This seminar includes classification, MOA, side effects of NSAIDS.

1. NON-STEROIDAL ANTI-
INFLAMMATORY DRUGS
PRESENTED BY - Dr. AKANKSHA SINGH
(MDS-1ST YEAR)

2. PART -1

3.  Introduction
 History
 Classification
 NSAIDS & prostaglandin
synthesis inhibition
 Major effects of pg synthesis
inhibition
 Salicylates
 Propionic acid derivatives
 Acetic acid derivatives
 Propionic acid derivatives
 Acetic acid derivatives
 Preferential cox-2 inhibitors
 Selective cox-2 inhibitors
 Para-amino phenol derivatives
 NSAIDS used in dentistry
 Role of prostaglandins in
periodontal disease
CONTENTS
PART-1 PART-2

4. INTRODUCTION
• All drugs grouped in this class have analgesic, antipyretic &
anti-inflammatory action.
• They do not produce physical dependence, have no abuse
liability & are weaker analgesics unlike opioids.
• They are also called as non-narcotic, non-opioid & aspirin
like analgesics.
4

5. HISTORY
 Willow bark (Salix alba) has
been used for many centuries.
 Salicylic acid was prepared by
hydrolysis of the bitter glycoside
obtained from this plant.
 Sodium salicylate was used for
fever & pain in 1875.
 Acetylsalicylic acid (aspirin) in
1899.
 Phenylbutyazone was developed
in 1949.
 Indomethacin was introduced in
1963.
5
Willow tree (Salix
alba)

6. CLASSIFICATION

7. 7
ON THE BASIS OF MECHANISM OF ACTION-
A) Non-selective COX inhibitors (traditional NSAIDS)
On basis of their chemical structure:-
1) Salicylates: Aspirin
2) Propionic acid derivatives: Ibuprofen, Naproxen, Ketoprofen,
Flurbiprofen.
3) Fenamate: Mephenamic acid.
4) Enolic acid derivatives: Piroxicam, Tenoxicam
5) Acetic acid derivatives: Ketorolac, Indomethacin, Nabumetone
6) Pyrazolone derivatives: Phenylbutazone, Oxyphenbutazone.

8. B. Preferential COX-2 inhibitors
Nimesulide, Diclofenac, Aceclofenac, Meloxicam, Etodolac.
C. Selective COX-2 inhibitors
Celecoxib, Etoricoxib, Parecoxib.
D. Analgesic-antipyretics with poor anti-inflammatory action
1. Paraaminophenol derivative: Paracetamol
(Acetaminophen).
2. Pyrazolone derivatives: Metamizol (Dipyrone),
Propiphenazone.
3. Benzoxazocine derivative: Nefopam.
8

9. 9
NSAIDS & PROSTAGLANDIN SYNTHESIS
INHIBITION
 In 1971 Vane & co-workers observed that aspirin & some NSAIDS blocked PG
generation.
 Prostaglandins, prostacyclin (PG I2) & thromboxane A2(TXA2) are produced
from arachidonic acid by the enzyme cyclocooxygenase.
 Cyclocooxygenase exists in 2 forms-
-Constitutive (COX-1): Physiological ‘housekeeping’ functions.
-Inducible (COX-2): At the site of inflammation, in brain,
juxtaglomelular cells & in foetus.
 Most NSAIDS inhibit COX-1 & COX-2 non-selectively & inhibit PG synthesis.
 Aspirin inhibits COX irreversibly- acetylation

10. 10
COX- ENZYME
COX-Enzyme (COX-1 & COX-2) catalyse the conversion of arachidonic acid into PG
(G2), an unstable intermediate that is rapidly converted to PGH2. PGH2 is then
metabolised into different structurally related to PGs, including PGE2, PGD2, PGF2,
PGI2 and TXA2.
COX-1
Introduced by Miyamoto et al in 1976. COX-1 derived PGs are essential for
physiological functions. Inhibition of constitutive COX-1 also contributes to
suppression of inflammation, especially in the initial stages.
COX-2
It was introduced by Kujubu et al in 1991. COX-2 derived PGs are non-essential for
physiological functions.

