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2. Contents
• Pain
• receptors of pain
• theories of pain
• chemical mediators of pain
• Opioid analgesics
• Morphine
• Other opioids
• Uses
• NSAIDS
• Prostaglandin synthesis & inhibition
• Aspirin
• Other NSAIDS
• Implication in periodontics
• References

3. Pain
Derived from Greek ”Poin”
…….penalty.
Derived from Latin “Poena”
…punishment from God

4. Definition of Pain
• International association for the study of pain (IASP)
(WHO)
– An unpleasant emotional experience associate with actual
or potential tissue damage or describe in terms of such
damage.
• Bell
– The subject’s conscious perception of modulated
nociceptive impulses that generate an unpleasant sensory
and emotional experiences associated with actual of
potential tissue damage or describe in terms of such
damage.
• Monheim
– An un pleasant emotional experience usually initiated by
noxious stimulus and transmitted over a specialized neural
network to CNS where it is interpreted as such

5. SENSORY RECEPTORS CLASSIFICATION

6. Classification of Nerve fibers

7. Three types of stimuli excite pain
receptors
• Thermal
• Mechanical
• Chemical
• Fast pain : Thermal , Mechanical
• Slow pain : All three

8. Neural pathway of pain

9. Theories of pain
1. Specificity theory
2. Pattern theory
3. Gate control theory

10. Specificity theory
• Described by Descartes in 1644
• pain system as a straight through channel from skin to the brain
• Muller informational transmission only by way of the sensory nerves
• Von Frey in 19th
century developed the concept of specific cutaneous
receptors for the mediation of touch ,heat ,cold & pain
• Free nerve ending …pain receptors
• A pain centre was thought to exist within the brain

11. Pattern theory
Goldscheider 1894  proposed that stimulus intensity & central
summation are critical determinants of pain
Particular pattern of nerve impulse that evokes pain are produced by
summation of sensory input within the dorsal horn of the spinal
column
Pain results when total output of the cell exceed a critical level

12. Gate control theory
Wall and Melzac
Gate control theory proposes that
Information about the presence of injury is transmitted to the central
nervous system by small peripheral nerves
large diameter fibers input has the ability to modulate the synaptic
transmission of small diameter fibers within the dorsal horn
Intentional stimulation of large fibers will inhibit transmission of small
fibers thus closes the gate to central progression of impulse ..
e.g. TENS & acupuncture

13. • It was proposed that control over transmission is affected not only by
the gate mechanism but also by the impulse descending from the
brain hence the signal that triggers the system responsible for pain
perception & pt response occurs when the T cell out put reaches a
certain critical level
• It was postulated that descending control system originating in the
brain modulate the excitability of the cell that transmit information
about injury

14. Chemical mediators in nociceptive pathway
• Excessive mechanical or thermal stimuli can obviously
cause acute pain but the persistence of such pain after
stimulus has been removed , reflects an altered chemical
environment
A no of biochemical mediators are associated with
transmission of pain

15. • Kinins
• Most active kinins are bradykinins & kallidin …produced in
tissue injury …
• Bradykinin is a potent pain producing substance ,acting
partly by release of PGs
• Powerful vasodilator ,increases capillary permeability
• It is also released during ischemic episode
• Prostaglandins
• Pgs do not themselves cause pain ,but strongly enhance
the pain producing effect of other agents e.g. 5HT ,
bradykinins

16. Other peripheral mediators
• Various metabolites & substances are released from
damaged or ischemic cells ,including 5HT ,histamine
,lactic acid .
• 5HT  causes excitation ,but studies with antagonist
suggests …it plays minor role
• Histamine causes itching rather than actual pain
• Lactic acid  low ph excites nociceptive afferent
neurons partly by opening proton activated cation
channel & partly by facilitation of vr1

17. Transmitters & modulators in the nociceptive
pathway
• Tachykinins
• Three endogenous tachykinins – substance P
,neurokinin A & neurokinin B ..widely distributed in
central & PNS
• Nociceptive sensory neurons express substance P &
NKA & release them in the periphery & in the dorsal horn
• Substance P is release in the periphery when
nociceptors are activated contributes to neurogenic
inflammation

18. Brain’s opiate system
Endorphin & Enkephalin
• multiple areas of brain show opiate receptors
• Enkephalin and Leu-Enkephalin---Brain stem and spinal cord
∀ β-Endorphin—Hypothalamus and spinal cord
• Dynorphin-- Brain stem and spinal cord
• naturally occurring transmitters –ENKEPHALINS
Mediates integration of sensory information pertaining to pain
& emotional behavior.
Intrinsic analgesic potency similar to morphine.

