Pharmacology of NSAIDs (Non-Steroidal Anti-Inflammatory Drugs) by Dr. Sohail Ahmad

1. NSAIDs
Non steroidal Anti- inflammatory drugs
Dr. Sohail Ahmad
1

2. 2

3. Inflammation
It is a non-specific manifestation of many diseases.
Acute
Chronic
Anti-inflammatory drugs are extensively used.
3

4. Non steroidal Anti- inflammatory drugs
(NSAIDs) mainly produce their effects by
inhibiting the biosynthesis of
Prostanoids
Prostaglandins , Thromboxane A2
& Prostacyclin.
4

5. Membrane phospholipids
Arachidonic acid
5

6. Membrane phospholipids
Arachidonic acid
Leukotrienes Prostaglandins Thromboxane Prostacyclin
Prostanoids
6

7. Membrane phospholipids
Arachidonic acid
Leukotienes Prostaglandins Thromboxane Prostacyclin
Prostanoids
COXLipoxygenase
Phospholipase
7

8. Membrane phospholipids
Arachidonic acid
Leukotienes Prostaglandins Thromboxane Prostacyclin
Prostanoids
COXLipoxygenase
Phospholipase
NSAIDS
Cosrticosteroids
8

9. Arachidonic acid is the primary precursor of prostanoids
Prostanoids are also called ‘Eicosanoids’
Arachidonic acid is a component of the phospholipids of
cell membrane.
Free Arachidonic acid is released by cell damage mainly
by the action of Phospholipase A2 enzyme.
Arachidonic acid undergoes 2 pathways, by the enzymes
Cyclooxygenase & Lipooxygenase,
Biosynthesis of Prostanoids: 9

10. Membrane phospholipids
Arachidonic acid
Leukotienes Prostaglandins Thromboxane Prostacyclin
COXLipoxygenase NSAIDS
Phospholipase
Cosrticosteroids
Prostanoids
10

11. Inhibition of cyclooxygenase enzyme & reduced
biosynthesis of Prostanoids
(Prostaglandins Prostacyclin ,Thromboxane A2)
Aspirin & older non-selective NSAIDs reduce
biosynthesis of Prostanoids by inhibiting both
isoforms of the Cyclooxygenase (COX) enzyme
(COX-1& COX-2)
MOA of ASPIRIN / NSAIDs
11

12. COX-1
It is responsible for the Physiologic production of
prostanoids.
It is “House keeping “enzyme that regulates the
normal cellular processes (via production of PGs)
such as
 Gastric cytoprotection
 Vascular homeostasis
 Platelet aggregation
 Kidney function.
12

13. COX-2
It is constitutively expressed only in brain, kidney & bone
Its expression at other sites is increased in inflammation.
It is responsible for the elevated production of prostanoids
in inflammation & disease.
The selective COX-2 inhibitors have been synthesized.
Its expression is inhibited by Glucocorticoids
COX-3 more effects in CNS
13

14.  Aspirin is unique, it acetylates , & irreversibly inhibits the
enzymes, all other drugs produce reversible inhibition
 There is ↓ PGs & Thromboxane synthesis throughout the body.
 Release of PGs for inflammation as well as for homeostatic
function is disrupted (specially cytoprotection in gastric mucosa
& auto regulation of renal function)
 Newer drugs, coxibs are COX2 selective inhibitors .
14

15. PGG2
PGH2
Scheme for prostaglandin Biosynthesis
Stimulus
Disturbance of cell membrane
Phospholipids
Corticosteroids inhibit Phospholipase – A2
Arachidonic Acid
Aspirin & NSAIDs inhibit
Cyclooxygenase
Lipoxygenase
Endoperoxides
Prostacycline
Hydroperxides
TXA2PGD2PGF2αPGE2Leukotrienes
X
15

16. 16

17. Classification of NSAIDs
A: Non-Selective COX Inhibitors.(Inhibitors of COX I & II)
1. Drugs with Analgesic & Marked Anti-inflammatory Effects:
a. Salicylic Acid Derivatives
 Aspirin (Acetylsalicylic acid)
 Diflunisal
 Sodium Salicylate
 Magnesium Choline salicylate
b. Pyrazolon Derivatives
Apazone, Phenylbutazone , Oxyphenbutazone
c. Acetic Acid Derivatives
Diclofenac , Tolmetin , ketorolac
Indomethacin , Etodolac , Sulindac
d. Oxicams ( Enolic acids): Piroxicam , Tenoxicam
e. Naphthylacetic Acid Prodrug: Nabumetone
17

