NSAIDS USE IN DENTAL TREATMENT AND PROCEDURES

1. NSAIDS

2. •
•
Chemicallydiverse,butmost are organicacids
Groupedtogetheras these drugshave common analgesic
(pain reducing)and antipyretic (fever-reducing)effectsand
which have,in higher doses,anti-inflammatoryeffects
Donot depress CNS– no physical dependence or abuse
liability
Weaker analgesic than Morphine – except inflammatory
pain
Also called non-narcotic, nonopioid andaspirin-like
analgesics
Primarily act on peripheral pain mechanism, and alsoin
CNS(Raisethreshold)
•
•
•
•

3.  Sodium salicylate was used for fever and pain in
1857 its great success led to the introduction of
acetylsalicylic acid (aspirin) in 1899
 Phenacetin and antipyrine were introduced at
the same time.
 The next major advance was the development of
phenylbutazone in 1949 & indomethacin in 1963

4. Traditional – Nonselective COX inhibitors
Group Drugs
Salicylic acids Aspirin
Propionic acids Naproxen, Ibuprofen, Ketoprofen,
Oxaprozin and Flurbiprofen
Anthranilic acid Mefenamic acid
Aryl-acetic acid derivative Diclofenac andAceclofenac
Oxicam derivatives Piroxicam and Tenoxicam
Pyrrolo-pyrrole derivative Ketorolac, Indomethacin,
Nabumetone
Indole derivatives Sulindac and Indomethacin
Pyrazolone derivative Phenylbutazone, Oxyphenbutazone

5.  PreferentialCOX-2inhibitors
 SelectiveCOX-2inhibitors
 Analgesic-antipyreticwith poor
antiinflammatory action:
 Paraaminophenol derivative
 Pyrazolone derivative
Benzoxazocine derivative
Nimesulide, Diclofenac,
Aceclofenac, Meloxicam and
Nabumetone
Celecoxib, Etoricoxib and
Parecoxib
Paracetamol (acetaminophen)
Metamizole andPropiphenazone
Nefopam

6. •
•
•
•
•
•
All Nsaids Inhibit PG Synthesis
Prostaglandins, Prostacyclines (PGI2) And
Tromboxane A2 (TXA2) Are Produced From
Arachidonic Acid
The Enzyme Responsible Is Prostaglandin
Synthase, Also Known As Cycloxygenase Or
COX
COX In 2 Isoforms: Constitutive - COX-1 And
Inducible COX-2
COX-1 Serves House Keeping Functions
COX-2 Is Generated By Cytokines And Others During
Inflammation (Constitutive In Brain And JG
Cells) – PG Synthesis
Most Nsaids Inhibit COX-1 And COX-2 Non-
selectively And Inhibit PG Synthesis
Aspirin Inhibits COX Irreversibly –
Acetylation Other Nsaids Are Competitive
Reversible Inhibitors
•
•
•

7. FEVER,PAIN
,INFLAMMATIO
N
SuPportspllatellet
funccttiion
CO
CO
X-
X-1
1
COX-
Cyclooxygenas
e
Thromboxane
Prostaglandins
ArachidonicAcid
Membrane
Phospholipid
Phospholipase
A2
Prostacyclin
LOX(LIPO
OXYGEN
ASE)
LTB4 LTC4,
LTD4
Broncho
constrict
or
Platelets
aggregati
on.
PGD2,PGE2,PGF2

8. Arachidonicacid
COX-2
(inducibl
e)
Bodyhomeostasis
• S
t
o
mach
• Intestine
• Kidney
• Platelet
Inflammatory Site
• Macrophages
• Synoviocytes
• Endothelialcells
X X
Selective
COX-2inhibitor
COX-1
(normal
constituent)
X
Normal Constituent
• CNS
• Kidney
• FemaleU/G tract
Glucocorticoids
(blockmRNAexpression)
X
X
Acetaminophen
COX-3
(normal
constituent)
Pain
Fever
?HTN
?GI
• CNS,Heart, Aorta
Nonselective
NSAID

