1

NSAIDs

Non steroidal Anti- inflammatory drugs

Dr. Sohail Ahmad

2
 Inflammation 3

It is a non-specific manifestation of many diseases.

Acute
Chronic

Anti-inflammatory drugs are extensively used.

 Non steroidal Anti- inflammatory drugs4
(NSAIDs) mainly produce their effects by
inhibiting the biosynthesis of

Prostanoids

Prostaglandins , Thromboxane A2
& Prostacyclin.
 5

Membrane phospholipids

Arachidonic acid
 6

Membrane phospholipids

Arachidonic acid

Leukotrienes Prostaglandins Thromboxane Prostacyclin

Prostanoids
 7

Membrane phospholipids
Phospholipase
Arachidonic acid

Lipoxygenase COX

Leukotienes Prostaglandins Thromboxane Prostacyclin

Prostanoids
 8

Membrane phospholipids
Cosrticosteroids
Phospholipase
Arachidonic acid

Lipoxygenase COX NSAIDS

Leukotienes Prostaglandins Thromboxane Prostacyclin

Prostanoids
 Biosynthesis of Prostanoids: 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,
 10

Cosrticosteroids Membrane phospholipids

Phospholipase
Arachidonic acid

Lipoxygenase COX NSAIDS

Leukotienes Prostaglandins Thromboxane Prostacyclin

Prostanoids
 11

MOA of ASPIRIN / NSAIDs

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)
 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.
COX-2 13

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

 Aspirin is unique, it acetylates , & irreversibly inhibits
14 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 .
 Scheme for prostaglandin Biosynthesis
15
Stimulus

Disturbance of cell membrane

Phospholipids
Corticosteroids inhibit Phospholipase A2
Arachidonic Acid

X
Aspirin & NSAIDs inhibit
Cyclooxygenase Lipoxygenase
X

Hydroperxides
PGG2
Endoperoxides
PGH2 Pr
sy osta

TX synthetase
e nth cy
e tase
ras

as eta clin
mer uc se e
me

Iso d
Re
Iso

Leukotrienes PGE2 PGF2 PGD2 TXA2 Prostacycline

16
 Classification of NSAIDs
A: Non-Selective COX Inhibitors.(Inhibitors of COX I & II) 17

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
 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.
 19

ASPIRIN
Prototype Drug
The oldest member used.
 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
 Salicylate is metabolized in liver into:
21

1.Salicyluric acid (glycine conjugate)

2.Glucuronide conjugate
3. Gentisic acid
22
 MOA of ASPIRIN / NSAIDs 23

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 .

As Analgesic:
24
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.

As Antipyretic:
Aspirin lowers raised body temperature , no effect on normal 25
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.
 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 & cant synthesize new enzyme.
Aspirin should be stopped 7-10 prior to operations, to avoid risk of
bleeding.
Therapeutics Uses of Aspirin/ NSAIDS

27
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.
2. Anti pyretic : body temp in fever 28

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.
5. Anti Platelet : 29

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.
6. In Bartters syndrome:
30
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 .
7.Chemoprophylaxis of cancer of colon .50% decrease
31 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.
Dosage of Aspirin: 32

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.
 Adverse Effects of Aspirin 33

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
To decrease gastric intolerance: 34

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
2. Impaired hemostasis: 35

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).
5. Decreased renal function: 36

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
37
6.Effects on Respiration: 38

In high doses stimulation of Respiratory Centerhyperventilation

respiratory alkalosiscompensated by kidney------ compensated
respiratory alkalosis
In toxic doses respiratory depression & a combination of
uncompensated respiratory & metabolic acidosis .
7. Effects on CNS: 39
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 .
8. Risk of Reyes syndrome: 40

Aspirin & other salicylates given in viral infection in young children

have been associated with an incidence of Reyes syndrome.
In Reyes syndrome there is fulminating hepatitis ,with cerebral
edema which may be fatal.
So Acetaminophen or Ibuprofen should be used instead of
Aspirin.
 41

