c
 



  



Dr. Saleem Akhtar Rana,

Dr. Arshad Javaid Sheikh,
Dr. Mahboob Ashraf
  
 Assessment of our shortcomings
 Assessment of Practice in USA
 Does any specific NSAID good for everyone?
 Factors to select any particular NSAIDs
 How these NSAIDS work?
 Differences between non selective NSAIDs and Cox-
Cox-2
inhibitors.
 Indications for NSAIDs
 Side effects of NSAIDS
 Questions marks on Cox-
Cox-2 inhibitors
 Some specific drugs; Celecoxib, Meloxicam, Aceclofenac,
Diclofenac.
  

 hat are our deficiencies? Shortcomings

 ‘ 
 
 uveruse
 Proper indication; proper NSAID
 Co--morbid conditions
Co
 Contra--indications
Contra
 Side effects
 Dosage
 Interactions
 Children
 Pregnancy





‘


‘
 NSAID-associated upper gastrointestinal adverse events
NSAID-
are estimated to result in

 103,000 hospitalizations per year

 16,500 deaths per year in the United States, and
 represent 43% of drug-
drug-related emergency visits.
 a review of physician visits and prescriptions estimated
that unnecessary prescriptions for NSAIDs were written
in 42% of visits.[
visits.[

An estimated 10-
10-20% of NSAID patients experience
dyspepsia,, and Many of these events are avoidable;
dyspepsia
 u 
 
ill any specific NSAID will work in all
individuals similarly?

After how many days any specific NSAID

should be changed?
 
 
 hat factors should be considered before
we select any specific NSAID?
` u
 c

 2heir potency, Difference is there!
 Duration of action,
 Mode uf eliminated from the body,
 Condition to be treated = Prostaglandin associated: Diagnosis,
Degree of Severity
 Age
 Y
 
   


  
 
 




 
 

 
Y  
 

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 Drug interactions = Mechanism of action
 Side effects = Cox 1 & 2 inhibition
 Effects on cartilage
 



 

 
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 2heir ability to cause ulcers and promote

bleeding.
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 @
  

 Most NSAIDs are metabolised in the liver by

oxidation and conjugation to inactive
metabolites which are typically excreted in the
urine,, although some drugs are partially
urine
excreted in bile.
bile. Metabolism may be abnormal in
certain disease states, and accumulation may
occur even with normal dosage.

 Ibuprofen and diclofenac have short half-

half-lives
(2
(2ƛ
ƛ3 hours). Some NSAIDs (typically oxicams)
have very long half-
half-lives (e.g. 20ƛ
20ƛ60 hours).
 
 ‘


 `efore we select one of the non-

non-selective
NSAIDs or Cox-
Cox-2 inhibitors we must know
what are the important differences?
 unly then we can select an appropriate
molecule.
 John Vane (1927
(1927--2004), who later
received a Nobel Prize for his work


 


Inflammation is induced by following 4
chemical mediators .
 Amines: Histamine & 5-5-uH 2ryptamine
 Prostaglandins
 Small peptides; `radykinin
 Larger peptides; Interleukin-
Interleukin-1
NSAIDs can benefit only where
prostaglandins are the chemical
mediators.
 

‘

 How these drugs act?
 P
 Arachidonic Acid (present in all cells)
 Many isoenzymes of Cyclooxegenase
 Prostaglandins + 2hromboxanes+
Prostacyclin

Different types of isoenzymes produce specific

types of prostaglandins so differences in actions.
Different isoenzymes present in different tissues
so differences in actions
YY
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NSAIDS
 Inhibits all isoenzymes, including 
Cox-1, so all kinds of
prostaglandins, good and bad.

