A presentation describing pain, analgesia, formation of prostaglandins along with a detailed description of NSAIDS, the mechanism of action, classification and an in depth discussion of each class along with key points to be kept in mind for dentists

1. NSAIDS
DR HRISHITA
MDS-PART 1

2. PAIN
o PAIN or ALGESIA is an unpleasant sensory &
emotional experience associated with actual or
potential tissue damage or described in terms of
these damage - IASP

3. Components of Pain
oPain Perception
oPain Reaction

4. ANALGESIC
o Analgesic is a drug that selectively relieves pain by acting on
the CNS or on peripheral pain mechanisms, without
significantly altering the consciousness

5. CLASSIFICATION
Opioid/
Narcotic/
Morphine like
Analgesic drugs
Non Opioid/
Non Narcotic/
Aspirin like/
Nonsteroidal Anti-
inflammatory drugs
1) 2)

6. NSAIDS vs OPIOID
o Do not depress CNS
o Do not produce physical dependence
o Have no abuse liability
o Act on peripheral pain mechanisms
o Acts on CNS to raise pain threshold

7. PROSTAGLANDINS
o Derivatives of arachidonic acid
o Main PGs in humans are PGE2 ,PGF2α ,PGI2

8. MEMBRANE
PHOSPHOLIPIDS
ARACHIDONIC ACID
PROSTAGLANDINS LEUKOTRIENES
PGI2
PGF2α
PGE2
PGD2
TXA2
PGE2
PGI2
TXA2
Other mediators (TNF-α,
ILs, BRADYKININ)
Cyclooxygenase
(COX)
Lipooxygenase
(LOX)
o Pain
o Inflammation
o Fever
COX-
1
COX-
2
Phospholipase A2

9. COX-1 COX-2
o Inducible enzyme
o Inflammatory response
o Pain
o Fever
o Constitutive enzyme
o Tissue Homeostasis
o Protect gastric mucosa
o Renal functions

10. NSAIDS
Nonsteroidal Anti-inflammatory drugs are the drugs with
o Analgesic
o Antipyretic
o Anti-Inflammatory action

11. MEMBRANE
PHOSPHOLIPIDS
ARACHIDONIC ACID
PROSTAGLANDINS LEUKOTRIENES
PGI2
PGF2α
PGE2
PGD2
TXA2
PGE2
PGI2
TXA2
OTHER MEDIATORES (TNF-
α, ILs, BRADYKININ)
Cyclooxygenase
(COX)
Lipooxygenase
(LOX)
COX-
1
COX-
2
Phospholipase A2
NON
SELECTIVE
COX
INHIBITORS
SELECTIVE
COX-2
INHIBITORS

12. ANTI-PYRESIS
ANALGESIA
CLOSURE OF DUCTUS
ARTERIOSUS
REDUCES
DYSMENORRHOEA
ANTI-
THROMBOTIC
DELAY LABOUR
ACTIONS
ANTI-
INFLAMMATORY

13. ANALGESIA
ACT CENTRALLY
ACT
PERIPHERALLY
NSAIDS
INHIBIT PAIN

14. ANTIPYRESIS
o Resets thermal set point of the hypothalamus
o Inhibits production of pyrogens
o Causes vasodilatation and sweating to reduce
temperature

15. ANTI-INFLAMMATORY
NSAIDS reduces inflammation by –
o Inhibiting PG synthesis in the peripheral tissues
o Reducing capillary permeability
o Inhibition of neutrophil aggregation and activation

16. ANTI-THROMBTIC
THROMBOXANES A2 (PROAGGREGATORY)
NSAIDS
PROSTAGLANDINS I2 (ANTI-AGGREGATORY)
Therapeutic doses of most NSAIDS inhibit platelet aggregation

17. DUCTUS ARTERIOSUS CLOSURE

18. DYSMENORRHOEA
o Dysmenorrhoea is associated with increased PG synthesis
by endometrium

19. PARTURITION
o Sudden spurt of PG synthesis by uterus triggers
labour and facilitates its progression
o NSAIDS have the potential to delay and retard
the labour