18. 2. Drugs with Analgesic & Moderate Anti-inflammatory
Effect:
a. Propionic acid derivatives
Ibuprofen, Fenoprofen, Flurbiprofen , Ketoprofen , Naproxen,
oxaprozin , carprofen , Tiaprofen
b. Fenamates:
Mefenamic , Meclofenamic & Flufenamic acid
3. Drug with Analgesic & no Anti-inflammatory Effect:
Para aminophenol Derivative :
Acetaminophen
B: Selective COX Inhibitors.(Inhibitors of COX II only)
Celecoxib , Etoribcoxib , Meloxicam ,Nimesulide.
18

19. ASPIRIN
Prototype Drug
The oldest member used.
19

20. ASPIRIN
Chemistry: Aspirin is Acetyl salicylic Acid.
Pharmacokinetics of Aspirin:
Absorption: Well from stomach & upper small intestine
Distribution: wide , crosses placental barrier
PPL: In 1-2hrs. t1/2: 15 min.
Metabolism: Rapid hydrolysis by Esterases in blood & tissues in to
Salicylate & Acetic Acid.
Salicylate is 80-90-% PPB
20

21. Salicylate is metabolized in liver into:
1.Salicyluric acid (glycine conjugate)
2.Glucuronide conjugate
3. Gentisic acid
21

22. 22

23. MOA of ASPIRIN / NSAIDs
As Anti-inflammatory:
Aspirin irreversibly acetylates both isoforms of cyclooxygenase
enzyme , COX-1 & COX-2 & inactivates them. So it inhibits
biosynthesis of PGs which, primarily modulates those aspects of
inflammation in which PGs act as mediators.
Aspirin inhibits inflammation in Rheumatoid Arthritis but it neither
arrests the progress of disease nor it induces remission.
Other NSAIDs reversibly inhibit cyclooxygenase enzyme .
23

24. As Analgesic:
1. Aspirin & Other NSAIDs inhibit cyclo-oxygenase enzyme ,
reduce production of PGs in injured tissue.
PGE2 is thought to sensitize the nerve ending
(pain receptors)to action of bradykinin , Histamine & other
mediators released by the inflammatory process.
So due to reduced production of PGE2 , they repress the sensation of pain.
2. Inhibit pain stimuli at subcortical sites --Thalamus & Hypothalamus.
24

25. As Antipyretic:
Aspirin lowers raised body temperature , no effect on normal
temperature
Fever occurs when the set point of the thermoregulatory
center in anterior hypothalamus is elevated.
This may be due to PGE2 synthesis , stimulated by pyrogen such as
cytokine.
Cytokine is released from WBCs, activated by infection, malignancy
or inflammation.
 Because of inhibition of PGE2 synthesis , the thermostat is reset
towards normal. & rapidly lowers body temperature by increasing
heat dissipation due to peripheral vasodilation & sweating.
25

26. AS Antiplatelet:
TXA2 normally promotes platelet aggregation. prostacyclin –PGI 2
normally inhibit platelet aggregation.
In low doses Inhibit Platelet Aggregation due to irreversible
acetylation of COX-1 enzyme in platelets.
 Low doses 81-100mg/ d inhibit TXA2 synthesis in platelets , higher
doses inhibit prostacyclin –PGI2 also.
 Platelet aggregations is the first step in coagulation so it prevents
coagulation & prolongs bleeding time .
 The action lasts for 3-8 days -- life span of platelets, because they
lack nuclei & can’t synthesize new enzyme.
 Aspirin should be stopped 7-10 prior to operations, to avoid risk of
bleeding.
26

27. Therapeutics Uses of Aspirin/ NSAIDS
1. Analgesic :
a. used alone in pain like.
: Headache, Myalgia, Arthralgia, Neuralgia
osteomyelitis, osteoarthritis. Toothache, Dysmenorhoea
b. With opioids – synergistic action
In pain of cancer metastases in bone
Post operative pain-  requirement of opioids.
27

28. 2. Anti pyretic :↓ body temp in fever
Not effective in raised body temp. due to heat stroke or malignancy.
Does not lower normal body temp .
3. Acute rheumatic fever :Both for antipyretic & anti-inflammatory
effects.
4. Rheumatoid Arthritis, Osteoarthritis:
To control symptoms.
No effect on progression of disease.
Does not induce remission.
28