 Active in baseline conditions

 Acts almost in all tissues of body
 So when good prostaglandins will 
be inhibited there are going to
undesirable side effects even if
pain and other symptoms are 
controlled.
 Cox-1 is present in platelets, I
tract,CNS,Kidneys. 
 Cox-1 inhibition takes away
protective mechanisms from GI2,
kidneys, blood vessels and blood 
clotting.
Cox--2 inhibitors
Cox
Inhibits only Cox-2 produced
prostaglandins, mainly required to
control pain fever and inflammation
Is induced, i.e., becomes active only
when inflammation is there.
Acts only where cox-2 isoenzyme is
present.
hen good prostaglandins are not
inhibited, less side effects should be
there.
Also present in kidneys and produces
prostacyclin. Affects hemodynamics of
kidneys probably in negative ways and
increases thrombotic tendencies
Supposed to protect GI2 against the ill
effects of NSAIDs. Does so but does
not bring the risk to zero.
Some studies suggest this increases
atherogenesis tendencies also.
 
 


Different Isoenzymes of Cyclooxygenase
Produce different PGDs, F,D,E etc

Y '
%   Y 
%  
Responsible for all side effects of Responsible for all therapeutic
NSAIDs benefits of NSAIDS

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Non selective NSAIDs

are
accused
of
what side effects?
 
  
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 GI side effects,
 raising blood pressure,
 Nephrotoxicity,
 Cardiotoxicity,
 Chondropathy,
 Allergies, photoxicities
 CNS symptoms
 $
 How do NSAIDS work as anti-
anti-pyretics?
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 Strength flexibility and capacity to bear weight depends upon the amount of
Protoglycans and Hyaloronic Acid in the matrix of cartilage.

 2his differential effect of NSAIDs on cartilage metabolism is most relevant

to clinical practice since any drug, that suppresses proteoglycan synthesis
and impairs the chondrocyte to repair its damaged extracellular matrix,
could potentially accelerate the breakdown of the cartilage tissue.

 Some NSAIDs inhibit the synthesis of cartilage proteoglycans whereas other

do not ; ability of the chondrocyte to repair its damaged extracellular matrix
may be impaired.
 In cartilage with MuA and SuA, the metabolic balance of proteoglycan and
HA was unaffected by diclofenac.
 Aceclofenac and Meloxicam did not hamper biochemical properties of
cartilage and so may delay the process in uA.
 a

 

 In the periphery NSAIDs work by decreasing the
sensitivity of the pain receptors to painful stimuli induced
by heat, trauma, or inflammation.
 In the central nervous system, they are thought to
function as antihyperalgesics and block the increased
transmission of repetitive incoming signals to higher
centers.
 In effect, they modulate perception of pain caused by
repetitive stimulation from the periphery. Since they
function by modulation of the perception of pain, they
may be useful when given in the preoperative period and
may reduce the need for postoperative analgesia.
analgesia.
       
 NSAIDs within a group will tend to have similar
characteristics and tolerability.
 2here is little difference in clinical efficacy
among the NSAIDs when used at equivalent
doses.
 Rather, differences among compounds tend to
be with regards to
ƥ Dosing regimens (related to the compound's elimination half life),
half--life),
ƥ Route of administration, and
ƥ 2olerability profile.
 Y



Propionic]] acid derivatives
Propionic
ùNaproxen  
  ) )

ùIbuprofen ƥMefenamic acid

ùKetoprofen ƥMeclofenamic acid
ùFlurbiprofen ƥFlufenamic acid
ùuxaprozin ƥ2olfenamic acid
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ƥIndomethacin
ƥSulindac #   )
Y-.
 
Y 

ƥEtodolac ƥCelecoxib
ƥDiclofenac (Safety alert by FDA ƥRofecoxib (withdrawn from market
+ 
 -
-
 ) )


 ) )
ƥValdecoxib (withdrawn from market
ƥPiroxicam ƥParecoxib FDA withdrawn
ƥMeloxicam ƥLumiracoxib 2GA cancelled registration
ƥ2enoxicam ƥEtoricoxib FDA withdrawn
ƥDroxicam
ƥLornoxicam
ƥIsoxicam
 ‘





ƥRheumatoid arthritis ƥIleus

ƥusteoarthritis ƥRenal colic
ƥInflammatory arthropathies ƥ2hey are also given to neonate infants
spondylitis,,
(e.g. ankylosing spondylitis whose ductus arteriosus
arthritis,
psoriatic arthritis, is not closed within 24 hours of birth
Reiter's syndrome)
syndrome) ƥResearch continues into their
ƥAcute gout potential for prevention of
ƥDysmenorrhoea (menstrual pain) cancer,
colorectal cancer,
ƥMetastatic bone pain and treatment of
ƥHeadache and migraine other conditions,
ƥPostoperative pain such as cancer
ƥMild
Mild--to
to--moderate pain due and cardiovascular disease
disease..
to inflammation and
tissue injury
ƥPyrexia (fever)
fever)
 
"! 
 
