PHENACETIN inhibits  subacute Carcinogenicity

PROSTAGLANDIN rheumatoid
SYNTHASE-I arthritis, Intestinal nephritis
 intercostal
neuralgia
 Analgesic
Antipyretic
 DRUG MECHANISM OF USES ADEVERSE EFFECTS
ACTION
ACETAMINOPHEN inhibition of Analgesic • Renal tubular necrosis,
(PARACETAMOL) cyclooxygenase (COX- Antipyretic • hypoglycemic coma,
1 and COX-2) Arthritis and
Repiratory tract •thrombocytopenia.
infections • Sometimes, liver
necrosis can occur as well
as liver failure
PHENACETIN inhibits  subacute Carcinogenicity
PROSTAGLANDIN rheumatoid
SYNTHASE-I arthritis, GI tract problems
 intercostal
neuralgia
 Analgesic
Antipyretic
SYNTHESIS OF IBUPROFEN
 DRUG MECHANISM USES ADEVERSE
OF ACTION EFFECTS
PHENYLBUTAZONE inhibition of Analgesic • bone-marrow
inactivates musculoskelet depression and
prostaglandin - al disorders, include
H synthase including • agranulocytosis and
sprains, overuse • aplastic anemia
injuries, •Blurred vision
tendinitis,
Arthralgias
(Analgesia due
to arthritis)