Analgesic is a drug that relieves pain by acting on the CNS or on the peripheral pain mechanism without altering consciousness Opioid analgesics Non Opioid analgesics (NSAIDs) NSAIDs are non-steroidal anti-inflammatory drugs. These are not only pain killers but also are anti-inflammatory drugs that are widely used in dentistry. These are weaker analgesics, also called nonnarcotic or aspirin-like or antipyretic analgesics. They do not depress CNS, do not produce physical dependence, and have no abuse liability. They act primarily on peripheral pain mechanisms.

1. ANALGESICS IN PERIODONTICS

2. INDEX
1. OPIOID ANALGESICS
2. NON OPIOID ANALGESICS
A. NONSELECTIVE COX INHIBITORS
• Aspirin
• Phenylbutazone
• Ibuprofen
• Mephenamic acid
• Ketorolac
• Diclofenac, Aceclofenac
• Paracetamol
B. SELECTIVE COX INHIBITORS
3. SERRATIOPEPTIDASE
4. ACECLOFENAC + PARACETAMOL + SERRATIOPEPTIDASE COMBINATION
5. CONCLUSION

3. DENTAL PAIN
• Pain that occurs in oral cavity due to
pulpitis or periodontitis is of
inflammatory origin

4. ANALGESICS
Analgesic is a drug that relieves pain by acting on
the CNS or on the peripheral pain mechanism without
altering consciousness
• Opioid analgesics
• Non Opioid analgesics

5. OPIOID ANALGESICS

6. OPIOID
• In addition to morphine and codeine, currently
available opioid analgesics are either semi
synthetic congeners of morphine-
Hydromorphone, Oxymorphone, Hydrocodone,
and Oxycodone or are entirely synthetic-
meperidine, fentanyl, methadone, and
proxyphene.

7. OPIOID ANALGESICS
• They depress CNS, produce physical dependence and have abuse
liability.
• They act primarily on central pain mechanisms.

8. NON- OPIOID ANALGESICS

9. NON OPIOID ANALGESICS
• NSAIDs are non-steroidal anti-inflammatory drugs
• These are not only pain killers but also are anti-inflammatory drugs
that are widely used in dentistry
• These are weaker analgesics, also called non narcotic or aspirin like
or antipyretic analgesics
• They do not depress CNS, do not produce physical dependence
and have no abuse liability.
• They act primarily on peripheral pain mechanisms.

10. NON OPIOID ANALGESICS
A. NONSELECTIVE COX INHIBITORS
• Salicylic acid derivatives Aspirin
• Pyrazolone Phenylbutazone, Oxybutazone
• Propionic acid Ibuprofen, Flurbiprofen
• Anthranilic acid derivative Mephenamic acid
• Pyrrolo-pyrrole derivative Ketorolac
• Phenyl acetic acid derivatives Diclofenac, Aceclofenac
• Oxicams Piroxicams

11. B. PREFERENTIAL COX-2 INHIBITORS:
Nimesulide, Meloxicam, Nabumetone
C. SELECTIVE COX-2 INHIBITORS:
Celecoxib, Rofecoxib, Valdecoxib
D. ANALGESIC- ANTIPYRETICS WITH POOR
ANTI-INFLAMMATORY ACTION:
1. Paraamino phenol derivative: Paracetamol (Acetaminophen).
2. Pyrazolone derivatives: Metamizol (Dipyrone),
Propiphenazone.
3. Benzoxazocine derivative: Nefopam.

12. MECHANISM OF ACTION

13. Mechanism of action
Phospholipids
Arachidonic acid
Prostaglandins Leukotrienes
Cyclo oxygenase
(COX)
Lipoxygenase
Phospholipase A2

14. MECHANISM OF ACTION
• NSAID’S acts by inhibiting prostaglandin (PG) synthesis
• PG are important mediators causing pain, inflammation
& antiplatelet mechanism
• They act on COX-1 & COX-2 pathways
• COX-1 is (house keeping) present in all cells

15. MECHANISM OF ACTION
• COX-2 enzyme is responsible for inflammation
and fever
• COX-1 performs functions such as protecting
the lining of the stomach (gastric mucosa) from
acid that the stomach naturally produces. It also
plays a role in making platelets stick together to
form blood clots.