9. 1. Analgesia:Prevention of pain nerveending
sensitization
2. Antipyresis:Reduction of Body temperature in
hyperthermia
3. Anti-inflammatory action: reduction in signsof
inflammation (pain, tenderness, swelling and
vasodilatation)
4. Antithrombotic action: Inhibition of platelet
aggregation

10. What isPain ?
“An unpleasant sensory and emotional
experience associated with actual or
potential tissue damage, or described
in terms of such damage.”
International Association for the Study ofPain (IASP)
Merskey and Bogduk. Classification of Chronic Pain. 1994.

11. Acute
Chronic
vs
Duration
Nociceptive
Neuropathic
vs
Pathophysiology

12. Acute Chronic
Usually accompanied by obvious
tissue damage
Increased autonomic nervous
activity
Pain resolves with healing of the
underlying injury
Serves a protective function
Pain that extends 3 or 6 months
beyond onset or beyond the
expected period of healing1
Ceases to serve a protective
function2
Degrades health and functional
capability2
Depressed mood3
vs.
1 Turk and Okifuji. Bonica’s Management of Pain. 2001.
2 Chapman and Stillman. Pain and Touch. 1996.
3 Fields. NNBN. 1991;4:83-92.

13. Nociceptive Neuropathic
•
•
•
• Pain that arises from astimulus
that is outside of the nervous
system– receptors stimulated
Proportionate to the
stimulation of thereceptor
When acute servesa protective
function
Musculoskeletal disorders are a
very common cause
of nociceptivepain
• Pain initiated or causedby a
primary lesion ordysfunction
in the nervoussystem
Nonociceptive stimulation
required
Disproportionate to the
stimulation of receptor
•
•
vs

14. •
•
•
•
•
Transduction
Transmission
Modulation
Perception
Interpretation
Peripheral
Nerve
Pain Behavior
•
Ascending
Pathways
Injury
Descending
Pathway
Dorsal
Root
Ganglion
C-Fiber
A-beta Fiber
A-delta Fiber
Dorsal
Horn
Brain
Spinal Cord

15. • Peripheral component:
– PGs(especially E2and I2) sensitize afferent nerve endings to pain
– induces chemical and mechanicalstimuli
– Induce hyperalgesia – by affecting transducing property offree
nerve endings – normal stimuli may becomepainful
– NSAIDsdo not block direct PGapplication related pain and
tenderness
– But, block the pain sensitizing mechanism induced by –
Bradykinin, TNFand Interleukins (IL) and others – by inhibiting
COX-2
– More effective against pain due toinflammation
Central Component:Antihyperalgesic (analgesic) effects
through inhibition of PGsrelease in spinal dorsal hornand
CNS
•

16. Trauma/inflammation
Release of arachidonic acid
COX-2
Prostaglandins E2
Pain
sensitization
COX-2
Prostaglandins
sensitization
Pain
IL-1ß
IL-6?

17. •
•
Against Pyrexia (Fever)
Reduction in body temperature in caseof hyperthermia- not
in normothermic individuals
MOA:During infection and tissueinjury
Fever– by generation of Pyrogens- Interleukins, TNF-alphaand
Interferones – induce production of PGE2
in Hypothalamus – raiseits
temperature setpoint.
NSAIDsblock the action of PGproduction in
hypothalumus and reduce temperature
•
•

18. • At the site ofinjury – enhanced COX-2mediated PG
synthesis
NSAIDs inhibit PGsynthesis at the site of injury –
antiiflammatory response of different NSAIDsdependon
capacity to inhibit COX(Potency)
Also inhibit other mechanisms: PGsare not sole mediators
of inflammation - other mediators - LT
s, P
AFand cytokines
etc. -
Also, adhesion molecules – ELAM-1& ICAM-1 –chemotaxis
Inflammatory cell express Selectins and Integrins
SomeNSAIDSalso act – inhibition of generation of
superoxide/free radicals - also GM-CSF
,IL-6 etc.
•
•
•
•
•

