Analgesics and Anti-inflammatory drugs in Periodontics and its applied aspects

1. ANALGESICS AND ANTI-
INFLAMMATORY DRUGS IN
PERIODONTICS
Presented by: Dr. Pankti Shah
Guided by: Dr. Ekta Shah

2. CONTENTS
• Introduction
• What are Analgesics ?
▫ Opioids
▫ Classification
▫ Pharmacological Action
▫ Opioid Analgesics
▫ Adverse effects

3. • What are NSAIDs ?
▫ Classification
▫ Mechanism of Action and functions
▫ Adverse effect and Drug interactions
▫ Indications and Contraindications
▫ Choice of NSAID
▫ Topical NSAID
▫ NSAID as Host modulatory agent
▫ NSAID – Enzyme combinations
• Conclusion
• References

4. INTRODUCTION
• Pain (Algesia) : Ill defined , unpleasant
sensation, usually evoked by an external or
internal noxious stimuli.
• It can be : ACUTE
CHRONIC

5. What are Analgesics?
• Analgesic is a drug that selectively relieves pain by
acting in the CNS or on peripheral pain
mechanisms, without significantly altering
consciousness
• Analgesics relieve pain as a symptom without
affecting its cause.
• Analgesics are divided into two groups
A. Opioid/narcotic/morphine-like analgesics.
B. Nonopioid/non-narcotic/aspirin-like/antipyretic or
anti-inflammatory analgesics

6. Opioids
• Opium: A dark brown, resinous material obtained
from poppy (Papaver somniferum) capsule.
• It contains two types of alkaloids.
• Phenanthrene derivatives : Morphine (10% in
opium) Codeine (0.5% in opium) Thebaine (0.2% in
opium), (Nonanalgesic)
• Benzoisoquinoline derivatives : Papaverine (1%)
Nonanalgesic Noscapine (6%)

7. Classification
• Morphine
• Codeine
Natural opium
alkaloids
• Diacetylmorphine (Heroin)
• Pholcodeine
• Ethylmorphine
Semisynthetic
opiates
• Pethidine (Meperidine)
• Dextropropoxyphene
• Methadone
Synthetic
opioids
• Tramadol
• Fenatyl

8. Pharmacological Actions
Depressant
Action
• Analgesia
• Sedation
• Mood and subjective
effects
• Respiratory center
• Cough center
• Temperature regulating
center
• Vasomotor center
Stimulant
Action
• CTZ (Chemoreceptor
trigger zone)
• Edinger Westphal
nucleus
• Vagal center
• Certain cortical areas of
hippocampal cells
1) CNS: Site specific depressant and stimulant
action

9. 2)CVS: Causes vasodilation due to
Histamine release
Depression of vasomotor center
Direct action decreasing tone of blood vessels

10. 3) GIT: causes constipation
4) SMOOTH MUSCLES:
Biliary tract
• Spasm of
sphincter of
oddi
• Inc.
intrabiliary
pressure
• Biliary colic
Urinary
bladder
• Inc. tone of
detrusor
and
sphincter
• Urinary
urgency and
difficulty in
micturition
Bronchi
• Broncho
constriction
due to
release of
histamine
• (dangerous
in
asthmatics)

11. 5) NEURO-ENDOCRINE
• ↑ GH and Prolactin
• ↓ ACTH, FSH, LH
Weakens hypothalamic influence on
pituitary
• ↓ urine volume
Enhances ADH release
• Mild hyperglycemia
Central sympathetic stimulation

12. Opioid Analgesics
• Dentists often prescribe Opioid analgesics such as Codeine and
Tramadol for management of dental pain.
• Historically the potency and efficacy of non opioid analgesics have
been thought to be lower than opioid analgesics
• But in contrast non opioid analgesics generally have less adverse
effects than opioid analgesics at therapeutic doses
• If non opioid analgesics fail to relieve pain, an opioid may be
administered in conjunction with non opioid analgesics to provide
synergistic analgesia

13. ADVERSE EFFECTS OF OPIOID ANALGESICS
• Nausea
• Vomiting
• Constipation
• Urinary retention
• Respiratory depression
• Sedation
• Dependence
• Addiction

14. CODEINE
• Methyl morphine occurs naturally in opium and
is partly converted in body to morphine
• Less potent and less efficacious than morphine
• Degree of analgesia – comparable to aspirin
• Can relieve mild- moderate pain
• More selective cough suppressant

15. Pharmacokinetics • Good activity by oral route
Use • In treatment of diarrhea and
cough
Adverse effects • Most prominent- constipation
Dosage • 60 mg codeine ≈ 600 mg aspirin-
as an analgesic
• Subanalgesic dosage- 10-30 mg-
suppresses cough
• Single OD dosage- works 4 to 6
hrs.