11. FIG- MECHANISM OF ACTION OF
NSAIDS2

12. 12
MAJOR EFFECTS OF PG SYNTHESIS INHIBITION
ANALGESIC EFFECT OF
NSAIDS:-
NSAIDS block the pain
sensitizing mechanism
induced by bradykinin, TNF
α, interleukins (ILs) by
inhibiting COX-2.
ANTIPYRETIC EFFECT OF NSAIDS:-
NSAIDS reduce body temperature in fever.
Fever occurs due to generation of pyrogens- ILs,
TNF α, Interferons which induce PGE2
production in hypothalamus.
NSAIDS block these pyrogens but not the PGE2
injected in the hypothalamus

13. ANTI INFLAMMATORY EFFECTS OF NSAIDS:-
13
Is due to inhibition of COX-2 mediated enhanced PG synthesis at the site of injury.s
In the initial stages inhibition of COX-1 also supresses inflammation.
Inhibition of COX does not depress the production of other mediators like LTs, PAF,
Cytokines etc.
NSAIDS inhibit generation of free radicals.

14. ANTI-PLATELET AGGREGATORY EFFECT OF
NSAIDS-
NSAIDS inhibit synthesis of both pro-aggregatory (TXA2) & anti-aggregatory
(PGI2) prostanoids.
The effect on platelet TXA2 (COX-1 generated) is most.
NSAIDS inhibit platelet aggregation, hence bleeding time is prolonged.
Aspirin is highly active & acetylates COX in circulation before the 1stpass
metabolism in liver.
Hence small doses can be used to exert an antithrombotic effect.
Risk of surgical & anticoagulant associated bleeding is enhanced.
14

15. The inhibition of COX-1 causes inhibition of gastroprotective PGs
because of which there is reduced mucus & HC03 secretion.haemiaA
Gastric pain, mucosal ulceration & blood loss are produced by all
NSAIDS to varying extents.
Stable PG analogues (misoprostol) administered with NSAIDS counteract
their gastric toxicity.
Selective COX-2 inhibitors are also relatively safer..
Paracetamol is a very weak inhibitor of COX and is free of gastric
toxicity.
Hence NSAIDS may cause gastric toxicity.
15
GASTRIC MUCOSAL DAMAGE DUE TO NSAIDS-

16. • COX-1 dependent impairment of renal blood flow & reduction
of GFR. (This worsens the renal insufficiency).
• They cause Na+ & Water retention.
• Ability to cause papillary necrosis on habitual intake.
• Renal effects of NSAIDS are not marked in normal
individuals, but become significant in those with CHF,
hypovolaemia, hepatic cirrhosis, renal disease & in patients
receiving diuretics & antihypertensive drugs.
• Analgesic nephropathy occurs after years of heavy ingestion
of analgesics.
RENAL
EFFECTS
OF
NSAIDS
16

17. ANAPHYLACTOID
REACTIONS-
Aspirin precipitates asthma,
urticaria or rhinitis in certain
individuals.
This occurs due to inhibition of
COX which causes diversion of
arachidonic acid to LTs.
DYSMENORRHOEA-
Levels of PGs are increased in
dysmenorrhoeic women.
Intermittent ischaemia of the
myometrium is responsible for
menstrual cramps.
NSAIDS lower uterine PG levels
hence cause excellent relief. Excess
flow may even be normalized.

18. During foetal circulation ductus arteriosus is kept patent by local
elaboration of PGE2 by COX-2.
Unknown mechanisms switch off this synthesis at birth & the
ductus closes.
When this fails to occur, small doses of Indomethacin or aspirin
bring about closure in majority of cases.
Administration of NSAIDS in late pregnancy is avoided as it promotes
premature closure of ductus.
18
DUCTUS ARTERIOSUS CLOSURE-

19. ACTION COX-1|COX-2 inhibitors COX-2 Inhibitors
Analgesic + +
Antipyretic + +
Anti-inflammatory + +
Antiplatelet aggregatory + -
Gastric mucosal damage + -
Renal salt/water retention + +
Delayed labour + +
Ductus arteriosus closure + ?
Aspirin sensitive asthma
precipitation
+ -
19
TABLE- Features of nonselective COX inhibitors
& selective COX-2 inhibitors