16. MECHANISM OF ACTION
• Non-selective NSAIDs block both types of the COX enzyme, so
while inflammation and pain are reduced, so are the good effects of
prostaglandins such as protection of the stomach lining.
• So ‘Selective NSAIDs’ were advented. These target the COX-2
enzyme that is responsible for pain and inflammation, without
impacting the production of protective factors for the stomach. They
do no have the anti-platelet effects associated with nonselective
NSAIDs and so do not alter clotting. But unfortunately they are
banned now.

17. EFFECTS

18. NSAIDs possess the following
qualities-
• Analgesic effect
• Antipyretic effect
• Anti inflammatory effect
• Anti platelet activity
• They are non-addicting
• They do not produce significant depression of
the CNS.

19. Effects
1. Analgesia:
• PG induce hyperalgesia affecting transducing
property of free nerve ending
• NSAID’S do not effect tenderness induced by
direct application of PG but block pain
sensitizing mechanism induced by bradykinin
and other analgesic substances
• Therefore more effective against inflammatory
associated pain

20. 2. Antipyretic:
• NSAID’s reduces body temp in fever but do
not cause hypothermia in normothermic
individuals.
• Fever during infection is produced through
the generation of pyrogens, interferons which
induce PG production in hypothalamus
raises the temperature set point

21. 3. Anti-inflammatory:
Anti-inflammatory action of NSAID’s is
considered to be inhibition of PG synthesis
at site of injury

22. 4. Antiplatelet aggregatory:
• Dose of most NSAIDS inhibit platelets
aggregation; bleeding time is prolonged
• Aspirin inhibit COX and irreversible action
takes place

23. ADVERSE EFFECTS

24. Adverse effects of NSAID’S
• Gastrointestinal
Gastric irritation, erosions, peptic ulceration,
gastric bleeding/perforation, esophagitis
• Renal
Sodium and water retention, chronic renal
failure, interstitial nephritis, papillary
necrosis (rare)

25. • CNS
Mental confusion, behavioral
disturbances, seizure precipitation
• Haematological
Bleeding, thrombocytopenia, haemolytic
anemia, agranulocytosis

26. • Hepatic
Raised transaminases, hepatic failure
(rare) skin rashes, pruritus, angioedema
• Other
Asthma exacerbation, skin rashes,
puruitus, Nasal polyposis

27. NONSELECTIVE COX INHIBITORS

28. SALICYLATES
(ASPIRIN)

29. SALICYLATES
ASPRIN (prototype)
• Aspirin is acetylsalicylic acid.
• Rapidly converted in the body to salicylic
acid which is responsible for most actions
• Oldest analgesic – anti inflammatory drug
& still widely used

30. • Aspirin is a weaker analgesic than morphine
type drugs: aspirin 600mg ≤ codeine 60mg
• It relieves inflammatory, tissue injury related
pain but is relatively ineffective in severe visceral
and ischemic pain
1. Analgesic, antipyretic,
anti-inflammatory actions:

31. • Analgesic action is mainly due to
obtunding of peripheral pain receptors and
prevention of PG mediated sensitization of
nerve ending
• No sedation, subjective effects, tolerance
or physical dependence is produced

32. • Aspirin resets the hypothalamic thermostat
and rapidly reduces fever by promoting
heat loss (sweating, cutaneous
vasodilatation), but does not decrease
heat production
• Anti-inflammatory action is exerted at high
doses (3—6 g/day or 100 mg/kg/ day)

33. • Signs of inflammation like pain,
tenderness, swelling, vasodilatation and
leukocyte infiltration are suppressed

34. 2. Metabolic effects
• These are significant only at anti-inflammatory
doses.
• Cellular metabolism is increased, specially in
skeletal muscles, due to uncoupling of oxidative
phosphorylation → increased heat production.
• However, hyperglycemia is often seen at toxic
doses: this is due to central sympathetic
stimulation → release of Adrenalin and
corticosteroids.