16. TRAMADOL
Pharmacokinetics
• Analgesic action of 100mg
tramadol ≈ 10mg of morphine
• Good oral bioavailability
• Effects lasts for 4 to 6 hrs.
• Causes less respiratory
depression, sedation,
constipation, urinary retention
and rise in intrabiliary pressure
than morphine
• It is well tolerated
Adverse Effects
• Dizziness
• Nausea
• Sleepiness
• Dry mouth
• Sweating
• Minimal hemodynamic action
Indication
• Mild to moderate short lasting pain due
to diagnostic procedures, injury,
surgery, dentistry etc.
• Chronic pain- cancer pain
• Not effective in severe pain
Dosage
• t1/2 – 3 to 5 hrs.
• 50-100 mg oral/i.m./i.v. infusion
• 2mg/kg, 4 to 6 hourly- in children

17. What are NSAIDs ?
• NSAIDs are chemically diverse class of drugs (>70 NSAIDs in use)
that have anti-inflammatory, analgesic, and antipyretic properties
• In 1971, JOHN VANE and co-workers made the landmark
observation that aspirin and some NSAIDs blocked prostaglandin
generation.
• This is now considered to be the main mechanism of action of
NSAIDs
• NSAIDs are used to suppress the symptoms of inflammation
associated with rheumatic disease.

18. Classification
A) Nonselective Cox inhibitors (Traditional NSAIDs)
1. Salicylates- Aspirin
2. Pyrazolone derivatives- Phenylbutazone,
oxyphenbutazone
3. Indole derivatives- Indomethacin, Sulindac
4. Propionic acid derivatives- Ibuprofen, Naproxen,
Ketoprofen
5. Anthranilic acid derivatives- Mephenaimic acid
6. Aryl-acetic acid derivatives- Diclofenac , Aceclofenac
7. Oxicam derivatives- Piroxicam, Tenoxicam
8. Pyrrole derivatives- Ketorolac

19. B) Preferential Cox-2 inhibitors
• Nimesulide, Meloxicam, Nabumetone.
C) Selective Cox- 2 inhibitors
• Celecoxib, Rofecoxib,Valdecoxib,Parecoxib.
D) Analgesics- Antipyretics with poor anti
inflammatory action
1. Para amino phenol derivatives : Paracetamol
(Acetaminophen).
2. Pyrazolone derivatives : Metamizol (Dypirone),
Propifenazone.
3. Benzoxazocine derivative : Nefopam.

20. Mechanism of Action
• When a tissue is injured, from any cause, inflammation results.
• Inflammation is defined as the local response of living tissues to
injury due to any agent.
• Due to inflammation, various inflammatory mediators are released
such as prostaglandin, histamine, bradykinin, IL-1, TNFalpha etc.
• PGs have TWO major actions:
 They are mediators of inflammation
 They also sensitize pain receptors at the nerve endings, lowering
their threshold of response to stimuli and allowing the other
mediators of inflammation.

21. • Naturally, a drug that prevents the synthesis of prostaglandin is
likely to be effective in relieving pain due to inflammation of any
kind.
• This is they do by inhibiting cyclo-oxygenase (COX) enzyme in the
pathway for prostaglandin synthesis.
• There are two COX enzymes- COX 1 and COX 2
1. COX 1- is a constitutive, housekeeping enzyme involved in
tissue hemostasis
2. COX 2 – is induced in inflammatory cells and produces the
prostanoid mediators of inflammation

23. Properties of Prostaglandins
• Pain: PGI2 and PGE2 sensitize nerve endings to bradykinin,histamine
and substance P and cause hyperalgesia
• 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

24. Due to Prostaglandin synthesis inhibition
Beneficial Action Shared toxicities
• Analgesia
• Antipyresis
• Anti-inflammatory
• Antithrombotic
• Closure of ductus arteriosus
• Gastric mucosal damage
• Bleeding- inhibition of
platelet function
• Limitation of renal blood flow
: Sodium and water retention
• Delay/ prolongation of labour
• Asthama and anaphylactoid
reaction in susceptible
individuals