20. o GASTROINTESTINAL-
Gastric irritation, erosion, peptic ulceration, gastric bleeding, perforation, esophagitis
o RENAL-
Na+ & water retention, chronic renal failure, interstitial nephritis, papillary necrosis
(rare)
o HEPATIC-
Raised transaminases, hepatic failure (rare)
ADVERSE EFFECTS

21. o CNS-
Headache, mental confusion, behavioral disturbances, seizures
o ANAPHYLAXIS-
Asthma exacerbation, nasal polyposis, skin rashes, pruritus,
angioedema
o HEMATOLOGICAL-
Bleeding, thrombocytopenia, haemolytic anaemia, agranulocytosis

22. NSAIDS
DIURETICS
ANTICOAGULANTS
ANTIHYPERTENSIVES
ANTIDEPRESSANTS
DRUG INTERACTIONS

23. CLASSIFICATION OF NSAIDS

24. o NON SELECTIVE COX INHIBITORS
GROUPS NAME OF DRUG
Salicylates Aspirin
Propionic Acid Derivatives Ibuprofen, naproxen
Antranilic Acid Derivatives Mefenamic Acid
Aryl-acetic Acid Derivatives Diclofenac, Aceclofenac
Oxicam Derivatives Piroxicam, Tenoxicam
Pyrrolo-pyrrole Derivatives Ketorolac
Indole Derivative Indomethacin
Pyrazolone Derivatives Phenylbutazone,oxyphenbutazone

25. o PREFERENTIAL COX-2 INHIBITORS
o Nimesulide
o Meloxicam
o Nabumetone
o SELECTIVE COX-2 INHIBITORS
o Celecoxib
o Etoricoxib
o Parecoxib

26. SALICYLATES
o Salicylates are the esters of SALICYLIC ACID
o ASPIRIN is Acetylsalicylic Acid
o Trade Name :
Aspirin
Colsprin
Ecosprin
Disprin
Losprin

27. PHARMACOKINETICS
o Rapidly deacetylated in the gut wall, liver and plasma
o Salicylic acid is the major circulating and active form
o 80% bound to plasma proteins
o Enters BBB, freely crosses placenta
o Plasma t ½ = 4 hours

28. PHARMACOLOGICAL
ACTIONS
ANTI-PYRETIC
ANALGESIC
ANTI-INFLAMMATORY
URATE
EXCRETIONMETABOLIC EFFECTS
RESPIRATION &
ACID BASE
BALANCE
BLOOD
CVS
GIT

29. o ADVERSE EFFECTS
AT ANALGESIC (300-
1500mg/day)
o Nausea
o Vomiting
o Epigastric distress
o Occult blood loss in stool
o Gastric mucosal damage and
ulcerations
AT ANTI-INFLAMMATORY
(3-6g/day)
o Dizziness
o Tinnitus
o Vertigo
o Hyperventilation
o Mental confusion

30. o SALICYLISM
o Salicylism is Salicylate Poisoning, also known as Aspirin
Poisoning
o Syndrome usually develops when the plasma salicylate
level exceeds 25mg%
o Serious toxicity is seen at serum salicylate levels >
50mg/dl
o It is more common in children

31. SYMPTOMS
o Dizziness
o Tinnitus
o Vertigo
o Hyperventilation
o Electrolyte imbalance
o Reversible impairment of hearing and vision
o Mental confusion

32. MANAGEMENT
o Hospitalisation
o External cooling and i.v fluid
o Gastric lavage (activated charcoal)
o Sodium Bicarbonate (i.v)
o Haemodialysis (severe cases)
o Blood transfusion and vitamin K (if bleeding occurs)

33. o HYPERSENSITIVITY
o MANIFESTATIONS
o Skin Rashes
o Urticaria
o Rhinitis
o Bronchospasm

34. o REYE’S SYNDROME
o Occurs in children
o Viral infection
o SYMPTOMS
o Persistent vomitting, lethargy, rapid
breathing, seizures, loss of
consciousness
o SIGNS
o Hepatic damage with fatty liver
o Encephalopathy

