ANALGESICS AND ANTI-

INFLAMMATORY DRUGS
IN PERIODONTICS
 CONTENT
1. DEFINITION.
2. INTRODUCTION.
3. NSAIDS 4. OPIOIDS
 Classifications  Classification
 Mechanism of action  Mechanism of action
 Pharmacological Actions  Pharmacological Actions
 Therapeutic Uses  Therapeutic Uses
 Adverse Effect  Adverse Effects
 Contraindication  Contraindications
5. PERIODONTAL CONSIDERATION.
6. CONCLUSION.
7. REFERENCES.
 DEFINITION:
ANALGESICS: A drug that selectively relieves pain by acting in CNS or on
peripheral pain mechanism, without significantly altering consciousness.

ANTI-INFLAMMATORY: A drug or substance that reduces inflammation

(redness, swelling, and pain) in the body.

ANAESTHESIA: Anaesthetic agent is one which bring about loss of all

modalities of sensation, particularly pain, along with a reversible
loss of consciousness.

PAIN: An unpleasant sensory and emotional experience associated

with actual or potential tissue damage or described in terms of
damage.
 INTRODUCTION
Analgesics are divided into two groups:

DRUGS ACTING ON DRUGS ACTING ON

CENTRAL NERVOUS AUTONOMIC NERVOUS
SYSTEM SYSTEM

Nonsteroidal Anti-inflammatory
Opioid Analgesics
Drugs & Antipyretic-Analgesics
 MOA

• The inhibition of COX-1

results in the loss of
some protective effects
of prostaglandins with
respect to the
gastrointestinal (COX-1),
cardiovascular, platelet
and renal function.
 PHARMACOLOGICAL ACTIONS
1. ANTI-INFLAMMATORY EFFECT:
 Due to inhibition of COX-2 mediated
enhanced PG synthesis at the site of injury.
 Effect is seen at high doses (aspirin: 4–6
g/day in divided doses)
 Also affect other mediators of inflammation
(bradykinin, histamine, serotonin, etc) thus inhibit
granulocyte adherence to the damaged
vasculature.
2. ANALGESIC EFFECT:
The analgesic effect of NSAIDs is thought to be related to:
• Peripheral inhibition of prostaglandin production
• They also increase pain threshold by acting at subcortical site. These
drugs relieve pain without causing sedation, tolerance or drug
dependence.

Analgesic dose: 2–3 g/day in divided doses.

3. ANTIPYRETIC EFFECT:
The antipyretic effect of NSAIDs is believed to be
related to:
 inhibition of production of prostaglandins induced
by interleukin-1 (IL-1), interleukin-6 (IL-6), TNFα
in the hypothalamus
 “resetting” of thermoregulatory system, leading to
vasodilatation and increased heat loss.
4. ANTIPLATELET AGGREGATORY:
TXA2 causes
vasoconstriction &
a y )
/d promotes platelet
mg
–325
(5 0 aggregation
Aspirin
(2–3 PGI2 causes
g/da
y)
vasodilatation
and inhibits platelet
aggregation
• Aspirin should be withdrawn 1 week prior to elective surgery.
Antiplatelet dose: 50–325 mg/day (low-dose aspirin).
 5. GASTRIC MUCOSAL DAMAGE:

NSAIDS Inhibits PGs in Increase in HCl production

Gastric mucosa

Loss of protective Gastric irritation,

action Peptic ulcer

Paracetamol, a very weak inhibitor of COX is practically free of gastric toxicity and
selective COX-2 inhibitors are relatively safer.
 6. RENAL EFFECTS:

NSAIDs produce renal effects by at least 3 mechanisms:

• COX-1 dependent impairment of renal blood flow and
reduction of g.f.r. → can worsen renal insufficiency.
• Juxtaglomerular COX-2 dependent Na+ and water retention.
• Ability to cause papillary necrosis on habitual intake.

