Willow bark, which contains salicylic acid, has been used for centuries to relieve pain and fever. Aspirin was the first drug classified as a nonsteroidal anti-inflammatory drug (NSAID) when it was introduced in 1899. NSAIDs work by inhibiting the cyclooxygenase (COX) enzymes and reducing the production of prostaglandins involved in pain and inflammation. Aspirin irreversibly inhibits both COX-1 and COX-2 enzymes, while most other NSAIDs reversibly inhibit both or selectively inhibit COX-2. Common adverse effects of NSAIDs include gastrointestinal issues like dyspepsia, diarrhea and bleeding. In high doses, aspirin can also cause

1. 11
Dr D.Rajesh;M.D.Dr D.Rajesh;M.D.
RIMS ONGOLERIMS ONGOLE
NSAIDsNSAIDs

2. HISTORY OF NSAIDSHISTORY OF NSAIDS
22
 Willow bark (salix alba)Willow bark (salix alba) had been used for manyhad been used for many
centuries.centuries.
 Salicylic acid was prepared by hydrolysis of bitterSalicylic acid was prepared by hydrolysis of bitter
glycoside obtained from this plant.glycoside obtained from this plant.
 Sodium salicylateSodium salicylate was used for fever and pain inwas used for fever and pain in 1875.1875.
Its great success led to the introduction ofIts great success led to the introduction of
acetylsalicylic acid (aspirin) in 1899.acetylsalicylic acid (aspirin) in 1899.
 Phenylbutazone in 1949.Phenylbutazone in 1949.
 Indomethacin - 1963Indomethacin - 1963

3. CLASSIFICATION OF NSAIDsCLASSIFICATION OF NSAIDs
1. NON SELECTIVE IRREVERSIBLE1. NON SELECTIVE IRREVERSIBLE
INHIBITORS OF COX (COX-1> COX-2)INHIBITORS OF COX (COX-1> COX-2)
 Aspirin (Acetylsalicylic acid)Aspirin (Acetylsalicylic acid)
 Sodium salicylateSodium salicylate
 SulfasalazineSulfasalazine
 OlsalazineOlsalazine
 Methyl salicylateMethyl salicylate
33

4. 2.NONSELECTIVE REVERSIBLE2.NONSELECTIVE REVERSIBLE
INHIBITORS OF COX (COX-1 = COX-2)INHIBITORS OF COX (COX-1 = COX-2)
1.1. Propionic acid derivativesPropionic acid derivatives:: Ibuprofen,Ibuprofen,
Naproxen, Ketoprofen,Flurbiprofen.Naproxen, Ketoprofen,Flurbiprofen.
2.2. Anthranilic acid derivatives:Anthranilic acid derivatives: MephenamicMephenamic
acidacid
3.3. Aryl-acetic acid derivatives:Aryl-acetic acid derivatives: Diclofenac,Diclofenac,
Aceclofenac.Aceclofenac.
4.4. Oxicam derivatives:Oxicam derivatives: Piroxicam, Tenoxicam.Piroxicam, Tenoxicam.
5.5. Pyrrolo-pyrrole derivative:Pyrrolo-pyrrole derivative: Ketorolac.Ketorolac.
6.6. Indole derivative:Indole derivative: Indomethacin.Indomethacin.
7.7. Pyrazolone derivatives:Pyrazolone derivatives: Phenylbutazone,Phenylbutazone,
Oxyphenbutazone.Oxyphenbutazone. 44

5. 3.PREFERENTIAL COX-2 INHIBITORS (103.PREFERENTIAL COX-2 INHIBITORS (10
TO 20 FOLD COX-2 SELECTIVE)TO 20 FOLD COX-2 SELECTIVE)
 NimesulideNimesulide
 MeloxicamMeloxicam
 EtodolacEtodolac
 NabumetoneNabumetone
4.SELECTIVE COX-2 INHIBITORS4.SELECTIVE COX-2 INHIBITORS (>50(>50
FOLD COX-2 SELECTIVE)FOLD COX-2 SELECTIVE)
 RofecoxibRofecoxib
 CelecoxibCelecoxib
 ValdecoxibValdecoxib
 ParecoxibParecoxib
 EtoricoxibEtoricoxib 55

