a short discussion on analgesics

2.  Dental pain is usually acute in nature and is
the main reason for which patient comes to
the dentist
 A protective mechanism to warn of damage
or the presence of disease
 Part of the normal healing process

3. • Selectively relieve pain by acting in CNS or
on peripheral pain mechanisms, without
significantly altering consciousness.
•Used when the noxious stimulus cannot be
removed or as an adjuvant to more etiologic
approach to pain such as antibiotic treatment
of apical tooth abscess.

4. Analgesics
Narcotic
analgesics
Non narcotic
analgesics

6. •NSAIDs mainly block the prostaglandin
generation.
•PG from arachidonic acid by cyclo-
oxygenase(COX)
•They inhibit the action of COX1 and COX2
enzyme found in blood vessels, stomach and
kidney.

7. A. Nonselective COX inhibitors(
conventional)
• Salicylates : Aspirin, calcium carbaspirine,
choline salicylates.
• Propionic acid derivatives: Ibuprofen,
Naproxen, Ketoprofen, Flurbiprofen,
Oxaprozin.
• Anthranilic acid derivatives : Mephenamic
acid.
• Aryl acetic acid derivative : Diclofenac ,
Aceclofenac.

8. • Oxicam derivatives: Piroxicam, Tenoxicam.
•Pyrrolo-pyrrole derivatives: Ketorolac.
• Indole derivatives: Indomethacin ,Sulindac
Tolmetin , Etodolac.
•Pyrazolone derivatives: Phenylbutazone,
Oxyphenbutazone.
B. Preferential COX-2 inhibitors
Nimesulide , Meloxicam , Nabumatone.

9. D. Analgesic – antipyretics with poor
antiinflammatory action
1. Paraaminophenol derivative :
paracetamol (Acetaminophen).
2. Pyrazolone derivatives : Metamizol
(Dipyrone), Propiphenazone.
3. Benzoxazocine : Nefopam.
C. Selective COX-2 inhibitors
Celecoxib , Etoricoxib, Parecoxib,
Rofecoxib

10.  PG play a role in the erythema, edema and
fever associated with inflammation and
generate pain either by its direct action or by
sensitizing pain receptors.

12. COX-1
Gastric ulcers
Bleeding
Acute renal failure
COX-2
Reduce inflammation
Reduce pain
Reduce fever

13. 1.Analgesic action
Blocks the pain sensitizing mechanism
induced by bradikinin, tumour necrosis factor
alfa, interleukins and other factors.
•used in dental caries and postextraction
pain.

14. 2.Antipyretic action
They block the action of pyrogens & help to
reduce the body temperature.
3. Anti- inflammatory
PG are only one mediator of the inflammation.
Anti-inflammatory potency of different
compounds correspond with their potency to
inhibit COX.

15. 4.Dysmenorrhea
PG synthesis in endometrium causes
uncoordinated uterine contraction with
compressed blood vessel results in uterine
ischemia and pain.
5.Antiplatelet Function/ Bleeding: Platelet
aggregation is due to thomboxane.
NSAIDs inhibit TXA2.

16. 6.Closure of ductus arteriosus
7.Gastric mucosal damage
8. Renal effect
COX-1 dependant impairment of renal blood
flow and reduction of GFR. Renal efferent is more
significant in hypovolemia, hepatic cirrhosis.

17. 9. Anaphylactic reaction
Aspirin precipitated asthma, angioneurotic
swelling and urticaria or rhinitis in some
individuals.
10. Parturition
Sudden spurt of PG synthesis by uterus
probably triggers labour and facilitates its
progression.

18. SALICYLATES
ASPIRIN
 It is developed by Bayer in 1899.
 Derived from salix, a Latin name willow tree.
 Aspirin is acetylsalicylic acid.
 It is rapidly converted into salicylic acid which
is responsible for most of the actions.
 Trade Name: Aspirin 350 mg
Disprin 35 mg
Ecosprin 75, 150, 325 mg
Loprin 75 mg

19. Mechanism of action for therapeutic use
• It acts both centrally but peripheral effect is
more.
• It has therapeutic action of analgesic and
antipyretic at low dose.
•At high dose anti-inflammatory action.

20.  Analgesic and anti-inflammatory action Due
to prevention of PG mediated sensitization of
nerve endings. It inhibits bradykinin and
histamine that brings about inflammatory
reaction.
Analgesic dose- 0.3-0.6 gm for toothache,
headache, joint pain, dysmenorrhea. Anti-
inflammatory dose- 3-5 g/day.

21. Antirheumatic action
Bradykinin and PG are inhibited by aspirin
which cause vasodilatation, increase in
capillary permeability that is sign of
inflammation.
• Dose- 3-5 g/ day.
Antipyretic action
Aspirin resets the hypothalamic thermostat
and rapidly reduces fever by promoting heat
loss( sweating, cutaneous vasodilatation) but
does not decrease heat production.

