Good morning

ANALGESICS

• Introduction • Opioid analgesics –Classification

- Mechanism of action

-Morphine

-Other opioids

-Uses • Prostaglandin synthesis & inhibition• NSAIDS - Classification

- Mechanism of action

-Aspirin

-Other NSAIDS

Contents

• Topical analgesics

• Enzyme derived analgesics

• NSAIDS as host modulating agent in

periodontal disease

• References

PAIN

An unpleasant sensory & emotional experience associated with actual or potential tissue damage, or described

in terms of such damage

-IASP

Management of pain

TOPICAL MEDICATIONS

SYSTEMIC MEDICATIONS

Analgesic

A drug that selectively relieves pain by acting in the

CNS or on peripheral pain mechanisms, without

significantly altering consciousness

Classes of analgesic drugs

• Opioid analgesics

• Nonsteroidal anti-inflammatory drugs (NSAIDS)

• Enzyme derived analgesics

OPIOIDS ANALGESICS

• OPIUM: A dark brown, resinous material obtained from Papaver somniferum capsule

• OPIOID: Drugs in a generic sense, natural or synthetic, with morphine- like actions

CLASSIFICATION OF OPIOIDS

• NATURAL

- Morphine

- Codeine

- Thebaine

• SEMISYNTHETIC – Heroin – Oxymorphone – Hydromorphone

• SYNTHETIC – Meperidine – Methadone – Fentanyl– Tramadol

OPIOID RECEPTORS - MU

– P hysical dependence – E uphoria – A nalgesia

(supraspinal) – R espiratory

depression

- KAPPA– S edation – A nalgesia (spinal) – M iosis

- DELTA • Analgesia (spinal

& supraspinal) • Respirstory

depression• Reduced GI

motility  

MECHANISM OF ACTION

1) Inhibit the transmission of nociceptive input from the periphery to the spinal cord

2) Activate descending inhibitory pathways that modulate transmission in the spinal cord

3) Alters limbic system activity

Action Of Morphine• Analgesia

• Sedation

• Euphoria

• Mood change

• Mental cloudiness

MORHINE

MORPHINE ANALGESIA

• Relieves all types of pain, but most effective against continuous dull aching pain • Sharp, stabbing, shooting pain also relieved by morphine• Sedation effect, but no loss of consciousness, drowsiness & without motor in-coordination• Morphine euphoria ,sense of well being

(Drug abuse)

Analgesia• Strong analgesic- most effective in most kind of acute & chronic

pain • Suppression of pain perception is selective ,without affecting

other sensation or producing proportionate generalized CNS depression ( contrast GA _)

Sedation • drowsiness • Higher doses causes sleep…coma• No anticonvulsant effects

Mood & subjective effects • It has calming effect ,loss of apprehension ,feeling of detachment

,inability to concentrate • Pt in pain or anxiety & addict s specially perceive it pleasurable

euphoric effect

1) CNSEFFECTS OF MORPHINE

D) Respiratory Centre • Depresses in dose dependent manner • Rate & tidal volume both decreases • Death in poisoning due to respiratory failure

E) Cough centre• depressed

F) Temperature regulatory centre • Depressed ,hypothermia in cold surrounding

Morphine stimulates

CTZ

• Nausea ,vomiting …specially if stomach is full

Edinger westpal nucleus

• Edinger westpal nucleus of third nerve stimulated to produce miosis

• Pin point pupil –diagnostic

vagal centre

• Stimulated causes bradicardia

• CVS

Causes Vasodilatation due to

- Decreasing tone of blood vessels

- Histamine release

• GIT

- Constipation

• NEUROENDOCRINE EFFECTS

- Hypothalmic influence on pituitary is reduced - Decreases levels of LH, FSH, ACTH whereas PROLACTIN & GH levels are increased

Effects on smooth muscles

• BILIARY TRACT Marked increase in the pressure in the biliary tract

• URINARY BLADDERHave urinary retention difficulty in

micturation

• BRONCHIAL MUSCLEBronchoconstriction can result. (Asthmatics)