19. •
•
•
•
TXA2is pro-aggregator (COX-1)
PGI2is anti-aggregator
Most NSAIDs- effects on TXA2predominatesand
inhibits aggregation – prolonged bleedingtime
Aspirin is highly active and acetylates COXin
circulation – before hepatic 1stpassmetabolism
• Evensmall dose
Antithrombotic effect – Myocardial Infarction and
other cardiacconditions

20. •
•
•
All NSAIDsproduce gastric mucosal damage, ulceration and
blood loss – varying extent
Dueto inhibition of COX-1mediated synthesis ofgastro
protective PG(PGE2andPGI2)
– Also back diffusion of H+in gastricmucosa
Deficiency of PGsreduces mucus and HCO3
secretion –
promote mucosalischaemia
• Enhanceaggressive factors over defensive factors -Ulcerogeic
Paracetamol – free of gastrictoxicities
Selective COX-2inhibitors
Misoprostol

21. •
•
During hypovolemia, decreased renalperfusion
Particularly important in conditionsof
– CHF
,hypovolaemia, cirrhosis and renal impairment (Na+retention
and edema)
– Patent under antihypertensives anddiuretics
PGscause: (Intrarenal regulator)
– Renalvasodilatation and inhibition of tubularreabsorption
– Frusemide like effect – inhibition of Cl-reabsorption
– Increased excretion of Na+,K+andwater
NSAIDsblock these renal effects by inhibition PGs
– Impairment of renal bloodflow
– Na+and water retention
– Papillary necrosis on prolongeduse
•
•
•

22. •
•
•
Weaker analgesic than Morphine – 600 mg VsCodeine 60 mg
Aspirin irreversibly inhibits COX-1& COX-2activity
Inhibits COXirreversibly by acetylation – fresh enzyme
synthesis requires for return
– Mainly effective in pains related toinflammation, tissue injury,
connective tissue and integument pain
– Not much effective in visceral and ischemicpain
Mechanism – prevention of PG-mediated sensitizationof
nerve endings
Other mechanisms:
– Raisingof pain threshold by acting centrally – morphine like – butno
sedation, subjective effects, tolerance or physicaldependence
– Resetting of hypothalamic thermostat – feverreduction
Anti-inflammatory dosesare higher than analgesicdoses
•
•
•

23. •ASPIRIN is acetylsalicylic acid, the Prototype - converted in the
Body to Salicylic acid – Oldest analgesic
•Other important salicylates – Sulfasalazine, Diflunisal
•Natural Sources - fruits, vegetables, herbs, spices, nuts, and tea

24. •
•
Absorbed from stomach and SI
Poorly water soluble –limitation
– Solubility can be increased by alkalizations – but ???
Converted to salicylicacidin gut, liver andplasma
80-85%bound to plasma protein - can crossplacenta andCSF
Metabolized in liver by conjugation with glycine– salicyluric
acid
Excreted asglomerular filtration and tubular secretion
T1/2 life is 15-20minutes
– 8 – 12 Hrsdue to metabolic processsaturation
– High doseshave long t1/2
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•
•
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•

25. • Metabolic effects: Increased cellular metabolism
• Uncoupling of oxydative phosphorylation →increased heat
production
Increased utilization of glucose – decreasedblood sugar and
glycogen depletion
Toxic doses: Hyperglycaemia
•
•
• Respiration:
•
•
•
Low doses:↑ CO2→stimulates respiration
Increased sensitivity of Respiratory centre to CO2
In Poisoning - Direct stimulation of respiratory center→
Hyperventilation
Higher doses- depression of respiratory center →Death dueto
Respiratory Failure
•