19. Endorphins
• Behave like morphine & bind to opiate receptors to obtund pain Like
morphine
• B – endorphin closely related to pituitary function
• May act like hormone.
• The Enkephalin & endorphins have antinociceptive effects,
• Underlying mechanism not fully analyzed

20. Other central mediators
• Glutamate excitatory amino acid
• released from primary afferent neuron
• responsible for fast synaptic transmission
• GABA  released by spinal cord interneuron
• inhibits transmitter release by primary afferent terminal in the dorsal
horn
• Noradrenalin  this is the transmitter of inhibitory pathway & anti
nociceptive pathway
• Adenosine  this plays a dual role in regulating nociceptive pathways
• activation of A1 receptors causing analgesia while A2 does the
reverse

21. Noxious
stimulus
C –fiber
activity
Excitation of
transmission
neuron
Descending
inhibitory
pathway
Mediator release
( BK,5-HT ,PGs,etc)
Mediator release
( BK,5-HT ,PGs,etc)
NGF
production
NGF
production
Opiates
NSAIDS
5HT ,NA5HT ,NA
Enkaphalins
& GABA
Enkaphalins
& GABA
inflammationinflammation
Modulation of Nociceptive
pathway
Opiates
Neuropeptide
release
( SP,CGRP)
Neuropeptide
release
( SP,CGRP)
NO formationNO formation
pain

22. Analgesics
A drug that selectively relives pain
by acting in CNS or on peripheral
pain mechanism ,without significant
altering consciousness

23. Opioid analgesics
Introduction
Term narcotics is imprecise since narcotics connotes a
somnolent state
Term opioid analgesics is more appropriate because it
implies production of analgesia without causing sleep or
loss of consciousness

24. Morphine
History
A German pharmacist ,isolated a pure active alkaline substance from opium
in 1803
Serturner proposed the name morphine for the compound after Morpheus
‘the Greek god of dreams’
Sir William Osler …god’s own medicine
Source
 The source of opium ,the crude substance &
morphine its active constituent is the opium poppy .
 It contain two type of major alkaloid
 1)phenantherene derivative
 Morphine 10%
 Codeine 0.5%
 Thebaine 0.2%
2) benzo isoquinolone derivative
Papaverine
Noscapine

25. Classification
•naloxone , naltreoxone
•tramadol

26. Opioid receptors
• Morphine & other opioids exert their action by interacting
with specific receptors present on neurons in the CNS &
in peripheral tissue
Mu Kappa delta
Analgesia Analgesia Analgesia
respiratory depression Resp depression Resp depression
Sedation Sedation Affective behavior
Euphoria Dysphoria ,hallucination Reinforced action
miosis miosis
Reduced g I motility Reduced gi motility
Physical dependence
(morphine type)
Physical dependence
(nalorphine type)

27. Mechanism of action

28. The descending control system, showing postulated sites of action of opioids on pain
transmission. Opioids excite neurons in the periaqueductal grey matter (PAG) and in t
he nucleus reticularis paragigantocellularis (NRPG), which in turn project to the rostro
ventral medulla, which includes the nucleus raphe magnus (NRM). From the NRM, 5-
HT-and enkephalin-containing neurons run to the substantia gelatinosa of the dorsal h
orn, and exert an inhibitory influence on transmission. Opioids also act directly on the
dorsal horn. The locus ceruleus (LC) sends noradrenergic neurons to the dorsal horn,
which also inhibit transmission.
Cortex
HypothalamusPAGThalamus
Opioids
NRMNRPG LC
Dorsal horn
Opioids
Opioids
DLF
5-HT Enkephalin
Noradrenaline
Nociceptive
afferent fibres
+
+
++
+ +
+/-
+/-
– – –
–

29. Pharmacological actions
1) CNS

31. Morphine stimulates

32. • 2)neuroendocrine
• Its influence on pituitary is reduced  as a result FSH
,LH & ACTH levels are decreased
• Sex hormones & corticosteroids levels are lowered in
short term ,but tolerance develops in long term
• Can release ADH  reduces urine volume