Pharmacokinetics

• Oral absorption-Unreliable

(High First pass Metabolism)

• Primarily metabolised in liver

• Freely crosses the placenta &

can effect the foetus

Adverse effects

• Side effects

• Idiosyncrasy and allergy

• Apnoea

• Acute morhine poisoning

( LD- 250mg )

• Tolerance and dependence

Therapeutic uses of morphine

• As Analgesic (Severe Pain)• Preanesthetic medications • Relief of anxiety & apprehension • Acute pulmonary edema • Diarrhoea • Cough • Obstetrical analgesia

• DOSE: 10-15 mg i.m/ s.c

MORPHINE SULPHATE 10, 15 mg inj

Contraindications

• Bronchial Asthma• Infants & Elderly • Head Injury• Undiagnosed Acute

Abdominal pain.• Respiratory diseases

(Emphysema, COPD)

CODEINE

• One tenth the potency (analgesic) of

morphine• More selective COUGH SUPPRESSANT • Good activity by oral route• Abuse Liability is low

AVAILABLE : COREX , COMTUS syp.

(10 mg / 5 ml)

FENTANYL

• 80 to 100 times more potent than morphine

• Rapidly Onset of action (5 min)• Used exclusively in Anaesthesia

alone as well in combination with Droperidol

• Transdermal fentanyl, is used in the management of persistent chronic pain

DOSE: 100-200 µg i.v

(FENT, FENDROP 50µg/ml)

TRAMADOL

• Recently introduced Centrally Acting Analgesic• Has dual Norepinephrine & Serotonin reuptake

inhibitory effects• 10 times potent than morphine & produces less

adverse effects• Used to treat osteoarthritis, low back pain,

diabetic neuropathy & cancer pain

DOSE: 50-100 mg oral/ i.v. 4-6 hrly (CONTRAMAL, DOMADOL)

PETHIDINE (MEPERIDINE)

• Equal analgesic efficacy to morphine & some properties like Atropine

• Unlike morphine:

- More respiratory depression

- Less histamine release (Safer in ASTHMATICS)

- Less constipation • Used primarily ANALGESIC (substitute of morphine)

• DOSE : 50-100 mg i.m, s.c/ orally

(PETHIDINE HCL 100mg/ 2ml inj.;50-100mg Tab

• Synthetic opioid with pharmacological activity & potency same as morphine • Long duration of activity( PPB >90%)• Powerful pain reliever • Used as SUBSTITUTION Therapy of opioid dependence

DOSE: 10 mg inj. PHYSEPTONE

METHADONE

PENTAZOCINE

• Mixed opioid agonist-antagonist action• Efficacy lower than morphine• Useful in Mild-Moderate pain conditions• Causes Tachycardia & rise in BP (C/I- MI)• Should not be used in opioid dependent subjects

DOSE: 50-100 mg oral , 30-60 mg i.m /s.c

(FORTWIN, FORTSTAR)

Strategies to minimize opioid side effects

• Slow titration of doses

• Changing the dosing regimen or route of

administration

• Using a Nonopioid Or Adjuvant Analgesic for an

opioid sparing effect

• Adding a drug to counteract the side effect

• Constipation prophylaxis

Pure opioid antagonist

Naloxone • Competitive antagonist of all type of opioid receptors • No physical or psychological dependence • 0.4 -0.8 mg : all action of morphine • 4-10 mg : action of nalorphine & pentazocine • Blocks action of endogenous opioid peptides • Inactive orally ,• i.v. : 2-3 mins

Uses

• Morphine poisoning , Neonatal asphyxia

Endogenous opioid peptide

• There are 3 distinct families of opioid peptides, derived from specific polypeptide