26. • GIT
:
– Salicylic acid – irritant to mucosacausing nausea andvomiting
Locally – back diffusion of acid – necrosis of mucosaand arteries – ulceration,
erosive gastritis etc.
Occult blood loss–haematemesis
Salicylate-induced gastric bleeding is painless and may lead to an iron
deficiency anemia
–
–
–
• CVS:
–
–
Therapeutic doseshave no significant cardiovascular effect
High doses-increased BP- increased COand peripheral vasodilation by
exerting adirect effect on smoothmuscle
Toxic doses- depress circulation directly and by central vasomotor paralysis
–

27. • Hematologic effects:
–
–
– Itinhibits the platelet aggregation by decreasing the
production of TXA2– lasts for aweek
In dosesgreater than 6 gm/day, aspirin mayreduce
plasma prothrombin levels
Prolonged use– decrease in synthesis of clotting factors
• Urate Excretion:
–
–
–
Doselessthan 2 gm/day – urate retention
2-5 gm/day – variable effects
More than 5 gm/day – increased urateexcretion

28. • Gastrointestinal disturbances
– Nausea, vomiting, epigastric distress and gastric mucosaldamage
• Hypersensitivity and Idiosyncrasy: rash, urticaria, asthma
(bronchospasm – aspirin sensitive asthmatics)
Salicylism: on repeated administration (3-5gm/day)
•
–
–
–
headache, mental confusion, lassitude, anddrowsiness
tinnitus and difficulty inhearing
hyperthermia, sweating, thirst, hyperventilation, vomiting, anddiarrhea
• Hepatotoxicity:
–
–
Risein serum transaminases – hepatotoxic
Reye`sSyndrome– rare diseaseof hepatic encephalopathy when given in
viral conditions of influenza andvaricella
•
•
•
Nephrotoxicity: Na+and water retention, ch. Renalfailure
Prolongation of bleed time or reduce prothrombin level
Respiratory:Asthma, rhinitis

29. •
•
•
Fatal dose: 15 – 30 gm
Low in caseof children
Features: Vomiting, dehydration, acidosis, petechial
haemorrhage, hyperglycaemia, hyperpyrexia, confusion
and coma etc.
Management:
•
–
–
Inducing emesisor administering gastriclavage
Appropriate infusion measuresto correct abnormalelectrolyte
balance and dehydration –Na+,K+,HCO3etc. asper need
Alkalinization of theurine
Dialysis asrequired
Vit.K injection
–
–
–

30. 1. Analgesic: Headache, migraine, backache, tothache,
dysmenorrhea etc (300 to 600 mg 8Hrly)
2. Rheumatoid arthritis: (3-5gm/day)
Usedto be standard first line ofdrug
Poorly tolerated – newerNSAIDS
1. Acute Rheumatic Fever: (4-5gm/day)
First drug of choice – other drugs are added when itfails
Doseis reduced after 1 weektherapy
Continued for 3-4weeks
gradual withdrawal for over 2weeks
1. Osteoarthritis
2. Antipyrretic

31. • Routinely prescribed forpost myocardial infarction patients –
prophylaxis purpose to preventre-infarction
Doseis very low (60 – 100mg/day)
High dosesinhibit PGI2(anti-aggregator)
Primary prophylaxis (100 to 150 mg – moreuseful)
ReducesTIAand lowers incidence of stroke
•
•
•
•
•
Aspirin preparations: Tablets of various strength – 75 mg,100
mg, 325 mg, 650 mg etc. Aspirin, Disprin, Loprin, Ecospirin
etc.

32. 1. Sensitive Persons
2. Children with viraldiseases
3. Peptic ulcer diseaseand bleeding disorders
4. Chronic liver diseases
5. Diabetes, CHFand juvenile Rh.Arthritis
6. G-6-PDdeficient persons
7. Stopprior to surgery, near termpregnancy,
breast feeding mothers etc