6. 5.COX-3 INHIBITOR (?)5.COX-3 INHIBITOR (?) OROR
REVERSIBLE INHIBITOR OFREVERSIBLE INHIBITOR OF
HYPOTHALAMIC COX-1HYPOTHALAMIC COX-1
 ParacetamolParacetamol
 Metamizol (Analgin)Metamizol (Analgin)
6.NSAIDS WHICH DO NOT6.NSAIDS WHICH DO NOT
INHIBIT PG SYNTHESISINHIBIT PG SYNTHESIS
 NefopamNefopam
 DiacerinDiacerin 66

7. 77
ASPIRIN (prototype)ASPIRIN (prototype)
 AspirinAspirin was thewas the firstfirst discovereddiscovered
member of the class of drugs known asmember of the class of drugs known as
NSAIDNSAID
 STRUCTURESTRUCTURE

8. 1515
 The brand nameThe brand name AspirinAspirin waswas
coined by thecoined by the BayerBayer
company ofcompany of GermanyGermany
 The name "aspirin" isThe name "aspirin" is
composed ofcomposed of aa- (from the- (from the
acetylacetyl group) -group) -spirspir- (from- (from
thethe spiraeaspiraea flower) and -flower) and -inin
(a common(a common endingending for drugsfor drugs
at the time).at the time).

9. 99

10. 1010

11. AnalgesiaAnalgesia
 Unlike opioid analgesics , produceUnlike opioid analgesics , produce relief ofrelief of
pain without hypnosispain without hypnosis or impairment ofor impairment of
mental activitymental activity
 AspirinAspirin inhibits biosynthesis of PGsinhibits biosynthesis of PGs
(PGI2 &PGE2) by(PGI2 &PGE2) by irreversibleirreversible
acetylation & inactivation of COXacetylation & inactivation of COX
 Other NSAIDs cause reversible inhibitionOther NSAIDs cause reversible inhibition1111

12. 
By inhibiting PG synthesis,By inhibiting PG synthesis, blocksblocks painpain
sensitizingsensitizing mechanisms induced bymechanisms induced by
Bradykinin, TNF-Bradykinin, TNF-αα & IL& IL
 Relieves integumental pain associatedRelieves integumental pain associated
with inflammation & tissue injurywith inflammation & tissue injury
 Ineffective inIneffective in severesevere visceralvisceral painpain
1212

13. Anti-inflammatory effect (3-6 gm/day)Anti-inflammatory effect (3-6 gm/day)

Action is due toAction is due to inhibition of PG synthesisinhibition of PG synthesis
 Decrease in vasodilator PGs (PGE2 & PGI2)Decrease in vasodilator PGs (PGE2 & PGI2)----------
means lesser vasodilation & indirectlymeans lesser vasodilation & indirectly lesser edemalesser edema
 Inhibition of neutrophil aggregationInhibition of neutrophil aggregation and activation.and activation.

AlsoAlso stabilizes leukocyte lysosomal membranestabilizes leukocyte lysosomal membrane &&
increases the resistance of connective tissueincreases the resistance of connective tissue
mucopolysaccarides to prevent the spread ofmucopolysaccarides to prevent the spread of
inflammationinflammation
1313

14. Inhibition of platelet aggregationInhibition of platelet aggregation
 TXA2 increasesTXA2 increases, while, while PGI2 decreasesPGI2 decreases platelet aggregationplatelet aggregation
 Aspirin irreversibly inactivates COX1Aspirin irreversibly inactivates COX1
(Should reduce both TXA2 synthesis in platelets & PGI2(Should reduce both TXA2 synthesis in platelets & PGI2
synthesis in vascular endothelium)synthesis in vascular endothelium)

