ANTIINFLAMMATORY AND

ANALGESICS IN DENTISTRY

SUBMITTED TO: SUBMITTED BY:

Department of Oral Chhanya Thapa
Medicine and Radiology Roll no:40
BDS 13th Batch
Contents:

1. Introduction
2. Analgesics for orofacial pain

 Non-steroidal Anti-inflammatory Drug

 Opioid Analgesics

 Adjuvant Analgesics: Anticonvulsant and Antidepressant Medications

3. Conclusion

4. Multiple choice questions

1. Introduction

 Algesia (pain) - unpleasant bodily sensation or suffering, usually evoked by an external

or internal noxious stimulus.

 Can be Acute or Chronic

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

 Systemic or topical medications.

 Orofacial pain is a common experience that can result from two general pathologic
mechanisms,

 Tissue injury and inflammation ( nociceptive pain)

 Dysfunction of the nervous system (neuropathic pain)

 The first step in management of orofacial pain is the determination if the pain is primarily
nociceptive or neuropathic or a combination of the two

 Relief of nociceptive pain is achieved by the use of medications in two broad classes:
NSAIDs and Opioid analgesics.
 Primary neuropathic pain may also have an inflammatory component, and effective
management may require medications in multiple classes (anti-inflammatory
medications).
 The two major classes of adjuvant analgesics for neuropathic pain are the anticonvulsants
and the antidepressants.

2. Analgesics for Orofacial Pain

2.1 NON-STEROIDAL ANTIINFLAMMATORY DRUGS

CLASSIFICATION
A. Nonselective COX inhibitors (traditional NSAIDS)
1. Salicylates: Aspirin.
2. Propionic acid derivatives: Ibuprofen, Naproxen, Ketoprofen
3. Anthranilic acid derivative: Mephenamic acid.
4. Aryl-acetic acid derivatives: Diclofenac, Aceclofenac.
5. Oxicam derivatives: Piroxicam, Tenoxicam.
6. Pyrrolo-pyrrole derivative: Ketorolac.
7.Indole derivative: Indomethacin.
8.Pyrazolone derivatives: Phenylbutazone, Oxyphenbutazone.
B. Preferential COX-2 inhibitors
1. Nimesulide, Meloxicam, Nabumetone.
C. Selective COX-2 inhibitors
1. Celecoxib, Etoricoxib, Parecoxib.
D. Analgesic- antipyretics with poor antiinflammatory action
1. Paraaminophenol derivative: Paracetamol(Acetaminophen).
2. Pyrazolone derivatives: Metamizol (Dipy-rone), Propiphenazone.
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, TNF-alpha 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.
 A drug that prevents the synthesis of prostaglandin is likely to be effective in
relieving pain due to inflammation of any kind.

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
The COX -2 hypothesis (1992)