 Significant effect in CHF, hypovolaemia, hepatic cirrhosis, renal disease and

in patients receiving diuretics or antihypertensives.
 CLINICAL USES OF NSAIDS
1. As analgesic
2. As antipyretic
3. Rheumatoid arthritis
4. Acute rheumatic fever: Aspirin is the preferred drug.
5. Osteoarthritis
6. Thromboembolic disorders:
a. Transient ischaemic attacks (TIA)
b. Myocardial infarction (MI)
(i) to reduce incidence of recurrent MI
(ii) to decrease mortality in post-MI patients
 ADVERSE EFFECTS
1. Side effects:
 At analgesic dose  nausea, vomiting,
epigastric distress, increased occult blood loss
in stools.
 The most important adverse effect gastric
mucosal damage and peptic ulceration.

2. Hypersensitivity:
 Skin rashes, urticaria, rhinitis, bronchospasm, angioneurotic oedema &
rarely anaphylactoid reaction.
 Bronchospasm (aspirin-induced asthma) is due to increased production
of leukotrienes.
3. Anti-inflammatory doses:
 Salicylism - dizziness, tinnitus, vertigo, reversible impairment of hearing and
vision, hyperventilation and electrolyte imbalance. Effects are reversible.

 Reye’s syndrome - Aspirin tends to raise serum transaminases, indicating liver

damage. Most cases are asymptomatic but it is potentially dangerous.
4. Hematologic adverse effects: 
 Nonselective NSAIDs due to their antiplatelet activity. This antiplatelet
effect typically only poses a problem if the patient has a history of GI
ulcers, diseases that impair platelet activity (hemophilia,
thrombocytopenia, von Willebrand, etc.), and in some perioperative
cases.
 Other non-selective NSAIDs
Drug Route and Formulations with Other Points
Oral Dose
1. Ibuprofen Oral and topical gel • Moderate effect
Dose: 400–600 mg TDS • It is better-tolerated than aspirin
• It can be used in children
2. Diclofenac Oral, i.m., rectal, topical, gel • Potent effect
and ophthalmic preparation • It gets concentrated in synovial fluid
(eyedrops) • Incidence of hepatotoxicity is more
Dose: 50 mg BD or 100 mg • Combination of diclofenac with
sustained-release preparation misoprostol (PGE1 analogue) reduces GI
OD irritation and peptic ulcer
3. Piroxicam Oral, i.m. and topical gel • Potent effect
Dose: 20 mg OD • It is long-acting
• ↑ed incidence of peptic ulcer and bleeding
4. Indomethacin Oral, eyedrops and suppository • Potent effect
Dose: 50 mg TDS • It inhibits migration of neutrophils to inflamed area
• It is very effective in ankylosing spondylitis, acute
gout and psoriatic arthritis
• CNS side effects are severe headache, confusion,
hallucinations, etc.
• It is contraindicated in epileptics, psychiatric
patients and drivers
5. Ketorolac Oral, i.m., i.v., • Potent analgesic effect & almost equal to
ophthalmic preparation and morphine.
transdermal patch • It relieves pain without causing respiratory
Dose: 10–20 mg QID depression, hypotension and drug dependence
• It is used in renal colic, postoperative and
metastatic cancer pain
6. Mefenamic Oral • It has analgesic , antipyretic and weak
acid Dose: 250–500 mg TID antiiflammatory effect
• It is used in dysmenorrhoea, osteoarthritis,
rheumatoid arthritis
 Selective COX-2 Inhibitors (‘ Coxibs’)
Etoricoxib
Parecoxib

Toxic to

Gastric friendly Kidney Heart

GI irritation and Inhibit COX-2 They mainly inhibit PGI2; TXA2
peptic ulcer are rare is unaffected. This may be
Na+, H2O responsible for ↑ed risk of
Retention cardiovascular events.
Harris, R. C. (2006). COX-2 and the Kidney. Journal of Das UN. Can COX-2 inhibitor-induced increase in cardiovascular
Cardiovascular Pharmacology, 47(Supplement 1), S37–S42. Oedema disease risk be modified by essential fatty acids?. JAPI. 2005
Jul;53.
Celecoxib:
• It is approved for use in osteo- and rheumatoid arthritis in a dose of 100–200 mg
BD.
• Common side effects: abdominal pain, dyspepsia and mild diarrhoea , rashes,
edema and a small rise in BP.