1. Endorphins : • β-END having 31 amino acids, derived from POMC

( Pro-opio-melanocortin)• Primarily μ agonist but also has δ action

2. Enkephalins: • met-ENK and leu-ENK are the most important• Both are Pentapeptides• met-ENK has equal affinity for μ and δ, leu-ENK

prefers δ receptors

3. Dynorphins: • DYN-A and DYN-B are 8-17 amino acid peptide• Are more potent on κ receptors

Prostaglandin synthesis and inhibition

Cell membrane phospholipids

Phospholipase A2

Arachidonic acid

Cyclooxygenase(COX-1; COX-2)

Endoperoxide(PGG, PGH)

TXAPGIPGEPGF

NSAIDs

Steroid’s

NON-STEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDS)

- Analgesic, Antipyretic & Anti-inflammatory actions.

- Act primarily on Peripheral Pain Receptors

& CNS to raise the pain threshold

- Compared to Morphine

- Weaker analgesics

- Do not depress CNS

- Do not produce physical dependence

& have no abuse liability

INTRODUCTION

CLASSIFICATION

A) NONSELECTIVE COX INHIBITORS (CONVENTIONAL NSAIDS)

1. Salicylates: Aspirin, Diflunisal

2. Pyrazolone derivatives: Phenylbutazone,

Oxyphenbutazone

3. Indole derivatives: Indomethacin, Sulindac

4. Propionic acid derivatives: Ibuprofen, Naproxen,

Ketoprofen

5.Anthranilic acid derivative: Mephenamic acid

6.Aryl-acetic acid derivatives: Diclofenac, Tolmetin

7.Oxicam derivatives: Piroxicam, Tenoxicam

8. Pyrrolo-pyrrole derivative: Ketorolac

B) PREFERENTIAL COX-2 INHIBITORS –

Nimesulide, Meloxicam, Nabumetone

C) SELECTIVE COX-2 INHIBITORS -

Celecoxib

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D) ANALGESIC-ANTIPYRETICS WITH

POOR ANTI-INFLAMMATORY ACTION -

1. Paraaminophenol derivative: Paracetamol

(Acetaminophen)

2. Pyrazolone derivatives: Metamizol, Propiphenazone

3. Benzoxazocine derivatives: Nefopam

- Act as Non-selective Inhibitors of the enzyme cyclooxygenase, inhibiting both, COX-1 & COX-2 isoenzymes - Cyclooxygenase catalyses the formation of PGs & TBX 2 from arachidonic acid

Mechanism of action

COX-1

- Present as part of everyday physiological function.

- Protects the stomach by limiting acid secretion

- Helps platelets limit bleeding by increasing their

adhesiveness

COX-2

- Its expression is induced by various stimuli such as

the inflammation or at the site of the injury

Pharmcological actions

ANALGESIA

ANTIPYRESIS

ANTI-INFLAMMATORY

GASTRIC MUCOSAL DAMAGE

ANTIPLATELET AGGREGATION

DUCTUS ARTERIOSUS CLOSURE

PARTURITION AND IN

DYSMENORRHOEA

RENAL EFFECTS

ANAPHYLACTIC REACTIONS

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ASPIRIN• Analgesic, Antipyretic & Anti-inflammatory Effects.

• RESPIRATORY SYSTEM -Increases rate & depth.

• GIT - Irritates the gastric mucosa - causes epigastric distress, nausea & vomiting

- Promotes the local back diffusion of the acid - acute ulcers, erosive gastritis, microscopic haemorrhages

SALICYLATES

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• CVS

- No direct effect- Larger doses increase cardiac output to meet increased peripheral O2 demand caused by direct vasodilation • BLOOD

- Inhibits TXA2 synthesis by platelets

- Interferes with Platelet aggregation (BT)