1.Analgesia
 NSAIDS block the pain sensitizing mechanism induced by bradykinin, TNF,
interleukins
 Therefore more effective against inflammatory pain.
2. Antipyresis
 Reduces body temperature in fever during infection .
3. Anti-inflammatory
 The most important mechanism of anti-inflammatory action of NSAIDs is
considered to be inhibition of PG synthesis at the site of injury.
4.Antiplatelet aggregatory
 NSAIDs inhibit synthesis of both proaggregatory (IXA2) and anti-aggregatory
(PGl prostanoids, but effect on platelet TXA2 (COX-1 generated) predominates
 Therapeutic doses of most NSAIDs inhibit platelet aggregation.
5.Dysmenorrhea:
 Increased levels of Prostaglandins in menstrual blood flow, endometrial biopsies,
and their metabolites is seen in dysmennorhic women-myometrial ischaemia -
menstrual cramps.
 6.Anti-platelet:
 Inhibit synthesis of TXA2 by acetylating platelet COX Irreversibly
7.Parturition:
 Sudden increase in Prostaglandin synthesis by uterus triggers labour and facilitate
its progression.
 NSAIDs -delay and retard labour.
8. Gastric Mucosal Damage:
 Inhibition of synthesis of gastro protective Prostaglandin (E2,12)- decrease in
mucus,HC03,increases acid secretion, may promote mucosal ischemia.
Commonly used NSAIDS
ASPIRIN
 Pharmacological Action: Analgesic, antipyretic, anti-inflammatory actions
 Metabolic effects: Blood sugar may decrease & cholesterol levels are 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
Adverse Effects
 Nausea, vomiting, epigastric distress, increased blood loss in stools
 Rashes, fixed drug eruptions, urticaria, rhinorrhea, angioedema, asthma,
anaphylactic 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
Precautions and Contraindications
 Peptic ulcer
 Bleeding tendencies
 Children with chicken pox or influenza
 Chronic liver disease
 Diabetics
 Pregnancy
  Breastfeeding mothers
Uses
 Analgesic - Antipyretic
 Acute rheumatic fever
 Rheumatoid arthritis
 Osteoarthritis
 Post-myocardial infarction
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
Dental Management of Cardiac Patients on Aspirin
Therapy
 Low-dose aspirin (75-300 mg daily) is routinely used as a prophylactic clotting
inhibitor in cardiac patients to prevent CV disease outcomes.
 However, it has been found to increase the risk of bleeding after dental
extractions.
 Earlier recommendations suggested discontinuation of aspirin use for 7-10 days,
but the current recommendation is up to 3 days of discontinuation before invasive
dental procedures.

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(6omg) to relieve dental surgery pain

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

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.
Adverse Effects
 Generally mild
  Epigastric pain, nausea, headache, dizziness, rashes
 Gastric ulceration and bleeding- less common
 Reversible elevation of serum amino transferases (kidney damage is rare)

Uses
 Toothache
 TMJ pain
 Rheumatoid arthritis
 Osteoarthritis
 Bursitis

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, pruritus, pain & fluid retention.
Dosage
 Orally in a dose of 10-20 mg 6 hrly.
 Commercially available as:
 KETOROL, ZOROVON, KETANOV, TOROLAC: 10mg tab,
 30mg in 1ml amp

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

NIMESULIDE
Pharmacokinetics:
 Almost completely absorbed orally.
 99% plasma protein bound.
 Extensively metabolized and excreted mainly in urine
Uses
 Short lasting painful inflammatory conditions like sports injury, sinusitis and ear nose
throat disorders.
 Dental surgery, bursitis, low backache, dysmenorrhoea
 Postoperative pain, osteoarthritis and fever
Adverse Effects
 GIT: Epigastralgia, heart burn, nausea, loose motions
  Dermatological: Rash and pruritus
 CNS: dizziness
 Ulcer complications
 Hematuria
Dosage
 t1/2 - 2 to 5 hours
 100mg BD

PARACETAMOL
 The demethylated 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 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
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
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
DOSE
 Recommended dose for adults and children 12 years and over is 500 to 1000mg every 4
to 6 hours as necessary, with a maximum of 4000mg in any 24hr period.
 Children:
1-3 yrs.: 80-160mg
4-8 yrs.: 240-320mg
9-12 yrs. : 300-600mg

Acute Paracetamol Poisoning

 Occurs especially 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 , hypoglycaemia progressing to
coma
 After 2 days: Jaundice
 Further fulminant hepatic failure and death
 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
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,
backache, 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 drug blood
levels
 Consequently the g.i. and other systemic adverse effects would be minimized and
first pass hepatic metabolism would also be avoided.
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
  Nimesulide 1% gel : NIMULID TRANS GEL
 Combination of aspirin and paracetamol is additive (not supra-additive) and a
ceiling analgesic effect is obtained when the total amount of aspirin + paracetamol
is ~ 1000 mg.
 The same is true of combinations of paracetamol with other
 NSAIDs like ibuprofen, diclofenac, etc.
 There is no convincing evidence that such combinations are superior to single
agents, either in efficacy or in safety. If used, such combinations should be limited
to short periods.