Etoricoxib: (Dose: 60–120 mg OD)

• once-a-day treatment of osteo/rheumatoid/acute gouty arthritis, ankylosing
spondylitis, dysmenorrhoea, acute dental surgery pain without affecting
platelet function or damaging gastric mucosa.
• Side effects: dyspepsia, abdominal pain, pedal edema, rise in BP, dry mouth,
aphthous ulcers, taste disturbance and paresthesias.
Paracetamol
 Paracetamol is effective by oral and parenteral
routes.
 It is well absorbed & metabolized in liver by
sulphate and glucuronide conjugation.
 The metabolites are excreted in urine.

Actions: It raises pain threshold. 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. (Dose: 325–650 mg (children 10–15
mg/kg) 3–5 times a day.)
Uses:
1. As antipyretic: reduce body temperature during fever.
2. As analgesic: To relieve headache, toothache, myalgia, dysmenorrhoea, etc.
3. It is the preferred analgesic and antipyretic in patients with peptic ulcer,
haemophilia, bronchial asthma and children.
Adverse effects:
1. Side effects are rare, occasionally causes skin rashes and nausea.
2. Acute paracetamol poisoning:
 (> 150 mg/kg or > 10 g in an adult) is taken, serious toxicity can occur.
Fatality is common with > 250 mg/kg.
 12–18 hours centrilobular hepatic necrosis, renal tubular necrosis
and hypoglycaemia coma. Jaundice starts after 2 days.
PRECAUTIONS AND CONTRAINDICATIONS
Peptic ulcer

Children suffering from influenza, chickenpox

Chronic liver diseases

Diabetics

CHF, lower cardiac reserve

Pregnancy Delayed labor, more postpartum bleed,
premature closure of ductus arteiosus
G6PD deficiency
 DENTAL CONSIDERATIONS
• Ibuprofen and acetaminophen – dental analgesia for mild to moderate intensity
of pain.
Authors Study Results
1. Jeffcoat et al  NSAIDs in altering the progression of alveolar  Inhibits alveolar bone loss as
bone loss. 2-year pre-treatment with measured radiographically.
flurbiprofen as adjunct to nonsurgical
periodontal therapy
 Naproxen as an adjunctive to SRP.  Significantly less bone loss
(500 mg naproxen twice per day for 3 months)
2. In a RCT   topical rinse containing ketorolac/50 mg twice  ketorolac rinse preserved more
per day flurbiprofen capsule as an adjunct to 3- alveolar bone than systemic
month prophylaxis. flurbiprofen.

Jeffcoat MK, Reddy MS, Haigh S, et al. A comparison of topical ketorolac, systemic flurbiprofen, and placebo for the inhibition of bone loss in
adult periodontitis. J Periodontol. ;66(5):329-338.
 DRUG INTERACTIONS
- NSAIDS with - NSAIDS with
- NSAIDS with
ALCOHOL: DIURETICS:
WARFARIN: increases
increases risk of furosemide ↑ses the risk
antiplatelet effect & risk
gastritis & GI of acute renal failure and
of bleeding
bleeding salicylate toxicity.

- NSAIDS with - NSAIDS with ACE

SULFONYLUREAS: inhibitors, Ca blockers
increases the effect of and β blockers :
antidiabetic agent decreases the effect of anti-
HTN agent
 CLASSIFICATION OF OPIOIDS
1. Opioid agonists
a. Natural opium b. Semisynthetic
c. Synthetic opioids:
alkaloids: opiates:
• Morphine • Heroin • Pethidine, Tramadol
• Codeine • Pholcodine* • Methadone
• Thebaine* • Hydromorphone • Dextropropoxyphene
• Papaverine* • Oxymorphone. • Fentanyl, Alfentanil,
• Noscapine*. Sufentanil,
Remifentanil.