29. 5. Anti Platelet :
Aspirin is used prophylactically :
For primary & secondary prevention (In Post myocardial
infarction & post stroke patients) of :
Transient ischemic attacks & stroke.
Unstable angina
Coronary artery thrombosis & Myocardial infarction.
To prevent Thrombosis after coronary artery bypass grafting.
29

30. 6. In Bartter’s syndrome:
There is defect in tubular transport of K---Hypokalemia----PG
synthesis stimulated---Increased Renin---
Hyperaldosteronism.
Aspirin prevents this secondary Hyperaldosteronism due to
inhibition of PG synthesis .
30

31. 7.Chemoprophylaxis of cancer of colon .50% decrease with
frequent use of aspirin
8.Closure of PDA . As PGs keep patency of Ductus arteriosus.
9. Diarrhea after Radiation & Cholera in which PGs are implicated.
10.Prophylaxis of Cataract: some studies indicate decrease in
incidence of cataract with frequent use of aspirin.
11. With Niacin to improve compliance because Aspirin ↓ flushing,
which is an A/E of Niacin due to PGs.
31

32. Dosage of Aspirin:
3 therapeutic dose ranges:
1. Low range<300mg/d(81, 100mg) as single dose --to↓ Platelet
Aggregation
2. Intermediate dose :300-2400mg/d as 3 divided doses) Analgesic,
Antipyretic.
3. High dose : 2400- 4000mg/d– as 3 divided doses --for Anti-
Inflammatory effect.
32

33. Adverse Effects of Aspirin
At therapeutic doses
1. Gastric Intolerance:
The most common & serious is gastritis, Gastric
ulceration or Exacerbation of Peptic ulcer
symptoms.
 Dyspepsia & Heart burn , Abdominal Pain .
 Nausea & Vomiting, Hematemesis
 Fecal blood loss
 Iron deficiency Anemia
33

34. To decrease gastric intolerance:
Aspirin may be given with Misoprostol.
Addition of Proton pump inhibitors with Aspirin.
 H2 Blockers, if aspirin has been stopped
Use of Special Prep. Of Aspirin: only marginally
effective
 Aloxiprin (Enteric coated aspirin)
 Buffered Aspirin
34

35. 2. Impaired hemostasis:
↓ Platelet Aggregation & Hypoprothrobinaemia:
3. Allergic / Hyper sensitivity Reactions:
Skin rashes, Rhinitis, Bronchial asthma
4. Hyperuricemia:
Retention of uric acid at low doses<2.5 g/d ,
(although at high doses> 3.6/d –increases uric acid
excretion).
35

36. 5. Decreased renal function:
Normally PGE2 & PGI2are responsible for maintaining
renal flow specially in presence of circulating
vasoconstrictors.
Inhibition of PGs synthesis may produce:
Retention of Sodium & water
Edema
Hyperkalemia.
Interstitial nephritis with other NSAIDs , but not Aspirin
36

37. 37

38. 6.Effects on Respiration:
In high doses– stimulation of Respiratory Center—hyperventilation–
respiratory alkalosis—compensated by kidney------ compensated
respiratory alkalosis
In toxic doses respiratory depression & a combination of
uncompensated respiratory & metabolic acidosis .
38

39. 7. Effects on CNS:
In large doses: Salicylism--- Vomiting ,tinnitus,
↓ hearing ,vertigo.
In Toxic Doses :Stimulation of CNS including convulsions ,followed by
depression.
 Repiratory depression
 Cardiotoxicity
 Hyperpyrexia because salicylates uncouple the oxidative
phosphorylation. The energy normally used for production of ATP
is dissipated as heat .
39

40. 8. ↑ Risk of Reye’s syndrome:
Aspirin & other salicylates given in viral infection in young children
have been associated with an ↑ incidence of Reye’s syndrome.
In Reye’s syndrome there is fulminating hepatitis ,with cerebral
edema which may be fatal.
So Acetaminophen or Ibuprofen should be used instead of
Aspirin.
40

41. In pregnancy & during lactation:
Avoid in pregnancy & lactation
 Aspirin & salicylates cross placental barrier & are secreted in breast
milk.
41

42. 10. Drug Interactions:
Corticosteroids ,other NSAIDs: ↑ GIT A/E.
With ACE inhibitors. ↓ Antihypertensive effect
With Warfarin or Heparin : ↑ GIT bleed.
With Probenecid & sufinpyrazone:
Aspirin antagonizes uricosuric action of Probenecid &
sufinpyrazone , as it inhibits tubular secretion of uric acid (in low
doses—< 2g/d). So C/I in Gout in low doses.
42