35. o Peptic ulcers and GIT problems
o In G-6-PD deficiency- Hemolytic anemia is seen
o Prolonged use of salicylates predisposes to prolonged bleeding
o In pregnancy, delays the onset of pregnancy and increases chances of post
partum haemorrhage
o In newborns, causes premature closure of ductus arteriosus
o Analgesic nephropathy-
o Slow progressive renal failure may occur due to chronic use of high
dose salicylates

36. CONTRAINDICATIONS
o Sensitivity
o Peptic ulcers
o Bleeding tendencies
o Children suffering from Chicken pox/ Influenza
o Chronic liver disease
o Diabetes
o Frank CHF
o Juvenile Rheumatoid Arthritis
o Pregnancy, Lactating mothers
o G-6-PD deficiency

37. USES AND DOSAGES
CONDITION DOSAGE
ANALGESIC 0.3-0.6g, 6-8 hourly
ANTIPYRETIC 0.3-0.6g, 4-6 hourly
ACUTE RHEUMATIC FEVER 4-8g daily in divided doses
RHEUMATOID ARTHRITIS 3-5g/day
OSTEOARTHRITIS 300-600mg, 6-8 hourly
POST MYOCARDIAL INFARCTION/
POSTSTROKE
60-150mg/day
ANTIPLATELET AGENT 75-100mg single dose

38. PARA-AMINO PHENOL DERIVATIVES
o PARACETAMOL (acetaminophen) is the
deethylated active metabolite of Phenacetin
o ACTIONS
Analgesic Promptly acting Negligible
(raises pain threshold) Antipyretic Antiinflammatory
action

39. PHARMACOKINETICS
o It is well absorbed orally
o About ¼ th is protein bound in plasma
o Plasma t1/2 is 2- 3 hours
o Effect after an oral dose last for 3-5 hours
o Metabolised in liver
o Excreted in urine

40. USES AND DOSAGE
It is most commonly used over the counter analgesics for :
o Headache
o Musculoskeletal pain
o Toothache
o Dysmenorrhoea
o Osteoarthritis
ADULTS :- 500- 1000 mg
INFANTS :- 50 mg
CHILDREN (1- 3 years) :- 80 -160 mg
(4-8 years) :- 240 -320mg
(9-12 years) :- 300-600mg

41. ADVERSE EFFECTS
o Safe and well tolerated
o Rarely nausea and rashes may occur
o Hepatotoxicity
o Nephrotoxicity

42. ACUTE PARACETAMOL POISONING
o Serious toxicity with large dose - >150mg/kg or >10g in adults and fatality with
>250mg/kg
o Early manifestations – Nausea, Vomiting, abdominal pain, liver tenderness
o After 12-18 hours – Centrilobular hepatic necrosis, Renal tubular necrosis,
Hypoglycaemia, Coma
o Alcoholics and premature infants are more prone to hepatotoxicity

44. TREATMENT
o Activated Charcoal given to prevent further absorption
o Treatment with sulfhydryl compounds such as cysteamine, 1-
methionine and n-acetyl cysteine is beneficial
o In acute poisoning, nac is administered by infusion initially , in
the dose of 150mg/kg in 5 minutes
o Charcoal hemoperfusion is effective in severe liver failure
o Hemodialysis may be required in cases with acute renal failure

45. ARYLACETIC DERIVATIVES
o DICLOFENAC SODIUM
o An analgesic, antipyretic and anti-
inflammatory drug
o Trade name – VOVERAN, DICLONAC

46. PHARMACOKINETICS
o Well absorbed orally
o 99% protein bound
o Metabolised in liver and Excreted- urine, bile
o t1/2 – 2 hours
o Good tissue permeability

47. USES
o Antiinflammatory agent
o Rheumatoid Arthritis
o Severe Osteoarthritis
o Ankylosing Spondylitis
o Toothache
o Dysmenorrhea
o Post Operative Pain
ADVERSE EFFECTS
Generally mild
o Epigastric pain
o Nausea
o Headache
o Dizziness
o Rashes
o Reversible elevation of serum
aminotransferases may occur
o Avoided in Children,
Pregnant Women, Nursing
Mothers, Renal Disease
Patients

