nsaids / orthodontic courses by indian dental academy
TRANSCRIPT
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Good Morning
INDIAN DENTAL ACADEMY
Leader in continuing dental education www.indiandentalacademy.com
www.indiandentalacademy.com
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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
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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
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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
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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
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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
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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
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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
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COMMON PROPERTIES OF ALL NSAIDS
Analgesia Antipyresis
Anti-inflammatory
Dysmenorrhoea
Antiplatelet aggregatory
Ductus arteriosus
closureParturition
Gastric mucosal damage
Renal effects
Anaphylactoid reactions
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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
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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)
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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
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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
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Interactions :
Warfarin, naproxen, sulfonylureas,
phenytoin and methotrexate.
Oral anticoagulants.
Uric acid
Probenecid
Methotrexate.
Furosemide and thiazides
Spironolactone.
Protein bound iodine levels. www.indiandentalacademy.com
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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
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PYRAZOLONES
Phenylbutazone
Pharmacokinetics
98% bound to plasma proteins.
Plasma t ½ = 60 hrs.
Dose 100-200 mg BD/TDSAdverse effects
Bone marrow
depression
Agranulocytosis
Stevens-Johnson
syndrome www.indiandentalacademy.com
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Interactions :
Sulfonamides, tolbutamide, warfarin, imipramine & methotrexate
Anticoagulants
Phenytoin & tolbutamide
Uses :
Rheumatoid arthritis
Ankylosing spondylitis
Rheumatic fever
Acute gout
Severe cases
Zolandin
P L
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Oxyphenbutazone
Metamizol (Dipyrone) : 0.5-1.5 g
Propiphenazone : 300-600 mg TDS
INDOLE DERIVATIVES
Indomethacin
Pharmacokinetics
90% bound to plasma proteins.
Plasma t ½ = 2-5 hrs.
Dose 25-50mg BD/QID
Sioril, phenabid
Analgin, novalgin
Saridon, anafebrin
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Adverse effects
Interactions :
Furosemide
Thiazides, furosemide, blockers, ACE inhibitors
Warfarin www.indiandentalacademy.com
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Uses :
Rheumatoid arthritis
Ankylosing spondylitis
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
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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
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Adverse effects
Interactions :
Anticoagulants
Furosemide, thiazides & blockers
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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
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Adverse effects
Uses :
Analgesic Osteoarthritis
Dysmenorrhoea Rheumatoid arthritis
Medol, meftal, ponstan
L
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ARYL-ACETIC ACID DERIVATIVES
Diclofenac sodium :
Pharmacokinetics
99% bound to plasma proteins.
Plasma t ½ = 2 hrs
50 mg TDS/BD, 75 mg i.m.
Adverse effects
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Uses :
Ankylosing spondylitis Osteoarthritis
Dysmenorrhoea Rheumatoid
arthritis
Bursitis Post-traumatic / post-op inflammatory condition
Tolmetin : 400-600 mg TDS
Voveran, diclonac, movonac
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OXICAM DERIVATIVES
Piroxicam
Pharmacokinetics
99% bound to plasma proteins.
Plasma t ½ = 2 days
20 mg BD / 20 mg OD
Adverse effects
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Uses :
Ankylosing spondylitis
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
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PYRROLO-PYRROLE DERIVATIVE
Ketorolac :Pharmacokinetics
Highly bound to plasma proteins.
Plasma t ½ = 5-7 hrs
10-20 mg / 6 hrly (orally)
Adverse effects
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Uses :
Post-op / acute musculoskeletal pain
(15-30 mg i.m. / 4-6 hrs
Renal colic Bony metastasis
Migraine
SULFONANILIDE DERIVATIVE
Nimesulide :
Pharmacokinetics
99% bound to plasma proteins.
Plasma t ½ = 2-5 hrs
100 mg BD
Ketorol, torolac
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Adverse effects
Uses :
Bursitis
Sports injuriesDental surgery
ENT disorders
Low backacheDysmenorrhoea
Post-op pain/osteoarthritis Nimulid, nimodolwww.indiandentalacademy.com
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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
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Adverse effects
Analgesic nephropathy
Acute paracetamol poisoning
150 mg/kg
Fatality > 250 mg/kg
Early manifestations / 12-18 hrs / 2 dayswww.indiandentalacademy.com
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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
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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
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• Exacerbation of rheumatoid arthritis, ankylosing
spondylitis, acute gout, acute rheumatic fever – aspirin,
indomethacin, naproxen, piroxicam
• Asthma or anaphylactoid reactions to aspirin – nimesulide
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Analgesics after certain endodontic procedures
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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
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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
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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
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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
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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.
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CONCLUSION
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Thank you
For more details please visit www.indiandentalacademy.com
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