This slide covers the details of NSAIDs, along with their classification based on their chemical structure and mechanisms of action; Also includes their adverse effects and uses.

1. NAME- SHUVAM SAR
ROLL- 19320219008
M.PHARM(PHARMACOLOGY)
1ST YEAR, 1ST SEMESTER
BENGAL SCHOOL OF TECHNOLOGY

2. WHAT IS NSAID ?
 Nonsteroidal anti-inflammatory drugs or NSAIDs are
commonest medication for inflammation, algesia and
pyrexia.
 They are so named because they don’t have steroidal
ring within their chemical structure, unlike steroidal
anti-inflammatory drugs, e.g. cortisone.

3. CLASSIFICATION OF NSAIDs
On the basis of mechanism of action and chemical nature --
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.
 Preferential COX-2 inhibitors-
Nimesulide, Diclofenac, Aceclofenac, Meloxicam, Etodolac.
Selective COX-2 inhibitors-
Celecoxib, Etoricoxib, Parecoxib.
Analgesic-antipyretics with poor anti-inflammatory action-
 1. Para aminophenol derivative: Paracetamol (Acetaminophen).
 2. Pyrazolone derivatives: Metamizol (Dipyrone), Propiphenazone.
 3. Benzoxazocine derivative: Nefopam.[1]

4. PHARMACOKINETIC PROFILE

5. PHARMACOKINETIC PROFILE
ACCESSED FROM GOODMAN & GILMAN’S
PHARMACOLOGICAL BASIS OF THERAPEUTICS,
CHAPTER 34, PAGE - 966-970; ON 28.11.2019

6. CLINICAL EFFECTS OF NSAIDs
ACCESSED FROM http://tmedweb.tulane.edu/pharmwiki/lib/exe/fetch.php/nsaid_harm.png?cache=; ON 28.11.2019

7. Nonselective COX inhibitors (traditional NSAIDs)–
Aspirin & other Salicylates ~
1. Mechanism - reversibly acetylates cyclooxygenase(except aspirin,
irreversible cox inhibitor)
2. Therapeutic uses – antipyretic, antiinflammatory, analgesic, increase
alveolar ventillation(increased CO2 production & respiration),
antiplatelet(Thromboxane A2 inhibition, inhibit thrombus formation)
& others(treat acne, corns, calluses, and warts, methyl salicylate/oil of
wintergreen as counterirritant).[1,5,6]
3. Adverse effects –
 Gastrointestinal- Epigastric distress, ulceration, hemorrhage, and iron-
deficiency anemia
 Prolonged bleeding time[8]
 Respiratory depression & metabolic acidosis in toxic dose, due to
increased CO2 production.
 Hypersensitive reaction - urticaria, bronchoconstriction, and
angioedema.
 CNS - Hearing impairment, tinnitus, confusion, dizziness, stupor.
 Reyes syndrome[8]
 Postpartum haemorrhage & premature closure of fetal ductus arteroisus.

8. PROPIONIC ACID DERIVATIVES
 Reversible non selective cyclooxygenase inhibitor.
 Used principally in Rheumatoid arthritis & chronic
osteoarthritis(ibuprofen & it’s congeners).
 Also used as anti-inflammatory, analgesic, antipyretic,
antiplatelet.[8]
 Indomethacin IV used to close a patent ductus arteriosus
(PDA).[6,9]
 Ibuprofen is effective in dysmenorrhoea.
 Adverse effects include~ in GI system- dyspepsia; in CNS-
headache, tinnitus, dizziness, fatigue, depression,
ototoxicity; and others include – dermatological problems,
agranulocytosis, impaired renal function, angioedema etc.