33. • CVS

35. • Oral absorption is unreliable because of high first pass
metabolism
• Oral bioavailability averages ¼ of parentally
administered drug .
• About 30% is bound to plasma protein
• Metabolized in liver by glucoronide conjugation
• Morphine 6 glucoronide is an active metabolite of
morphine which accumulates during chronic dosing &
contribute to analgesia

36. Adverse effects
1)Side effects

37. • 2) Idiosyncrasy & allergy
• Urticaria ,itching & swelling of lip
• A local reaction at injection site—>
histamine release
• Allergy is uncommon & anaphylactic reaction is rare
• 3)Apnoea
• This may occur in new born when morphine is given to mother during labour
• The BBB of foetus is underdeveloped ,morphine attains higher
concentration
• Naloxone 10 ug /kg injected in chord  treatment of choice

38. • 4)Acute morphine poisoning
• It is accidental ,suicidal or seen in drug abusers
• 50mg serious toxicity
• Human lethal dose is 250mg
• Symptoms
• Shallow & occasional breathing ,cyanosis ,pinpoint pupil ,fall in BP & shock .
• Pulmonary edema at terminal stage
• Death due to resp.failure
• Treatment
• Resp. support
• Maintenance of BP
• Lavage with potassium permagnate
• Specific antidotenaloxone 0.4-0.8mg i.v
repeated every 2-3 min till resp.picks up

39. • 5) Tolerance & dependence
• High degree of tolerance … used repeatedly
• Tolerance is exhibited to most actions except miosis & constipation
• It produces pronounced psychological & physical dependence
• Physical manifestations
• Lacrymation ,sweating ,anxiety ,fear ,restlessness, tremor
,insomnia, abdominal colic ,diarrhea ,dehydration
• Treatment  withdrawal of morphine &
substitution with methadone followed by
gradual withdrawal of methadone

40. Precaution & contraindications
Dangerous in pts with respiratory insufficiency
Bronchial asthma
Head injury
Hypotensive state & hypovolumia
Undiagnosed acute abdominal pain
Elderly male
Doses 
10-15mg i.m. or s.c. ( rarely orally ) or 2-10 mg i.v ;
2-3 mg epidural / intrathecal

43. Drug Uses Route of
administrati
on
Pharmac
okinetics
Main adverse
effects
Pentazocine Mainly
acute pain
Oral injection T1/2 – 2-
4hr
Psychotomimetic
effects
Irritation at injection
site
May ppt morphine
withdrawal
syndrome
buprenorphine Acute and
chronic
pain
Sublingual
injection
intrathecal
T1/2 12
hrs
As morphine but
less pronounced
Respiratory
depression not
reversed by
naloxone

44. Pure opioid antagonist
• Naloxone
• Competitive antagonist of all type of opioid receptors
• No physical or psychological dependence seen
• 0-4 -0-8 mg antagonizes all action of morphine
• 4-10 mg antagonizes the agonist action of nalorphine & pentazocine
• Blocks action of endogenous opioid peptides
• it is inactive orally ,given i.v. ,acts in 2-3 mins
• Uses
• Morphine poisoning ,
• Neonatal asphyxia

45. 1)as analgesic 
provide symptomatic relief without affecting the cause .
Adequate use of morphine is indicated in an emergency .
may prevent neurogenic shock & other autonomic effects
of excruciating pain
2) Preanesthetic medication 
morphine & pethidine ------- commonly used
3) Balanced anesthesia and neurolept analgesia
-  morphine ,pethidine ,fentanyl ,alfentanil or sufentanil

46. 4) Relief of anxiety and apprehension 
specially in MI, internal bleeding ..morphine or pethedine have been
employed .
should not be used as anxiolytics or to induce sleep
5) acute left ventricular failure
• a)reducing preload on heart due to vasodilatation & peripheral
pooling of blood
• B)tending to shift blood from pulmonary to systemic circuit ;relives
pulmonary congestion and edema
• C)allays air hunger by depressing resp centre
• D) cut down sympathetic stimulation by calming the patient

47. • 6)cough 
• codeine or its substitute are widely used
for suppressing dry ,irritating cough.
• 7)diarrhea 
• the constipating action of codeine and tincture opii has been used to
check diarrhea and to increase the consistency of stool in colostomy
.