20. 20
SALICYLATES

21. 21
Salicylate are derivatives of salicylic acid that occur naturally in plants & serves as
a natural immune hormone & preservative protecting the plant against infection.
Salicylate can also be found in many medications, perfumes & preservatives.
It can also occur as salicylate esters of organic acids such as acetyl salicylic acid
(aspirin).
It is one of the oldest analgesic anti-inflammatory drugs and is still widely used.

22. 22
ASPIRIN
 Aspirin is acetylsalicylic acid.
 It is rapidly converted in to body to salicylic
acid.
 It’s one of the oldest analgesic/anti-
inflammatory drugs which is still being
used.

23. 23
PHARMACOLOGICAL ACTIONS
• Aspirin is a weaker analgesic than morphine
type drugs (aspirin 600mg is equiv to codeine
60mg)
• It irreversibly inhibits COX-1 & COX-2
activity.
• It is effective in inflammatory, connective tissue
pain but is relatively ineffective in severe
visceral & ischaemic pain.
ANALGESIC,
ANTIPYRETIC,
ANTIINFLAMM
ATORY
ACTIONS-

24. Analgesic action is due to prevention of PG-mediated sensitization of
nerve endings.
It raises the pain threshold by acting centrally like morphine but has no
sedation, tolerance or physical dependence.
Antipyretic effect is by resetting of the hypothalamic thermostat.
Anti-inflammatory action requires higher dosage.
24

25. 25
METABOLIC EFFECTS-
• Are significant only at anti-inflammatory doses.
• Cellular metabolism is increased, esp in skeletal muscles.
(due to uncoupling of oxidative phosphorylation).
• There is increased heat production which causes increase
glucose utilization (esp in diabetics) & the liver glycogen
is depleted.
• Hyperglycaemia occurs at toxic doses.

26. RESPIRATORY EFFECTS-
• The effects are dose dependant.
• At anti-inflammatory doses, respiration is stimulated by
peripheral & central actions. (inc.co2 production)
• Hyperventilation is prominent in salicylate poisoning.
• Rise in salicylate level causes respiratory depression &
respiratory failure.
26

27. ACID-BASE & ELECTOLYTE BALANCE-
• Anti-inflammatory (4-5gm/day) doses produce significant changes in
the acid-base & electrolyte composition of body fluids.
• Initially Respiratory stimulation occurs. There is an increased expelling
of CO2 in spite of increased production ‘Respiratory alkalosis’ occurs.
• This is compensated by increased renal excretion of HCO3
- with Na+, K+
& water.
• Higher doses cause respiratory depression with CO2 retention, while
excess CO2 production continues causing ‘Respiratory acidosis’
27

28. EFFECTS ON CVS-
• Aspirin has no direct effect on heart or blood vessels in therapeutic
doses.
• Direct vasodilatation occurs when larger doses are taken as cardiac
output is increased to meet the peripheral oxygen demand.
• Toxic doses depress vasomotor centre & BP may fall.
• Chronic heart failure maybe precipitated in some patients due to Na+ &
water retention.
28

29. EFFECTS ON GIT-
• Aspirin & released salicylic acid irritate gastric mucosa causing epigastric
stress, nausea & vomiting.
URATE EXCRETION-
• Dose related effect is seen.
• Dose less than 2gm/day- urate retention is seen
• 2-5gm/day- variable effects are seen
• More than 5gm/day- increased urate excretion seen
29

30. EFFECTS ON BLOOD-
• Aspirin in small doses even irreversibly inhibits TXA2 synthesis by
platelets.
• It interferes with platelet aggregation & BT is prolonged. This effect
lasts for about a week (turnover time of platelets)
• Long term intake of large doses decreases synthesis of clotting factors
in liver and hence predisposes to bleeding.
• This is prevented by prophylactic VIT-K therapy.
30