43. Displacement of PPB drugs:
As aspirin is 90-95 % PPB Aspirin can displace many drugs from
PPB sites , ie Warfarin , Phenytoin , Valproic acid ,
Sulfonylureas, Methotrexate , Indomathacin , Naproxen ,
Ketoprofen, Fenoprofen & Bilirubin ----Increased level of free
drugs/ Bilirubin– toxicity.
Aspirin ↓ diuretic action of Fursemide, Thiazides,
Spironolactone.
Aspirin blocks the active transport of Penicillin from CSF to
blood.
43

44. Contraindications / Precautions:
 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
 Consider drug interactions.
44

45. Management of Aspirin/Salicylate Overdose
toxicity/Poisoning
 Aspirin/Salicylate poisoning is a medical emergency, &
death may result.
 There is no antidote.
 Management begins with rapid assessment, followed
by
 A(airway),B(breathing), C(circulation),
D(decontamination) approach.
 Gastric Lavage , Activated Charcoal to prevent further
absorption, specially if enteric coated tablets have
been used
 Measurement of serum salicylate level & pH
 Correct fluid, electrolyte & acid base balance.
 Maintain high urine out put.
 Keep airway patent.
 Lower body temperature by cold sponging.
45

46.  Vit. K I/V to correct hypopthrombinemia.
 Diazepam I/V for convulsions.
 Promote excretion by NaHCO3 I/V to alkalinize
urine, maintain pH at 8.o.
 Hemodialysis /Peritoneal dialysis in severe
acidosis & coma.
 Ventilatory assistance in severe cases.
46

47. Topically used salicylates:
Methyl salicylate: As counter irritant
Salicylic acid :Topically on skin for corns ,warts
Salfasalazine , Mesalamine --- suppository & rectal
suspension enema in Inflammatory bowel disease.
47

48. 48

49. Therapeutic uses:
1. Mild to moderate pain like Aspirin
2. Antipyretic
Preferred to Aspirin
 In children with viral infections
 In pt. with Peptic ulcer, Hemophilia
 Pt. allergic to Aspirin.
 Concomitantly with Probenecid & sulfinpyrazone in patients of
gout.
49

50. Pharmacokinetics of Acetoaminophen
 Rapid absorption from GIT.
 Significant First pass metabolism in gut wall & liver.
 When given in doses up to 0.5-4g/d:
 90-95% metabolized to inactive glucuronide & sulphate conjugates
which are excreted in urine.
 5-10 % hydroxylated to form N- Acetyl=p benzoquinoneimine
50

51.  N- Acetyl-p benzoquinoneimine is a highly reactive
metabolite which reacts with sulhydral groups.
 Normally it reacts with sulhydral group Of Glutathion & forms
a non-toxic substance.
At doses above 4g/d Glutathion reserves are depleted & it can
produce toxicity– Hepatic necrosis & Renal tubular necrosis.
51

52. Toxicity: At therapeutic doses
 Rash & Allergic reactions.
 Drug fever.
 Mild increase in hepatic enzymes.
With over dosage:
 Doses above 4g may be toxic.
 15g may be fatal due to metabolite N-Acetylbenzoiminoquinone which
produces:
 Hepatic necrosis--- potentially fatal
 Renal tubular necrosis---may occur
 Hypoglycemic coma --may occur
52

53. 53

54. Management of Acetoaminophen toxicity:
 It constitutes a medical emergency, early diagnosis & treatment is
required.
 Activated Charcoal to prevent further absorption.
 Correct fluid, electrolyte & acid base balance
 Antidote--N-Acetylsysteine by I/V infusion.
 It provide SH-groups to neutralize the toxic metabolite.
 It is life saving if given within 10 hrs of overdose.
 Avoid in severe hepatic impairment.
54

55. Prevention of toxicity:
Base line & periodic estimation of hepatic enzymes
should be undertaken in patients on high dose
acetoaminophen.
55

56. B: Selective COX-2 Inhibitors (Coxibs)
Prototype—Celecoxib : A Sulfonamide
MOA: Celecoxib is 10-20 times more selective in inhibiting COX-2 than COX-
1.
COX-2
 It is constitutively expressed only in brain, kidney & bone .
 Its expression at other sites is increased in inflammation.
 It is responsible for the elevated production of prostanoids in inflammation &
disease.
 It has larger & more flexible substrate channel than COX-I .
& a large space where the Celecoxib binds..
 Its expression is inhibited by Glucocorticoids
56

