This document provides information on analgesics and anti-inflammatory drugs. It begins by defining analgesics as drugs that relieve pain without altering consciousness, and anaesthesia as loss of sensation. It then classifies analgesics into two main groups - opioid analgesics like morphine and non-opioid analgesics like NSAIDs. The document goes on to describe various opioid and non-opioid analgesics in detail, their mechanisms of action, uses, and adverse effects. It focuses on the role of prostaglandins in pain and inflammation, and how different NSAIDs work by inhibiting prostaglandin synthesis.

1. ANALGESICS AND
ANTI-INFLAMMATORY
DRUGS
DR Bhaumik Thakkar
Part-1 P.G
Dept of Periodontology and
Implantology

2. INTRODUCTION
ANALGESICS
A drug that selectively relieves pain by acting in CNS
or on peripheral pain mechanism, without significantly
altering consciousness.
ANAESTHESIA
Anaesthesia means loss of sensation. Anaesthetic
agent is one which bring about loss of all modalities of
sensation, particularly pain, along with a reversible
loss of consciousness.
PAIN (ALGESIA)
An unpleasant sensory and emotional experience
associated with actual or potential tissue damage or
described in terms of such damage.

3. CLASSIFICATION
Divided into 2 groups:
1. Opioid Analgesics -Narcotics/Morphine like
analgesics
2. Non Opioid Analgesics -NSAIDs/Non
narcotic/aspirin like analgesics

4. History of Opioid.
 Obtained from poppy { papaver somniferous }
capsule called “ opium ”, known from earliest
times.
 Mentioned in Eber’s papyrus[1500BC] and in
writings of theophrastus [300BC] and Galen [
2nd century AD ]
 Serturner ,a pharmacist isolated the active
principle of opium in 1806 and named it ‘
morphine ’ after a Greek god of dreams
Morpheus .

5. OPIOID ANALGESICS
Natural Opium alkaloids
Morphine & Codeine.
Semi synthetic opiates
Diacetylmorphine
oxymorphone
Pholcodeine
Synthetic opioids
Pethidine
Fentanyl
Methadone
Dextropropoxyphene
Ethoheptazine
Tramadol

6. NON OPIOID ANALGESICS
& NSAIDs
Analgesic and Anti inflammatory
A. NON-SELECTIVE COX INHIBITORS
1. Salicylates – Aspirin, Salicylamide, Benorylate,
Diflunisal.
2. Pyrazolone derivatives – Phenyl butazone,
Oxyphenyl-butazone.
3. Propionic acid derivatives – Ibuprofen,
Naproxen, Ketoprofen, Fenoprofen,
Flurbiprofen, Oxaprozin.
4. Indole derivatives – Indomethacin, Sulindac.
5. Anthranilic acid derivative – Mephanimic acid,
Flufenamic acid.
6. Aryl acetic acid derivative – Diclofenac,
Tolmetin..
7. Oxicam derivative – Piroxicam, Tenoxicam.
8. Pyrrolo pyrrole derivatives – Ketorolac,

7. B. Preferential COX-2 inhibitors
- Nimesulide
- Meloxicam
- Nabumetone
C. Selective COX-2 inhibitors
- Valdecoxib
- Celecoxib
- Rofecoxib

8. D. Analgesics with poor Anti inflammatory action-
1. Paraminophenol derivative
- Paracetamol (Acetaminophen)
2. Pyrazolone derivative
- Metamizol, Propiphenazone
3. Benzoxazocine derivative
- Nefopam

9. Pharmacological Actions
1.CNS – Depressant and stimulant action
2.CVS – Causes vasodilation
3. GIT – Constipation
4. Smooth muscles – Increased ureter
contraction, Broncho constriction
5. ANS – Mild hyperglycemia

10. Adverse effects
Analgesics doses are usually well tolerated but anti-
inflammatory doses are usually associated with adverse
effects whed used for a long period.
A. G.I tract:- Epigastric distress, nausea, vomiting, erosive
gastritis, peptic ulcer, increase occult blood loss in stools are
common
B. Allergic reactions are not common and may be manifested as
rashes, photo sensitivity..etc
C. Haemolysis
D. Nephrotoxicity
E. Reye’s syndrome
F. Salicylism
G. Acute salicylate intoxication

11. Functions of NSAIDs
 Analgesia –
PGs induce hyperalgesia by affecting the
transducing property of free nerve endings – stimuli that
normally do not elicit pain are able to do so . NSAIDs do
not affect the tenderness induces by direct application of
PGs but block the pain sensitization mechanism induced
by bradykinin .
 Antipyresis –
NSAIDs reduce body temperature in fever , but do
not cause hypothermia in normothermic individuals .
NSAIDs block the action of pyrogens but not that of
PGE2 injected into the hypothalamus .