33. • Analgesic: Backache,myalgia, toothache, joint pain, pulled muscle and
dysmenorrhoea
Antipyretic : Feverof any origin – Paracetamolsafer
AcuteRheumaticfever: 75 – 100 mg/kg/day (or, 4 – 5 gm/day) – marked
symptomatic relief – all cases
– dose reduced after 4 - 7 daysand maintained for 2 - 3 weekstill s/s
stops - withdrawal should begradual
RheumatoidArthritis: Reduction in pain, swelling and stiffness – large
dose
Osteoarthritis: Asand when needed –Paracetamol is the choice
Post-myocardialinfarctionand poststroke:Routinely used– inhibits
platelet aggregation (TXA2)at low dose (60 – 100mg/day) – but, highdose
canreverse (PGI2 inhibition)
– New onset or sudden onset angina (risk of infarction) - 75 to 150 mg/day for
12 weeks ….Also in TIA
Other uses:PIH,PDA,Familial colonic polyposis and Prevention of colonic
cancer
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•
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34. •
•
Ibuprofen, Naproxen, Ketoprofen,Flurbiprofen
Analgesic, antipyretic and anti-inflammatory efficacy islower
than aspirin (low potency) – all inhibits PGsynthesis
(Naproxen – most potent)
– Antiplatelet activity – short with Ibuprofen but longer with naproxen
Adverse Effects: Better tolerated than aspirin and
Indomethacin – milder – gastric discomfort, nausea,vomiting,
– gastric erosion rarely
– CNSeffects - headache, dizziness,blurring of vision, tinnitus and
depression
– Rash,itching and hypersensitivity are less
– Precipitates aspirin induced asthma
•

35. • Pharmacokinetics: All are well absorbed orally – 90-99%plasma protein
bound
–
–
–
But lesser displacement of otherdrugs
Inhibits platelet function – usewith anticoagulants areavoided
Decreasesantihypertensive and diuretic actions of furosemide, thiazides and
beta-blockers
Uses:Not given in pregnancy and Peptic ulcer patient
Ibuprofen: Simple analgesic and antipyretic – like low dose aspirin–
dysmenorrhoea
Also in Rh.Arthritis, musculoskeletal disorders – pain prominent
conditions
Also in fractures, vasectomy, tooth extraction, postpartum andpost
operative pain
Naproxen – preferred in acute gout – stronger anti-inflammatoryand
inhibition of leucocyte migration – longer half-life(12-16 hours)
•
–
–
–
–

36.  Analgesic, antipyretic and weak anti-inflammatory –
inhibition of certain PGsynthesis – peripheral + central
analgesic dose:500mg initially followed by 250 mg day 2-3
times.
 ADRs:Diarrhoea, epigastric distress, skin rash,
dizziness and other CNSADRs
 Kinetics:Slow oral absorption, but complete,bound
to plasma protein – displacementreactions
 Uses:asanalgesic in muscle, joint and soft tissue
pain ---- Dysmenorrhoea
•
•
•
•

37. • Multiple action NSAID,Longacting, good anti-inflammatory, good
analgesic-antipyretic action.Dose: 10-20 mgday
–
–
–
Reversible, non-selective COXinhibition
Synovial fluid – lowers PGsynthesis and inhibits platelet aggregation
DecreasesIgM rheumatoid factor and leucocyte chemotaxis
•
•
ADRs:Contrast COX-1 blocking action - More GI effects than Ibuprofen -
but less than Indomethacin, lesser ulcerogenic – lesser occult blood than
aspirin - also rash, pruritus and serious skinreactions
• Kinetics: Rapid complete absorption, 99% plasma bound, t1/2– 2 days (ss –
1 week); excreted in bile and urine – EHcirculation
Uses:Longterm anti-inflammatory – rheumatoid arthritis, osteo-arthritis,
ankylosing spondylosis, acute gout etc. – Not first choice for any
conditions …Relative higher toxicity thanOthers