31. PHARMACOKINETICS
Aspirin is absorbed from the stomach & small intestine.
It’s poor water solubility is the limiting factor in absorption.
It is rapidly deacetylated in the gut wall, liver, plasma & other tissues to
release salicylic acid which is the major circulating & active form.
It freely crosses placenta but the entry in brain is slow.
31

32. It is metabolized in liver by conjugation with glycine forming Salicyluric
acid.
The metabolites are excreted by glomerular filtration & tubular secretion.
The elimination of aspirin is dose dependant.
The plasma half- life of aspirin is 15-20 min, half –life of anti-inflammatory
dose may be 8-12hrs while that during poisoning maybe high as 30 hours.
32

33. ADVERSE EFFECTS
 SIDE EFFECTS- At analgesic dose (0.3-1.5g/day) side effects are nausea,
vomiting, epigastric distress, increased occult blood loss in stools. The most
important adverse effect of aspirin is gastric mucosal damage & peptic
ulceration.
 HYPERSENSTIVITY & IDIOSYNCRASY- Rashes, rhinorrhoea,
angioedema, asthma & anaphylactoid reaction.
33

34.  ANTI-INFLAMMATORY DOSES-
a) (3-5g/day) produce Salicylism dizziness, tinnitus, vertigo, reversible
impairment of hearing & vision, excitement, mental confusion,
hyperventilation & electrolyte imbalance.
b) Aspirin therapy in children with rheumatoid arthritis has been found to
raise serum transaminases, indicating liver damage.
c) An association between salicylate therapy & Reye’s syndrome (a form
of hepatic encephalopathy seen in children having viral infection).
d) In adults also long term therapy with high dose aspirin can cause
insidious onset hepatic injury.
34

35.  ACUTE SALICYLATE POISONING-
a) Is more common in children.
b) Fatal dose in adults is estimated to be 15-30gm but it is considered lower in
children.
c) Serious toxicity is seen at serum salicylate levels greater than 50mg/dl.
• Following manifestations are seen- (vomiting, dehydration, electrolyte
imbalance, acidotic breathing, hyper/hypoglycaemia, petechial haemorrhages,
restlessness, delirium, hallucinations, hyperpyrexia, convulsions, coma &
death due to respiratory failure and cardiovascular collapse)
35

36.  TREATMENT-
(Is symptomatic & supportive)
- Done by external cooling & I.v. fluid with Na+, K+, HCO3
- & glucose.
- Gastric lavage to remove unabsorbed drug.
- Alkaline diuresis or haemodialysis to remove absorbed drug in severe
cases.
- Blood transfusion & vit K given if bleeding occurs.
36

37. PRECAUTIONS & CONTRAINDICATIONS
Contraindicated in patients who are sensitive to it & in peptic ulcer, bleeding tendencies, in
children suffering from chickenpox or influenza
Due to risk of Reye’s syndrome pediatric formulations of aspirin are prohibited in India &
the U.K.
Cases of hepatic necrosis in chronic liver disease has also been seen.
Salicylates should be avoided in diabetics, in low cardiac reserve patients.
Aspirin should be stopped 1 week before elective surgery.
If taken during pregnancy, low birthweight babies, delayed or prolonged labour, greater
postpartum blood loss & premature closure of ductus arteriosus. Should be avoided in
lactating mothers.
37

38. INTERACTIONS
Aspirin displaces warfarin, naproxen, sulfonylureas, phenytoin & methotrexate
from binding sites on plasma proteins as toxicity of these drugs may occur. Its
antiplatelet action increases the risk of bleeding in patients on oral anticoagulants.
Aspirin at analgesic doses inhibits tubular secretion of uric acid. Tubular action of
methotrexate is also interfered.
Aspirin blunts diuretic action of furosemide & thiazides & reduces K+ conserving
action of spironolactone.
Aspirin reduces protein bound iodine levels by displacement of thyroxine; but
hypothyroidism does not occur.
38