25. Prostaglandins And Periodontitis
• Prostaglandins - mediators of the cardinal signs of
inflammation: redness, edema, pain, heat, and loss of
function. (Weeks 1972, Hinman 1972, Kuehl 1980)
• Multiple studies found that in addition to
prostaglandins, the prostacyclines and phospholipases
also caused bone resorption (Raisz et al 1977, Dewhirst
et al 1984, Newman et al 1984, Loning et al, 1980; El
Attar et al, 1981; Ohm et al, 1984; Yoda et al, 1984;
Mendieta et al, 1985; El Attar et al, 1986; Williams et al,
1988; Dewhirst et al, 1983)

26. FUNCTIONS OF NSAIDs
ANALGESIA • Prostaglandins induce hyperalgesia by increasing
sensitivity of afferent nerve endings to chemical and
mechanical stimuli and thus amplify action of other
algesics- bradykinins, histamine, TNF-alpha, ILs.
• Prostaglandins in CNS lowers threshold of central pain
circuit.
• NSAIDs block this pain sensitizing mechanism
therefore effective against inflammation associated
pain.
• The opioids are the drugs of choice for the treatment of
moderate-to-severe pain, the NSAIDs are most
frequently used for mild-to moderate pain.
ANTIPYRESIS • Fever in infection is produced by pyrogens, TNF, ILs, interferon-
induce production of Prostaglandins in hypothalamus-raise its
temp. set point.
• NASIDs block the action of pyrogens.(cox2).

27. ANTI-
INFLAMMATORY
• Inhibition of Prostaglandin synthesis at the site of
injury.
• Anti-inflammatory action of each drug corresponds
with their potency to inhibit COX.
• NSAIDs -also inhibit expression/ activity of adhesion
molecules, growth factors like granulocyte
macrophage-CSF,IL-6,and lymphocyte
transformation factors.
• NSAIDs-Stabilizes leucocytes lysosomal membrane,
and antagonizes certain action of kinins.
DYSMENORRHEA • Increase levels of Prostaglandins in menstrual blood flow,
endometrial biopsies, and their metabolites is seen in
dysmennorhic women-myometrial ischaemia –menstrual
cramps.
• NSAIDs-lowers uterine Prostaglandins— relief.
ANTIPLATELET • Inhibit synthesis of TXA2 by acetylating platelet COX
irreversibly
DUCTUS
ARTERIOSUS
• Prostaglandins E2, I2

28. PARTURITION • Sudden increase in Prostaglandin synthesis by uterus
triggers labour and facilitate its progression.
• NSAIDs –delay and retard labour.
GASTRIC MUSCOSAL
DAMAGE
• Inhibition of synthesis of gastro protective Prostaglandin (E2,I2)-
decrease in mucus,HCO3,increases acid secretion, may promote
mucosal ischemia.
• Ion trapping with NSAIDs also play role.
RENAL EFFECT • Conditions like hypovolaemia, decrease renal perfusion, and Na+
loss- induce renal Prostaglandin synthesis –leading to
vasodilatation, inhibition of cl – reabsorption.
1. Cox dependent impair renal blood flow-decrease in gfr-renal
insufficiency.
2. JG Cox 2 dependent Na and water retention.
3. Rare ability to cause papillary necrosis on habitual intake.
• Renal effects more marked in pts of CHF, Hypovolemia, hepatic
cirrhosis renal disease, pts on diuretics and antihypertensive edema
ANAPHYLACTOID
REACTION
• Aspirin precipitates bronchial asthma, angioneurotic swelling,
urticaria or rhinitis in certain individuals
• These subjects react similarly to chemically diverse NSAIDs , ruling
out immunological basis for the reaction.

30. INDICATIONS
• Acute or chronic conditions where pain and inflammation are present.
(Rossi, 2006)
• Rheumatoid arthritis
• Osteoarthritis
• Inflammatory arthropathies (e.g. ankylosing spondylitis, )
• Acute gout
• Dysmenorrhea
• 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

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

32. ASPIRIN
Pharmacological Action Analgesic, antipyretic, anti-inflammatory
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

33. 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
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

34. Precautions and
Contraindications
• Peptic ulcer
• Bleeding tendencies
• Children with chicken pox or influenza
• Chronic liver disease
• Diabetics
• Pregnancy
• Breast feeding mothers
Dosage • Analgesic: 0.3–0.6 g 6–8 hourly.
• Analgesic effect is maximal at ~ 1000 mg (single
dose).
• Anti-inflammatory action: 3–6 g/day or 100 mg/kg/
day
• t1/2 of inflammatory dose- 8 to 12 hrs.
• Elimination is dose dependent
• Commercially available as:
• ASPIRIN: 350 mg tab.
• DISPRIN: 350mg tab.
• COLSPRIN: 100, 325,650mg tab.
• ECOSPRIN: 75, 150, 325mg tab.