• METABOLIC EFFECTS

- Increased utilization of Glucose, blood sugar may

decrease specially in diabetics

@drashishagg

Pharmacokinetics- Poor Absorption- Stomach & Small Intestine- Metabolism- Gut wall, Liver, Plasma & other tissues

to release salicylic acid. Excretion- Urine

Adverse effects- Nausea,Vomiting, Epigastric distress & occult

blood in stools, rashes, urticaria, asthma, angioedema - Anti-inflammatory doses – syndrome Salicylism –

dizziness, tinitus, reversible impairment

of hearing & vision, excitement

use

analgesic

antipyretic

Acute rheumatic

fever

Rheumatoid arthritis

Osteoarthritis

Post MI & post stroke

patients

pregnancy induced

hypertension &

preeclampsia

to delay labour

patent ductus

arteriosus

DOSE: 300-900 mg every 4 hrs (Max 3.6 gm) ( ASA, ASCAD, ECOSPRIN 50mg,75mg Tab.)

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PHENYLBUTAZONE

- Potent anti-inflammatory drug.

- Poor analgesic & antipyretic activity

Adverse effects:

- More toxic than Aspirin

- Bone marrow depression, Agranulocytosis

- Banned in some countries DOSE: 100-200 mg BD or TDS after meals

(ZOLANDIN 100,200 mg Tab)

PYRAZOLONE DERIVATIVES

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INDOMETHACIN - Potent anti-inflammatory, antipyretic & good

analgesic

- Analgesic action better than PBZ

Adverse effects:

- High incidence of GI & CNS side effects

- C/I in drivers, epileptics, pregnancy & children

Uses:

- Rheumatoid Arthritis not controlled by aspirin

- Acts rapidly in Acute Gout

DOSE: 25-50 mg BD /TDS (INDOCAP, IDICIN)

INDOLE DERIVATIVES

IBUPROFEN

- Analgesic, Antipyretic & Anti-inflammatory activity

is lower than aspirin

- Inhibit platelet aggregation & prolong bleeding time

Adverse effects:

- Better tolerated than aspirin (Incidence is lower)- Gastric discomfort, nausea & vomiting are most common side effects- Headache, dizziness, blurring of vision, tinnitus

PROPIONIC ACID DERIVATIVES

Pharmacokinetics: - Absorbed orally, highly bound to plasma proteins (90-99%) - Metabolized in liver & excreted in urine & bile

- Enter brain, synovial fluid & cross placenta

Interactions:

- As they inhibit platelet function, use with anticoagulants should be avoided - Likely to decrease diuretic & antihypertensive action of thiazides, furosemide and --blockers

- As Analgesic & Antipyretic- In Rheumatoid Arthritis, Osteoarthritis & other

Musculoskeletal Disorders, specially where pain is more prominent than inflammation

- Indicated in soft tissue injuries, fractures, tooth extraction, supppress swelling & inflammation

DOSE: 400-800 mg TDS (BRUFEN, EMFLAM, IBUGESIC 200, 400, 600 mg Tab)

Uses

MEPHENAMIC ACID

- An Analgesic, Antipyretic & Anti-inflammatory drug, - Exerts Peripheral as well as Central Analgesic Action

Adverse effects :- Diarrhoea - Epigastric distress is complained, but gut bleeding is not significant

ANTHRANILIC ACID DERIVATIVE

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Pharmacokinetics:

- Oral absorption is slow but almost complete

- Partly metabolized & excreted in urine & in bile

Uses: - Analgesic in muscle, joint & soft tissue pain where strong anti-inflammatory action is not needed (MPDS)

- Useful in rheumatoid & osteoarthritis

DOSE: 250-500 mg TDS

(MEFTAL, PONSTAN, MEDOL

250, 500 mg cap)

GOOD MORNING

• Introduction • Opioid analgesics –Classification

- Mechanism of action

-Morphine

-Other opioids

-Uses • Prostaglandin synthesis & inhibition• NSAIDS - Classification

- Mechanism of action

-Aspirin

-Other NSAIDS

Contents

CLASSIFICATION

A) NONSELECTIVE COX INHIBITORS (CONVENTIONAL NSAIDS)