48. Non opioids analgesics /NSAIDS
• Classified as mild analgesics
• Do not depresses CNS ,do not produces physical
dependence & have no abuse liability
• primarily act on peripheral pain mechanism & also in
CNS to raise pain threshold

49. Mechanism of action of NSAIDS

52. Salicylates aspirin ,salicylamide ,benorylate,diflunisal
Pyrazolone derivatives phenyl butazone ,oxyphenbutazone
Indole derivative indomethacin ,sulindac
Propionic acid derivative ibuprofen ,flubiprofen ,naproxen ,ketoprofen
Anthranilic acid Mephenamic acid
Aryl acetic acid derivative diclofenac ,tolmetin
Oxicam derivative Piroxicam ,tenoxicam ,meloxicam
Pyrrolo –pyrrole derivatives Ketarolac
Sulfonanilide derivatives Nimesulide
Alkanones nabumetone
Analgesics and anti-inflammatory
Para aminophenol derivative Paracetamol(acetaminophen)
Pyrazolone derivatives Metamizol ,propiphenazone
Benzoxazocine derivative nefopam
Analgesic but poor Anti-inflammatory

54. • Analgesia 
• PGS induce hyperalgesia by affecting the transducing property of free nerve
endings
• nSAIDS are particularlly useful when inflammation has caused sensitization of
pain receptors.
• Do not effect the tenderness induced by direct application of PGS ,but block the
pain sensitizing mechanism induced by bradikinins ,TNFa ,ILS therefore more
effective against inflammation associated pain

55. • Antipyresis 
• reduces body temp ,but does not cause hypothermia in normothermic individual
• Fever during infection is produced through the generation of pyrogen ,ILS TNFa,
Interferon's which induce PG production in hypothalamus – raise its temp set point
• NSAIDS block the action of pyrogens but not that of PGE2 injected into the thalamus

58. • Parturition 
• sudden spurt of pg synthesis by uterus probably triggers labour & facilitates its
progression
• Accordingly NSAIDS have the potential to delay & retard labour ..however labour can
occur in the absence of pgs
• Renal effects 
• condition leading to hypovolumia ,decreased
renal perfusion& na loss induce renal pg synthesis
• intrarenal adjustment by promoting vasodilatation ,
• inhibiting tubular Cl re absorption & opposing adh action
• .renal effects become significant in CHF ,
• hypovolumia ,hepatic cirrhosis ,renal disease

59. • Gastric mucosal damage ->
• gastric pain ,mucosal erosion /ulceration and blood loss are produced by all
NSAIDS to varying extent
• Inhibition of synthesis of gastro protective PGS is clearly involved ,though
local action inducing back diffusion of h=+ ions in gastric mucosa also plays
role
• Deficiency of pgs reduce mucous & HCO3 production ,tends to enhance
acid secretion & promote mucosal ischemia
• Nsaids enhance aggressive factors and contain defective factors in gastric
mucosa .
• Paracetamol ,a weak inhibitor of Cox is practically free of gastric toxicity &
selective Cox 2 inhibitors are safer
• Anaphylactic reaction 
• aspirin pptes asthma ,angioneuretic swelling ,urticaria ,or rhinitis in certain
susceptible individuals

60. Salicylates
• Aspirin
Prototype
Pharmacological action
Analgesic central and peripheral action
relieves low intensity pain
Antipyretic act in hypothalamus to lower the set point of temperature
control elevated by fever , also causes sweating
anti-inflammatory inhibition of peripheral prostaglandin synthesis
Respiratory
stimulation -
direct action on respiratory centre, indirectly by ↑ CO2
production

61. • Metabolic effects
i .) ↑ peripheral O2 consumption (uncoupled oxidative
phosphorylation) hence ↑CO2 production with ↑
respiration, and direct analeptic action - respiratory alkalosis
ii) renal loss of bicarbonate with sodium, potassium and
water
iii) dehydration
iv) metabolic acidosis - effects on Krebs cycle, ↑ ketone
body, salicylic acid in blood, renal insufficiency due to
vascular collapse, dehydration
v) hypoglycaemia or even hyperglycaemia can occur

63. • Does low dose aspirin therapy complicate
oral surgical procedure ? ( leon ardekian
et al 2000

65. Pharmacokinetics
• Absorbed from stomach & intestine
• Limiting factor poor water solubility
• Absorption enhanced by  micro fining the drug particles &
inclusion of an alkali ,gastric empting time
• Rapidly deacytylated to salicylic form
• Slowly enters the brain but freely crosses placenta
• T1/2 is 15-20 min,salicilic acid …3-5 hrs