 NSAIDs, like all drugs, may interact with other
medications. For example, concurrent use of NSAIDs and
quinolones may increase the risk of quinolones' adverse
central nervous system effects, including seizure.

Y   


 If a Cu -2 inhibitor is taken, one should not use a
traditional NSAID (prescription or over-
over-the-
the-counter)
concomitantly. In addition, patients on daily aspirin
therapy (e.g. for reducing cardiovascular risk) need to be
careful if they also use other NSAIDs, as the latter may
block the cardioprotective effects of aspirin.
 @  #
 NSAIDS are toxic drugs. `e alert and always keep warning patients
to keep looking for expected side effects.
 2hese effects are dose dependent. Use minimum dose for minimum
duration.
 Do not hesitate to stop these immediately if problem arises.
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 †0% increase in the risk of myocardial infarction with

both newer Cu -2 antagonists and high dose traditional
anti--inflammatories compared with placebo.
anti
 Doubled risk of symptomatic heart failure in patients
without a history of cardiac disease.
 In patients with such a history, however, use of NSAIDs
(aside from low-
low-dose aspirin) was associated with more
than 10-
10-fold increase in heart failure. If this link is found
to be causal,
 NSAIDs are estimated to be responsible for up to 20
percent of hospital admissions for congestive heart
failure.
 #$&
`#@
"
'# 

 NSAIDs reduce the blood flow to the kidneys leading to

salt & fluid retention.
 2his can lead to edema and hypertension.
 If high doses are used for longer periods of times as in
chronic conditions, can lead to renal failure.
 Combination with nephrotoxic agents increase the risk
of renal failure.
 Renal failure is especially a risk if the patient is also
concomitantly taking an ACE inhibitor and a diuretic.
NSAIDs are excreted by kidneys.
 c
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‘ 

  
2
 2he acidic molecules directly irritate the gastric mucosa
mucosa,,
 Inhibition of Cu -1 reduces the levels of protective prostaglandins
prostaglandins..
Inhibition of prostaglandin synthesis in the GI tract causes

Increased gastric acid secretion,

Diminished bicarbonate secretion,
Diminished mucous secretion and
Diminished trophic effects on epithelial mucosa.

 Risk of ulceration increases with duration of therapy, and with higher doses.
In attempting to minimise GI ADRs, it is prudent to use the lowest effective
dose for the shortest period of time, a practice which studies show is not
often followed.
 Recent studies show that over 50% of patients taking NSAIDs have
sustained damage to their small intestine.
 ‘
%&'


 Nausea,
 Dyspepsia,
 Vomiting,
 Diarrhea
 A burning, bloated feeling in the pit of the
stomach,
 Gastric ulceration/bleeding.
 2o help protect the stomach, NSAIDs should
always be taken with food or directly after a
meal.
 
  c
 ()#
 Indomethacin, ketoprofen and piroxicam appear to have the highest
Indomethacin,
prevalence of gastric ADRs, while ibuprofen (lower doses) and
Diclofenac appear to have lower rates.

 Certain NSAIDs, such as aspirin, have been marketed in enteric

enteric--
coated formulations which are claimed to reduce the incidence of
gastrointestinal ADRs. However, in consideration of the mechanism
of such ADRs and indeed in clinical practice, these formulations
have not been shown to have a reduced risk of GI ulceration.