48. PYRROLO-PYRROLE DERIVATIVES
o KETOROLAC
o Potent analgesic and modest anti-inflammatory activity
o Longer duration of action
o Trade name : KETOROL, KETANOV, TOROLAC

49. PHARMACOKINETICS
o Rapidly absorbed after oral and i.m. administration
o Highly plasma protein bound
o Metabolized in Liver and 60% excreted unchanged in
urine
o t1/2 : 5-7 hours

50. ADVERSE
EFFECTS
o Frequently used in post
operative dental pain
o Renal colic
o Migraine
o Bony metastasis
Dosage recommended for short
term management of moderate
pain is 10-20mg 6 hourly orally
o Nausea
o Abdominal pain
o Dyspepsia
o Ulceration
o Loose Stools
o Drowsiness
o Pain at site of injection
o Rise is serum transaminase
o Fluid Retention
USES

51. Analgesic Efficacy of Paracetamol Vs
Ketorolac after Dental Extractions
Tinesh Dayaa Rao, Dr. M.P. Santhosh kumar M.D.S.
o Evaluated analgesic efficacy of paracetamol(500mg) and ketorolac(10mg)
after dental extractions and concluded that Ketorolac 10 mg is more
effective than Paracetamol 500mg as an analgesic after dental extractions

52. PROPIONIC ACID DERIVATIVES
o IBUPROFEN was the first member of the class
to be introduced
o Better tolerated than Aspirin
o Trade name : BRUFEN, EMFLAM, IBUGESIC
o Dosage : 400-600mg TDS

53. PHARMACOKINETICS
o Well absorbed orally
o Highly bound to plasma protein-90-99%
o Enter brain, synovial fluid and cross placenta
o Metabolized in liver and excreted in urine

54. USES
o Simple analgesic and antipyretic
o Rheumatoid arthritis
o Osteoarthritis
o Soft tissue injuries
o Tooth extraction
o Fractures
o Better tolerated than aspirin
o Gastric discomfort, nausea, vomiting
o Headache, dizziness, tinnitus,
depression, blurring of vision
o Aspirin induced asthma
o Not to be prescribed to pregnant
woman and patients with peptic ulcers
ADVERSE EFFECTS

55. Comparison Of Paracetamol, Ibuprofen, And Diclofenac Potassium
For Pain Relief Following Dental Extractions And Deep Cavity
Preparations
Giath Gazal and Khalid H. Al-Samadani
o To compare the effectiveness of different oral analgesics for relieving pain and
distress in adults following the extraction of teeth and deep cavity preparations
under local anesthesia and concluded that diclofenac potassium was more
effective than paracetamol or ibuprofen for reducing postoperative analgesia in
adults who are having teeth extracted

56. ANTHRANILIC ACID DERIVATIVES
o MEPHENAMIC ACID
o Analgesic, Antipyretic and Anti-inflammatory
o Trade name : MEFTAL, MEDOL, PONSTAN
o Dosage : 250-500mg TDS

57. PHARMACOKINETICS
o Slow oral absorption
o Highly bound to plasma proteins
o Excreted in urine as well as bile
o Plasma t1/2 : 2-4 hours

58. USES
o Primarily as analgesic in
muscle, joint & soft tissue
pain
o Effective in Dysmenorrhea
ADVERSE EFFECTS
o Diarrhoea
o Epigastric distress
o Hemolytic anemia

59. OXICAM DERIVATIVES
o PIROXICAM
o Potent anti-inflammatory and good analgesic-antipyretic
actions
o Trade name : DOLONEX, PIROX
o Dosage : 20mg BD

60. USES
o Rheumatoid arthritis,
Osteoarthritis
o Ankylosing Spondylitis
o Acute Gout
o Musculoskeletal injuries
ADVERSE EFFECTS
o Heart burn
o Nausea
o Anorexia
o Rashes