But ifBut if low doseslow doses (75-150mg) are used,(75-150mg) are used, inhibits TXA2inhibits TXA2
production in plateletsproduction in platelets (By inhibiting COX1 of platelets) for(By inhibiting COX1 of platelets) for
their total life span of 7 daystheir total life span of 7 days
 Because platelets lack nuclei & can not synthesize COXBecause platelets lack nuclei & can not synthesize COX
1414

15.  SuchSuch smallsmall dosesdoses does not effectdoes not effect
PGI2 synthesisPGI2 synthesis in the widelyin the widely
distributed vascular endotheliumdistributed vascular endothelium
 Consequently low doses of aspirinConsequently low doses of aspirin
given intermittently are sufficient togiven intermittently are sufficient to
decrease synthesis of TXA2 withoutdecrease synthesis of TXA2 without
drastically reducing PGI2 synthesisdrastically reducing PGI2 synthesis
1515

16. RespirationRespiration
 Therapeutic dosesTherapeutic doses of salicylatesof salicylates ↑ consumption of oxygen↑ consumption of oxygen
by skeletal muscles leading toby skeletal muscles leading to ↑production of co2↑production of co2 whichwhich
directlydirectly stimulates respiratorystimulates respiratory centre.centre.
 AlsoAlso stimulates resp centrestimulates resp centre directly. This causesdirectly. This causes
hyperventilation, washing out of plasma co2 resulting inhyperventilation, washing out of plasma co2 resulting in
resp alkalosis.resp alkalosis.
 Resp alkalosis is countered by excretion of alkaline urineResp alkalosis is countered by excretion of alkaline urine
containing bicarbonate along with sodium and potassium.containing bicarbonate along with sodium and potassium.
 WithWith acute toxic dosesacute toxic doses of salicylates,of salicylates, resp centreresp centre isis
depresseddepressed leading toleading to metabolic acidosis.metabolic acidosis.

17. Gastrointestinal tractGastrointestinal tract
 Dyspepsia, nausea and vomiting due to gastricDyspepsia, nausea and vomiting due to gastric
irritation. May lead to ulceration, haemorrhage andirritation. May lead to ulceration, haemorrhage and
iron deficiency anaemiairon deficiency anaemia..

18. Anaphylactoid reactionsAnaphylactoid reactions
 Precipitates asthmaPrecipitates asthma,, angioneurotic swellingsangioneurotic swellings,,
urticariaurticaria oror rhinitisrhinitis in certain susceptiblein certain susceptible
individuals.individuals.
 Inhibition of COX with consequent diversionInhibition of COX with consequent diversion
of arachidonic acid to LTs and other productsof arachidonic acid to LTs and other products
of lipoxygenase pathway may be involved.of lipoxygenase pathway may be involved.

19. Uricosuric effectsUricosuric effects
 InIn Small dosesSmall doses (1-2 gm per day),aspirin interferes(1-2 gm per day),aspirin interferes
with urate secretion by distal tubule andwith urate secretion by distal tubule and elevateelevate
plasma uric acidplasma uric acid level. Block the action of otherlevel. Block the action of other
uricosuric drugs like probenecid.uricosuric drugs like probenecid.
 InIn larger doseslarger doses (over 5 gms per day), inhibit(over 5 gms per day), inhibit
reabsorption of urate by proximal tubule which canreabsorption of urate by proximal tubule which can
causecause uricosuriauricosuria..

20. Cardiovascular systemCardiovascular system
NoNo deleteriousdeleterious effectseffects but NSAID users may showbut NSAID users may show
rise in BP due to retention of sodium and water.rise in BP due to retention of sodium and water.
Hepatic and renal effectsHepatic and renal effects
 Affect renal function in compromised kidneys byAffect renal function in compromised kidneys by
inhibitinginhibiting COX-1COX-1..
 Large dosesLarge doses particularly in children can causeparticularly in children can cause
hepatic damage and necrosishepatic damage and necrosis..