39. USES
 AS ANALGESIC- For headache, backache, myalgia, joint
pain, pulled muscle, toothache, neuralgias &
dysmenorrhoea. Analgesic effect is maximal at dose of
1000mg approx.
• AS ANTIPYRETIC- Aspirin is effective in fever of any
origin. Paracetamol being safer is generally preferred.
Antipyretics are not useful in fever due to heat stroke only
external cooling lowers body temperature.
39

40. IN ACUTE RHEUMATIC FEVER- Aspirin is the first drug to be used in all
cases. In a dose of (4-5g or 75-100mg/kg/day) brings out marked symptomatic
relief in 1-3 days.
 Dose reduction maybe started after 4-7 days & maintenance doses
(50mg/kg/day) are continued for 2-3 weeks or till signs of active disease
(raised ESR) persist. Withdrawal should be gradual over the next 2 weeks.
RHEUMATOID ARTHRITIS- Aspirin in a dose of (3-5g/day) is effective in
most cases. It produces relief of pain, swelling & morning stiffness but the
progress of the disease process is not affected.
Since large doses of aspirin are poorly tolerated for long periods it is rarely
used now other NSAIDS are preferred.
40

41.  IN OSTEOARTHRITIS- Provides symptomatic relief.
 IN POSTMYOCARDIAL INFARCTION & POSTSTROKE PATIENTS-
By inhibiting platelet aggregation aspirin lowers the incidence of
reinfarction. TXA2 synthesis in platelets is inhibited at low doses. Studies
have demonstrated that aspirin 60-100mg/day reduces the incidence of MI
so is routinely prescribed to post infarct patients.
Aspirin reduces ‘transient ischaemic attacks’ & lowers the incidence of stroke.
But the risk of Stroke in post-MI patients is not reduced.
41

42. • Aspirin is available in forms of tablets like- ASPIRIN 350mg;
COLSPRIN 100/325mg; ECOSPRIN 75, 150, 325mg; DISPRIN 350mg,
LOPRIN 75mg etc.
• Aspirin is also available in form of injectable preparation-
BIOSPIRIN (lysine acetylsalicylate 900mg + glycine 100mg/ vial for
dissolving in 5ml water & i.v. injection.)
42

43. NON-STEROIDAL ANTI-
INFLAMMATORY DRUGS
PRESENTED BY - Dr. AKANKSHA SINGH
(MDS-1ST YEAR)

44. PART-2

45.  Introduction
 History
 Classification
 NSAIDS & prostaglandin
synthesis inhibition
 Major effects of pg synthesis
inhibition
 Salicylates
 Propionic acid derivatives
 Acetic acid derivatives
 Propionic acid derivatives
 Acetic acid derivatives
 Preferential cox-2 inhibitors
 Selective cox-2 inhibitors
 Para-amino phenol derivatives
 NSAIDS used in dentistry
 Role of prostaglandins in
periodontal disease
CONTENTS
PART-1 PART-2

46. 46
PROPIONIC
ACID
DERIVATIVES

47. IBUPROFEN
Ibuprofen was the first member of this class to be introduced in 1969.
Its analgesic, antipyretic & anti-inflammatory efficacy is lower than that
of high dose of aspirin.
47

48. PHARMACOKINETICS
Well absorbed orally, highly bound to plasma proteins (90–99%).
They are likely to decrease diuretic & antihypertensive actions of thiazides,
furosemide & β- blockers just like other NSAIDS.
They inhibit platelet function so use with anti-coagulants should be avoided.
All propionic acid derivatives enter brain, synovial fluid & cross placenta.
They are largely metabolized in liver & excreted in urine as well as bile.
48

49. USES
 Ibuprofen is available as an OTC drug. It is used as a simple analgesic and antipyretic
in the same way as low dose of aspirin.
 It is particularly effective in dysmenorrhoea.
 Ibuprofen is used in rheumatoid arthritis, osteoarthritis and other musculoskeletal
disorders, especially where pain is more prominent than inflammation.
 They are indicated in soft tissue injuries, fractures, tooth extraction, postpartum &
postoperatively.
 Ibuprofen (400mg) has been found equally or more efficacious than a combination of
aspirin (650mg) + codeine (60mg).
49