57. MOA of Celecoxib--- conti
 Arachidonic acid is the primary precursor of Prostaglandins,
is a component of the phospholipids of cell membrane.
 Free Arachidonic acid is released by cell damage mainly by
the action of Phospholipase A2 enzyme.
 Arachidonic acid is converted to prostaglandins at site of
inflammation by Cyclo-oxygenase-2 (COX 2) enzyme.
 It reduces PG synthesis by selectively inhibiting COX-2
enzyme induced at sites of inflammation without affecting the
actions of COX-1--- gastric cytoprotection & platelet
aggregation
 Inhibition of COX-2 enzyme is time dependent & reversible.
57

58. 58

59. PGG2
PGH2
Scheme for prostaglandin Biosynthesis
Stimulus
Disturbance of cell membrane
Phospholipids
Corticosteroids inhibit Phospholipase – A2
Arachidonic Acid
Lipoxygenase Cyclooxygenase
Aspirin & NSAIDs inhibit
Endoperoxides
Prostacycline
Hydroperxides
TXA2PGD2PGF2αPGE2Leukotrienes
X
59

60. Pharmacologic Effects :
 Analgesic
 Antipyretic
 Anti-inflammatory effects
No inhibition of platelet aggregation. Does not
prolong bleeding time.
No inhibition of protective gastric PGs--- No gastric
irritation.
60

61. PhK:
 Long half life: 11 hrs– Once or twice daily dose.
 Metabolized by CYP2C9.
 Excreted in feces & urine.
 Can inhibit CYP2D6
 Dose adjustment in hepatic dysfunction
61

62. Therapeutic uses:
 Specially useful in osteoarithritis & Rheumatoid Arthritis.
 Useful in Dysmenorrhea, acute gouty arthritis, acute
musculoskeletal pain & ankylosing spondylitis
 Also used in Primary familial adenomatus polyposis.
 Useful in patients undergoing bone repair / operation.
62

63. A/E:
 Potential for increasing thrombotic events– --------Myocardial
infarction & stroke, specially in cases of Rheumatoid Arthritis Who are
at risk of myocardial infarction.
 Selective COX-2 inhibitors depress PGI2 formation by endothelial cells,
without concomitant inhibition of platelets TXA2. PGI2 restrains the effects
of TXA2 on CVS, so selective COX-2 inhibitors increase the risk of
thrombosis.
 Renal toxicities similar to non selective NSAIDs: depressed renal
function, edema , Hypertension.
 Less GIT A/E (mediated by inhibition of COX-1)
 Skin rash---because it is a Sulfonamide
63

64. D/I:
 Inhibitors of CYP2C9-- Fluconazole , Fluvastatin ,& Zafirlukast may
increase the serum levels of Celecoxib
 Celecoxib can inhibit CYP2D6--- may increase the serum levels of
Beta blockers , Antidepressants & Antipsychotic drugs
64

65. C/I:
 Sulfonamide allergy
 Anaphylactoid reaction with Aspirin.
 Hepatic dysfunction.
 Severe renal insufficiency
 Severe heart disease
 Volume depletion
65

66. Meloxicam: Related to Piroxicam. Preferentially selective COX-2
inhibitor.
Etoricoxib: Resembles diclofenac
 Monitoring of hepatic functions required.
 Long half life: 22 hrs
Nimesulide: new compound less gastric irritation.
Valdecoxib & Rofecoxib
Withdrawn due to. higher risk of incidence of Cardiovascular
thrombotic events----Myocardial Infarction & stroke.
66

67. Pyrazolone Derivatives
 Phenylbutazone: Obsolete --- Agranulocytosis
 Apazone / Azopropazone: less risk of agranulocytosis
These are now rarely used.
67

68. Acetic Acid Derivatives
Phenylacetic acid derivative: Diclofenac , Tolmetin , ketorolac
Indomethacin , Etodolac , Sulnidac
Diclofenac: Very commonly used NSAID.
MOA: Non-selective COX inhibitor.
Good anti- inflammatory.
More potent than Indomethacin & Naproxen.
Accumulates in synovial fluid .
Drug & its metabolites are eliminated via kidney.
t1/2 --- 1.1 hrs
A/E: Nephrotoxic– Impaired renal blood flow & GF, fluid retention and
edema
 Less Gastric irritation
 ↑ Liver enzymes
68