22. Antiplatelet effect
It causes acetylation of COX in nucleus of
platelet & reduces thromboxane synthesis.
Therapeutically used in cerebral or myocardial
infarction.
• Dose-60-100 mg / day.
Other uses
After birth, if ductus arteriosus is kept patent, it
brings about closure of ductus within few hours
by inhibiting PG production.

23. Uses
• As an analgesic- 0.3-0.6 gm 8 hourly.
• As an antipyretic.
• Acute rheumatic fever- 4-6 gm/ day.
• Rheumatoid arthritis-3-6 gm/day.
• Osteoarthritis- symptomatic relief only.
• Postmyocardial infarction - 100-300gm/ day
for 12weeks
• Patent ductus arteriosus.

24. Reye’s syndrome
Use of aspirin in children below 12 years
with influenza or chicken pox cause life
threatening condition characterized by
•vomiting,
•lethargy,
•delirium,
•coma &
•even death.

25.  Toxicity is seen with serum salicylates level
more than 50 mg/dl
 Clinical feature-
• vomiting,
• dehydration,
• electrolyte imbalance,
• anorexia.
• In severe cases, CNS abnormalities, , coma
and even death may occur due to respiratory
failure.

26. Treatment
• Gastric lavage to remove unabsorbed drug
• Activated charcoal to reduce absorption of
salicylates
• Glucose for hypoglycemia
• Blood transfusion or vit K for hemorrhage

27. Contraindication
• Peptic ulcer
• Pregnancy
• Nursing mother
• G6PD deficiency
• Before dental extraction
• Chronic liver disease
• Diabetes
• Hepatic damage
• Chicken pox
• Gout
• Haemophilia

29. Pharmacokinetics
•Aspirin is absorbed from stomach and small
intestine
•Approximately 80% plasma protein binding
capability
•Half life at therapeutic dose is 15-20 minutes
At anti-inflammatory dose is 8-12 hours
During poisoning 30 hours

30. Drug interaction
• It increases toxicity of oral anticoagulants,
heparin, naproxen, phenytoin, indomethacin &
methotrexate.
• Vitamin C & ammonium chloride increases
its action
•It decreases beta blocker’s action
• In patient taking aspirin, gastrointestinal
bleeding increases by steroids, alcohol,
indomethacin etc
• It increases insulin & sulphonyl ureas
• Antacid & activated charcoal decreases its
absorption

31. IBUPROFEN
• Action- analgesic, antipyretic, anti-
inflammatory
• Use-
 rheumatoid arthritis,
osteoarthritis,
muskuloskeletal disorders
dental inflammation.

32. Adverse effects- less than aspirin.
 Headache,
 dizziness,
 blurring of vision,
 tinnitus,
 nausea,
 vomiting
 depression may occur.
• Contraindication-
 bronchial asthma,
 pregnant &lactating women,
 peptic ulcer
• Pharmacokinetics- 99% bound to plasma
protein,t1/2 is 2 hrs, can cross blood-brain barrier
&placenta.

33. •
• Drug interaction- it aggrevates action of
Aspirin, anti-platelet agent. It decreases action of
diuretic &anti-hypertensive.
• Preparation- Brufen 400,200,600,800 mg
Enflam
Febrilix
Duoflam
Nalyxan

34. NAPROXEN
• Plasma t half- 12-15 hrs
• Dose- 250 mg BID after meal
• Trade name: Naprosyn 500mg
Xenobid 250 mg

35. FLURBIPROFEN
• Action- it suppresses both PGE2 and PGE2
alpha by COX enzyme.
• It inhibits leukocyte migration, 99% plasma
protein binding.
•Use- as an anti-inflammatory in ocular
infections- OCUFLUR(0.03%) eyedrop, 1
drop 6 hourly
•Trade Name- Arflur 50,100 mg
Flurofen 100 mg
Ocuflur 0.03%eyedrop

36. ANTHRANILIC ACID DERIVATIVE
MEPHENAMIC ACID
• Action- analgesic, antipyretic, anti-
inflammatory
• Use-
as an analgesic primarily in muscles, joints
and soft tissue pain.
Dysmenorrhea
rheumatoid arthritis
osteosrthritis.
• Dose- 500 mg TDS

37. • Adverse effect: diarrhea, dizziness, rashes
& megaloblastic anaemia,agranulocytosis.
• Contraindication: gastrointestinal ulceration,
impairment of renal function.
• Trade Name: Meftal 250 mg
Medol 250, 500 mg
Ponstan 250 mg
Meftal forte
Spasmodol forte