35. 3. GIT
• Aspirin and released salicylic acid irritate
gastric mucosa — cause epigastric
distress, nausea and vomiting.

36. 4. Urate excretion
Dose related effect is seen:
• < 2 g/day — urate retention and
antagonism of all other uricosuric drugs.
• > 5 g/day — increased urate excretion.
• Aspirin is not suitable for use in chronic
gout because high doses are tolerated
only by few.

37. 5. Blood
• Aspirin, even in small doses, irreversibly
inhibits TXA2 synthesis by platelets
• Thus, it interferes with platelet aggregation
and bleeding time is prolonged to nearly
twice the normal value
• This effect lasts for about a week (turnover
time of platelets)

38. • Long term use of large dose decreases
synthesis of clotting factors in liver and
predisposes to bleeding; can be prevented
by prophylactic Vit K therapy

39. ADVERSE EFFECTS
• Side effects that occur at analgesic dose (0.3—1.5 g/day) are
nausea, epigastric distress, increased occult blood loss in stools.
• The most important adverse effect of aspirin is gastric mucosal
damage and peptic ulceration
• Hypersensitivity and idiosyncrasy though infrequent, these can
be serious. Reactions include rashes, fixed drug eruption, urticaria,
rhinorrhoea, angioedema, asthma and anaphylactic reaction.
Profuse gastric bleeding occurs in rare instances.

40. Anti-inflammatory doses (3—6 g/day) produce
the syndrome called salicylism — dizziness,
tinnitus, vertigo, reversible impairment of hearing
and vision, excitement and mental confusion,
hyperventilation and electrolyte imbalance.
• The dose has to be titrated to one which is just
below that producing these symptoms; tinnitus is
a good guide

41. • Aspirin therapy in children with rheumatoid
arthritis has been found to raise serum
transaminases, indicating liver damage
• Most cases are asymptomatic but it is
potentially dangerous
• An association between salicylate therapy
and ‘Reye’s syndrome’, a rare form of
hepatic encephalopathy seen in children
having viral (varicella, influenza) infection
has been noted

42. • Acute salicylate poisoning: It is more
common in children. Fatal dose in adults is
estimated to be 15—30 g, but is
considerably lower in children.
• Serious toxicity is seen at serum salicylate
levels > 50 mg/dl

43. Precautions and contraindications
• Aspirin is contraindicated in patients who are sensitive to
it and in peptic ulcer, bleeding tendencies, in children
suffering from chicken pox or influenza. Due to risk of
Reye’s syndrome pediatric formulations of aspirin are
prohibited in India and U.K.
• In chronic liver disease: cases of hepatic necrosis have
been reported.

44. • It should be avoided in diabetics, in those
with low cardiac reserve and juvenile
rheumatoid arthritis.
• Aspirin should be stopped one week
before elective surgery (by the consent of
physician)

45. • Given during pregnancy it may be
responsible for low birth weight babies,
delayed or prolonged labor & greater
postpartum blood loss

46. USES
• As analgesic: For headache, backache,
myalgia, joint pain, pulled muscle,
toothache, neuralgias and
dysmenorrhoea; it is effective in low doses
(0.3—0.6g 6-8 hourly)
• As antipyretic: It is effective in fever of
any origin; dose is same as for analgesia

47. • Acute rheumatic fever: Aspirin is the first
drug to be used in all cases; other are
added or substituted only when it fails or in
severe cases (corticosteroids act faster) in
a dose of 4—6 g or 75—100 mg/kg/day (in
divided portions) producing steady state
serum