21. 2121
Aspirin - PharmacokineticsAspirin - Pharmacokinetics
 Rapidly absorbedRapidly absorbed from GI tract through passive diffusionfrom GI tract through passive diffusion
 Distributed throughout most body tissuesDistributed throughout most body tissues
 80-90%80-90% is bound to plasma proteins, mainlyis bound to plasma proteins, mainly albuminalbumin
 Can displace several other drugs from plasma protein resultingCan displace several other drugs from plasma protein resulting
in higher effective plasma concentrationsin higher effective plasma concentrations

Rapidly hydrolyzed in blood and liver toRapidly hydrolyzed in blood and liver to salicyclic acidsalicyclic acid
 Inactivation occurs mainly in the hepatic ER and mitochondriaInactivation occurs mainly in the hepatic ER and mitochondria
and is mainly through the formation ofand is mainly through the formation of conjugatesconjugates that arethat are
excreted in the urineexcreted in the urine..

22. ADVERSE EFFECTSADVERSE EFFECTS
Gastrointestinal tract:Gastrointestinal tract:
 AspirinAspirin inhibits COX-Iinhibits COX-I andand nullifies gastronullifies gastro
protective effects of PGsprotective effects of PGs (PGE2 & PGI2 inhibit(PGE2 & PGI2 inhibit
gastric acid secretion , stimulate mucus andgastric acid secretion , stimulate mucus and
bicarbonate formation & dilates mucosalbicarbonate formation & dilates mucosal
blood vessels)blood vessels)
 Dyspepsia, diarrhea, nausea vomiting, gastricDyspepsia, diarrhea, nausea vomiting, gastric
bleeding & ulcerationbleeding & ulceration

OccasionallyOccasionally HaematemesisHaematemesis (15/100000)(15/100000) 2222

23. Adverse effectsAdverse effects
 Side effectsSide effects that occur at analgesic dose (0.3- 1.5 g /that occur at analgesic dose (0.3- 1.5 g /
day)are nausea, vomiting, epigastric distress, increasedday)are nausea, vomiting, epigastric distress, increased
occult blood loss in stools. Gastric mucosal damageoccult blood loss in stools. Gastric mucosal damage
and peptic ulceration.and peptic ulceration.
Hypersensitivity and idiosyncrasy-Hypersensitivity and idiosyncrasy- infrequent,infrequent,
these can be serious rashes, fixed drug eruption,these can be serious rashes, fixed drug eruption,
urticaria, rhinorrhoea, angioedema, asthma andurticaria, rhinorrhoea, angioedema, asthma and
anaphylactoid reaction.anaphylactoid reaction.

24.  Antiinflammatory doses (3 – 5g / day)Antiinflammatory doses (3 – 5g / day) produce theproduce the
syndrome calledsyndrome called salicylismsalicylism – dizziness , tinnitus, vertigo,– dizziness , tinnitus, vertigo,
reversible impairment of hearing and vision, excitementreversible impairment of hearing and vision, excitement
and mental confusion, hyperventilation and electrolyteand mental confusion, hyperventilation and electrolyte
imbalance.imbalance.
 Aspirin therapyAspirin therapy in childrenin children with rheumatoid arthritis haswith rheumatoid arthritis has
been found tobeen found to raise serum tranasaminasesraise serum tranasaminases, indicating liver, indicating liver
damage. Most cases aredamage. Most cases are asymptomaticasymptomatic but it is potentiallybut it is potentially
dangerous.dangerous.
 In adults also long term therapy with high dose aspirin canIn adults also long term therapy with high dose aspirin can
cause insidious onset hepatic injury.cause insidious onset hepatic injury.

25. Acute salicylate poisoningAcute salicylate poisoning It is more common inIt is more common in
children.children.
Fatal dose in adults is estimated to beFatal dose in adults is estimated to be 15 – 30g15 – 30g but isbut is
considerably lower in children. Serious toxicity is seen atconsiderably lower in children. Serious toxicity is seen at
serum salicylate levelsserum salicylate levels > 50 mg / dl> 50 mg / dl
Manifestations are :Manifestations are :
Vomiting, dehydration, electrolyte imbalance, acidoticVomiting, dehydration, electrolyte imbalance, acidotic
breathing, petechial haemorrhages, restlessness, delirium,breathing, petechial haemorrhages, restlessness, delirium,
hallucination, hyperpyrexia, convulsions, coma and deathhallucination, hyperpyrexia, convulsions, coma and death
due to respiratory failure + cardiovascular collapse.due to respiratory failure + cardiovascular collapse.