1. Salicylates: Aspirin, Diflunisal

2. Pyrazolone derivatives: Phenylbutazone,

Oxyphenbutazone

3. Indole derivatives: Indomethacin, Sulindac

4. Propionic acid derivatives: Ibuprofen, Naproxen,

Ketoprofen

5.Anthranilic acid derivative: Mephenamic acid

6.Aryl-acetic acid derivatives: Diclofenac, Tolmetin

7.Oxicam derivatives: Piroxicam, Tenoxicam

8. Pyrrolo-pyrrole derivative: Ketorolac

B) PREFERENTIAL COX-2 INHIBITORS –

Nimesulide, Meloxicam, Nabumetone

C) SELECTIVE COX-2 INHIBITORS -

Celecoxib

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DICLOFENAC SODIUM

- Analgesic, Antipyretic, Anti-inflammatory action - Inhibits PG synthesis & has short lasting antiplatelet action

Pharmacokinetics:- Well absorbed orally, metabolized & excreted both in urine & bile

- Has good tissue penetrability & conc. in synovial fluid is maintained longer period, exerting extended therapeutic action in joints

ARYL-ACETICACID DERIVATIVE

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Adverse effects - Are generally mild: Epigastric pain, nausea, headache, dizziness, rashes - Gastric ulceration & bleeding -less common

Uses: - Most extensively used NSAID - Rheumatoid & Osteoarthris, post-traumatic inflammatory conditions - affords quick relief of pain & wound edema (Dental Extractions)

DOSE: 50 mg TDS, 75 mg i.m (VOVERAN, DICLONAC, DICLOMAX (25, 50 mg Tab., 75 mg /3ml inj)

PIROXICAM - Long acting potent NSAID with good anti- inflammatory, analgesic & antiplatelet action - Reversible inhibitor of COX; lowers PG conc. in synovial fluid & inhibits platelet aggregation- prolonging bleeding time

- In addition, it decreases the production of IgM rheumatoid factor

OXICAM DERIVATIVES

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Pharmacokinetics:- Rapidly & completed absorbed- Metabolized in liver & excreted in urine - Plasma t1/2 is 2 days. So, single daily administration is sufficient

Adverse effects:

- Heart burn, nausea & anorexia, but it is tolerated &

less ulcerogenic than PBZ; causes less faecal blood

loss than aspirin

Uses:

- Suitable for use as short term analgesic as well as long term anti-inflammatory action in –

Rheumatoid & Osteo-arthritis, Ankylosing spondylitis,

acute gout, musculoskeletal injuries, dental pain

DOSE: 20 mg BD for 2 days followed by 20 mg OD

(DOLONEX, PIROX)

10, 20 mg cap)

KETOROLAC - Potent analgesic & modest anti-inflammatory activity.

- In postoperative pain it has equalled the efficacy of

morphine

- Inhibits PG synthesis & is believed to relieve pain by

a peripheral mechanism

- Rapidly absorbed after oral & i.m. administration

& excreted unchanged in urine

PYRROLO-PYRROLE DERIVATIVE

Adverse effects:

- Nausea, abdominal pain, dyspepsia, ulceration, loose stools, drowsiness, headache, dizziness, nervousness, pruritus, pain at injection site- Rise in serum transaminases & fluid retention have been noted

Contra-indications:

- Should not be given to patients on the anti-coagulants

Uses:

- In post-operative & acute musculoskeletal pain:

15-30 mg every 4-6 hours (max. 90 mg/ day)

- Also for renal colic, migraine & pain due to

due to bony metastasis

- Used in a dose of 10-20 mg 6 hourly short term

management of moderate pain

AVAILABLE : KETOROL, KETANOV (10 mg Tab)

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NIMESULIDE - Sulfonamide derivative

- Selective inhibitor of PG synthesis & there is

some relative COX-2 selectivity

Uses

- Short lasting painful inflammatory conditions like sports injuries, sinusitis & other ENT disorders, dental surgery, bursitis, low backache, Postop pain, osteoarthritis & for fever