12.  Anti - inflammatory –
Due to inhibition of PG synthesis at the site of injury.
Inflammatory cells express integrins and selectins and
NSAIDs act by inhibiting some of these molecules . Growth
factor like GM-CSF, IL-6, lymphocyte transformation factor
may also be affected. Stabilization of leukocyte lysosomal
membrane and antagonism of certain actions of kinin may be
contributing to NSAIDs action.
 Antiplatelet aggregatory –
NSAIDs inhibit synthesis of both proaggregatory
{ TXA2 } and antiaggregatory { PGI2 } prostanoids , but effect
on platelet aggregation TXA2 predominated producing
therapeutic doses of most NSAIDs inhibit platelet aggregation
: bleeding time is prolonged .

13.  Ductus arteriosus closure- Administration of
NSAIDs in late pregnancy has been found to
promote premature closure of ductus in some
cases.
 Parturation – Sudden spurt of PG synthesis by
uterus probably triggers labor and facilitates its
progression .NSAIDs has the capacity to retard

14.  Gastric mucosal damage –
Gastric pain , mucosal damage are
produced by all NSAIDs .Inhibition of synthesis of
PG { PGE2 , PGI2 } is clearly involved . Deficiency
of PGs reduces mucus and HCO3- secretions ,
tends to enhance acid secretion and may promote
mucosal ischaemia. Thus, NSAIDs enhance
aggressive factors and contain defencive factors
in gastric mucosa – which are ulcerogenic. PCM,
a very weak inhibitor of COX is practically free of
gastric toxicity and selective COX – 2 inhibitor are
safer..

15.  Anaphylactoid reaction –
Aspirin PPts asthma , angioneuretic
swellings , urticaria or rhinitis in certain
susceptible individual . These subjects react
similarly to chemically diverse NSAIDs ,ruling
out immunological basis for the reaction .

16. Uses
Acute or chronic conditions where pain and inflammation are
present.
(Rossi, 2006)
 Rheumatoid arthritis
 Osteoarthritis
 Inflammatory arthropathies (e.g. ankylosing spondylitis, )
 Acute gout
 Dysmenorrhoea
 Metastatic bone pain
 Headache and migraine
 Postoperative pain
 Mild-to-moderate pain due to inflammation and tissue injury
 Pyrexia
 Renal colic
 They are also given to just born infants whose ductus arteriosus is
not closed within 24 hours of birth

17. Prostaglandins synthesis inhibiton
Membrane phospholipids
Phospholipase A
Arachidonic acid
Cyclo oxygenase
PG G2 + PG H2
Isomerases Thromboxane
sythetase
Prostacyclin
synthetase
PG E2, PG D2, PG F TX A
TX B2
PG I2PG E2, PG D2, PG F TX A2

18. Physiological Functions of
Prostaglandins
- Pain: PGI2 and PGE2 sensitize nerve endings to bradykinin,
histamine
- Inflammation: PGI2, PGD2 and PGE2 are
vasodilators (edema, erythema)
- Protection of the gastric mucosa: PGI2
- Maintenance of renal blood flow: PGE2
- Fever: PGE2
- Platelets: PGI2 and PGD2 inhibit platelet
aggregation.
TXA2 stimulates platelet aggregation
- Uterus: PGD2 contracts uterus
- Other:PGE2 keeps ductus arteriosus open
following birth

19. COX-2 Hypothesis (1990s)
Normal Tissue Inflammation Site
Physiolgical
Prostaglandin
Production
Pathological
Prostaglandin
Production
COX-1
Constitutive
COX-2
Inducible
Arachidonic Acid
Normal Functions Inflammation, pain, fever
NSAIDs
Cytokines
Growth factors+

20. Role of PGs in inflammation
By 2 roles:
1. Promote development
2. Modulate and regulate inflammatory cell function{ Gordon et
al 1976 }
 PG can induce pain , edema , redness and vasodilation
when they are induced by other mediators .
 PG inhibits lysosomal enzyme release during phagocytosis ,
enhances chemotaxix , chemokinesis
{ Estensen et al 1973 }
 Inhibit clonal proliferation of macrophages stem cells
migration of macrophages
 On lymphocytes it supress cell transformation { Mihas 1975
}