 Commonly, gastrointestinal adverse effects can be reduced through

suppressing acid production, by concomitant use of a proton pump
inhibitor,, e.g. omeprazole
inhibitor omeprazole,, esomeprazole
esomeprazole;; or the prostaglandin
analogue misoprostol
misoprostol.. Misoprostol is itself associated with a high
incidence of gastrointestinal ADRs (diarrhea).
 #$

!*  

 NSAIDs can also cause extreme allergic reactions.

 People with asthma are at a higher risk for experiencing
serious allergic reaction to NSAIDs.
 Patients with asthma, sinusitis and nasal polyps should
stay away from NSAIDS.
 Allergy with one NSAIDS predisposes to allergy to others
also.
 Use of aspirin in children and teenagers with chicken pox
or influenza has been associated with the development
of Reyes's syndrome. Please stop using brufen syrups.
 #$*  #%
#
"!
  
 2he mechanism of these renal ADRs is due to changes in renal
haemodynamics (blood flow), ordinarily mediated by prostaglandins,
which are affected by NSAIDs.
 Prostaglandins normally cause vasodilation of the afferent arterioles
of the glomeruli
glomeruli.. 2his helps maintain normal glomerular perfusion
and glomerular filtration rate (GFR), an indicator of renal function.
function.
 2his is particularly important in renal failure where the kidney is
trying to maintain renal perfusion pressure by elevated angiotensin
II levels. At these elevated levels, angiotensin II also constricts the
afferent ateriole into the glomerulus in addition to the efferent
arteriole one it normally constricts. Prostaglandins serve to dilate
the afferent arteriole; by blocking this prostaglandin-
prostaglandin-mediated
effect, particularly in renal failure, NSAIDs cause unopposed
constriction of the afferent arteriole and decreased renal perfusion
pressure.
 
*  #+ 
#
 
"   "#$
 Salt and fluid retention
 Hypertension (high blood pressure)
 2hese agents may also cause renal impairment, especially in
combination with other nephrotoxic agents. Renal failure is
especially a risk if the patient is also concomitantly taking an ACE
inhibitor and a diuretic - the so-
so-called "triple whammy" effect.
 In rarer instances NSAIDs may also cause more severe renal
conditions:
 Interstitial nephritis
 Nephrotic syndrome
 Acute renal failure
 Acute tubular necrosis
 NSAIDs in combination with excessive use of phenacetin and/or
paracetamol may lead to analgesic nephropathy.
nephropathy.
 #$@ %

 Photosensitivity is a commonly overlooked adverse effect

of many of the NSAIDs. It is somewhat ironic that these
anti--inflammatory agents may themselves produce
anti
inflammation in combination with exposure to sunlight.
2he 2-2-arylpropionic acids have proven to be the most
likely to produce photosensitivity reactions, but other
piroxicam,,
NSAIDs have also been implicated including piroxicam
diclofenac and benzydamine
benzydamine..
 hile ibuprofen is somewhat of an exception, having
weak absorption, it has been reported to be a weak
photosensitising agent.
 ‘
‘
 
 NSAIDs are not recommended during pregnancy, particularly during the
third trimester.
trimester.

 hile NSAIDs as a class are not direct teratogens

teratogens,, they may cause
premature closure of the fetal ductus arteriosus

 and renal ADRs in the fetus.

 premature birth.
birth.

 Aspirin, however, is used together with heparin in pregnant women with

antiphospholipid antibodies.
antibodies.

 In contrast, paracetamol (acetaminophen) is regarded as being safe and

well--tolerated during pregnancy. Doses should be taken as prescribed, due
well
to risk of hepatotoxicity with overdoses.
 ‘
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 Raised liver enzymes,
 Headache,
 Dizziness.
J  
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 !
 Hyperkalaemia,
 Confusion,
 `ronchospasm
 Rash.
 Rapid and severe swelling of the face and/or body.
 Ibuprofen may also rarely cause irritable bowel syndrome symptoms.
 In very rare cases, ibuprofen can cause aseptic meningitis.
 % 
  