35. AUTHOR
AND
JOURNAL
TITLE STUDY CONCLUSION LOE
Shiloah J et al
Journal of
Periodontal
Research 2014;
49: 102–109
The effect of
long-term
aspirin intake
on the outcome
of non-surgical
periodontal
therapy in
smokers: a
double-blind,
randomized
pilot study
The study includes 24
smokers. The following
clinical parameters were
measured
preoperatively and at 3,
6, 9 and 12 month
postoperatively:
(i) gingival index;
(ii) plaque index; (iii)
probing depth; (iii)
probing attachment
level; (iv) gingival
recession; and (v)
bleeding scores. Study
subjects received scaling
and root planing over
several visits and were
randomly assigned into
two equal groups; a
control group (C), which
received a placebo and a
test group (T), which
took a daily dose of 325
mg ASA. No additional
therapy was provided
over the 1 year
observation period.
Daily intake of 325
mg of ASA
following scaling
and root planing
improved
treatment
outcomes in
smokers, without
an increase in
gingival bleeding
tendency. ASA
promoted a higher
incidence of
shallow pockets
and more gain in
attachment level.
1b

36. IBUPROFEN
Pharmacokinetics • Well absorbed orally, highly bound to plasma
protein
• Inhibit platelet function – use with
anticoagulants should be avoided
• Can enter brain, synovial fluid and placenta
• Largely metabolized in liver and excreted in
urine as well as bile
Uses • Analgesic & Antipyretic
• Rheumatoid arthritis, osteoarthritis, musculoskeletal
disorders
• Soft tissue injuries, fractures, vasectomy, tooth
extraction
• Postpartum & postoperatively : suppress swelling &
inflammation
• 400mg Ibuprofen- more effective than
Aspirin(650mg)+codeine(60mg) to relieve dental

37. Adverse effects • Gastric discomfort,
• Nausea & vomiting
• Headache, dizziness, blurring of vision,
tinnitus & depression
• Rashes, itching & other hypersensitivity
phenomena are infrequent- may induce
aspirin induced asthma
• Avoided in pregnancy, peptic ulcer patient &
asthmatic patients
Dosage • t1/2- 2 hours
• 400-600 mg ( 5-10 mg/kg) TDS
• Commercially available as
• BRUFEN, EMFLAM, IBUSYNTH : 200, 400,
600mg tab.
• IBUGESIC : 100mg, 400 mg tab/ 5 ml susp.

38. TITLE and
JOURNAL
AUTHOR METHODOLOGY CONCLUSION LOE
The effect of
ketoprofen in
chronic
periodontitis:
A clinical
double-blind
Study.
Journal of
Indian Society
of
Periodontolog
y 15(3):255-9
M. Srinivas,
Sangeetha
Medaiah, S.
Girish, M.
Anil,
Jagadish Pai,
Amit
Walvekar
Two similar local drug delivery
preparations of a poloxamen gel
containing 1.5% ketoprofen and a
placebo were indigenously
prepared for this purpose. Ten
subjects aged 33-55 years with
moderate to severe chronic
periodontitis were
recruited and were monitored for
a period of 90 days. Three sites
in each patient (total 30 sites)
with a probing
pocket depth of 5-8 mm were
selected and divided randomly
into three groups: 1) group A:
scaling and root planing
(SRP) + drug A; 2) group B: SRP
+ drug B; and 3) group C: SRP.
Clinical parameters and blood
smear (from
intracrevicular blood) were
assessed to determine the
differential count and Arneth
index. All parameters were
assessed at baseline, 30 days and
90 days, respectively.
The results of
this double-blind
trial indicate that
the combined
effect of locally
delivered
ketoprofen with
SRP was more
effective in
controlling
periodontal
disease than SRP
alone.
1b

39. MEMPHENAMIC ACID
Pharmacokinetics
• Slow oral absorption
• Highly bound to plasma protein-
displacement interactions can
occur
• Partly metabolized and excreted in
urine and bile
Uses
• Analgesic in muscle joint and soft
tissue pain
• Effective in dysmenorrhea
• May be used in dental pain- no
distinct advantage
Adverse Effects
• Diarrhea
• Epigastric distress
• Gut bleeding- not significant
• Hemolytic anemia- rare but serious
Dosage
• t1/2- 2 to 4 hours
• 250-500 mg TDS
• Commercially available as:
• MEDOL: 250mg, 500mg cap.
• MEFTAL: 250mg, 500mg tab,
100mg/5ml susp.
• PONSTAN: 125mg, 250mg, 500mg
tab, 50mg/ml syrup