26. PRINCIPLES OF MANAGEMENT OFPRINCIPLES OF MANAGEMENT OF
SALICYLATE POISONINGSALICYLATE POISONING
 HospitalizationHospitalization
 Activated charcoal 50gm orallyActivated charcoal 50gm orally
 Correct hyperthermia, dehydration (5%Correct hyperthermia, dehydration (5%
dextrose), hypokalemia, acid base disturbancesdextrose), hypokalemia, acid base disturbances
& ketosis& ketosis
 Increase elimination by alkalinization,Increase elimination by alkalinization,
peritoneal dialysis or haemoperfusionperitoneal dialysis or haemoperfusion
 Vit.K, blood transfusionVit.K, blood transfusion
 Exchange transfusion in very small childrenExchange transfusion in very small children
2626

27. Reye's syndromeReye's syndrome
 A rare disorder ofA rare disorder of childrenchildren that isthat is
characterised bycharacterised by hepatichepatic
encephalopathyencephalopathy following anfollowing an
acute viral illness and a 20-40%acute viral illness and a 20-40%
mortality.mortality.
 Since the withdrawal of aspirinSince the withdrawal of aspirin
for pediatrics use in the UK, thefor pediatrics use in the UK, the
incidence of Reye's syndromeincidence of Reye's syndrome
has fallen dramaticallyhas fallen dramatically

28. Uses:Uses:
 Anti-inflammatory 3-6 g/dayAnti-inflammatory 3-6 g/day
 Analgesic – 300 to 600mg 6 to 8 hrlyAnalgesic – 300 to 600mg 6 to 8 hrly
 AntipyreticAntipyretic
 Acute rheumatic fever – 75 to 100 mg/kg /dayAcute rheumatic fever – 75 to 100 mg/kg /day
 Rheumatoid arthritis- 3-6 g/dayRheumatoid arthritis- 3-6 g/day
 OsteoarthritisOsteoarthritis
 Post myocardial infarction and post stroke patients -Post myocardial infarction and post stroke patients -
75-150 mg/day75-150 mg/day

29. Aspirin-Miscellaneous usesAspirin-Miscellaneous uses
1.1. Colonic and rectal cancerColonic and rectal cancer
2.2. Pre-eclampsiaPre-eclampsia
3.3. Alzheimer’s diseaseAlzheimer’s disease
4.4. Familial colonic polyposisFamilial colonic polyposis
5.5. Niacin induced cutaneousNiacin induced cutaneous
flush and pruritisflush and pruritis
6.6. To slowdown cataractTo slowdown cataract
progressionprogression
2929

30. Aspirin contraindicationsAspirin contraindications
 Peptic ulcerPeptic ulcer
 Children suffering fromChildren suffering from
chickenpox &influenzachickenpox &influenza
 Chronic liver diseaseChronic liver disease
 Should be stopped 1 weekShould be stopped 1 week
before elective surgerybefore elective surgery
 PregnancyPregnancy
 Breastfeeding mothersBreastfeeding mothers
3030

31. INDOLE DERIVATIVESINDOLE DERIVATIVES
INDOMETHACININDOMETHACIN
It isIt is potent anti-inflammatorypotent anti-inflammatory drug withdrug with
prompt antipyretic. Relieves only inflammatoryprompt antipyretic. Relieves only inflammatory
or tissue injury related pain.or tissue injury related pain.
It is a highly potentIt is a highly potent inhibitor of PG synthesisinhibitor of PG synthesis
andand suppresses neutrophilsuppresses neutrophil motility.motility.
Adverse effects -Adverse effects -
Gastric irritation, nausea, anorexia, gastricGastric irritation, nausea, anorexia, gastric
bleeding and diarrhoea are prominent.bleeding and diarrhoea are prominent.
Frontal headache (very common), dizziness,Frontal headache (very common), dizziness,
ataxia, mental confusion, hallucination,ataxia, mental confusion, hallucination,
depression and psychosis can occur.depression and psychosis can occur.