50. ADVERSE EFFECTS
Ibuprofen is 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.
CNS side effect are headache, dizziness, blurring of vision, tinnitus,
depression.
Rashes, itching and other hypersensitivity phenomena are infrequent.
50

51. 51
ACETIC ACID
DERIVATIVES

52. KETOROLAC
It has a potent analgesic but a modest anti-inflammatory
action.
In postoperative pain it has equalled the efficacy of
morphine, but does not interact with opioid receptors and
is free of opioid side effects.
It inhibits PG synthesis and relieves pain primarily by a
peripheral mechanism.
52

53. PHARMACOKINETICS
Is rapidly absorbed after oral & i.m. administration. It is highly plasma
protein bound & 60% excreted unchanged in urine.
Major metabolic pathway is glucuronidation.
Plasma half-life is 5-7 hours.
53

54. USES
Ketorolac is frequently used in postoperative, dental and acute musculoskeletal pain
Is used in doses of 15-30 mg i.m. or i.v. every 4-6 hours (max 90mg/day).
Orally it is used in doses of 10-20 mg 6 hourly for short term pain management.
Continuous use for more than 5 days is not recommended.
It may also be used for migraine and pain due to bony metastasis.
Short term alternative to opioids for moderate to severe pain.
54

55. • Is available in the form of –
• KETOROL, ZOROVON, KETANOV, TOROLAC 10mg, 30mg tab
• KETLUR, ACULAR 0.5% eye drops; 1-2 drops 2-4 times a day for
noninfective ocular inflammatory conditions.
55

56. 56
PREFERENTIAL
COX-2
INHIBITORS

57. DICLOFENAC SODIUM
57
An analgesic, antipyretic and anti-inflammatory drug
It inhibits PG synthesis and is somewhat COX-2 selective. The
antiplatelet action is not appreciable due to sparing of COX-1.

58. PHARMACOKINETICS
It is well absorbed orally, 99% protein bound and metabolized and
excreted both in urine and bile.
The plasma half-life is ~2 hours.
However, it has good tissue penetrability, and concentration in synovial
fluid is maintained for 3 times longer period than in plasma, exerting
extended therapeutic action in joints.
58

59. USES
Diclofenac is among the most extensively used NSAID.
Is used in rheumatoid and osteoarthritis, bursitis, ankylosing spondylitis,
toothache, dysmenorrhoea, renal colic, post-traumatic and postoperative
inflammatory conditions—affords quick relief of pain and wound edema.
59

60. ADVERSE EFFECTS
Adverse effects of diclofenac are generally mild. Such as:-
• Epigastric pain, nausea, headache, dizziness.
• Gastric ulceration and bleeding are less common.
• Reversible elevation of serum amino-transferases has been reported more
commonly.
• Kidney damage is rare.
60

61. • Is used in doses of- 50mg TDS, BD oral, 75mg deep i.m.
 Is available as-VOVERAN, DICLONAC, DICLOMAX
25, 50 mg Tab.,
 (Diclofenac potassium is available as- VOLTAMAX 25,
50 mg tab, ULTRA- K 50 mg tab, VOVERAN 1% topical
gel)
61

62. ACECLOFENAC
• A moderately COX-2 selective congener of diclofenac having
similar properties.
 DOSE -100 mg BD
 USES = Toothache, Rheumatoid and osteoarthritis, ankylosing
spondylitis
 AVAILABLE AS- ACECLO, DOLOKIND 100mg tab, 200mg
SR tab
62

63. 63
SELECTIVE
COX-2
INHIBITORS

64. They inhibit COX-2 without affecting COX-1 function.
They cause less gastric mucosal damage & lower the risks of ulcer bleeds.
They do not depress TXA2 production by platelets (COX-1 dependent)
Do not inhibit platelet aggregation or prolong bleeding time.
These are used in patients with high risk of peptic ulcer, perforation or bleeds.
They must be avoided in patients with history of ischaemic heart disease,
hypertension, cardiac failure etc.
COX-1 generated PGs also have a role in inflammation so the COX-2 inhibitors
may not have as broad range of efficacy as traditional NSAIDS.
64