!
NSAIDs
 


!
NSAIDs are never to be used in
individuals with Inflammatory `owel Disease (e.g., Crohn's Disease or
Ulcerative Colitis)
Colitis) due to their tendency to cause gastric bleeding and form
ulceration in the gastric lining. Pain relievers such as paracetamol or drugs
containing codeine (which slows down bowel activity) are safer medications
for pain relief in I`D.
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 Allergy to aspirin or any NSAID

 Aspirin should not be used under the age of 16 years
 Chronic liver and kidney diseases
 During pregnancy
 During breast feeding
 un blood thinning agents (anticoagulants)
 Suffering from coagulation disorder.
 Active peptic ulcer
 
 
 

 Combination with quinolones may increase the risk for convultions and
other CNS affacts.
 NSAIDs may rarely cause hypo or hyperglycemia.
 ACE Inhibitors (eg. `enazepril Hydrochloride)ModerateMay decrease
antihypertensive and natriuretic effectsMonitor blood pressure and
cardiovascular function
 ProbenecidModerateMay result in reversal of the uricosuric effects of the
other drugAvoid concurrent use of high-
high-dose aspirin with probenecid
 LithiumModerateMay increase lithium plasma levels and decrease its
clearance renallyMonitor for lithium toxicity
 arfarinModerateMay result in an increased risk of bleedingMonitor P2
(prothrombin time) and INR (international normalized ratio)
 MethotrexateSevereMay result in increased risk of methotrexate toxicityDu
Nu2 administer NSAIDs within 10 days of high dose methotrexate
Ô
(Y
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(Y 



 hile it was hoped that this Cu -2
selectivity would reduce gastrointestinal
adverse drug reactions (ADRs), there is
little conclusive evidence that this is true.
 Ã 
 
   
   
  

   





     
  


ñ

 Y ,
ñ

  , professor of clinical epidemiology and general practice
practice1,
1, Y 
Y ,
, senior lecturer in
medical statistics1,
statistics1, 
0 ,
, professor of clinical epidemiology
epidemiology2
2

`MJ 2005;330 (11 June), doi:10.1136/bmj.330.7504.0-

doi:10.1136/bmj.330.7504.0-c

Y 
  No consistent evidence was found of
enhanced safety against gastrointestinal events
with any of the new cyclo-
cyclo-oxygenase-
oxygenase-2 inhibitors
compared with non-
non-selective non-
non-steroidal anti-
anti-
inflammatory drugs. 2he use of ulcer healing
drugs reduced the increased risk of adverse
gastrointestinal outcomes with all groups of non-
non-
steroidal anti-
anti-inflammatory drugs, but for
diclofenac the increased risk remained
significant.
 
 
     
  


  




 


 

 !
!

 

  
1
2  ,, clinical research fellow
 
1
2   fellow1,
1, Y 
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,  , reader in clinical epidemiology
epidemiology1,
1, ñ 
* ,
, research fellow
fellow1,
1,
   

,, research assistant
   

assistant1,
1, ñ  

+ 
,
, senior statistician
statistician1,
1, Y
   , professor of pharmacology
pharmacology22

 






 Selective Cu 2 inhibitors are associated with a moderately

increased risk of vascular events, largely attributable to a twofold
increased risk of myocardial infarction
 High dose regimens of some traditional NSAIDs, such as diclofenac
and ibuprofen, but not high dose naproxen, are associated with a
similar excess risk of vascular events
 2he choice between different anti-
anti-inflammatory regimens requires
assessment of the individual expected absolute attributable risks of
cardiovascular and serious gastrointestinal events
 J

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 In patients with acute renal colic, non-
non-steroidal
anti--inflammatory drugs ("#$%&

anti ("#$%&
)) should be
the drug treatment of choice. Reviewing 20 trials
including 1613 patients with renal colic,
Holdgate and Pollock (p(p 1401)
1401) found that
patients taking non-
non-steroidal anti-
anti-inflammatory
drugs had slightly less pain and were less likely
to need additional analgesia than those taking
opioids. 2hose taking opioids were more likely to
have vomiting or other adverse events.
 2able 2: Conversion Dosing Guide for Chronic NSAID 2herapy* NSAID
Agent
 0 
&