66. Adverse effects
• A)side effects occurs at analgesic dose
• Nausea ,vomiting ,Epigastric distress ,
• increased occult blood loss in stool
• Most important gastric mucosal
damage & peptic ulceration
• B)hypersensitivity & idiosyncrasy
reaction include rashes ,fixed dug
eruption ,urticaria ,rhinorrhoea ,
angioedema ,asthma ,& anaphylactoid
reaction
gastric bleeding in rare instances

67. c)Anti-inflammatory doses
syndromesalisysm
Dizziness ,tinitus ,vertigo ,reversible impairment of healing ,mental
confusion
D) acute salicylate poisoning --.
• common in children
• Fatal dose in adult 15-30 gm
• Serious toxicity serum salicylate level >50 mg /dl
• manifestations ….vomiting ,dehydration ,electrolyte imbalance ,acidotic
breathing ,restlessness ,delirium ,hallucination , hyperpyrexia ,convulsion
,coma …death

68. • symptomatic & supportive
most imp is ext .cooling ,i.v fluid with Na ,k ,HCO3 & glucose
gastric lavage to remove unabsorbed drug
Forced alkaline diuresis
haemodialysis to remove absorbed drugs
Blood transfusion & vit k if bleeding occurs
Treatment

70. Precautions & contraindications
• 1)sensitive to peptic ulcer ,bleeding tendencies .
• Reye syndrome …. pediatric formulation is prohibited in India & uk
• In chronic liver disease  hepatic necrosis
• Avoided in diabetic ,CHF ,& juvenile rheumatoid arthritis.
• Should be stopped one week before elective surgery ?
• Avoid high doses in G6 PD deficiency pt haemlysis occurs

71. • Effectiveness of diflunisal on a preoperative measure to
reduce pain pain following periodontal surgery
• ( James S M 1988)
Double blind

72. Pyrazolones
1) phenylbutazones 
inhibits COX & is more potent anti-inflammatory than aspirin
Analgesic & antipyretic effect slower in action
Phenylbutazone causes definite retention of Na & water by direct action of
renal tubules edema ,expansion of plasma volume can occur after 1-2
weeks of useCHF may be pptd
Pharmacokinetics 
completely absorbed orally
absorbed from i.m. sites is slower and causes local tissue damage.
T1/2 is 60 hrs
Metabolized in liver

73. Adverse
effects

74. • Uses
• Rheumatoid arthritis
• Rheumatic fever
• Acute gout
Metamizol
• it is a amidopyrine derivative
• In contrast to phenylbutazone ,it is more potent & analgesic &
antipyretic but poor anti-inflammatory & not uricosuric
• Orally I m I v
• Gastric irritation & pain at injection site

75. • potent anti-inflammatory drug.
•Analgesic action is better than phenylbutazone ,but it relives only
inflammatory or tissue injury related pain .
• potent inhibitor of PG synthesis & suppresses neutrophil motility
•Uncouples oxidative phosphorylation at supratherapeutic conc.
•Depresses biosynthesis of mucopolysaccharides
•Observational studies
•Controlled clinical trials
Pharmacokinetics 
well absorbed orally
Partially metabolized in liver ,excreted by kidney .
T1/2 2-5hrs

76. Adverse
effects
Frontal headache

77. • Uses 
• Rheumatoid arthritis
• Ankylosing spondilytis
• Acute gout
• Most common drug for closure of
patent ductus arteriosus
• Batter syndrome respond dramatically
• Contraindication 
• machinery operators ,drivers ,psychiatric pt ,epileptics ,kidney disease
,pregnant women ,peptic ulcers
• Interaction --.
• indomethacin & triamterene given together cause renal failure

78. Animal experiments

79. Propionic acid derivative
• first to be introduced in 1969
• The analgesic ,antipyretic & anti-inflammatory efficacy is lower than
that of high dose of aspirin
• All inhibit PG synthesis ,naproxen being most potent
• They inhibit platelet aggregation & prolong bleeding time
Ibuprofen

80. • Pharmacokinetics 
• Well absorbed orally
• Highly bound to plasma protein
• They are likely to decrease diuretics & antihypertensive actions of
thiazides ,frusamide & B blockers
• All propionic acid enter brain ,synovial fluid & crosses placenta
• They are largely metabolized in liver & excreted in urine