9. Fenamates
 Mefenamic acid, flufenamic acid and meclofenamate
are common.[8]
 Mostly used in treatment of soft tissue injuries,
dysmenorrhoea and rhematoid & osteoarthritis.
 Common side effects include diarrhoea associated
with steatorrhoea and inflammation of bowel.[8]

10. Enolic acid derivatives
 Inhibitor of COX-1 & COX-2 .
 Anti-inflammatory, analgesic, antipyretic.
 Piroxicam and meloxicam is used for Rheumatoid &
osteoarthritis and acute gout.[5,8]
 Other oxicam derivatives include droxicam, pivoxicam
– designed to reduce gastric irritation.
 Toxicities include slight gastric & serious skin
reactions.[1]

11. Acetic acid derivatives
 Potent non selective reversible COX inhibitor.
 Anti-inflammatory, analgesic.
 Indomethacin is limitedly used in the treatment of
acute gouty arthritis, to close a PDA in neonates, in
ankylosing spondylitis, and in osteoarthritis of the hip.
 Sulindac(prodrug), less potent than indomethacin, it
is useful in the treatment of RA, ankylosing
spondylitis, osteoarthritis, and acute gout.[6,8]
 Adverse reactions are like other NSAIDs.

12. Pyrazolone derivatives
 Metamizole & propiphenazone are major 2 drugs in
this class, promptly acting analgesic and antipyretic,
but poor antiinflammatory and not uricosuric.
 Show high gastric toxicity and edema ; hypersensitivity
reactions and hypothyroidism are also common.[6,8]

13. Preferential COX-2 inhibtors
 Antiinflammatory action of Nimesulide may be exerted by
e.g. reduced generation of superoxide by neutrophils,
inhibition of PAF synthesis and TNFa release, free radical
scavanging, inhibition of metalloproteinase activity in
cartilage.Analgesic, antipyretic and antiinflammatory
activity. Adverse effects are like other NSAIDs.[8]
 Diclofenac is among the most extensively used NSAID;
employed in rheumatoid and osteoarthritis, bursitis,
ankylosing spondylitis, toothache, dysmenorrhoea, renal
colic, posttraumatic and postoperative inflammatory
conditions—affords quick relief of pain and wound edema.
 Aceclofenac, etodolac & meloxicam are others.[2]

14. SELECTIVE COX-2 INHIBITOR
 Celecoxib, Etoricoxib and Parecoxib are commonly used in
India.
 Should be used only in patients at high risk of peptic ulcer,
perforation or bleeds.[1]
 Potent anti-inflammatory, analgesic, antipyretic, along
with used as pre & post surgery medicaion.
 Side effects include abdominal pain , hepatitis, headache,
dyspepsia, diarrhoea.[8,9]
 Selective COX-2 inhibitors, are able to stimulate adherence
of leukocytes to the vascular endothelium in the
mesenteric circulations [5] and that has been strongly
associated with NSAID-induced gastric damage [7].

15. THERAPEUTIC ADVANTAGES &
DISADVANTAGES OF NSAIDs
ACCESSED FROM LIPPINCOTT’S ILLUSTRATED REVIEWS : PHARMACOLOGY,
5TH EDITION, CHAPTER 41, PAGE – 537; ON 28.11.2019

16. SIDE EFFECTS OF
NSAIDs
Accessed from Lippincott’s illustrated reviews:pharmacology, page 973;on 28.11.19

17. REFERENCES :-
1. Essentials of Medical Pharmacology, K.D.Tripathi,7th edition
2. Asako H, Kubes P, Wallace J, Wolf RE, Granger DN. Modulation of leukocyte adhesion
to rat mesenteric venules by aspirin and salicylate. Gastroenterology. 1992;103(1):146-
152
3. Wallace JL, McKnight W, Miyasaka M, Tamatani T, Paulson J, Anderson DC, Granger
DN, Kubes P. Role of endothelial adhesion molecules in NSAID-induced gastric
mucosal injury. American Journal of Physiology. 1993;265:G993-G998
4. Wallace JL, McKnight W, Reuter BK, Vergnolle N. NSAID-induced gastric damage in
rats: Requirement for inhibition of both cyclooxygenase 1 and 2. Gastroenterology.
2000;119:706-714
5. Wallace JL, Arfors KE, McKnight GW. A monoclonal antibody against the CD18
leukocyte adhesion molecule prevents indomethacin-induced gastric damage in the
rabbit. Gastroenterology. 1991;100:878-883
6. Lippincott’s Illustrated Reviews: Pharmacology[5th edition]
7. Basic and Clinical Pharmacology 12th Edition=Bertram Katzung Susan Masters
Anthony Trevor=007
8. Goodman & Gilman's The Pharmacological Basis of Therapeutics, 12th Edition
9. ArthroScope. Toronto: The Arthritis Society; 1995.