Preferential COX-2 inhibitors

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Pharmacokinetics:

- Completely absorbed orally - Metabolism-Liver & Excretion- Urine

Adverse effects

- Epigastralgia, heart burn, loose motions- Dermatological rash, pruritus

- Hepatic failure & Renal failure in neonate (BANNED)

DOSE- 100mg BD

( NIMULID, NIMEGESIC, NIMODOL 100 mg Tab)

- Recently developed preferential COX-2 inhibitor - Has less analgesic, antipyretic activities, effective in the treatment of rheumatoid & osteoarthritis as well as soft tissue injury - Lower incidence of gastric erosions, ulcers & bleeding

DOSE: 500 mg OD (NABUFLAM, NILTIS 500 mg Tab)

NABUMETONE

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• Directly targets COX-2 which is produced at the site of inflammation

• Selectivity for COX-2 can half the risk of peptic ulceration

• Cox-2-selectivity might be an increase in the risk for heart attack, thrombosis & stroke by a relative increase in thromboxane

Selective COX-2 inhibitors

CELECOXIB, ETORICOXIB,PARECOXIB

Uses-- Osteoarthritis - Rheumatoid arthritis - Ankylosing spondylitis - For the management of acute pain in adults

Pharmacokinetics:- Slow absorption - Metabolism-Liver & Excretion- Urine

Dose :

- Celecoxib- 100-200 mg BD (CELACT,ZYCEL)

- Etoricoxib- 60-120 mg OD (ETODY,ETOXIB)

- Parecoxib- 40 mg 6-12 hrs (REVALDO,PAROXIB)

Precautions: - In patient who has clinical signs of liver toxicity or if

systemic manifestations arise, valdecoxib should be discontinued

- Should be used with caution in patients with CHF or hypertension since fluid retention & edema can occur

PARACETAMOL (ACETAMINOPHEN)

-- Central Analgesic action is like aspirin, i.e. it raises

- pain threshold, but has weak Anti-inflammatory

- action

- Paracetamol is a good & promptly acting Antipyretic

Para-amino phenol derivatives

Uses: -Most commonly used analgesic for Headache, Musculoskeletal pain - Best drug to be used as Antipyretic - Can be used in All Age groups(infants to elderly), pregnant/lactating women, & in patients in whom aspirin is contraindicated

Adverse effects: Safe & Well tolerated, Nausea occur occasionally, High doses-Hepatic necrosis

Pharmacokinetics:

Well absorbed orally. Metabolism-Liver Excretion in Urine

DOSE- 0.5-1gm TDS 500mg Tab

(CROCIN, PARACIN, METACIN, PYRIGESIC)

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Diuretics : ↓ Diuresis

--blockers : ↓ Anti-hypertensive effect

ACE inhibitors : ↓ Anti-hypertensive effect

Anticoagulants :↑ risk of G.I. Bleed

Sulfonylureas : ↑ Hypoglycaemia

Alcohol : ↑ risk of G.I. Bleed

Cyclosporine : ↑ Nephrotoxicity

Drug interactions with NSAIDs

Allergy to Asprin or any NSAID

Peptic Ulcers

During Pregnancy / Breast feeding

Anticoagulant Therapy

Suffering from blood clotting system disorders

Chronic liver diseases

Contraindications

- Mild To Moderate Pain With Little Inflammation

– PARACETAMOL or low dose IBUPROFEN

- Acute Musculoskeletal Pain, Osteoarthritic,

Injury Associated Inflammation

- IBUPROFEN, DICLOFENAC

- Postoperative or other acute but Short Lasting Painful Conditions With Minimal Inflammation

- KETEROLAC, NEFOPAM

- Patients with history of asthma/ anaphylactoid reaction

- NIMESULIDE

- Gastric intolerance to conventional NSAID

-CELECOXIB, ETORICOXIB,PARECOXIB

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TOPICAL PREPARATIONS

Advantages of topical medications

• Greater safety • Rapid onset of action• High concentrations can be attained at desired site

without exposing the rest of the body• Fewer chances of drug interactions• Non-invasive• Better acceptability

