NSAIDs / orthodontic courses by Indian dental academy

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INDIAN DENTAL ACADEMY

Leader in continuing dental education www.indiandentalacademy.com

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CONTENTS

Introduction History Classification Mechanism of action Beneficial action and toxicities of PG synthesis inhibition Common properties of all NSAIDs Drugs proper Choice of analgesic after certain endodontic procedures Pain management strategy Flexible prescription plan Advances References Conclusion www.indiandentalacademy.com

HISTORY

Willow Bark – Centuries ago.

1875 – Sodium salicylate

1899 – Phenacetin + antipyrine

1899 – Acetyl salicylic acid

1949 – Phenyl butazone

1963 – Indomethacin

1963 – Propionic acid derivatives (NSAIDS)

1971 – Vane and coworkers observed that NSAIDS

blocked PG synthesis. www.indiandentalacademy.com

CLASSIFICATION

(Acc. to Tripathi)

A. Analgesic and antiinflammatory :Aspirin, Salicylamide, Benorylate, DiflunisalSalicylates

Phenylbutazone, oxyphenbutazonePyrazolone derivatives

Indomethacin, sulindacIndole derivatives

Ibuprofen,Naproxen, Ketoprofen, Fenoprofen, Flurbiprofen.

Propionic acid derivatives

Mephenamic acid Anthranilic acid derivative

Diclofenac, Tolmetin Aryl-acetic acid derivatives

Piroxicam, Tenoxicam, Meloxicam.Oxicam derivatives

Ketorolac.Pyrrolo-pyrrole derivative

NImesulideSulfonanilide derivative

NabumetoneAlkanones www.indiandentalacademy.com

B. Analgesic but poor antiinflammatory:

Paracetamol (Acetaminophen)Paraaminophenol derivative

Metamizol (Dipyrone), propiphenazone Pyrazolone derivatives

NefopamBenzoxazocine derivative

Acc. to Goodman and Gillman

A. Non selective Cox inhibitor

Aspirin, sodium salicylate, choline magnesium trisalicylate, salsalate, diflunisal, salfasalazine, olsalazine.

Salicylic acid derivatives

Acetaminophen Para amino derivatives

Indomethacin, sulindacIndole & indene acetic acid

Tolmetin, diclofenac, ketorolac. Heteroaryl acetic acid www.indiandentalacademy.com

Ibuprofen, naproxen, flurbiprofen, ketoprofen, fenoprofen, oxaproxin.

Aryl propionic acid

Mefenamic acid, meclofenamic acid Anthranilic acid (fenamates)

Oxicams (piroxicam, Meloxicam) Enolic acid

Nabumetone. Alkanones

RofecoxibDiaryl substituted furanones

B. Selective cox-2 inhibitor

Celecoxib Diaryl substituted Pyrazoles

Etodolac Indole acetic acid

NimesulideSulfonanilides


MECHANISM OF ACTION

Odontogenic pain Acute pain

Noxious stimuli Tissue destruction or injury

Cellular destruction

Release / synthesis of histamine / prostaglandin / bradykinin

Peripheral nociceptor / free nerve endings

PAIN

+

Disease process +

Surgical intervention


Beneficial actions due to PG Synthesis inhibition

• Analgesia • Antipyresis • Antiinflammatory • Antithrombotic • Closure of ductus arteriosus

Shared toxicities due to PG synthesis inhibition

• Gastric mucosal damage • Bleeding • Limitation of renal blood flow • Delay / prolongation of labour • Asthma & anaphylactoid

reactions


COMMON PROPERTIES OF ALL NSAIDS

Analgesia Antipyresis

Anti-inflammatory

Dysmenorrhoea

Antiplatelet aggregatory

Ductus arteriosus

closureParturition

Gastric mucosal damage

Renal effects

Anaphylactoid reactions


SALICYLATES Aspirin (prototype)Pharmacological actions • Analgesic (0.3-1.5 g/day) • Antipyretic • Antiinflammatory (3-6 g/day or 100mg/kg/day) • Metabolic effects• Respiration • Acid base and electrolyte balance • CVS• GIT • Urate excretion

• Blood

2-5 g/day <2g/day > 5g/daywww.indiandentalacademy.com

Pharmacokinetics

80% bound to plasma proteins.

Volume distribution 0.17 L/kg.

Plasma t ½ = 15-20 min.

Release salicylic acid (t ½) = 3-5

hrs.

Antiinflammatory doses (t ½) =

8-12 hrs. (30 hrs in poisoning)


Adverse effects

Salicylism : dizziness, tinnitus, vertigo, reversible impairment of hearing & vision, excitement & mental confusion, hyperventilation & electrolyte imbalance.Acute salicylate poisoning : fatal dose-15-30g , > 50 mg/dl. www.indiandentalacademy.com

Contraindications :

Sensitivity, peptic ulcers, bleeding tendency, chicken pox or influenza.