21. Role in Bone Resorption
 In number of ways and may induce bone resorption by facilitating
the release of osteoclasts activating factor from lymphocytes
{ Yoneda & Mundy 1979 }
 Inhibit bone collagen formation which result in inhibition of the
repair of resorbed bone { Raisz & Koolemans – Beynen 1974 }
Role in periodontal destruction
–
Production of arachidonic acid metabolites :
 Recently the role of host’s immuno inflammatory system is
understood . After activation of inflammatory cells in the
periodontium by bacteria , phospholipids in the plasma
membrane of cells become available for actions by
phospholipase. This leads to free arachidonic acid in the area
{AAP 1992}

22. INDICATIONS OF NSAIDS IN
DENTISTRY
 Irreversible pulpitis
 Apical periodontitis
 Acute alveolar abscess
 Infected cyst
 Sinusitis
 TMJ Arthritis
 MPDS
 After tooth extraction
 Dry socket
 Recurrent apthous ulcers
 Lichen planus
 Agranulocytosis
 Cyclic neutropenia

23. GENERAL
CONTRAINDICATIONS
 Ulcer
 Asthma
 Patient with nasal polyp
 Diabetes
 Gout
 Influenza (Reye’s syndrome)
 Hypo coagulation state
 Chronic allergic disorders
 Chronic liver disease
 Renal failure
 Salicylate allergy
 Breast feeding mothers
 Pregnancy

24. NSAIDs as Host Modulation
Therapy
 Treatment concept that 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.
(CARRANZA)
 HMTs are systemically or locally delivered
pharmaceuticals that are prescribed as part of
periodontal therapy and are used as adjuncts
to conventional periodontal treatments.

25.  HMTs offer the opportunity for modulating or
reducing this destruction by treating aspects of
the chronic inflammatory response.
 HMTs do not “switch off” normal defense
mechanism or inflammation; instead, they
ameliorate excessive of pathologically
elevated inflammatory processes to enhance
opportunities for wound healing.

26. The Effect of Non-Steroidal Anti-
Inflammatory Drugs on Bleeding
During Periodontal SurgeryJournal of Periodontology
July 2005, Vol. 76, No. 7, Pages 1154-
1160
15 medically healthy subjects (seven males and eight
females), each having two sites requiring periodontal
surgery of similar complexity, type, and duration, were
selected for the study. The subjects were instructed to
take ibuprofen prior to one of the surgeries. A standard
bleeding time and papillary bleeding index score were
recorded at initial consultation, and prior to the first and
second surgeries.
The volume of aspirated blood was measured during
each surgery by subtracting the amount of water used
for irrigation from the total volume of fluid (blood +
irrigation water) collected at 15-minute intervals during
the surgery.

27. In vivo models
First evidence that NSAID block PG production
in gingival tissue was produced by Gomes in
1976 , who demonstrated that inflammed
gingival fragments taken from monkeys
consistently release PG into the culture medium
, and that the pyrazole compd indomethacin
reduced the amount of PG released by at least
90% . The NSAID indomethacin , ibuprofen ,
piroxicam , flurbiprofen , and zomepirac sodium
have significant inhibitory effect on the
production of PG.

28.  NSAIDS block PGE2 production , thereby
reducing inflammation & inhibiting osteoclast
activity in periodontal tissue
 Studies have shown that systemic NSAIDS such
as indomethacin, flurbiprofen & naproxen
administered daily for upto 3 yrs significantly
slowed the rate of alveolar bone loss compared
with placebo
 However daily administration for extended period
is necessary for periodontal benefits

29. ASPIRIN
 Acetylsalicylic acid
 Pharmacological actions
- Analgesic, antipyretic, antiinflammatory actions
- Metabolic effects: Blood sugar may decrease, plasma
free fatty acid & cholesterol levels reduced
- Respiration: Hyperventilation in salicylate poisoning
- Acid base & electrolyte balance: Compensated
respiratory alkalosis
- CVS: Vasodilation, increase in cardiac output
- GIT: Epigastric distress, nausea & vomiting
- Blood: Prolongs bleeding time

30.  ADVERSE EFFECTS:
- Nausea, vomiting, epigastric distress, increased blood
loss in stools
- Rashes, fixed drug eruptions, urticaria, rhinorrhea,
angioedema, asthma, anaphylactoid reaction
- Salicylism – dizziness, tinnitus, vertigo, impairment of
hearing & vision, excitement & mental confusion,
hyperventilation & electrolyte imbalance
- Acute salicylate poisoning: Fatal dose in adults 15-30g,
lower in children