40. DICLOFENAC SODIUM
• Aryl-acetic acid derivative
• Neutrophil chemotaxis, super oxide production
at inflammatory site are reduced
Pharmacokinetics • Well absorbed orally
• 99% protein bound
• Metabolized and excreted both in urine and
bile
• Because of good tissue permeability ,
concentration in joints and other sites of
inflammation is maintained for a longer
period , extending the therapeutic effect

41. Adverse Effects
• Generally mild
• Epigastric pain, nausea, headache,
dizziness, rashes
• Gastric ulceration and bleeding-
less common
• Reversible elevation of serum
amino transferases can occur
(kidney damage is rare)
Uses
• Toothache
• Rheumatoid arthritis and
osteoarthritis
• Bursitis
• Ankylosing spondylitis
• Dysmenorrhea
• Post traumatic & post
inflammatory conditions
Contraindications
• Peptic ulcer
• Hypertension
• Congestive heart failure
• Renal insufficiency
• Hemostatic disorders
Dosage
• t1/2- 2 hours
• 50mg TDS, then BD oral, 75mg deep i.m
• Commercially available as:
• VOVERAN, DICLONAC,
MOVONAC 50 mg enteric coated
tab, 100 mg S.R. tab, 25 mg/ml in 3
ml amp. for i.m. inj.
• DICLOMAX 25, 50 mg tab, 75 mg/3
ml inj.
• Diclofenac potassium:
• VOLTAFLAM 25, 50 mg tab,
• ULTRAK 50 mg tab;
• VOVERAN 1% topical gel.

42. PIROXICAM
Pharmacokinetics
• Rapidly and completely absorbed
• 99% plasma protein bound
• Largely metabolized in liver and
excreted in urine and bile
• Single daily administration is
sufficient
Uses
• Short term analgesic
• Long term anti-inflammatory drug
in rheumatoid and osteoarthritis
• Ankylosing spondylitis
• Acute gout
• Musculoskeletal injuries and in
dentistry
Adverse Effects
• Heart burn, nausea and anorexia
• Causes less fecal blood loss than aspirin
• Rashes and pruritus in <1% patients
• Oedema and reversible azotemia
Dosage
• t1/2- nearly 2 days(long)
• 20mg BD for 2 days followed by 20mg
OD
• Commercially available as:
• DOLONEX, PIROX: 10,20 mg cap,
20 mg dispersible tab, 20mg/ml inj
1 and 2 ml amps
• PIRICAM: 10,20 mg cap.

43. KETOROLAC
Pharmacokinetics
• Rapidly absorbed after oral & i.m
administration
• Highly plasma protein bound and
60% excreted unchanged in urine
Uses
• Postoperative & acute
musculoskeletal pain: 15-30 mg
i.m or i.v every 4-6 hrs. (max
90mg/day)
• Used for renal colic, migraine,
pain due to bony metastasis
Adverse Effects
• Nausea, abdominal pain, dyspepsia
• Ulceration, loose stools, drowsiness,
headache
• Dizziness, nervousness, pruritis, pain &
fluid retention
• Not be given to patients on
anticoagulants
Dosage
• t ½ - 5 to 7 hrs.
• Orally in a dose of 10-20 mg 6 hrly.
• Commercially available as
• KETOROL, ZOROVON, KETANOV,
TOROLAC : 10mg tab, 30mg in 1ml
amp.

44. INDOMETHACIN
Pharmacokinetics:
• Well absorbed orally, 90% bound to plasma protein, partly metabolized in
liver to inactive products and excreted by kidney.
Adverse Effects
• Gastric irritation, nausea, anorexia,
gastric bleeding & diarrhea, frontal
headache, dizziness, ataxia, mental
confusion, depression, psychosis,
leukopenia, rashes, increased risk of
bleeding
Uses
• Conditions requiring potent anti-
inflammatory action like acute
spondylitis, psoriatic arthritis, gout
• Malignancy associated fever
• Medical closure of ductus arteriosus
• Bartter’s syndrome
Contraindications
• machinery operators, drivers
• psychiatric patients, epileptics, kidney
disease
• pregnant women & children
Dosage
• t1/2 – 2 to 5 hours
• 25-50mg BD-QID
• Commercially available as:
• IDICIN, INDOCAP, INDOFLAM : 25mg,
75mg tab