Chronic liver disease

Diabetics, low cardiac reserve or frank CHF, juvenile rheumatoid arthritis.

Precautions :

Stopped 1 week before elective surgery.

During pregnancy

Avoided by breast feeding mothers.

G-6-PD deficient individualswww.indiandentalacademy.com

Interactions :

Warfarin, naproxen, sulfonylureas,

phenytoin and methotrexate.

Oral anticoagulants.

Uric acid

Probenecid

Methotrexate.

Furosemide and thiazides

Spironolactone.

Protein bound iodine levels. www.indiandentalacademy.com

Uses :

Analgesic

Antipyretic

Acute rheumatic fever (4-6 g)

Rheumatoid arthritis (3-5 g)

Osteoarthritis

Postmyocardial infarction &

poststroke patients

Pregnancy induced hypertension and

preeclampsia

Delay labour

Patent ductus arteriosus

* Aspirin, dispirin, colosprin www.indiandentalacademy.com

PYRAZOLONES

Phenylbutazone

Pharmacokinetics


Plasma t ½ = 60 hrs.

Dose 100-200 mg BD/TDSAdverse effects

Bone marrow

depression

Agranulocytosis

Stevens-Johnson

syndrome www.indiandentalacademy.com

Interactions :

Sulfonamides, tolbutamide, warfarin, imipramine & methotrexate

Anticoagulants

Phenytoin & tolbutamide

Uses :

Rheumatoid arthritis

Ankylosing spondylitis

Rheumatic fever

Acute gout

Severe cases

Zolandin

P L


Oxyphenbutazone

Metamizol (Dipyrone) : 0.5-1.5 g

Propiphenazone : 300-600 mg TDS

INDOLE DERIVATIVES

Indomethacin

Pharmacokinetics


Plasma t ½ = 2-5 hrs.

Dose 25-50mg BD/QID

Sioril, phenabid

Analgin, novalgin

Saridon, anafebrin


Adverse effects

Interactions :

Furosemide

Thiazides, furosemide, blockers, ACE inhibitors

Warfarin www.indiandentalacademy.com

Uses :

Rheumatoid arthritis


Psoriatic arthritis

Acute gout

Acu. Exa. destructive

arthropathies

Malignancy asso. fever

Patent ductus arteriosus closure (0.1/0.2 mg/kg/12 hrly

P L

Indicin, indocap www.indiandentalacademy.com

PROPIONIC ACID DERIVATIVES

Pharmacokinetics

90-99% bound to plasma proteins.

Drug Plasma t ½

Dosage

Ibuprofen 2 hr 400-800 mg TDS Brufen, emflam Naproxen 12-16 hr 250 mg BD/TDS Xenobid, naxidKetoprofen 2-3 hr 100 mg BD/TDS Ketofen Fenoprofen 2-4 hr 300-600 mg TDS Arflur Flurbiprofen 4-6 hr 50 mg BD/QID Flurofen


Adverse effects

Interactions :

Anticoagulants

Furosemide, thiazides & blockers


Uses :

Analgesic Antipyretic

Dysmenorrhoea

ANTHRANILIC ACID DERIVATIVE (Fenamate)

Mephenamic acid

Pharmacokinetics

Highly bound to plasma proteins.

Plasma t ½ = 2-4 hrs

250-500 mg TDS www.indiandentalacademy.com

Adverse effects

Uses :

Analgesic Osteoarthritis

Dysmenorrhoea Rheumatoid arthritis

Medol, meftal, ponstan

L


ARYL-ACETIC ACID DERIVATIVES

Diclofenac sodium :

Pharmacokinetics


Plasma t ½ = 2 hrs

50 mg TDS/BD, 75 mg i.m.

Adverse effects


Uses :

Ankylosing spondylitis Osteoarthritis

Dysmenorrhoea Rheumatoid

arthritis

Bursitis Post-traumatic / post-op inflammatory condition

Tolmetin : 400-600 mg TDS

Voveran, diclonac, movonac


OXICAM DERIVATIVES

Piroxicam

Pharmacokinetics


Plasma t ½ = 2 days

20 mg BD / 20 mg OD

Adverse effects


Uses :


Osteoarthritis

Dysmenorrhoea Rheumatoid arthritis

Acute gout

Musculoskeletal injuries

Dentistry

Episiotomy

Tenoxicam : 20 mg OD

Meloxicam : 7.5-15 mg/day (rheumatoid & osteo-arthritis)

Dolonex, pirox, piricam, toldin

P L

Melflam, Meloxiwww.indiandentalacademy.com

PYRROLO-PYRROLE DERIVATIVE

Ketorolac :Pharmacokinetics

Highly bound to plasma proteins.