82. • Precaution
• They should not be prescribed to pregnant women & should be
avoided in peptic ulcer patient

83. • Naproxen
• Potent in inhibiting leukocyte migration
• More valuable in acute gout ,ankylosing spondilitis
• Ketoprofen
• Has been shown to stabilize lysosome
• Flubiprofen
• More effective than ibuprofen
• More gastric side effects
• Used as an ocular anti-inflammatory

84. • Fernando gallardo 1990

88. Anthranilic acid derivative
Mephenamic acid

89. Aryl acetic acid derivative
• Diclofenac sodium
• Similar in efficacy to naproxen
• Inhibit PG synthesis & has short lasting antiplatelet action
• Neutrophil chemataxis & superoxide production at the inflammatory site are
reduced
• Reduce intracellular concentration of free arachidonates in leukocytes
• Pharmacokinetics
• Well absorbed orally
• Metabolized & excreted both in urine & bile
• T1/2 2hrs
• Good tissue penetrability*

90. • Adverse effects
• Epigastric pain ,nausea ,headache ,dizziness
• Gastric ulceration & bleeding are less common
• Reversible elevation of serum amino transferase
• Drug interaction
• Raises plasma level of lithium & digoxin
• Uses
• Rheumatoid arthritis ,osteoarthritis ,bursitis
• Post traumatic & post operative inflammatory conditions
• Afford quick relief of pain & wound edema

91. Oxicam derivative
piroxicam

93. Pyrrolo pyrrole derivative
• ketarolac
•Post operative and musculoskeletal pain
•May be used for renal colic ,migraine & pain
due to bony metastasis
Short term alternative to opioids for moderate to
severe pain

94. Trombelli et al 1996

95. Sulfonanilide derivatives

97. Para aminophenol derivative
• Phenacitin was introduced in 1887
• Paracetamol ..the deethylated active metabolite of phenacitin was also
introduced in the last century but gain popularity only after 1950
• Pharmacological action
• It raises pain threshold ,but has weak peripheral anti-inflammatory
component
• Basically antipyretic
• Negligible anti-inflammatory action
• Poor inhibitor of pg synthesis but more active on COX in brain *
• Contrast to aspirin  1)does not stimulate respiration
• 2)does not increases cellular metabolism
• 3)does not effect acid base balance
• 4)no effect on CVS
• 5) no effect on platelet function
• 6) not uricosuric

98. • Pharmacokinetics
• Well absorbed orally
• T1/2 2-3 hrs
• Uses
• OTC
• One of the Best drug to be used as antipyretic
• Can be used in pt in whom aspirin is contraindicated
• Adverse effects
• Safe & well tolerated
• Nausea & rashes occur occasionally
• Leucopenia is rare

99. Acute paracetamol poisoning
• Occur in children … low hepatic glucronide conjugation
ability
• Stage 1 (0-24 hours)
– Often no symptoms
– Nausea, vomiting, anorexia, diaphoresis may occur
• Stage 2 (24-48 hours)
– LFT’s , bilirubin
• Stage 3 (3-4 days)
– Coagulation defects, jaundice, renal failure hepatic
encephalopathy may be present
– Death is usually due to hepatic failure

100. • Stage 4 (Recovery)
– LFT’s begin to normalize if damage not irreversible
– Liver returns to normal within 3 months
Management
Stabilization
• AC if within 1 hr of ingestion
– 1gm/kg orally or via NG tube
• Determine if antidote needed N acetylcysteine

101. selective COX 2 inhibitors
• The therapeutic use of NSAids has been limited by poor
tolerability
• COX 2basically regulated by cytokines & mitogens
• It was proposed that it is a dominant source of
prostaglandin formation in inflammation & cancer
• Thus selective inhibition of COX 2 was given for better
tolerability

102. COX -2 inhibitors
• Colecoxib
• Potent anti-inflammatory .analgesic & antipyretic with low
ulcerogenic potential
• Pharmacokinetics
• Slowly absorbed
• T1/2 –11 hrs
• Metabolized predominantly by CYP2C9
• Uses
• Osteoarthritis ,rheumatoid arthritis
• Adverse effects
• Abdominal pain ,dyspepsia ,mild diarrhea
• Hypertension & edema