61. INDOLE DERIVATIVES
o INDOMETHACIN
o Potent anti-inflammatory drug
o Prompt antipyretic action
o Trade name : IDICIN, INDOCAP, ARTICID
o Dosage : 25-50mg BD-QID

62. USES
o Potent anti-inflammatory
when other drugs not
acting
o Ankylosing spondylitis
o Acute gout
o Acute exacerbation of
destructive arthropathies
o Prominent adverse effects,
so not used commonly
ADVERSE EFFECTS
o GI- Nausea, gastric
irritation, bleeding,
anorexia and diarrhea
o CNS- Frontal headache,
dizziness, mental
confusion, depression,
psychosis
o Others- Leukopenias,
rashes, hypersensitivity,
increased bleeding

63. PYRAZOLONES DERIVATIVES
o PHENYBUTAZONE, OXYPHENBUTAZONE, METAMIZOL
o Potent anti inflammatory drugs
o Slow onset
o Have weak analgesic and antipyretic action (EXCEPT
METAMIZOL)
o ADVERSE EFFECTS-
-Gastric toxicity
-CNS side effects
-Na+ water retention
-Hypersensitivity reactions

64. PREFERENTIAL COX-2 INHIBITORS
o Selectively blocks COX-2
o Less interference with protective action of COX 1
o They are :
NIMESULIDE
MELOXICAM
NABUMETONE

65. NIMESULIDE
o Relatively weak inhibitor of PG synthesis
o Blocks COX 2 selectively
o Has analgesic, antipyretic and anti-inflammatory effect
o Dose : 100mg BD

66. USES
o Post operative Pain
o Sport injuries
o Ear, nose, throat disorders
o Dental surgeries
o Backache
o Dysmenorrhoea
o Osteoarthritis
o Fever
ADVERSE EFFECTS
o GI - Epigastralgia
- Heart burn
- Nausea
- Loose motions
o Dermatological – Rashes
- Pruritus
o CNS – Somnolence
- Dizziness
o Nephrotoxicity
o Hepatotoxicity, Fulminant
hepatic failure
o Banned in UK, Australia,
Canada, Turkey, Spain

67. SELECTIVE COX-2 INHIBITORS
o Inhibits COX 2 without affecting COX 1
o THEY CAUSE:- Little gastric mucosal damage
Little occurrence of peptic ulcer
Do not depress TXA2
o HIGH RISK OF MYOCARDIAL INFARCTION
o They are :-
CELECOXIB
ETORICOXIB
PARECOXIB

68. NSAIDS IN DENTISTRY
MILD TO
MODERATE PAIN
WITH
INFLAMMATION
o PARACETAMOL
o LOW DOSE
IBUPROFEN
POST
EXTRACTION/
SIMILAR
EXTRACTION PAIN
o KETOROLAC
o IBUPROFEN
o DICLOFENAC
o ASPIRIN
GASTRIC
INFLAMMATION TO
CONVENTIONAL
NSAIDS
o ETORICOXIB
o PARACETAMOL

69. NSAIDS IN DENTISTRY
ANAPHYLAXIS/
ASTHMA
o NIMESULIDE
o COX2 INHIBITORS
PEDIATRIC
PATIENTS
o PARACETAMOL
PREGNANCY
o PARACETAMOL

70. KEY POINTS FOR DENTISTS
o NSAIDs should be advised to be taken after food
o Preferred analgesics for patients with peptic ulcer are paracetamol and selective
COX-2 inhibitors
o Patients on aspirin should inform the doctor if surgery/dental procedure is planned.
Advise patient to report signs of bleeding, if any
o Aspirin should be stopped for a week before elective surgeries
o The preferred analgesic in patients with chronic renal failure is paracetamol

71. REFERENCES
o David E Golan Principles of Pharmacology 4th Edition
o R.S. Satoskar Pharmacology Revised 23rd Edition 2013
o K.D. Tripathi Pharmacology For Dentistry 2nd Edition
o Tara V Shanbhag Pharmacology for Dentistry 2nd Edition

72. THANK YOU