32. Increased risk of bleeding due toIncreased risk of bleeding due to
decreased platelet aggregability.decreased platelet aggregability.
UsesUses
Because of prominent adverse effects,Because of prominent adverse effects,
indomethacin isindomethacin is used as a reserveused as a reserve drugdrug
in conditions requiring potent anti-in conditions requiring potent anti-
inflammatory action likeinflammatory action like ankylosingankylosing
spondylitisspondylitis, acute exacerbations of, acute exacerbations of
destructive arthropathies, psoriaticdestructive arthropathies, psoriatic
arthritisarthritis andand acute goutacute gout that are notthat are not
responding to better tolerated NSAIDs.responding to better tolerated NSAIDs.

33. PYRROLO-PYRROLE DERIVATIVESPYRROLO-PYRROLE DERIVATIVES
KETOROLACKETOROLAC
A novel NSAID withA novel NSAID with potent analgesicpotent analgesic andand modest anti-modest anti-
inflammatoryinflammatory activity.activity.
Adverse effectsAdverse effects-Nausea, abdominal pain,-Nausea, abdominal pain,
dyspepsia, ulceration, loose stools, drowsiness,dyspepsia, ulceration, loose stools, drowsiness,
headache, dizziness, nervousness, pruritus, painheadache, dizziness, nervousness, pruritus, pain
at injection site, rise in serum transaminase andat injection site, rise in serum transaminase and
fluid retention have been noted.fluid retention have been noted.
Uses:Uses: postoperative, dental and acutepostoperative, dental and acute
musculoskeletal pain, renal colic, migraine andmusculoskeletal pain, renal colic, migraine and
pain due to bony metastasispain due to bony metastasis

34. ANTHRANILIC ACID DERIVATIVEANTHRANILIC ACID DERIVATIVE
MEPHENAMIC ACIDMEPHENAMIC ACID
 An analgesic, antipyretic with potentAn analgesic, antipyretic with potent
anti-inflammatory actionanti-inflammatory action
 DiarrhoeaDiarrhoea is the most important doseis the most important dose
related side effectrelated side effect
 Haemolytic anaemia is a rare butHaemolytic anaemia is a rare but
serious complicationserious complication
 Used primarily as analgesic in muscle,Used primarily as analgesic in muscle,
joint and soft tissue pain where strongjoint and soft tissue pain where strong
anti-inflammatory action is neededanti-inflammatory action is needed 3434

35. ARYL-ACETIC ACID DERIVATIVESARYL-ACETIC ACID DERIVATIVES
DICLOFENAC SODIUMDICLOFENAC SODIUM
It inhibits PG synthesis and is somewhat COX –It inhibits PG synthesis and is somewhat COX –
22 selective.selective.
The antiplatelet action is short lastingThe antiplatelet action is short lasting
Most extensively used NSAIDMost extensively used NSAID employed inemployed in
rheumatoid and osteoarthritis, bursitis,rheumatoid and osteoarthritis, bursitis,
ankylosing spondylitis, toothache,ankylosing spondylitis, toothache,
dysmenorrhoea, post – traumatic anddysmenorrhoea, post – traumatic and
postoperative inflammatory conditions affordspostoperative inflammatory conditions affords
quick relief of pain and wound edema.quick relief of pain and wound edema.
ACECLOFENAC-ACECLOFENAC-Congener of Diclofenac-longerCongener of Diclofenac-longer
actingacting

36. OXICAM DERIVATIVESOXICAM DERIVATIVES
PIROXICAMPIROXICAM
 Long acting potent NSAIDLong acting potent NSAID
 Anti-inflammatory efficacy similar toAnti-inflammatory efficacy similar to
IndomethacinIndomethacin
 Good analgesic-anti-inflammatoryGood analgesic-anti-inflammatory
actionaction
 Better tolerated than Indomethacin andBetter tolerated than Indomethacin and
aspirinaspirin
 Used inUsed in rheumatoid and osteo-arthritis,rheumatoid and osteo-arthritis,
ankylosing spondylitis, acute gout,ankylosing spondylitis, acute gout,
musculoskeletal injuries, dentistry,musculoskeletal injuries, dentistry,
episiotomy, dysmenorrhoea, etcepisiotomy, dysmenorrhoea, etc
3636