2. Opioid agonist–antagonists: Pentazocine, butorphanol.

3. Partial μ-receptor agonist: Buprenorphine.
* Have no analgesic activity.
 MECHANISM OF ACTION

OPIOID RECEPTOR CLINICAL EFFECT

µ (mu) Primarily in central Analgesia, Resp. Depression,
depression & Analgesia Bradycardia, Hypothermia, Miosis,
Constipation, Euphoria
κ (kappa) Primarily in sedation Sedation, Analgesia, Marginal resp.
depression
δ (delta) Primarily in analgesia Regulation of analgesia, Feeling
Behavior & Endocrine function
Lippincott Illustrated Reviews Pharmacology, 7th Edition
 PHARMACOLOGICAL ACTIONS
1. CNS
a. The depressant effects are:

Euphoria (feeling Respiratory

Analgesic effect Sedation
of well-being) depression
• Mediated • lack of • Drowsiness and • direct effect on
mainly through initiative, limbs decreases the the respiratory
μ-receptors at feel heavy and physical centre in the
spinal and body warm, activity. medulla; both
supraspinal mental clouding rate and depth
sites. and inability to are reduced.
concentrate
occurs.
 b. The stimulant effects are:

Miosis Nausea and

Vagal centre
vomiting
• Morphine produces
• It is due to direct • It stimulates vagal
constriction of the
pupils due to stimulation of centre in the
stimulation of III chemoreceptor medulla and can
trigger zone (CTZ) cause bradycardia.
cranial nerve
nucleus. in the medulla.
2. CVS:

It mainly causes vasodilatation of peripheral vessels, which results in shift

of blood from pulmonary to systemic vessels leading to relief of
pulmonary oedema associated with acute left ventricular failure.
3. GIT: It causes constipation by direct action on the GIT; the CNS action
↓es GI motility and ↑es the tone of the sphincters.
4. Urinary bladder: It may cause urinary retention by
increasing the tone of urethral sphincter.
5. Biliary tract: It increases intrabiliary pressure by increasing
the tone of sphincter of Oddi.
6. Bronchi: It can cause bronchospasm by releasing histamine
from the mast cells.
 THERAPEUTIC USES
1. AS ANALGESICS

acute pulmonary
myocardial burns fracture of bullet wound terminal
embolism mandible and stages of
infarction
(MI) long bones cancer

2. Pre-anaesthetic medication
3. Acute pulmonary oedema (cardiac asthma)
4. Cough & Diarrhoea.
ADVERSE EFFECTS

• Drug dependence &

tolerance
• Acute morphine poisoning
CONTRAINDICATIONS

Head injury

Bronchial asthma
Chronic obstructive pulmonary disease
(COPD)
Hypotensive states

Hypothyroidism and hypopituitarism

Infants and elderly

Undiagnosed acute abdominal pain

 DENTAL CONSIDERATION
• Hydrocodone 5 mg every 6 h • Due to high potential of abuse,
(moderate to severe pain) tramadol is not the drug of choice
• Tramadol 25 mg daily with increase for the treatment of severe
every 2–3 days with 25mg up to 100 odontogenic pain.
mg. (25–50% dose reduction from • In patients with unsatisfactory level
recommended dose) of pain control, the combination of
• The first choice of drug is full dose opioid agents and NSAIDs
hydrocodone 10 mg, oxycodone 5 is recommended.
mg