10-20 mg / 6 hrly (orally)

Adverse effects


Uses :

Post-op / acute musculoskeletal pain

(15-30 mg i.m. / 4-6 hrs

Renal colic Bony metastasis

Migraine

SULFONANILIDE DERIVATIVE

Nimesulide :

Pharmacokinetics



100 mg BD

Ketorol, torolac


Adverse effects

Uses :

Bursitis

Sports injuriesDental surgery

ENT disorders

Low backacheDysmenorrhoea

Post-op pain/osteoarthritis Nimulid, nimodolwww.indiandentalacademy.com

PARA-AMINO PHENOL DERIVATIVES

• Phenacetin 1887 • Paracetamol (acetaminophen) 1950

Actions

Pharmacokinetics 1/3 bound to plasma proteins. Plasma t ½ = 2-3 hrs 3-5 hrs (orally) 0.5-1g TDS Infants - 50 mg Children 1-3 yrs- 80-160 mg

4-8 yrs 240-320 mg

9-12 yrs 300-600 mg www.indiandentalacademy.com

Adverse effects

Analgesic nephropathy

Acute paracetamol poisoning

150 mg/kg

Fatality > 250 mg/kg

Early manifestations / 12-18 hrs / 2 dayswww.indiandentalacademy.com

Mechanism of toxicity Treatment –

• Gastric lavage• N-acetylcysteine 150 mg/kg / i.v./ 15 min / 20 hrs• 75 mg/kg / orally / 4-6 hrs / 2-3 days

Uses :

‘Over the counter’ analgesic

Musculoskeletal pain

Dysmenorrhoea

Antipyretic

Crocin, metacin, paracin www.indiandentalacademy.com

BENZOXAZOCINE DERIVATIVE

Nefopam

30-60 mg TDS oral

20 mg i.m. 6 hrly

CHOICE OF NSAIDS

• Mild to moderate pain – paracetamol, ibuprofen

• Acute musculoskeletal, osteoarthritic, injury associated inflammation – ibuprofen, diclofenac, piroxicam

• Post-op / acute / short lasting painful condition – ketorolac, nefopam

Nefomax


• Exacerbation of rheumatoid arthritis, ankylosing

spondylitis, acute gout, acute rheumatic fever – aspirin,

indomethacin, naproxen, piroxicam

• Asthma or anaphylactoid reactions to aspirin – nimesulide


Analgesics after certain endodontic procedures


PAIN MANAGEMENT STRATEGY

3D iagnosis efinitive Rxrugs

Definitive treatment :

•Pulpotomy, pulpectomy

•Extraction

•Incision & drainage

Drug :

•Pretreat with NSAIDs

•Prescribe by clock

•Long acting LA

•Flexible prescription plan


Flexible analgesic prescription plan

Aspirin like drugs indicated

Aspirin like drugs contra indicated

Ibuprofen 200 mg Acetaminophen 600-1000mg

NSAIDs (alone max.effective dose) OR NSAID +

acetaminophen Acetaminophen 600-1000

mg + codine 60 mg

Ibuprofen 400 mg/4 hrly and equivalent of acetaminophen 600 mg / codine 60 mg 4 hrly

Acetaminophen 1000 mg with equivalent of oxycodone 10

mg

NSAID (max. dose) & acetaminophen / oxycodone

10 mg combination

Mild pain

Moderate pain

Severe pain www.indiandentalacademy.com

ADVANCES Selective cox-2 inhibitors : Celecoxib, rofecoxib, valdecoxib, etoricoxib, meloxicam, diisopropyl flurophosphate.Action Celecoxib P L

Use-osteoarthritis, rheumatoid arthritis Dose – 200 mg / day OD or 100 mg BD. Commercial names – Celebrex, Celib, Celfast, Celact etc. Banned – July 2001 Rofecoxib P L

Dose – 12.5 mg OD (max. dose 25 mg) Commercial name – Vioxx, Dolib MD, Roff, Rofaday Banned – September 2004


Valdecoxib

Dose – 10-20 mg OD

Commercial name – Valed, Valus, Vorth, Bextra

Banned –7 April 2005.

Other drugs banned by FDA

Benoxaprofen

Phynylbutazone

Oxyphenbutazone

Saprofen

Piroxicam www.indiandentalacademy.com

REFERENCES :

1) Effectiveness of prophylactic use of refecoxib is comparison with ibuprofen on postendodontic pain. JOE. Jan 2003, Vol. 29, No. 1, pg. 62-64.

2) Evaluation of meloxicam (cox-2 inhibitor) for management of post operative endodontic pain – A double blind placebo controlled study. JOE, Oct 03, Vol. 29, No. 10, Pg. 634-637.

3) The efficacy of pain control following nonsurgical root canal treatment using ibuprofen in a combination of ibuprofen and acetaminophen in a randomized, double-blind, placebo controlled study. IEJ, 2004, Vol. 37, Pg. 531-541.


CONCLUSION


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NSAIDs / orthodontic courses by Indian dental academy

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