45. NIMESULIDE
Pharmacokinetics
• Almost completely absorbed orally
• 99% plasma protein bound
• Extensively metabolized &
excreted mainly in urine
Uses
• Short lasting painful
inflammatory conditions like
sports injuries, sinusitis, ear nose
throat disorders
• Dental surgery, bursitis, low
backache, dysmenorrhea
• Post operative pain, osteoarthritis
& for fever
Adverse Effects
• GIT: Epigastralgia, heart burn, nausea,
loose motions
• Dermatological: rash, pruritus.
• Central: Somonolence, dizziness
• Ulcer complications
• Hematuria & fulminant hepatic failure
in few cases
Dosage
• t1/2- 2 to 5 hours
• 100 mg BD
• Commercially available as:
• NIMULID, NIMEGESIC,
NIMODOL: 100mg tab, 50 mg/5 ml
susp.

46. CELECOXIB
Pharmacokinetics
• Slowly absorbed
• 97% plasma protein bound and
metabolized primarily by CYP2C9
Adverse Effects
• Abdominal pain
• Dyspepsia
• Mild Diarrhea
• Rashes
• Oedema
• Small rise in BP
Use
Osteoarthritis and Rheumatoid arthritis
Dosage
• t1/2- 10 hrs.
• 100–200 mg BD.
• Commercially available as:
• CELACT, REVIBRA, COLCIBRA
100, 200 mg caps.

47. ETORICOXIB
Pharmacokinetics
• This newer COX-2 inhibitor has
the highest COX-2 selectivity
Use
• It is suitable for once-a-day
treatment of
osteo/rheumatoid/acute gouty
arthritis, ankylosing spondylitis,
dysmenorrhea, acute dental
surgery pain and similar
conditions, without affecting
platelet function or damaging
gastric mucosa
Adverse effects
• Dyspepsia, abdominal pain, pedal
edema, rise in BP, dry mouth, aphthous
ulcers, taste disturbance and
paresthesias.
Dosage
• t½ is ~ 24 hours
• 60–120 mg OD;
• Commercially available as:
• ETOSHINE, TOROCOXIA,
ETOXIB, NUCOXIA : 60, 90, 120
mg tabs.

48. PARACETAMOL
• The deethylated active metabolite of phenacetin but came into common
use since 1950.
• The central analgesic action of paracetamol is like aspirin,it raises pain
threshold
• Paracetamol is a good and promptly acting antipyretic
•
• Paracetamol is a poor inhibitor of PG synthesis in peripheral tissues,
but more active on COX in brain (poor ability to inhibit COX in
presence of peroxides generated at site of inflammation)
• Gastric irritation is insignificant; Mucosal erosion and bleeding occur
rarely only in overdose
• It does not affect platelet function or clotting factors.

49. Pharmacokinetics • Well absorbed orally;
• Only 1/4th is plasma bound
• Uniform distribution in body
• t1/2 is 2-3hrs
• Effect of an oral dose lasts for 3-5hrs
Adverse Effects • Nausea and rashes are occasional
• Leukopenia is rare
• Acetaminophen overdose can cause hepatotoxicity
• Severe hepatotoxicity has been reported even after
therapeutic doses
Analgesic Neuropathy • Occurs after years of heavy ingestion of analgesics;
such persons have some personality defect

50. Uses
• Headache
• Musculoskeletal pain
• Toothache
• Dysmenorrhea
• Pregnant women & lactating
mothers
• Much safer than aspirin in
terms of GI manifestations
• Does not prolong bleeding time
; so less chance of post
extraction hemorrhage
• Can be used in all age groups
Dosage
• 0.5- 1g TDS
• Infants 50mg
• Children:
 1-3 yrs.: 80-160mg
 4-8 yrs.: 240-320mg
 9-12 yrs. : 300-600mg
• Commercially available as:
 CROCIN 0.5, 1.0 g tabs;
 METACIN, PARACIN 500 mg tab,
125 mg/5 ml syrup, 150 mg/ml
paed. drops,
 ULTRAGIN, PYRIGESIC,
CALPOL 500 mg tab, 125 mg/5 ml
syrup,
 NEOMOL, FEVASTIN, FEBRINIL
300 mg/2 ml inj.,
 CROCIN PAIN RELIEF: 650 mg +
Caffeine 50 mg tab.
 JUNIMOL-RDS 80, 170, 250 mg
suppository (for children),
PARACETAMOL RECTAL
SUPPOSITORY 80, 170 mg.