1 
&



1
&

Salsalate


Salsalate 500-
500-750mg bid
750mg tid 1000mg tid Fenoprofen 200-
200-300mg qid 600mg tid
tid--qid †00mg
qid Flubriprofen 50mg bid 50mg tid-
tid-qid 100mg tid Ibuprofen 400mg tid
600mg tid-
tid-qid †00mg qid** Ketoprofen 25-
25-50mg tid 75mg tid IR
=300mg/day (divide), SR =200mg/day Naproxen 250mg tid 500mg bid
1250mg/day (divided) Naproxen sodium 275mg tid 550mg bid
1375mg/day (divided) uxaprozin 600mg qd 1200mg qd 1200mg qd
Diclofenac potassium 50mg bid 50mg tid 50mg qid (in uA/RA only)
Diclofenac sodium 50mg bid 75mg bid 50mg qid or 100mg SR bid (in RA
only) Etodolac 200mg tid 400mg bid 1200mg max (IR or SR divided
doses) Sulindac 150mg bid 200mg bid 200g bid Piroxicam 10mg qd
20mg qd 40mg per day (not indicated for uA or RA) Nabumetone
1000mg qd 1000mg bid 2000mg/day (qd or divided bid)
Meloxicam/Mobic # 7.5mg qd 7.5mg qd 15mg qd
Celecoxib/Celebrex # 200mg qd 200mg bid 200mg bid
Rofecoxib/Vioxx # 12.5mg qd 25mg qd 50mg qd for max of 5 days
(acute pain) Valdecoxib/`extra # 10mg qd 10mg qd 20mg bid (primary
dysmenorrhea only)
Drug Low dose Med Dose Max dose
Fenoproen 200-300 mg qid 750 mg tid 1000 mg tid

Flubriprofen 50 mg bid 50 mg tid or qid 100 mg tid

Ibuprofen 400 mg tid 600 mg tid or qid †00 mg qid
Naproxen 250 mg tid 500 mg bid 1250 mg/day
uxaprozin 600 mg qd 1200 mg qd 1200 mg qd
Diclofenac Na 50 mg bid 75 mg bid 50 mg qid or 100
mg bid
Diclofenac K 50 mg bid 50 mg tid 50 mg qid or 100
mg bid
Etodlac 200 mg tid 400 mg tid 1200 mg/day
Sulindac 150 mg bid 200 mg bid 200 mg bid
Piroxicam 10 mg qd 20 mg qd 40 mg qd
Meloxicam 7.5 mg qd 7.5 mg qd 15 mg qd
Aceclofenac 100 mg bid 100 mg bid
Celecoxib 200 mg qd 200 mg bid 200 mg bid
 #"u
@ " 
 2he selection of a specific formulation of
diclofenac is important because only one of the
available formulations (sodium or potassium
salts ) of diclofenac provides prompt relief
(potassium formulation), a characteristic
essential in the management of acute pain.
 Efficacy has been demonstrated with
postoperative pain including gynecologic, oral,
and orthopedic surgery models, as well as
dysmenorrhea.
 hat is the most powerful analgesic?
 ‘

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 is a unique NSAID, not only
because of its many uses, but because it
is the only NSAID that is able to inhibit the
clotting of blood  

   
  

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8

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. 2his prolonged effect of
aspirin makes it an ideal drug for
preventing the blood clots that cause
heart attacks and strokes. 1

 

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 Aceclofenac is well tolerated, with most adverse events being minor
and reversible and affecting mainly the GI system. Most common
events include dyspepsia (7.5%), abdominal pain (6.2%), nausea
(1.5%), diarrhea (1.5%), flatulence (0.†%), gastritis (0.6%),
constipation (0.5%), vomiting (0.5%), ulcerative stomatitis (0.1%),
pancreatitis (0.1%).
 uther adverse effect, which is not common such as dizziness (1%),
vertigo (0.3%), and rare cases: par aesthesia and tremor.
 It is probably best,even better than meloxicam, as a cartilage
protector, delaying cartilage damage in usteo
usteo--arthritis.
 