69. Uses & dosage forms
 Diclofenac is used for long term use in Rheumatoid arthritis ,Osteoarthritis , &
Ankylosing spondylitis.
 Also for short term treatment of Dysmenorhea, post operative pain, acute
musculoskeletal disorders.
Oral tablets , capsules, intramuscular Injection
Also available in combination with misoprostol & omeprazole.
 Prevention of postoperative ophthalmic inflammation after intraocular lens implantation
& strabismus surgery: 1% Eye drops
 Solar keratoses: 3% gel
 Choice for analgesia with nausea -- rectal suppository.
 Oral mouthwash.
69

70. Etodolac:
 10 times more selective Cox-2 inhibitor.
 Good for post-operative relief after coronary artery bypass operation.
 Less gastric intolerance.
70

71. Indomethacin: Indole derivative.
 Potent non selective COX inhibitor.
 May also inhibit Phospholipase- A2 & C.
 ↓ neutrophils migration also ↓ T & B cell proliferation.
Th. Uses:
 Gout, ankylosing spondylitis, PDA.
 Conjunctival & gingival inflammation.
 Postlaminectomy syndrome-- epidural inj.
71

72. A/E of Indomethacin:
 More GIT A/E & Pancrentitis
 Headache, Dizziness confusion & Depression.
Rare: Thrombocytopenia , Aplstic anemia.
 Psychosis with hallucination
 Hepatic abnormalities.
 Renal papillary necrosis.
Tolmetin: Ineffective in gout
A/E: Thrombocytopenia.
72

73. Ketorolac:
 Mainly Analgesic.Not anti-inflammatory
 Can replace Morphine in post surgical pain .
 More Nephrotoxic on chronic use
Sulnidac: Sulfoxide prodrug, undergoes, EHC.
 DOA: 12-16 hrs.
 Suppresses familial polyposis, ↓ incidence of cancer colon , breast &
prostate.
 A/E: Serious
 Stevens Johnsons syndrome
 Nephrotic syndrome
 Agranulocytosis
 Hepatic toxicity.
73

74. Oxicams ( Enolic acids) : Piroxicam ,Tenoxicam
Piroxicam (Feldene): Oxicam derivative.
MOA: Non-selective Cox inhibitors
 Inhibition of chemotaxis  migration of polys & macrophages , Inhibits
lymphocyte function.
 ↓ O2 radical production.
 Long t ½ - once daily dosage.
 Metabolized in liver-
 A/E: peptic ulcer & bleeding (at higher dose > 20 mg/d ) 9.5 times higher
than other NSAIDs.
74

75. Naphthylacetic Acid Prodrug:
Nabumetone : Non-acid NSAID.
Active metabolite has t ½ > 24hrs--- once daily
A/E: Pseudoporphyria & photosensitivity.
75

76. Drugs with Analgesic & mild to moderate
anti-inflammatory effect
Propionic acid derivatives:
Ibuprofen – prototype
MOA: Like Aspirin– Non-selective COX inhibitor & also inhibits leukocyte
migration.
 Good anti- inflammatory.
 2400 mg = 4 g of aspirin. t ½ : 2 hrs
 More effective in closure of PDA
76

77. Preparations & Uses Oral tablet, liquid , I/V : For Anti-rheumatoid
effects
For closure of PDA in pre-term infants.
 Topical cream for Osteoarthritis , liquid gel for post surgical dental
pain.
A/E: Like other NSAIDs
 Less Gastric irritation
 Nephrotoxic —Ac. renal failure , Interstitial nephritis. Nephrotic
syndrome.
 Aseptic meningitis in SLE patients
 Interaction with anticoagulant uncommon.
 Rare agranulocytosis & aplastic anaemia
77

78.  Flurbiprofen: Non-selective COX inhibitors & also inhibits TNF-α& Nitric
oxide synthesis.
Given orally. Other preparation also available
Topical ophthalmic prep.– for inhibition of intraoperative miosis.
I/V for periopretive analgesia.
Lozenges for sore throat.
Additional A/E: cogwheel rigidity , ataxia , tremor & myoclonus.
 Fenoprofen: A/E--interstitial nephritis
 Ketoprofen: Also inhibits lipo-oxygenase, not superior to other NSAIDs.
78

79.  Naproxen: More Toxic, rare allergic pneumonitis, vasculitis,
pseudoporphyria.
 Oxaprozin: t ½: 50-60hrs. Has uricosuric effect
b. Fenamates
Mefenamic, Meclofenamic & Flufenamic acid:
Inhibit both COX & Phospholipase A2.
Have no advantages over other NSAIDs.
A/E: Severe diarrhea , inflammation of bowel , Hemolytic anemia.
79

80. 80