51. ACUTE PARACETAMOL
POISONING
• Occurs specially in small
children who have low hepatic
glucuronide conjugating ability
• If large dose is taken
(>150mg/kg or >10g in an adult)
serious toxicity can occur ;
fatality common with
>250mg/kg
• Early manifestation : nausea,
vomiting, abdominal pain, liver
tenderness
• After 12-18hrs: hepatic , renal
tubular necrosis hypoglycemia
progressing to coma
• After 2 days: Jaundice
• Further fulminating hepatic
TREATMENT
• If patient is bought early:
vomiting is induced, gastric
lavage done, activated charcoal
given to prevent further
absorption
• ANTIDOTE : N-acetyl cysteine
infused iv /orally
• Paracetamol is not
recommended in premature
infants for fear of
hepatotoxicity

52. CHOICE OF NSAIDs
• paracetamol or low dose- ibuprofen.
Mild to moderate pain with little
inflammation
• a propionic acid derivative, diclofenac or
rofecoxib.
Acute musculoskeletal, osteoarthritic,
injury associated inflammation
• ketorolac, diclofenac, nimesulide,a propionic acid
derivative
Post-extraction or other acute short
lasting pain

53. • etoricoxib, paracetamol
Gastric intolerance to conventional
NSAIDs
• nimesulide, COX2 inhibitor
H/o asthma, anaphylactic reaction to
aspirin or other NSAIDs
• paracetamol best preferred, second best low dose
aspirin
Pregnancy
• paracetamol, aspirin, ibuprofen, naproxen
Paediatric

54. TOPICAL NSAIDs
• Many NSAIDs have been marketed in topical formulations
(mostly as gels) for application over painful muscles or joints.
• These preparations are being used for osteoarthritis, sprains,
sports injuries, tenosinovitis, backache, spondylitis and other
forms of soft tissue rheumatism.
• It is presumed that the drug would penetrate to the subjacent
tissues attaining high concentrations in the affected
muscles/joints, while maintaining low blood levels.
• Consequently the g.i. and other systemic adverse effects would be
minimized and first pass hepatic metabolism would also be
avoided

55. Preparations
 Diclofenac 1% gel : VOLINI GEL, RELAXYL GEL,
DICLONAC GEL
 Ibuprofen 10% gel : RIBUFEN GEL
 Naproxen 10% gel : NAPROSYN GEL Ketoprofen
2.5% gel : RHOFENID GEL
 Flurbiprofen 5% gel : FROBEN GEL
 Nimesulide 1% gel : NIMULID TRANS GEL,
ZOLANDIN GEL, NIMEGESIC-T-GEL
 Piroxicam 0.5% gel : DOLONEX GEL, MOVON
GEL, PIROX GEL, MINICAM GEL

56. NSAID as Host Modulatory Agent
Treatment concept that aims to reduce tissue
destruction and stabilize or even regenerate the
periodontium by modifying or down regulating
destructive aspects of host response and up
regulating protective or regenerative responses.

57. Actions :
• Inhibits prostaglandins
• Reduce inflammation – Used to treat pain, acute
inflammation, and chronic inflammatory conditions.
• Inhibits osteoclastic activity in periodontitis
• NSAIDs such as indomethacin(williams RC 1987) flurbiprofen
(jeffcoat MK JP 1989) and naproxen(Howell TH 1993)
administered daily for up to 3 years, significantly slowed the
rate of alveolar bone loss compared with placebo

58. Disadvantages :
• Administration for extended periods is necessary for
periodontal benefits to become apparent, and are
associated with significant side effects:
– gastrointestinal problems,
– hemorrhage (from decreased platelet aggregation),
– renal and hepatic impairment
• Research shows that the periodontal benefits of taking
long-term NSAIDs are lost when patients stop taking the
drugs, with a return to or even an acceleration of the rate
of bone loss seen before NSAID therapy, often referred to
as a “rebound effect.”(William RC j dent res 1991)

59. • Inhibition of COX-1 by nonselective NSAIDs causes side
effects
– gastrointestinal ulceration
– impaired hemostasis.
• Use of selective COX-2 inhibitors reduce periodontal
inflammation without the side effects typically observed after
long-term (nonselective) NSAID
• Selective COX-2 inhibitors slowed alveolar bone loss in
animal models(Bezerra MM J Periodontol 1993) and
modified prostaglandin production in human periodontal
tissues (Vardar S J Periodontol 2003)