65. ETORICOXIB
Has the highest COX-2 selectivity.
Is suitable for treatment of osteo/rheumatoid/acute gouty arthritis, ankylosing
spondylitis, dysmenorrhoea, acute dental surgery pain & similar conditions without
affecting platelet function or damaging gastric mucosa.
Plasma half -life is 24hours.
COX-2 inhibition without COX-1 inhibition will preserve the synthesis of thromboxane
& inhibit production of prostacyclin which causes an imbalance & increases risk of
thrombosis.
65

66. SIDE EFFECTS
 Dyspepsia, pedal edema, rise in BP, dry mouth, aphthous ulcers,
paresthesias.
IS AVAILABLE IN FORMS OF- (60-120mg) OD ETOSHINE,
TOROCOXIA, ETOXIB, NUCOXIA
66

67. 67
PARA- AMINO PHENOL
DERRIVATIVES

68. PARACETAMOL
Phenacetin introduced in 1887 was extensively used as analgesic-
antipyretic, but is now banned because it was implicated in
analgesic abuse nephropathy.
(Acetaminophen) the de-ethylated active metabolite of
phenacetin was introduced in the last century but gained
popularity only after 1950.
68

69. ACTIONS
s
It raises pain threshold, but has weak peripheral anti-inflammatory component.
Paracetamol has negligible anti-inflammatory action.
It is a poor inhibitor of PG synthesis in peripheral tissues, but more active on COX
in the brain. In contrast to aspirin -
1) It does not stimulate respiration
2) It does not increase cellular metabolism
69

70. 3) It does not affect acid base balance
4) No effect on CVS
5) No effect on platelet function
70

71. PHARMACOKINETICS
Paracetamol is conjugated in the liver as the inactive glucuronide and
sulphate. Paracetamol is well absorbed orally, only about 1/4th is protein
bound in plasma and it is uniformly distributed in the body.
• Half Life is 2-3 hrs
• Effects after an oral dose last for 3–5 hours.
71

72. USES
Most commonly used analgesic for Headache, Musculoskeletal pain.
Unlike aspirin it does not increase the risk of Reye syndrome.
It does not cause any gastric complications hence can be used in patients
where other NSAIDS are contraindicated.
Best drug to be used as Antipyretic.
Can be used in all age groups (infants to elderly), pregnant/lactating
women, & in patients to whom aspirin is contraindicated.
72

73. ACUTE PARACETAMOL POISONING
Patients having liver diseases, history of heavy alcohol consumption, HIV
infection etc are at a risk.
Is not recommended in premature infants for fear of hepatotoxicity.
Toxicity occurs in adults if more than 150mg/kg dose is in taken.
Fatality is common in dose more than 250mg/kg.
73

74. EARLY MANIFESTATIONS- (24hours) Nausea, vomiting, abdominal
pain, liver tenderness. Lab tests are normal.
(24-72 hours)- Nephrotoxicity. Increase in serum transaminases, bilirubin
seen.
(>72 hours)- hepatotoxicity occurs and signs of jaundice & liver failure
start to occur.
Death usually occurs in this stage from multiorgan system failure.
74

75. TREATMENT
If patient is brought early, vomiting should be induced or gastric lavage
done.
Activated charcoal is given to prevent further absorption.
N-ACETYLCYSTEINE infused i.v. or given orally is the specific
antidote.
Replenish hepatic glutathione as it prevents binding of toxic metabolite to
other cellular constituents.
75

76. 76
NSAIDS USED IN
DENTISTRY

77. NSAIDS have been shown to be more effective at reducing pain than opioid analgesics &
are hence recommended as first-line therapy for acute pain management.
In cases of mild to moderate pain with little inflammation paracetamol or low dose of
ibuprofen is advised.
In post extraction cases or similar are advisable.
77

78. During pregnancy- paracetamol is safest drug of choice.
Acute but short-lasting pain – ketorolac, diclofenac, nimesulide or aspirin
are used.
Patients suffering from gastric intolerance to traditional NSAIDs or
predisposed patients- etoricoxib or paracetamol are advised.
Patients with history of asthma- nimesulide or other COX-2 inhibitors
used.
78