37. PREFERENTIAL COX-2 INHIBITORSPREFERENTIAL COX-2 INHIBITORS
(10-20 fold COX-II selective action)(10-20 fold COX-II selective action)
3737
NIMESULIDENIMESULIDE-has relative COX-2 selectivity-has relative COX-2 selectivity
• Instances of fulminant hepatic failure reportedInstances of fulminant hepatic failure reported
MELOXICAMMELOXICAM-newer-newer congener of Piroxicamcongener of Piroxicam
• Long actingLong acting can be given once dailycan be given once daily
• Gastric side effects are milder compared toGastric side effects are milder compared to
PiroxicamPiroxicam
• Used inUsed in osteo arthritisosteo arthritis andand rheumatoid arthritisrheumatoid arthritis
NABUMETONENABUMETONE -effective in the treatment of-effective in the treatment of
rheumatoid arthritis, osteo arthritis and softrheumatoid arthritis, osteo arthritis and soft
tissue injurytissue injury

38. COX-2 selective inhibitorsCOX-2 selective inhibitors
 TheyThey selectivelyselectively bind to andbind to and blockblock the active site ofthe active site of COX-2COX-2
enzyme much more effectively than that of COX-1.enzyme much more effectively than that of COX-1.
 Have analgesic, antipyretic and and anti-inflammatoryHave analgesic, antipyretic and and anti-inflammatory
similar to that of non selective NSAIDS but with withsimilar to that of non selective NSAIDS but with with
lesser gastrointestinal side effects.lesser gastrointestinal side effects.
 COX-2 inhibitorsCOX-2 inhibitors at usual doses have been shown to haveat usual doses have been shown to have
no impact onno impact on platelet aggregationplatelet aggregation, which is mediated by, which is mediated by
thromboxane produced by the COX-1 isoenzyme.thromboxane produced by the COX-1 isoenzyme.

39.  InIn contrast,contrast, theythey do inhibit COX-2-mediateddo inhibit COX-2-mediated
prostacyclinprostacyclin synthesis in the vascularsynthesis in the vascular
endothelium. As a result, COX-2 inhibitorsendothelium. As a result, COX-2 inhibitors do notdo not
offer the cardioprotective effectsoffer the cardioprotective effects of traditionalof traditional
nonselective NSAIDs.nonselective NSAIDs.
 COX-2 is constitutively active within the kidney,COX-2 is constitutively active within the kidney,
recommended doses of COX-2 inhibitors causerecommended doses of COX-2 inhibitors cause
renal toxicities similar to those associated withrenal toxicities similar to those associated with
traditional NSAIDs.traditional NSAIDs.

40. CelecoxibCelecoxib
 Celecoxib is aCelecoxib is a selective COX-2selective COX-2 inhibitor—about 10–inhibitor—about 10–
20 times more selective for COX-2 than for COX-1.20 times more selective for COX-2 than for COX-1.
 Probably because it is a sulfonamide, celecoxib mayProbably because it is a sulfonamide, celecoxib may
cause rashes. It does not affect platelet aggregationcause rashes. It does not affect platelet aggregation
at usual doses.at usual doses.
 It is approved for use in osteoarthritis andIt is approved for use in osteoarthritis and
rheumatoid arthritisrheumatoid arthritis
 Dose: 110-200mg BDDose: 110-200mg BD