103. Valdecoxib
• It can elevate bp in predispose individual
• Pharmacokinetics
• Absorbed rapidlly
• Hepatiic metabolization by CYP3A4.& CYP2C9
• T1/2 7-8 hrs
• Uses
• Osteoarthritis ,rheumatoid arthritis
• Moderate to severe pain ,particularly if given preemptively ( eg
before a dental procedure
• Adverse effects
• Cardiovascular risk
• Stevens johnsons syndrome

105. Briggs w .morrison 2000

106. Pain Relief versus Perioperative Risk
Effective pain
management
Adverse
effects

108. NSAIDS as host modulating
agent in periodontal disease
• NSAIDS have a role in management of
periodontal inflammation

109. • The ability of NSAIDS to block PGE2 production , thereby reducing
inflammation & inhibiting osteoclast activity in periodontal tissue has been
investigated
• Studies have shown that systemic nsaids such as indomethacin ,flurbifrofen
& naproxen administered daily for upto 3 yrs significantly slowed the rate of
alv bone loss compared with placebo
• However daily administration for extended period is necessory for
periodontal benefits
• nNSAIDS are associated with severe side effect
• Research shows that periodontal benefits of taking long term NSAIDS are
lost when pt stops taking drug
• For this reason it has not gone beyound research studies

110. References
• Text book of pharmacology 4th
ed k .D Tripathi
• Text book of therapeutic pharmacology 11th
ed
:goodmann & gillmann
• Text book of pharmacology 3rd
ed : lippincotts
• The optimal analgesic dose of rofecoxib: an
overview: JADA,2000 Dec
• Analgesic efficacy of Flubiprofen as compared to
acetaminophen & placebo after PD surgery:
JP:1990
• Does low dose asprin therapy complicates oral
surgical procedures : JADA 2000

111. • An evidence based update of the use of
analgesics in dentistry: perio2000: 2008
• Textbook of pharmacology: Rang & Dale

116. A B
C
Platelet cyclooxygenase-1
With ibuprofen + ASA
Catalytic site
Serine residue
at position 529
Channel
of access
With aspirin
Arachidonic
acid
Acetyl
serine
Y
Aspirin
Ibuprofen
Platelet

117. 117
Prothrombotic
LessGIsideeffect
Prostacyclin Inhibition
( COX-2 mediated )
Thromboxane Inhibition
( COX-1 mediated )
Anti-thrombotic
MoreGIsidetoxicity
RofecoxibRofecoxib
CelecoxibCelecoxib
EtoricoxibEtoricoxib
LumiracoxibLumiracoxib
DiclofenacDiclofenac IbuprofenIbuprofen ASAASA
NaproxenNaproxen
COX-2 Inhibitors : COX-SelectivityCOX-2 Inhibitors : COX-Selectivity

118. GI Side EffectsGI Side EffectsRenal SideRenal Side

119. •
Opium, a gum exuded by the poppy
flower,

124. Neural pathway of pain
• Transduction—Noxious stimuli lead to electrical
activity in appropriate sensory nerve endings
• Transmission—Neural events that carry
nociceptive input into CNS for processing
• Modulation—Ability of CNS to control the pain
permitting neurons
• Perception—Subjective experience of pain

125. Three types of stimuli excite pain
receptors
• Thermal
• Mechanical
• Chemical
• Fast pain : Thermal , Mechanical
• Slow pain : All three

126. PHASES OF PAIN
• A) Phases I (Acute nociceptive pain ) :
• brief noxious stimuli--fairly simple & direct route-- centrally towards
the thalamus & cortex --- conscious perception of pain-- possibility
for modulation -- synaptic relays along the way
• Close correlation the discharges in peripheral nociceptors &
subjective expression pain

127. B) Phase 2 ( Inflammatory pain )
• Noxious stimulus very intense or prolonged
tissue damage & inflammation .
• Increased activity and responsiveness of sensitized nociceptors.
• Increased afferent inflow to CNS from injured area
• Nociceptive neurons in spinal cord modify their responsiveness.

128. C) Phase 3(NEUROPATHIC PAIN)
• Symptom of neurological disease
•Lesions of peripheral nerves or damage to any portion of
somatosensory system within the CNS.
• Spontaneous pain ,triggered by innocuous stimuli or are
exaggerated responses to minor noxious stimuli.
•Probable reason
1) Pathological changes in damaged neurons
2) Reactive changes in response to nociceptive afferent input
and to loss of portions of the normal afferent inputs

134. • αα