79. 79
ROLE OF
PROSTAGLANDINS IN
PERIODONTAL DISEASE

80. (PROSTAGLANDINS AS A MEDIATOR OF BONE
RESORPTION)
Inflammatory mediators released as a result of cellular activation leads to tissue
destruction & bone resorption. (Dharshini.D 2020)4
Prostaglandins play key role in trauma response. For example, PGE2 and PGI2 have
significant vasodilatory properties, whereas platelet-released TXA2 is known as a
vasoconstrictor that increases platelet aggregation. (Lisowska B et al 2018)5
80

81. Tissue culture experiments have also shown that stimulation of bone resorption
by PGs is correlated with increased Osteoclastic activity, in common with the
bone-resorbing hormones parathormone and 1,25-dihydroxycholecalciferol.
(Harvey W et al 2020)6
The manifestation of periodontitis related inflammatory reaction is inevitably
bound to the production of Prostaglandins E2 & D2 which have been suggested
to mediate osteoclastic & osteogenic effects within the tissue. PGE2 is
increased in periodontal sites & causes inflammation & attachment loss. (Ern
C et al 2019)7
81

82. (EFFECTS OF NSAIDS ON BONE HEALING)
PGs produced by bone cells can have either a stimulatory or resorptive effect on bone
formation.
Studies have demonstrated that aspirin and other non-steroidal anti-inflammatory
drugs (NSAIDs) activate cytokines and mediators on osteoclasts, osteoblasts and their
constituent progenitor cells located around the remodelling area. These cells contribute
to a complex metabolic scenario, resulting in degradative or synthetic functions for
bone mineral tissues. (Xie Y et al 2019)8
82

83. Negative effect of NSAIDS has been
seen on bone healing. In pediatric
patients, NSAIDs did not have a
significant effect. (Wheatley BM et al
2019)9
Studies in mice suggest that
nonselective COX inhibitors can
negatively impact orthopedic healing.
(Huss M et al 2019)10
83
van Esch RW, Kool MM, van As S. NSAIDs can have adverse effects on bone healing. Medical hypotheses. 2013 Aug 1;81(2):343-6.
Fig : NSAIDS influence allostasis
during hypoxia

84. (EFFECTS OF NSAIDS ON PERIODONTAL
DISEASE)11
NSAIDs can affect the alveolar bone by either stimulating or inhibiting bone formation or
preventing the progression of alveolar bone loss in periodontitis patients.
The products of the cyclooxygenase pathway might be responsible for bone loss occurring
in periodontal disease, and controlling this regulatory step can prevent bone destruction.
84

85. (NSAIDS AS HOST MODULATORY AGENTS)12
HOST MODULATION THERAPY- Aims to reduce tissue destruction and
stabilize or even regenerate the periodontium by modifying or downregulating
destructive aspects of host response and upregulating protective or regenerative
responses.
To lower excessive levels of enzymes, cytokines, prostanoids [PGE2]), as well as
to modulate osteoclast functions, host modulation therapy (HMT) are being used.
85

86. The therapeutical agents or perioceutics that are mainly used to control
periodontitis is a rising branch in the treatment of periodontal diseases
along with mechanical debridement.
Nonsteroidal anti-inflammatory drugs (NSAIDS) like flurbiprofen,
ketoprofen, indomethacin and naproxen are found to be beneficial in
inhibiting gingivitis and periodontitis.
These effects are seen because of the blocking of the activity of
cyclooxygenase isoenzymes (COX-1 & COX-2).
86

87.  There is ample evidence presented here
supporting the role of non-steroidal anti-
inflammatory drugs in the treatment of
periodontal disease.
 These drugs may serve as the potential
adjunctive treatments.
 Research into NSAIDs in periodontal
therapy may ultimately prove to have only
opened the door to research into host
modulation as an additional but exciting,
approach to periodontal disease prevention
and treatment.
87
CONCLUSION

88. Thank you

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