41. EtoricoxibEtoricoxib
 Highest COX – 2 selectivityHighest COX – 2 selectivity. It is suitable for one – a. It is suitable for one – a
day treatment of osteo / rheumatoid / acute goutyday treatment of osteo / rheumatoid / acute gouty
arthritis, dysmenorrhoea, acute dental surgery painarthritis, dysmenorrhoea, acute dental surgery pain
and similar conditions, without affecting plateletand similar conditions, without affecting platelet
functin or damaging gastric mucosa.functin or damaging gastric mucosa.
 The t ½ is ~24 hours. Side effects are dry mouth,The t ½ is ~24 hours. Side effects are dry mouth,
aphthous ulcers, taste disturbance and paresthesias.aphthous ulcers, taste disturbance and paresthesias.
 Dose: 60-90mg ODDose: 60-90mg OD

42. Paraaminophenol derivatives:Paraaminophenol derivatives: ParacetamolParacetamol
 Active metabolite of phenacetin. Came into use since 1950.Active metabolite of phenacetin. Came into use since 1950.
 Actions: The central analgesic action of paracetamol is likeActions: The central analgesic action of paracetamol is like
aspirin, i.e. it raises pain threshold, but has weak peripheralaspirin, i.e. it raises pain threshold, but has weak peripheral
anti-inflammatory component. Analgesic action of aspirinanti-inflammatory component. Analgesic action of aspirin
and paracetamol is additive.and paracetamol is additive.
 Paracetamol is a good and promptly acting antipyretic.Paracetamol is a good and promptly acting antipyretic.
 Negligible anti-inflammatory property.Negligible anti-inflammatory property.

43.  It is a poor inhibitor of PG synthesis in peripheralIt is a poor inhibitor of PG synthesis in peripheral
tissues, but more active on COX in the brain.tissues, but more active on COX in the brain.
 To inhibit COX – 3 (an isoenzyme ) could alsoTo inhibit COX – 3 (an isoenzyme ) could also
account for its analgesic antipyretic action.account for its analgesic antipyretic action.
 Paracetamol does not stimulate respiration or affectParacetamol does not stimulate respiration or affect
acid base balance .acid base balance .
 It has no effect on CVS.It has no effect on CVS.
 Gastric irritation is insignificant. Mucosal erosionGastric irritation is insignificant. Mucosal erosion
and bleeding occur rarely only in overdose.and bleeding occur rarely only in overdose.

44. Acute paracetamol poisoningAcute paracetamol poisoning
 In small children who have low hepatic glucuronideIn small children who have low hepatic glucuronide
conjugating ability.conjugating ability.
 If a large dose ( 150mg / kg or > 10g in an adult) is˃If a large dose ( 150mg / kg or > 10g in an adult) is˃
taken, serious toxicity can occur.taken, serious toxicity can occur.
Early manifestations areEarly manifestations are
nausea, vomiting, abdominal pain and liver tendernessnausea, vomiting, abdominal pain and liver tenderness
with no impairment of consciousness.with no impairment of consciousness.

45. After 12-18 hoursAfter 12-18 hours centrilobular hepatic necrosiscentrilobular hepatic necrosis
occurs which may be accompanied by renal tubularoccurs which may be accompanied by renal tubular
necrosis and hypoglycemia that may progress tonecrosis and hypoglycemia that may progress to
coma. Jaundice starts after 2 days.coma. Jaundice starts after 2 days.
Fulminating hepatic failure and death are likely ifFulminating hepatic failure and death are likely if
plasma levels exceed further.plasma levels exceed further.

46. Specific :Specific : N-acetylcysteineN-acetylcysteine:: 150 mg / kg should150 mg / kg should
be infused i.v. in 15 min, followed by 50-100 mg/kgbe infused i.v. in 15 min, followed by 50-100 mg/kg
slowly to total maximum of 300mg/kg in 20hrs.slowly to total maximum of 300mg/kg in 20hrs.
Uses -Uses - Analgesic mild migraineAnalgesic mild migraine
musculoskeletal pain, dysmenorrhoea,musculoskeletal pain, dysmenorrhoea,
As first choice analgesic .As first choice analgesic .
It is one of the best drugs to be used asIt is one of the best drugs to be used as
antipyretic, especially in children (no risk of Reye’santipyretic, especially in children (no risk of Reye’s
syndrome).syndrome).