48. PYRAZOLONES
(PHENYBUTAZONE)

49. PYRAZOLONES
• Antipyrine (phenazone) & amidopyrine
(aminopyrine) were introduced in 1884 as
antipyretic & analgesics

50. Phenylbutazone
• It inhibits COX and is more potent anti-
inflammatory than usually tolerated doses
of aspirin; somewhat comparable to
corticosteroid.
• The analgesic and antipyretic action is
poorer and slower in onset

51. Uses
• Because of risk of fatal agranulocytosis
and other serious reactions,
phenylbutazone and oxyphenbutazone
have been banned
• With the availability of safer NSAID’s,
these drugs should be used only in severe
cases not responding to other drugs

52. PROPIONIC ACID DERIVATIVE
(IBUPROFEN)

53. Propionic acid derivatives
• Ibuprofen was the first member of this class to
be introduced in 1969 as a better tolerated
alternative to aspirin
• Many others have followed.
• All have similar pharmacodynamic properties but
differ considerably in potency and to some
extent in duration of action.

54. • The analgesic, antipyretic and anti-
inflammatory efficacy is rated somewhat
lower than high dose of aspirin
• All inhibit PG synthesis, naproxen being
most potent; but their in vitro potency for
this action does not closely parallel in vivo
anti-inflammatory potency
• They inhibit platelet aggregation and
prolong bleeding time.

55. Adverse effects
• lbuprofen and all its congeners are better
tolerated than aspirin. Side effects are
milder and their incidence is lower.
• Gastric discomfort, nausea and vomiting,
though less than aspirin or indomethacin,
are still the most common side effects
however, even some peptic ulcer patients
are able to tolerate these drugs. Gastric
erosion and occult blood loss are rare.

56. • They are not to be prescribed to pregnant
women and should be avoided in peptic ulcer
patient.
• Safe in lactating mothers

57. Uses
 Ibuprofen is used as a simple analgesic and
antipyretic in the same way as low dose aspirin.
 It is particularly effective in dysmenorrhoea in
which the action is clearly due to PG synthesis
inhibition.
 It is available as an ‘over the counter’ drug.

58.  Ibuprofen and its congeners are widely used in rheumatoid arthritis,
osteoarthritis and other musculoskeletal disorders, specially where
pain is more prominent than inflammation
 They are indicated in soft tissue injuries, fractures, vasectomy, tooth
extraction
 Postpartum and Postoperatively: suppress swelling and
inflammation.
• Ibuprofen has been rated as the safest NSAID by the spontaneous
adverse drug reaction reporting system in U.K.

59. ANTHRANILIC ACID
(MEPHENAMIC ACID)

60. ANTHRANILIC ACID
DERIVATIVE (FENAMATE)
MEPHENAMIC ACID
• An analgesic, antipyretic and anti-inflammatory
drug, known from 1950’s. but has not gained
popularity because of lower efficacy.
• It inhibits PG synthesis and antagonises certain
actions of PGs as well.
• Mephenamic acid exerts peripheral as well as
central analgesic action.

61. Adverse effects
• Diarrhoea is the most important dose related
side effect.
• Epigastric distress is complained, but gut
bleeding is not significant.
• Rashes, dizzines and other CNS manifestations
have occurred.
• Haemolytic anaemia is rare but serious
complication.

62. Uses
• Mephenamic acid is indicated primarily as
analgesic in muscle, joint and soft tissue
pain where strong anti-inflammatory action
is not needed.
• It is quite effective in dysmenorrhoea.

63. • Dose: 250-500mg TDS; MEDOL
250,500mg cap; MEFTAL, PONSTAN
250,500mg tab/cap, 50 mg/5 ml susp

64. ARYL-ACETIC ACID
(DICLOFENAC SODIUM,
ACECLOFENAC)

65. ARYL-ACETIC ACID.
DERIVATIVES.
DICLOFENAC SODIUM
• Analgesic-antipyretic-anti-inflammatory drug,
similar in efficacy to naproxen.
• It inhibits PG synthesis and has short lasting anti
platelet action
• Neutrophil chemotaxis and superoxide
production at the inflammatory site are reduced.