38. ARYL-ACETIC ACID DERIVATIVE
DICLOFENAC
• Action- Analgesic, antipyretic, anti-
inflammatory
• Indication-
 rheumatoid arthritis,
osteoarthritis,
 post- traumatic and post- operative
inflammation,
ankylosing spondylitis
• Dose- 100-200 mg BID or TID

39. •Trade name- Diclomax 25,50,100 mg
Voveran 50 mg
Voveran IM 75
Diclofen

40. Adverse effects-
 epigastric pain
 nausea,
 headache,
 dizziness,
 rashes. Kidney
 damage is rare.
Contraindication-
 Peptic ulcer,
 hypersensitivity,
 pregnancy
 lactation
 asthma.

41.  A relatively COX-2 selective congener of
diclofenac having similar properties.
 Dose-100mg BID

42.  Acemak-P
Aceclofenac100mg+Paracetamol(500mg)
 Indications
 Ankylosing spondylitis
 Osteoarthritis
 Rheumatoid arthritis
 Dentalgia
 Pre and post operative pain
 Acute gout
 Contraindications
 Pregnancy
 lactation

43. OXICAM DERIVATIVES
PIROXICAM
• Action- it reversibly inhibits COX, so it has
analgesic, antipyretic, anti-inflammatory
action
• Adverse effect-
heart burn,
 nausea,
anorexia

44. • Indication-
 rheumatoid & osteoarthritis,
 ankylosing spondylitis,
 postextraction pain,
 pulpitis in dentistry
 Dose- 20 mg BD for 2 days followed by 20
mg OD
 Trade Name- Pirox 10, 20 mg

45. TENOXICAM
• Similar properties and uses
• Trade Name: Tabitil 20 mg
Dolonex
Movon

46. PYRROLO-PYRROLE DERIVATIVE
KETOROLAC
• Action- relieves pain by peripheral
mechanism
• Indication-
 postoperative, dental and acute
musculoskeletal pain,
pain due to bony metastasis
migraine
•

47. • Adverse effect-
nausea,
abdominal pain,
ulceration,
loose stools,
drowsiness,
pain at injection site,
dizziness
•Dose- 10-20 mg tablets 6 hourly
15-30 mg IM or IV every 4-6 hours
• Trade Name: Ketorol 10 mg
Toralac 10 mg
Ketanov 10 mg

48.  Contraindication-
 syndrome of nasal polyps,
 coagulation disorders,
 angioedema

49. PREFERENTIAL COX-2 INHIBITORS
NIMESULIDE
• Action- it has inhibition of PG synthesis but
action on COX-2 selectively, has potent anti
inflammatory by inhibition of histamine release
• Use
 postoperative dental pain,
dysmenorrhea,
inflammation of ear, throat
•

50. • Adverse effect-nausea,pruritis,hepatic failure
• Dose-100 mg BID
• Trade Name: Nimulid, Nimegesic, Nimodol

51. PARA-AMINO PHENOL DERIVATIVE
PARACETAMOL
• Action- analgesic and antipyretic but no
anti-inflammatory
• Use-
 headache,
musculoskeletal pain,
dysmenorrhea,
first drug of choice for
osteoarthritis
Dose- 0.5-1 gm 6 hourly or TDS

52. • Adverse effect- it has safer action.
•On prolonged use liver damage can occur
ACUTE PARACETAMOL POISONING:
Early manifestations are:
• Nausea, vomiting, abdominal pain
• After 24 hrs, centrilobular hepatic
necrosis, hyperglycemia & then coma.

53. Treatment
•Induce vomiting or gastric lavage.
•Activated charcoal to prevent further absorption
Trade name: Crocin 0.5-1gm
Febrinil 300 mg/2 ml injection
Calpol 1 gm

55. • Also called as narcotic drugs
• The term narcotic is derived from the Greek
word meaning “Stupor” & was used for
agents that produce sleep
• The dark brown resinous material obtained
from poppy capsule is called “opium”

56. • These are plant products containing
pharmacologically active ingredient i.e
alkaloid
• Two types of alkaloids viz. phenanthrene
and benzoisoquinoline derivatives
• Opioids bind to receptors located in the
central nervous system, producing an altered
perception of and response to pain

57.  group of G-protein coupled receptors with
opioids as ligands.
 The endogenous opioids are dynorphins,
enkephalins, endorphins, endomorphins and
nociceptin.
Subtypes of opiod receptors:
mu, delta, kappa, epsilon, sigma

59. Classification
1. Natural opium alkaloids: Morphine
Codeine
2. Semisynthetic opiates:
Diacetylmorphine(Heroine)
Pholcodeine
3. Synthetic opoids:
Pethidine(Meperidine)
Fentanyl
Methadone
Tramadol
Dextropropoxyphene