ADVERSE EFFECTS OF NSAIDs

1. Gastric mucosal damage : Gastric irritation, erosions , peptic ulcers
2. Haematological : Bleeding due inhibition of platelet function ,
thrombocytopenia ,haemolytic anaemia, agranulocytosis
3. CNS : Headache , mental confusion
4. Limitation of renal blood flow: Na and water retention, chronic renal failure
5. Delay / prolongation of labour
6. Asthma and anaphylactoid reactions in susceptible individuals

Specific Dental Pain Condition With Drug Of Choice

1. Pulpal pain : Pain during endodontic therapy is usually controlled with local anaesthesia, but
post-treatment pain should be controlled by NSAIDs.
• Ibuprofen (200-400 mg, every 4-6 hrs).
• Acetaminophen/Paracetamol (325-650 mg, every 4-6 hrs).
2. Postoperative pain : Combination of ibuprofen and acetaminophen should be advised.
3.Orthodontic pain : Acetaminophen is the drug of choice for orthodontic pain without affecting
orthodontic tooth movement.
4. Temporomandibular disorders ( i.e synovitis, capsulitis ,rheumatoid arthritis etc) : Diclofenac
50 mg and Piroxicam 20 mg, Ibuprofen 400 mg
5. Oral cancer pain : coX-2, i.e., coxib can be prescribed, but take precaution while treating
cardio patients.
• NSAIDS can be used in case moderate pain.
 • For severe pain combination of NSAID and opioid should be prescribed.
• Should follow WHO ladder .

WHO analgesic ladder 1986

2.2 Opioid analgesics

CLASSIFICATION
1. Natural opium alkaloids: Morphine, Codeine
2. Semisynthetic opiates: Diacetylmorphine (Heroin), Pholcodeine.
Many others like Hydromorphone, Oxymorphone, Hydrocodone, Oxycodone, are not
used in India.
3. Synthetic opioids: Pethidine (Meperidine), Fentanyl, Methadone,
Dextropropoxyphene, Tramadol.

Opioid Receptors
1.MU
• Physical dependence
• Euphoria
• Analgesia (supraspinal)
• Respiratory depression
2. DELTA
• Analgesia (spinal &e supraspinal)
• Respiratory depression
• Reduced GI motility
3.KAPPA
• Sedation
• Analgesia (spinal)
• Miosis

Pharmacological Actions
1) CNS: Site specific depressant and stimulant action
 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
2) CVS: Causes vasodilation due to
 Histamine release
 Depression of vasomotor center
 Direct action decreasing tone of blood vessels
3) GIT: causes constipation
4) Smooth muscles:
Urinary bladder
 Increases tone of detrusor and sphincter
 Urinary urgency and difficulty in micturition
Biliary tract
 Spasm of sphincter of oddi
 Increase in intrabiliary pressure
  Biliary colic
Bronchi
 Bronchoconstriction due to release of histamine
 Dangerous in asthmatics
5) Neuro-Endocrine:
 Weakens hypothalamic influence on pituitary:
 Increased GH and Prolactin
 Decreased ACTH, FSH, LH

USES OF MORPHINE AND ITS CONGENERS

1. As analgesic : Indicated in severe pain of any type.
 Eg : Traumatic ,visceral ,ischaemic, postoperative, burn, cancer pain
 Epidural 2 3 mg injection morphine produces segmental analgesia used in
abdominal ,pelvic surgeries and during labour.
 For milder pain, e.g. toothache, headache, neuralgias, etc., aspirin-like analgesics are
preferred.
 When they are not effective codeine/ dextropropoxyphene may be used orally, either
alone or in combination with aspirin-like drug.
2. Preanaesthetic medication: Morphine and pethidine are used in few selected patients
3. Balanced anaesthesia and surgical analgesia : Fentanyl, morphine, pethidine, alfentanil or
sufentanil are an important component of anaesthetic techniques
4. Relief of anxiety and apprehension : Especially in myocardial infarction, internal bleeding
(haematemesis, threatened abortion, etc.) morphine or pethidine have been employed. However,
they should not be used as anxiolytics or to induce sleep.
5.Acute left ventricular failure :
 Morphine (i.v.) affords relief by
 Reducing preload on heart due to vaso-dilatation and peripheral pooling of blood.
 Tending to shift blood from pulmonary to systemic circuit; relieves pulmonary
congestion and edema.
 Allays air hunger by depressing respiratory centre.
 Cuts down sympathetic stimulation by calming the patient, reduces cardiac work.
 It is also indicated to relieve pulmonary edema due to infarction of lung and other causes.
It is contraindicated in bronchial asthma.
6.Cough : Codeine or its substitutes are widely used for suppressing dry, irritating cough
7.Diarrhoea : The constipating action of codeine has been used to check diarrhoea and to
increase the consistency of stools in colostomy. The natural Synthetic opioids used are
diphenoxylate and loperamide.