31.  USES:
- Analgesic
- Antipyretic
- Acute rheumatic fever
- Rheumatoid arthritis
- Osteoarthritis
- Postmyocardial infarction
- Patent Ductus Arteriosus
- Familial colonic polyposis
- Prevention of colon cancer
- Treatment of Bartter’s syndrome

32.  Precautions & Contraindications:
- Peptic ulcer
- Bleeding tendencies
- Children with chicken pox or influenza
- Chronic liver disease
- Diabetics
- Pregnancy
- Breast feeding mothers
•Dose
- 0.3-0.6 g 4-6 hrly orally

33.  Commercially available as:
• Aspirin: 350 mg tab.
• Disprin: 350mg tab.
• Colsprin: 100, 325,650mg tab.
• Ecosprin: 75, 150, 325mg tab.

34. Dental consideration in a patient
who is on aspirin therapy
 BT
 CT
 PT
 INR

35. INDOMETHACIN
 Indole derivative
 Potent inhibitor of PG synthesis & suppresses neutrophil
motility
 Well absorbed orally & t ½ is 2-5 hrs
 Adverse effects: Gastric irritation, nausea, anorexia,
gastric bleeding & diarrhoea, frontal headache,
dizziness, ataxia, mental confusion, depression,
psychosis, leukopenia, rashes, increased risk of
bleeding
 Contraindicated in machinery operators, drivers,
psychiatric patients, epileptics, kidney disease, pregnant
women & children
 Dose: 25-50mg BD-QID
 Commercially available as-
Idicin, Indocap, Indoflam : 25mg, 75mg tab

36. IBUPROFEN
 Propionic acid derivative
 Adverse effects:
- Gastric discomfort, nausea & vomiting
- Headache, dizziness, blurring of vision, tinnitus &
depression
- Avoided in pregnancy, peptic ulcer patient & asthmatic
patients

37.  USES:
- Analgesic & Antipyretic
- Rheumatoid arthritis, osteoarthritis,
musculoskeletal disorders
- Soft tissue injuries, fractures, vasectomy, tooth
extraction
- Postpartum & postoperatively : suppress swelling
& inflammation
- Dose: 400-800 mg TDS
• Comercially available as-
Brufen, Emflam, Ibusynth : 200, 400, 600mg tab.
Ibugesic : 100mg, 400 mg tab.

38. DICLOFENAC SODIUM
 Aryl-acetic acid derivative
 Well absorbed orally
 Plasma t ½ - 2 hrs
 Adverse effects: Epigastric pain, nausea, headache,
dizziness, rashes
 Uses: Rheumatoid arthritis, ankylosing spondylitis,
dysmenorrhea, post traumatic & post inflammatory
conditions
 Dose: 50mg TDS, then BD oral, 75mg deep i.m
 Commercially available as:
Voveran, Diclonac, Movonac : 50 mg tab.
Diclomax : 25, 50 mg tab.

39. KETOROLAC
 Pyrrolo-pyrrole derivative
 Potent analgesic & modest anti inflammatory
 Rapidly absorbed after oral & i.m administration
 Plasma t ½ is 5-7 hrs
 Adverse effects: Nausea, abdominal pain, dyspepsia,
ulceration, loose stools, drowsiness, headache,
dizziness, nervousness, pruritis, pain & fluid retention
 Not be given to patients on anticoagulants

40.  USES:
- Postoperative & acute musculoskeletal pain: 15-30 mg
i.m or i.v every 4-6 hrs
- Used for renal colic, migraine, pain due to bony
metastasis
- Orally in a dose of 10-20 mg 6 hrly.
- Commercially available as –
Ketorol, Zorovon, Ketanov, Torolac : 10mg tab.

41. NIMESULIDE
 Preferential COX-2 inhibitors
 Used for short lasting painful inflammatory conditions
like sports injuries, sinusitis, ear nose throat disorders,
dental surgery, bursitis, low backache, dysmenorrhoea,
post operative pain, osteoarthritis & for fever
 Completely absorbed orally, excreted in urine, t ½ of 2-5
hrs

42.  Adverse effects:
- Epigastralgia, heart burn, nausea, loose motions, rash
pruritus.
- Hematuria & fulminant hepatic failure in few cases
Useful in asthmatics, bronchospasm or intolerance to
aspirin & other NSAIDs
 Dose: 100 mg BD
 Commercially available as-
Nimulid, Nimegesic, Nise, Nobel, Nimodol : 100mg tab.

43. Conclusion
 Analgesics are definitely useful in reducing
pain & improving the quality of life but have
their own spectrum of adverse effects.
 No single drug is superior to all others for
every patient. Choice of drug is inescapably
empirical.