60. •Analgesia- increase the threshold for painful
stimuli
• And alter emotional reaction to pain
• CNS- euphoria in presence of pain dysphoria in
absence of pain -sleep with increased dose
• Respiration- respiratory depression
• Pupil- miosis resulting in pin-point pupils
• CTZ- nausea and vomiting
• Cough- suppress cough by depressing cough
center
Pharmacological actions

61. • Neuroendocrine- sex hormone and
corticosteroid levels are lowered
• GIT- produce spasm of intestine and
sphincters, constipation
• Biliary tract- may cause bilary colic
• CVS- hypotension may occur at toxic doses
Pharmacokinetics
• Absorption- well absorbed when taken orally
& occurs from lungs, nasal and oral mucosa

62. • Distribution- partially bound to plasma
proteins
• Metabolism- in the liver
• Excretion- by the urine within 24 hours
Adverse effects
• Constipation
• Respiratory depression
• Nausea and vomiting
• Miosis
• Urinary retention
• CNS effects- anxiety, restlessness or
nervousness

63. • CVS effects- with high dose, postural
hypotension, bradycardia and even
syncope
• Biliary tract constriction- biliary colic
• Apnea- in newborns when given to mothers
during labour pain
• Addiction- since its use is very less, this
does not produce problem for dentist
• Allergic reaction- skin rashes and urticaria
• Others- allergy, tremor, sedation, lethargy

64. Contraindications
• Infant and elderly persons
• Head injury
• Respiratory insufficiency
• Bronchial asthma
• Hypotensive states and hypovolemia

65. Therapeutic uses
• Analgesics- traumatic, visceral,
postoperative, burn and cancer pain
• Preanesthetic medication- morphine and
pethidine
• Balanced anesthesia & neurolept analgesia
• Relief of anxiety and apprehension
• Acute left ventricular failure
• Cough
• Diarrhea
• Postoperative pain in dentistry

66.  Narcotic (opioid) analgesics are extremely
effective in reducing acute dental and
postoperative pain.
 The narcotic analgesics have established a
niche for the treatment of pain in those
situations where the NSAIDs are less effective.
 Hydrocodone, oxycodone, codeine, and
occasionally meperidine are the narcotics used
to treat dental pain.

67. MORPHINE
Principal alkaloid in opium and still widely used
Pharmocological actions
• CNS- analgesia
sedation
mood and subjective effects
respiratory centre
cough centre
temperature regulating centre
vasomotor centre

68. • It stimulates CTZ, causes miosis &
bradycardia
• Neuro-endocrine- ACTH, FH,LH decreases
while GH and prolactin increase. It can reduce
urine volume and cause mild hyperglycemia
• CVS- causes vasodilatation. Postural
hypotensionand fainting can occur
• GIT- constipation
• Other smooth muscles- biliary colic, urinary
urgency and difficulty in micturition,
bronchoconstriction

69. Routes of administration
 subcutaneously and intramuscularly (analgesic action after
10-15 min)
 oral administration – presystemic elimination ( 20-60 %
enters general blood circulation)
 sublingually – quick absorption
 i.v. is indicated even in emergency
 Epidural or intrathecal ( into the spinal canal ) injection
produces segmental analgesia lasting 12 hours without
affecting other sensory, motor or autonomic modalities
 Duration of analgesic action – 4-6 hours
Maximum single dose of morphine is 0,02 g,
maximum daily dose – 0,05 g

70. Adverse effects
• Sedation
• Lethargy
• Constipation
• Respiratory depression
• Blurring of vision
• Urinary retention
• Urticaria

71. ACUTE MORPHINE POISONING
• It is accidental, suicidal or seen in drug
abusers
• In non-tolerant adult, 50 mg IM produces
serious toxicity
• Manifestations are: stupor or coma
shallow or occasional
breathing
cyanosis
pinpoint pupil
fall in BP
convulsions
death

72. Acute miosis
(Pinpoint
pupils)
Cheyne Stokes
respiration
deep tendon
reflexes
increased

73. Treatment
• Respiratory support and maintenance of BP
• Gastric lavage with potassium
permanganate to remove unabsorbed drug
• Naloxone 0.4-0.8 mg IV repeated every 2-3
min till respiration picks up, is the specific
antidote

74. • NSAIDs are more effective and more suitable
than opioid analgesics
• The opioids are occasionally employed as
additional drugs with aspirin, paracetamol etc
to boost their analgesic effect
• Clearly, the place of analgesics in dental pain
is secondary to treatment of cause of pain by
local and systemic measures like antibiotics
• Short term use of opioids as in dentistry has
no significant drug interaction
CONCLUSION