ADVERSE EFFECTS
1.Side effects
 Sedation, mental clouding, lethargy and other subjective effects which may even be
dysphoric in some subjects; vomiting and constipation is common.
 Respiratory depression, blurring of vision, urinary retention (especially in elderly male)
are other side effects.
 BP may fall, especially in hypovolaemic patient and if he/she walks about.
2. Idiosyncrasy and allergy
3. Apnoea :This may occur in the newborn when morphine is given to the mother during labour.
4. Tolerance and dependence:
 High degree of tolerance can be developed to morphine and related opioids if the drug is
used repeatedly.
 Withdrawal of morphine is associated with marked drug-seeking behaviour. Physical
manifestations are lacrimation, sweating, yawning, anxiety, fear, restlessness, gooseflesh,
mydriasis, tremor, insomnia, abdominal colic, diarrhoea, dehydration, rise in BP,
palpitation and rapid weight loss.
 Treatment: consists of withdrawal of morphine and substitution with oral methadone
(long-acting, orally effective) followed by gradual withdrawal of methadone.
5. Acute morphine poisoning
 It is accidental, suicidal or seen in drug abusers. In the non-tolerant adult, 50 mg of
morphine i.m produces serious toxicity. The human lethal dose is estimated to be about
250 mg.
 Treatment
 Respiratory support, maintenance of BP, gastric lavage
 Specific antidote: Naloxone 0.4-0.8 mg i.v. repeated every 2-3 min till respiration picks
up, is the preferred specific antagonist

2.3 Adjuvant Analgesics: Anticonvulsant & Antidepressant Medications

 This category of medications includes three major classes of medication: the
anticonvulsants , antidepressants , anxiolytics and muscle relaxants.
 Anticonvulsant and antidepressant classes generally affect conductance of ions that
reduce neuronal excitability (Na, K, Ca, Cl).
  Muscle relaxants are generally centrally acting agents (ie, not at the neuromuscular
junction).
INDICATIONS IN ORAL DISEASE
 Different neuralgias
 Trigeminal neuralgia
 Glossopharyngeal neuralgia
 Geniculate neuralgia
 Post herpetic neuralgia
 Post traumatic neuralgia
 Atypical facial pain
 Burning mouth syndrome
ANTICONVULSANT USED IN ORAL DISEASES
1. Carbamazepine
2. Oxcarbazepine
3. Phenytoin
4. Baclofen
5. Lamotrigine
6. Valproic acid
7. Zonisamide
INDICATIONS IN ORAL DISEASE
 •Different neuralgias
 Trigeminal neuralgia
 Glossopharyngeal neuralgia
 Geniculate neuralgia
 Post herpetic neuralgia
 Post traumatic neuralgia
 Atypical facial pain
 Burning mouth syndrome
 3. CONCLUSION
 Analgesics are useful in reducing pain and have predictable side effects.
 NSAIDs have are safe profile drugs used for acute dental pain.
 Observant clinician should have thorough knowledge of mechanism of action,
pharmacokinetics, pharmacodynamics, dosage and adverse effects of each drug before
prescribing to the patient.

REFERENCES
1. Essentials of Medical Pharmacology - KD Tripathi 8th Edition
2. Lippincot’s Illustrated review Pharmacology
3. Burket’s ORAL MEDICINE 12th Edition
4. Textbook of Oral Medicine & Oral Radiology 2nd Edition 2021 (Peeyush Shivhare, Ajay
Parihar)
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