 It is an NSAID which has mixed qualities, in between non- non-selective and
Cox--2 inhibitors.
Cox
 It does not inhibit Cox-
Cox-1 as strongly as other non
non--selective NSAIDs so it has
few GI2 side effects. Still it canMeloxicam use can result in gastrointestinal
toxicity and bleeding, tinnitus
tinnitus,, blinding headaches, rash, very dark or black
stool (sign of intestinal bleeding).
 It is as good as other NSAIDs for pain reduction.
 Meloxicam may also have a cardio protective role: in patients with acute
coronary syndrome without S2- S2-segment elevation, a lower incidence of
cardiovascular events was observed in those who received meloxicam plus
aspirin and heparin versus aspirin and heparin alone, both during coronary
care stay and at 90-
90-day follow-
follow-up.
 It has protective role in usteoarthritis, for delaying cartilage damage.
 Although meloxicam does inhibit thromboxane A, it does not appear to do
so at levels that would interfere with platelet function.
 


 "
 is a relatively Cu -2 selective,
selective, non
non--
steroidal anti-
anti-inflammatory drug (NSAID) with analgesic
and antipyretic properties.
 Its approved indications are the treatment of acute pain,
the symptomatic treatment of osteoarthritis and primary
dysmenorrhoea in adolescents and adults above 12
years old. Due to concerns about the risk of
hepatotoxicity,, nimesulide has been withdrawn from
hepatotoxicity
market in many countries.
 2he drug has certain side effects, that can affect
individuals in different ways. 2he following are some of
the side effects, that are often associated with the
drug:Diarrhoea, Vomiting, Skin rash, Pruritis, Dizziness,
Headache
 

 Most powerful NSAIDs
 Diclofenac may also be a unique member of the NSAIDs NSAIDs.. 2here is some
evidence that diclofenac inhibits the lipoxygenase pathways,[
pathways,[citation
citation
needed]] thus reducing formation of the leukotrienes (also pro-
needed pro-inflammatory
speculation[by whom?]
autacoids). 2here is also speculation[by whom?] that diclofenac may inhibit
phospholipase A2 as part of its mechanism of action.[citation
action.[citation needed]
needed]
2hese additional actions may explain the high potency of diclofenac ƛ it is
basis.[citation needed]
the most potent NSAID on a broad basis.[citation needed]
 Diclofenac has a low to moderate preference to block the Cu 2 2--isoenzyme
(approximately 10-
10-fold) and is said to have therefore a somewhat lower
incidence of gastrointestinal complaints than noted with indomethacin and
aspirin..
aspirin
 Causes less gastric irritation than Piroxicam, Naproxin, Indomethacin, but
more than ibuprofen
 Available as u2C in many counteries
 Is neutral for cartilage
 Can be given by all routes
 Diclofenac potassium is estabished as fast reliever of pain; within minutes
 Diclofenac has been found to be effective against all strains of multi drug resistant E.
coli, with a MIC of 25 micrograms/mL. 2herefore, it may be suggested that diclofenac
has the capacity to treat uncomplicated urinary tract infections (U2I) caused by E.
coli..[6] It has also been shown to be effective in treating Salmonella infections in
coli
mice[7]
mice [7] and is under investigation for the treatment of tuberculosis.[†]
tuberculosis.[†]
 Diclofenac is an antiuricosuric
 Diclofenac may prevent the development of Alzheimer's disease if given daily in small
doses during many years.
 ver due to malignant lymphogranulomatosis (Hodgkin's
(Hodgkin's lymphoma)
lymphoma) often responds to
diclofenac.
 In many countries[where?
countries[where?]] eye-
eye-drops are sold to treat acute and chronic non-
non-
bacterial inflammations of the anterior part of the eyes (e.g. postoperative
citation needed]
states).[citation
states).[ needed] A common brand name is Voltaren-
Voltaren-ophta.
 An external, gel-
gel-based formulation containing 3% of diclofenac (Solaraze) is available
for the treatment of facial actinic keratosis which is caused by over-
over-exposure to
sunlight. Some countries have also approved the external use of diclofenac 1% gel to
treat musculoskeletal conditions