38. • Indole acetic acid derivative - Potent anti-inflammatory andprompt
antipyretic
–
–
Relieves only inflammatory and injury related pain
Highly potent inhibitor of PGand neutrophil motility
• Use:Reservedrug - ankylosing spondylitis, destructive arthropathies,
psoriatic arthritis, postoperative pain, malignancy associated fever,
medical closure of PDA,DOSE:50-75 mg/day 2-3times.
Kinetics:well absorbed orally, 90%PPbound and t1/22 – 5 Hours
ADRs:High incidence of gastric and CNSside effects (COX-1related) –
gastric, irritation, nausea,anorexia, bleeding anddiarrhoea
•
•
– CNS:Frontal headache, dizziness, ataxia, mental confusion, hallucination,
depression and psychosis
– Leucopenia, hypersensitivity, rashetc.
– Increased risk of bleeding – low plateletaggregation
• Contraindications:machinery operators, drivers, psychiatric & epileptic
patients kidney disease,pregnancy & children

39. • Potent analgesic – but modest anti-inflammatory – post operative pain–
equal efficacy with Morphine (butno receptor interaction)
Inhibits PGsynthesis – inhibits painperipherally .DOSE:max.40mgday
Uses:GivenIM andorally - Post-operative, dental, musculo-skeletal pain
– also in renal colic, migraine – short term management of moderate pain
– rated superior to aspirin and paracetamol and equivalent toibuprofen
– Concurrent usewith morphine (reduce dose) – but notusedwith
anticoagulant – not to be used for more than 5 days
Kinetics:Well absorbed orally and IM – highly plasma protein bound; t1/25
– 7 Hrs– 60%excretes unchanged in urine
ADRs:Nausea,abdominal pain, dyspepsia, ulceration, dizziness,
nervousness,pain in injection site, rise in serum transaminase,fluid
retention etc.
•
•
•
•

40. • Metamizole (Analgin) is aderivative of
Amidopyrine. It is apotent and promptly
acting analgesic, antipyretic, andspasmolytic
- but poor antiinflammatory and noturicosuric
activity.Dose:10-20mgkgday.2-3-times.
– Analgin can be given orally, i.m. aswell asi.v.
(very slowly)
• ADRs:Agranulocytosis
• Analgin, Novalgin, Baralgan, Ultragin etc

41. •
• Weak PG synthesis inhibitor, moderate COX-2 selective
– Other Mechanisms: reduced superoxide generation by
neutrophils, inhibition of PAF, TNFα release & free radical
scavenging
– Completely absorbed and 99% plasma protein bound
– Half life – 4-5 hours and excreted in urine
Uses: sports injuries, sinusitis, dental surgeries, renal
colic, arthritis, postoperative inflammatory condition,
fever, low back pain, ENT disorders– no cross
reaction of aspirin and other NSAIDS related
bronchospasm – specific usefulness
• ADRs:epigastric pain, nausea, loose motion, heart
burn, rash, pruritus, somnolence and dizziness – GIT
tolerant but Ulceration - Fulminant hepatic failure

42. •
•
Analgesic-antipyrretic and antiinflammatory – efficacy similar to
naproxen Inhibits PG synthesis – somewhat COX-2 selective
–
–
Reduced Neutrophil chemotaxis and reduced superoxide
generation No antiplatelet action (COX-1 sparing)
•
•
•
99% plasma protein boung – 2 hours
half-life Good tissue and synovial fluid
penetration
Uses: Most widely used drug – RA, OA, Bursitis, ankylosin
spondi;it is, bursitis, toothache, dysmenorrhoea, renal colic,
post trauma and post inflammatory conditions
ADRs: Mild epigastric pain, nausea, headache, dizziness and
rashes – less gastric ulceration and bleeding - Risk of heart attack
and stroke
•

43. •
•
•
• Inhibit COX-2 without inhibiting COX-1 - benefits
– Less peptic ulcer occurrence, less ulcer bleeds
– Do not depress TXA2 production (COX-1) of platelets
– Do not inhibit platelet aggregation, & do not prolong bleeding
time – But reduce PGI2 production
Disadvantage: Reduce PGI2 production by vascular
endothelium leading to increase prothrombotic
effect & enhance cardiovascular risks
Uses: Patients with high risks of PU, perforation at
lowest dose and shortest period
Contraindications: History of IHD, hypertension, CHF
and CVA