TOPICAL PREPARATIONS

MEDICATIONS EXAMPLE

Topical anesthetics •Benzocaine in orabase (20%)•Lidocaine gel•Eutectic mixture of local anesthetic (EMLA cream)

Neuropeptides •Capsaicin cream (0.025% & 0.075%)

NSAIDs •Ketoprofen (10-20%)•Diclofenac (10-20%)

Sympathomimetic agents

•Clonidine (0.01%)

MEDICATIONS EXAMPLE

NMDA blocking agents

•Ketamine (0.5% in orabase)

Anti-convulsants •Carbamazapine (2% in PLO base)

Tricyclic medications

•Amitriptyline (2% in PLO base)

Anti-spasmodics •Baclofen (2% in PLO base)

NEUROPEPTIDES(CAPSAICIN)

Available as: Cream

Indications: Post herpetic neuralgia Diabetic Neuropathy Postmastectomy pain

syndrome Trigeminal neuralgia

TOPICAL ANESTHETICS(BENZOCAINE,LIDOCAINE)

Available as - Gels

- Ointments

- Sprays

- Adhesive patches

Indications:• Post Herpetic Neuralgia• Oral ulcers• Burning mouth syndrome

NSAIDs(KETOPROFEN,DICLOFENAC)

Available as:

Cream

Patch

Indications:

Localized treatment of acute pain

associated with soft tissue injury e.g.

Musculoskeletal pain

Local drug delivery systems

• Mucoadhesive creams

• Transdermal creams

• Medicated chewing gums

• Dissolving tablets & lozenges

• Adhesive patches & powders

• Mouthwashes

- NSAIDs- Acetaminophen- Opioids- Antidepressants- Anticonvulsants- Neuroleptics- Corticosteroids- Systemic L. A.’s- Alpha adrenergic agonists- Botulinum toxin

Drugs used in management of chronic pain

Analgesics in pregnancy

• Acetaminophen -Most Useful -Any Stage• Morphine• Meperidine• Aspirin (Not in 3rd trim.)• Ibuprofen (Not in 3rd trim.)• Pentazocine (With Caution)

NSAIDS as host modulating agent in periodontal disease

In vitro model

The first evidence that NSAIDs block PG production in gingival tissue ( Gomes & co workers in 1976 )

He demonstrated that inflamed gingival fragment taken from monkey, release PG in culture medium ,& indomethacin reduced the PG

production by 90 %

• 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

• NSAIDS are associated with severe side effects

• Research shows that periodontal benefits of taking long term NSAIDS are lost when patient stops taking drug

Trombelli et al 1996

Parallel double blind RCT ,pt undergoing periodontal surgery

Pre op ketarolac 20 mg vs placebo Hourly VAS scores for 10 hrs ,time & dose of rescue analgesics

Pre op ketarolac reduced pain scores & delayed the onset of post op pain compared to placebo

• Sakuma et al+ and Miyaura et al* - IL-1α, TNF- α, lipopolysaccharide, and basic fibroblast growth factor failed to induce osteoclast formation in EP4- deficient mice cultures

• Suggesting that osteoclast formation is mediated by EP4 receptors by PGE2, which was produced through COX-2

+ J Bone Miner Res 2000:15:218-227*J Biol Chem 2000:275: 19819-19823

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.

REFERENCES

• Essentials of Medical Pharmacology

- K.D.TRIPATHI (6th Ed.)• Drugs, Diseases and the Periodontium

-Robin A. Seymour and Peter A. Heasman • Pharmacology

- DALE,RANG AND RITTER (4th Ed.) • The role of COX-2 and prostaglandin E2 in periodontal

diseases periodontology 2000,vol.40,2006,144-163• Dental Therapeutic Update October 2002

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