Analgesics Use in Dentistry; Shaip Krasniqi and Armond Daci; Pain Relief - From Analgesics to Alternative Therapies
 PERIODONTAL
CONSIDERATION
Postoperative pain following periodontal surgeries is a common clinical complaint,
which may vary considerably among patients according to sex, age, and type of
surgery
SEVERITY OF RECOMMENDED DRUGS
PAIN
Mild Acetaminophen 325–650 mg every 6 hours or Ibuprofen 200–
400 mg every 4 to 6 hours
Moderate Ibuprofen 400–600 mg every 4 to 6 hours or Naproxen 500 mg
(or naproxen sodium 550 mg) every 12 hours
Severe Ibuprofen 400–600 mg + Acetaminophen 500 mg every 6
hours or Ibuprofen 400–600 mg + Acetaminophen 500 mg +
Opioids, such as hydrocodone 10 mg, every 6 hours

Caporossi et al. Pharmacological management of pain after periodontal surgery: a systematic review with meta-analysis(2020).
 PROCEDURE INTERVENTION RESULTS
1. Open flap surgeries Pharmacological protocols Contradictory Results:
(oral administration) with placebo pill/absence of therapy Flurbiprofen promoted superior
pain relief up to 3 h but
acetaminophen & caffeine
showed significantly lower pain
scores, after 1 to 2 h of follow-
up.
2. Open flap surgeries 0.074% diclofenac-containing  significantly lower pain
(topical administration) mouthwash, with a placebo rinse & levels for 7 days.
oral diclofenac sodium (50mg).
mucoadhesive films with minimum effective dosage for
meloxicam (45 mg, 30 mg, 20 mg, meloxicam is 30 mg
and 10 mg)

Caporossi et al. Pharmacological management of pain after periodontal surgery: a systematic review with meta-analysis (2020).
3. Crown lengthening 325 mg acetaminophen+ 200 mg after 1 h and 3 h of follow-up, the
surgeries ibuprofen+40 mg of caffeine with a placebo placebo group had significantly
higher pain levels.
4. Root coverage  combination of preemptive  No statistically significant
procedures and postoperative administration of difference
ibuprofen
(400 mg–60 min preemptively; 400 mg–
postoperatively) and dexamethasone (4mg–
60 min preemptively; 4mg– postoperatively)  No statistically significant
 nimesulid (100 mg) and ibuprofen (200 difference
mg) 8h postoperatively  No statistically significant
 Oral diclofenac sodium (100 mg) and difference
transdermal diclofenac patch

Caporossi et al. Pharmacological management of pain after periodontal surgery: a systematic review with meta-analysis
(2020).
 CONCLUSION
• Rational prescription of analgesics in dentistry involves the selection of appropriate
pain reliever, adequate dosage, route of administration and implementation of cost-
effectiveness and risk-benefits standards.
• Experienced dental clinicians select a safe and effective analgesic therapy using
individual drugs or different analgesic combinations to treat dental pain based on
individual conditions.
• Use of NSAID and/or analgesics is recommended for relieving pain after
periodontal surgical procedures.
• IBUPROFEN most commonly used in acute pain considered as 1st DOC with its
anti-inflammatory action.
• PARACETAMOL possess antipyretic and analgesic effect and is the 1st DOC for
patients who cannot tolerate NSAIDS.
REFERENCES:
1. Essentials of Medical Pharmacology Seventh Edition by KD Tripathi.
2. Pharmacology for Dentistry by Tara V Shanbhag, Smita Shenoy, Veena Nayak.
3. Lippincott Illustrated Reviews Pharmacology, 7th Edition
4. Caporossi, L.S., dos Santos, C.S., Calcia, T.B.B. et al. Pharmacological management of pain after
periodontal surgery: a systematic review with meta-analysis. Clin Oral Invest 24, 2559–2578 (2020
5. Das UN. Can COX-2 inhibitor-induced increase in cardiovascular disease risk be modified by
essential fatty acids?. JAPI. 2005 Jul;53.
6. Jeffcoat MK, Reddy MS, Haigh S, et al. A comparison of topical ketorolac, systemic flurbiprofen,
and placebo for the inhibition of bone loss in adult periodontitis. J Periodontol. 1995;66(5):329-
338.