66. Adverse effects
• Generally mild: epigastric pain, nausea,
headache , dizziness, rashes.
• Gastric ulceration and bleeding are less
common.

67. Indications
• Rheumatoid and osteoarthritis, Ankylosing
spondylitis, Dysmenorrhoea
• Post-traumatic postoperative anti-
inflammatory conditions — affords quick
relief of pain and wound edema.
• Dose: 50 mg TDS, 75 mg deep i.m.

68. • VOVERAN, DICLONAC, MOVONAC 50
mg enteric coated tab, 100 mg s.r. tab, 25
mg/mI in 3 ml amp. for i.m. inj.
• DICLOMAX 25, 50 mg tab, 75 mg/3ml inj.
• Diclofenac potassium: VOLTAFLAM
25,50mg tab, ULTRA-K 50mg tab’;
VOVERAN 1% topical gel

69. BANNED
• Diclofenac sodium and potassium are
banned due to cardiovascular risks.
• Aceclofenac is analog of Diclofenac and is
considered safe. Its potency is considered
to be same as of Diclofenac and its gastric
ulcerogenicity is lower.

70. PYRROLO-PYRROLE
DERIVATIVE
(KETOROLAC)

71. PYRROLO-PYRROLE DERIVATIVE
KETOROLAC
• A novel NSAID with potent analgesic and
modest anti-inflammatory activity in
postoperative pain
• It has equaled the efficacy of morphine, but does
not interact with opioid receptors and is free of
respiratory depressant, dependence producing,
hypotensive and constipating side effects.
• It inhibits PG synthesis and is believed to
relieve pain by peripheral mechanism.

72. • In short lasting pain, it has compared favorably
with aspirin.
• Platelet aggregation is inhibited for short
periods.
• Ketorolac is rapidly absorbed after oral and i.m.
administration, it is highly plasma protein bound
and,60%. excreted unchanged in urine

73. USE
• Ketorolac is frequently used in
postoperative pain, pulpitis and acute
musculoskeletal pain 15-3O mg i.m. every
4-6 hours, (max. 120 mg/day).
• lt may also be used for renal colic,
migraine and pain due to bony metastasis.

74. Adverse effects
• Abdominal pain
• Dyspepsia
• Ulceration
• Loose stools
• Drowsiness
• Headache
Dizziness
Nervousness
Pruritus
Pain at injection site
Rise in serum
transaminase
Fluid retention

75. PARA-AMINO PHENOL
DERIVATIVE
(PARACETAMOL)

76. PARA-AMINO PHENOL
DERIVATIVE
• Paracetamol (the dethylated active metabolite
of phenacetin), was also introduced in the last
century but has come to common use only since
1950

77. Actions
• The central analgesic action of paracetamol is
like aspirin i.e. it raises pain threshold, but has
weak peripheral anti inflammatory component.
• Analgesic action of aspirin and paracetamol is
additive.
• Paracetamol is a good and promptly acting
antipyretic

78. • It has negligible anti-inflammatory action.
• Poor inhibitor of PG synthesis in peripheral
tissue but more active on COX in brain.
• One explanation for the discrepancy
between its analgesic-antipyretic and anti-
inflammatory action is poor ability to inhibit
COX in the presence of peroxides which
are generated at site inflammation

79. Adverse effects
• In isolated antipyretic doses paracetamol
is safe and well tolerated
• Safe in pregnancy, children, lactation

80. Uses
• Paracetamol is one of the most commonly
used ‘over the counter’ analgesic for
headache, musculoskeletal pain,
dysmenorrhoea etc.
• It is one of the best drug to be used as an
antipyretic.