44. Other concerns of selective COX-2
inhibition:
•
•
Efficacy: COX-1 generated PGs may play role in
inflammation – broad range action
Gostroprotectivity disturbed: Injury and H. pylori induce
COX-2 – gatsroprotective PG synthesis locally
…. Delay in ulcer healing
Concern over COX-2 Physiological Role: Constitutive in JG
renal cells – Na+ and water retention, oedema,
precipitation of CHF and rise in BP

45.  Phenacetin 1887 – banned now
(Nephropathy) Its deethylated active
metabolite of Phenacetin
 Analgesic – Like aspirin - Antipyretic , raises
pain threshold but no PG inhibition exceptCOX
inhibition in brain – no peripheral anti-
inflammatory action
•
•
•
–
–
–
–
–
–
–

46. • Kinetics:orally absorbed, 1/4thPP bound, t1/2: 3 – 5 hours;
Metabolism by conjugation with glucoronic acid and sulfate
ADRs:Safe and well tolerated – analgesic nephropathy (after years)
ACUTEP
ARACETAMOLPOISONING
Commonly occur in Children – low hepatic glucoronidation
conjugation capacity – also in adults
Large dose - >150 mg/kg or >10 gm in adults
Manifestations: Nausea, vomiting, abdominal pain and liver
tenderness
•
•
•
•
•
– Jaundice after 2 days
– High dose poisoning – fulminating hepatic failure and DEATH
– After 12 – 18 hours – centrilobular hepatic necrosis, renal tubular
necrosis and hypoglycaemia … and coma

47. •
•
Most commonly used – over the counter drug
Headache, mild migraine, musculoskeletal
pain dysmenorrhoea etc.
1stchoice in osteoarthritis, not effective in
Rheumatoid arthritis
Safest Antipyretic in children – no Reye`s syndrome
Advantages – 1) lesser gastric irritation, ulceration and
bleeding (can be given in ulceration) 2) does not
prolong bleeding time 3)
Hypersensitivity rarely 4) no metabolic
disturbances 5) can be given in all age group –
pregnancy- lactation 6) No significant
drug interactions
•
•
•

48. •
•
NSAIDS are also effective topically –
gel/spray etc.
Advantages:
1. Attains higher conc. Locally in muscles and joints – low blood
levels
2. GI and other systemic ADRs are minimized
3. First pass metabolism avoided
•
Kinetics:slow absorption – 10 times longer time to attain peak
plasma conc. to oral dosing
•
•
• Highest blood level – 15% of the same oral dose,
Local conc. Upto 4 - 6mm high (dermis); 25 mm in
muscles (low) Overall efficacy depends on site
•
Uses:Osteoarthritis, sprains, sports injuries, spondylitis and soft
tissue rheumatism etc. – safety no issue but efficacy (!) local
application, massaging – counter irritant - menthol and methyl
salicylate

49. 1. Mild to moderate pain – Paracetamol or low dose Ibuprofen
2. Post operative acute short lasting pain – Ketorolac, Propionic acid
derivatives, diclofenac or nimesulide
3. Acute musculo-skeletal, osteoarthritic or injury pain – Paracetamol or
propionic acid
4. Exacerbation of Rh. Arthritis, acute gout, ankylosing spondylosis –
naproxen, piroxicam, indomethacin
5. Gastric intolarance to NSAIDS - Selective COX-2 inhibitors
6. H/o asthma – nimesulide or selective COX-2 inhibitors
7. Hypertension or risk of heart attack – COX-2 inhibitors and PA derivatives
8. Paediatric – paracetamol, elderly – low dose of NSAIDS
9. Pregnancy – Paracetamol
10. Fast acting ones – fever, headache and other short lasting pain SR
preparations for chronic long lasting pain
11. IHD, hypertension, DM – consider drug interactions