In pregnancy & during lactation:

Avoid in pregnancy & lactation
Aspirin & salicylates cross placental barrier & are secreted in breast
milk.
10. Drug Interactions:
42
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.
 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.
Contraindications / Precautions: 44

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.
 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.
 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.
Topically used salicylates: 47

Methyl salicylate: As counter irritant

Salicylic acid :Topically on skin for corns ,warts

Salfasalazine , Mesalamine --- suppository & rectal

suspension enema in Inflammatory bowel disease.
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.
 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
 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.
Toxicity: At therapeutic doses 52

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
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.
 55

Prevention of toxicity:
Base line & periodic estimation of hepatic enzymes
should be undertaken in patients on high dose
acetoaminophen.
 56
B: Selective COX-2 Inhibitors (Coxibs)
PrototypeCelecoxib : 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
 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.
58
 Scheme for prostaglandin Biosynthesis
59
Stimulus

Disturbance of cell membrane

Phospholipids
Corticosteroids inhibit Phospholipase A2
Arachidonic Acid
Lipoxygenase X
Cyclooxygenase
Aspirin & NSAIDs inhibit

Hydroperxides
PGG2
Endoperoxides
PGH2 Pr
sy osta

TX synthetase
e nth cy
e tase
as

e r as eta clin
uc
er

Isom d se e
om

Re
Is

Leukotrienes PGE2 PGF2 PGD2 TXA2 Prostacycline

 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.
 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
 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.
A/E: 63

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
 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
C/I: 65

Sulfonamide allergy
Anaphylactoid reaction with Aspirin.
Hepatic dysfunction.
Severe renal insufficiency
Severe heart disease
Volume depletion
Meloxicam: Related to Piroxicam. Preferentially selective COX-2
66
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.
Pyrazolone Derivatives
Phenylbutazone: Obsolete --- Agranulocytosis 67

Apazone / Azopropazone: less risk of agranulocytosis

These are now rarely used.
 Acetic Acid Derivatives
68
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
Uses & dosage forms
Diclofenac is used for long term use in Rheumatoid arthritis ,Osteoarthritis , & 69
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.
Etodolac:
70
10 times more selective Cox-2 inhibitor.
Good for post-operative relief after coronary artery bypass operation.
Less gastric intolerance.
Indomethacin: Indole derivative.
71
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.
A/E of Indomethacin:
More GIT A/E & Pancrentitis 72

Headache, Dizziness confusion & Depression.

Rare: Thrombocytopenia , Aplstic anemia.
Psychosis with hallucination
Hepatic abnormalities.
Renal papillary necrosis.
Tolmetin: Ineffective in gout
A/E: Thrombocytopenia.
Ketorolac:
Mainly Analgesic.Not anti-inflammatory 73

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.
Oxicams ( Enolic acids) : Piroxicam ,Tenoxicam 74
Piroxicam (Feldene): Oxicam derivative.
MOA: Non-selective Cox inhibitors
Inhibition of chemotaxis migration of polys & macrophages , Inhibits
lymphocyte function.
O2 radical production.
Long t - once daily dosage.
Metabolized in liver-
A/E: peptic ulcer & bleeding (at higher dose > 20 mg/d ) 9.5 times
higher than other NSAIDs.
 75

Naphthylacetic Acid Prodrug:

Nabumetone : Non-acid NSAID.
Active metabolite has t > 24hrs--- once daily
A/E: Pseudoporphyria & photosensitivity.
 Drugs with Analgesic & mild to moderate
76
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 : 2 hrs
More effective in closure of PDA
 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
 Flurbiprofen: Non-selective COX inhibitors & also inhibits TNF-&
78 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.
 Naproxen: More Toxic, rare allergic pneumonitis, vasculitis,
79
pseudoporphyria.
Oxaprozin: t : 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.
80