60. Risk versus Benefits of NSAIDs for
Periodontal Disease Treatment
NSAIDs - harmful side effects
• Gastrointestinal upset
• Hemorrhage
• Renal and hepatic impairment
• Induction of aseptic meningitis in previously healthy patients.
• Ibuprofen in high doses impairs wound healing (Proper et al, 1988)
• It is not clear whether NSAIDs promote or hinder the overall
mineralization process in contemporary periodontal regenerative
therapy (McAllister et al, 1995)

61. NSAID’s – Enzymes Combinations
• Enzyme combination of NSAIDs helps in reduction of unwanted drug
effects while maintaining the anti-inflammatory/analgesic efficacy.
• Protease enzymes belonging to family metalloprotease, have been
successfully tested for their anti-inflammatory properties, which
include trypsin, chymotrypsin and serratiopeptidase(Miyata et al.,
1971; McQuade and Crewther, 1969; Lyerly and Kreger, 1981; Aiyappa
and Harris, 1976; Decedue et al 1979)
• Proteolytic enzymes are large protein molecules and they will be
absorbed in an active form from GIT.
• To overcome their destruction in stomach by hydrolysis, these tablets
are given in enteric coated dosage form and in combinations.

62. Commercially available combinations:
1. Aceclofenac, Paracetamol, Serratiopeptidase-
Acecloren, Acekem-SP
2. Diclofenac Potassium, Serratiopeptidase- Acfast
d, Aldase D (50mg)
3. Diclofenac Sodium, Serratiopeptidase- Actimol
S, Alnec -S
4. Diclofenac Potassium, Chymotrypsin- Alfapsin-
D, Alzibit-D
5. Diclofenac Potassium, Trypsin,Chymotripsin-
Chemofast-D, Chymobel Plus
6. Diclofenac Potassium, Trypsin

63. CONCLUSION
• Analgesics are definitely useful in reducing pain and
improving quality of life but have their own spectrum of
adverse effects
• NSAIDs have an extremely safe profile when used for acute
dental pain
• No drug is superior to all others to every patient
• So a clinician should have a thorough knowledge of
mechanism of action, pharmacokinetics,
pharmacodynamics, dosage and adverse effects of each drug
before prescribing the same
• Hence choice of drug is empirical

64. REFERENCES
• Essentials of medical pharmacology- KD Tripathi
• Lippincots illustrated rewiew pharmacology
• Pharmacology – padmaja uday Kumar
• Enantiospecific inhibition of ligature-induced periodontitis in
beagles with topical (S)-ketoprofen: D.W.Paquette J,P.Fioretlini, C
Martusceili R,J. Oringer, T H. Howell, J R. McCullough,D.S.Reasner
and R. C williams: J Clin periodontol 1997: 24: 521-528.
• The analgesic efficacy of ibuprofen in periodontal surgery: A
multicentre study: B. Pearlman, S. Boyatzis, C. Daly, R. Evans, J.
Gouvoussis, J. Highfield, S. Kitchings, V. Liew, S. Parsons, P. Serb,
P. Tseng, C. Wallis: Australian Dental Journal 1997;42:5.

65. • Aspirin-induced post-gingivectomy haemorrhage: a timely
reminder, Thoniason JM, Seymour RA, Murphy P, Brigkam
KM, Jones P: Aspirininduced post-gingivectomv
haetnorrhage: a timely reminder, J Clin Periodontol 1997; 24:
136-138
• Effect of Meloxicam and diclofenac sodium on peri implant
bone healing in rats: AB Pablos, satunino AR, B Konig,
Cristiane F, Vera C de Arujo and Patricia R Cury: J
periodontol 2008; 79; 300-306.
• The effect of a selective cycloxygenase-2 inhibitor (Celecoxib)
on chronic periodontitis: C Alen Yen, Petros D Damoulis, Paul
C Stark, Patricia L Hibberd, Medha Singh and Anthena S
Papas. J Periodontol 2008; 79: 104- 113.

66. • Evaluation of novel adhesive film containing ketorolac for
post surgery and pain control: a safety and efficacy study:
Khalid Al-Hezaimi, Mansour AlAskar, Zuied Selamhe, Jia-
Hui Fu, Ibrahim A. Alsarra, and Hom Lay Wang: J
periodontol 2011; 82: 963-968
• Multiple applications of Flurbiprofen and chlorhexidine chips
in patients with chronic periodontitis: a randomized, double
blind, parallel, 2- arms clinical trial: Eli E Machtei, Ilan Hirsh,
Maher Falah, Eyal Shoshani, Avi Avramoff and Adel Penhasi.
J Clin Periodontol 2011; 38: 1037-1043.

67. THANK YOU !!