81. • Dose to dose it is equally efficacious as
aspirin for non inflammatory conditions
• It is much safer than aspirin in terms of
gastric irritation, ulceration and bleeding
• Can be given to ulcer patients, does not
prolong bleeding time.

82. • Dose 0.5-1g tds in infants
• 80-160mg in children 1-3 years
• 300-600mg in children 9-12 years
• To be given tds

83. SELECTIVE COX-2 INHIBITOR

84. • Due to the theoretical advantage of
inhibiting COX-2 without affecting COX-1
function , some highly selective COX-2
inhibitors were introduced

85. Celecoxib
• It exerts anti-inflammatory , analgesic and
antipyretic action with low ulcerogenic
potential
• Its tolerability is still better but abdominal
pain dyspepsia and mild diarrhoea are
common

86. Rofecoxib
• It is most COX 2 selective inhibitor
• More effective in osteoarthritis rheumatoid
arthritis, dental ,post operative and
musculoskeletal
• Dose : 12.5 – 25 mg once daily. ROFACT ,
ROFEGESIC, ROFIBAX, ROFLAM 12.5 – 25
mg tabs

87. Valdecoxib
• Recently marked selective COX-2 inhibitor
• Similar efficacy & tolerability profile as
rofecoxib
• Plasma t1/2 is 8-11 hrs

88. • In osteoarthritis & rheumatoid arthritis
dose – 10 mg once daily
• For primary dysmenorrhoea or post
operative pain – 20 mg twice daily
• VORTH, VALUS 10 mg tab

89. Banned
• Selective COX2 inhibitors like Valdecoxib,
Rofecoxib and Preferential COX-2
inhibitors like Nimesulide though are
gastroprotective drugs, but are banned in
2004-2005 as they increased the risk of
heart attacks and stroke on long term use.

90. SERRATIOPEPTIDASES

91. SERRATIOPEPTIDASES
• Block the release of certain chemical messengers in the
brain that cause pain and fever.
• It is an enzyme which works by breaking down abnormal
proteins at the site of inflammation and promotes
healing.
• Used as combination medicine with paracetamol,
Aceclofenac for relieving pain and inflammation

92. Aceclofenac + Paracetamol + Serratiopeptidase
combination
• Aceclofenac is a NSAID and Paracetamol is an antipyretic (fever
reducer). They work by blocking the release of certain chemical
messengers in the brain that cause pain and fever.
• Serratiopeptidase is an enzyme which works by breaking down
abnormal proteins at the site of inflammation and promotes healing.
• Highly recommended in dentistry to control pain and inflammation. It
is recommended thrice daily for 3 or 5 days.

93. Aceclofenac + Paracetamol + Serratiopeptidase
combination
• Its use should preferably be avoided in patients
with a history of stomach ulcers or in patients
with active, recurrent stomach ulcers/bleeding. It
should also be avoided in patients with a history
of heart failure, high blood pressure, and liver or
kidney disease.

94. CONCLUSION
• Non-selective NSAIDs are the most recommended
analgesics in dentistry. But it block both types of the
COX enzymes, so while inflammation and pain are
reduced, so are the good effects of prostaglandins such
as protection of the stomach lining and sticking of
platelets together to form clots. So should be avoided in
gastric ulcer, asthmatic, active gastrointestinal bleeding.

95. CONCLUSION
• Combination of Paracetamol, Aceclofenac,
Serratiopeptidase is highly recommended
anti-inflammatory analgesic in dentistry.

96. CONCLUSION
• Mefenemic acid is potent painkiller and
effective in dysmenorrhoea.
• Ibuprofen combination with paracetamol is
effective analgesic and antipyretic. Should
be avoided in asthma and heart related
ailments.

97. Conclusion ……
• Paracetamol is considered as safest, well
tolerated antipyretic and analgesic. Can be
given in pregnancy, children and lactation.
Though it is not effective in acute pain.
• Ketorolac is potent analgesic in acute pain
like pulpitis. Higher doses should be
avoided.