Acetaminophen

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??????? ?? ??? ???? CT ? MRI ???? ?? ?? ??
???? CBC ESR ?? ??? ???? CT ? MRI ???? ?? ?? ????
???? RA factor ANA, ESR ??? ?????? ?????? ??????
?? ???? ???? Amylase ????? ???? ????? ?CT ????? ???? ?? ?????? ????? ??? ???
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???

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• Acetaminophen
• NSAIDs
• COX-2 inhibitors
• traditional NSAIDs, ASA
• Opioids
• Central analgesics (tramadol)

• ????
• Local anesthetics
• ?2 agonists (clonidine)
• NMDA antagonists
• Antidepressants

N-methyl D-aspartate
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NSAIDs????????Nonsteroidal anti-inflammatory
drugs

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NSAIDs???

• ??COX?????,???????????,??????????

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• ???NSAIDs ????COX-1?COX-2 (Aspirin, Ibuprofen,
  Ketoprofen, Indomethacin, Piroxicam)
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• COX (????,Cyclooxygenase)????????????
• COX-1 ????????,? ???????
• COX-2 ?????????? ??

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???NSAIDs
Salicylates acetylsalicylic acid magnesium choline solicylate salsalate diflunisal Indoles indomethacin sulindac tolmetin Phenylacetic Acid cliclofenac
Propionic Acids ibuprofen, fenoprofen flurbiprofen ketoprofen naproxen Axicams piroxicam Pyrazole phenylbutazone
Propionic Acids ibuprofen, fenoprofen flurbiprofen ketoprofen naproxen Fenamates meclofenamate mefenamic acid Pyrazole phenylbutazone
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?? NSAIDs????
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?????

• ??????????,????????
• ?????????,?????NSAIDs????????????
• NSAIDs????,???PH???????(????????)
• NSAIDs????????,???????,???????
• ??NSAIDs??????????
• ??NSAIDs?????????,??3-4???????????????????

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????Prostaglandin??????

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• COX-2 ???,?????????

COX-1
COX-2
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COX-2????????
COX-2 specific inhibitor Celecoxib
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COX-2????????

• ??????????,????COX-2??,????????,????????,?????????
  ??????
• ?????(????????) ??????,?????????????????(hyperalge
  sia) ,???????????????????(Secondary hyperalgesia)

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The Pain Response
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The Pain Pathway
Pain Perception
Brain
Dorsal Horn
Dorsal Root Ganglion
Spinal Cord
Nociceptor
Gottschalk A, Smith DS. Am Fam Physician.
2001631979-84. Fields HL, Martin JB. In
Harrisons Principles of Internal Medicine.
199853-58.
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?????

• ??????????????COX-2??,????????????,???????????
• ??????(hyperalgesia)???,????????????

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Sensitization
10 8 6 4 2 0
Normal Pain Response
Injury
Pain Intensity
Hyperalgesia heightened sense of pain to
noxious stimuli Allodynia pain resulting from
normally painless stimuli
Stimulus Intensity
Gottschalk A, Smith DS. Am Fam Physician.
20011979-84.
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NSAIDs??????

• 3-10?????(??????????)
• ? 65??????????????,????????
• COX-2 ????????????????

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??NSAID????????
30
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Patients with Ulcer ()
10
0
Others (n260)
etodolac, aspirin,
Ibuprofen (n173)
Naproxen (n247)
Diclofenac (n461)
Indomethacin (n180)
sulindac, ketoprofen,
Cheatum et al. Clin Ther 199921992
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Safety Less GI Toxicity
Incidence of Gastroduodenal Ulcers
Emery P, et al. Lancet 1999 3542106-11
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Safety Less GI Toxicity
Incidence of Gastroduodenal Ulcers

Significantly different from all other
treatments P lt 0.001
Placebo n 99 Celecoxib 100mg n 148 Celecoxib
200mg n 145 Celecoxib 400mg n 130 Naproxen
500mg n 137
Simon LS , et al. JAMA. 19992821921-1928
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• ??---
• COX-2???????????????
• ??---
• ????COX-1?COX-2?NSAIDs??????????
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• FDA 4/7/2005???????NSAIDs?????????
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????NSAIDs????COX-2?Coronary Heart Disease?????
???,??AMI????CHD?????? (95 CI) New Users During
Study
Ibuprofen (n 4319) 1.01 (0.77-1.33)
Reference Nonusers IRR 1.0
Naproxen (n 6489) 0.92 (0.73-1.16)
Celecoxib (n 4509) 0.88 (0.67-1.16)
Rofecoxib ?25 mg/day (n 3430) 1.02 (0.76-1.37)
Rofecoxib gt25 mg/day (n 500) 1.93 (1.09-3.43)
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0.1
10
Better than nonuser
Worse than nonuser
IRR incidence rate ratio N expressed in
person-years. 5316 events. P 0.024 vs
reference P 0.014 vs celecoxib (2.20 95 CI,
1.17-4.10). Ray WA et al. Lancet.
20023601071-1073.
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COX-2 ? NS-NSAIDs - AMI ? SCD ???
P0.016
P0.03
3.00 (1.09-8.31)
P0.06
1.69 (0.97-2.93)
P0.05
P0.03
P0.005
1.23(0.89-1.71)
1.33 (1.09-1.63)
Adjusted Odds Ratio (95 CI)
1.14 (1.00-1.30)
1.13 (1.01-1.27)
1.06 (0.96-1.17)
1.00(reference)
0.84 (0.67-1.04)
Control (remote use)
Celecoxib
Ibuprofen
Naproxen
Rofecoxibgt25 mg
Other NSAIDs
Indomethacin
Diclofenac
Rofecoxib?25 mg
AMIacute myocardial infarction SCDsudden
cardiac death. Adjusted for age, gender, health
plan region, medical history, smoking, and
medication use. Adapted from Graham et al.
Lancet. 2005365475-81.
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????????????

• NSAIDs??(?celecoxib, etodolac, meloxicam,
  nabumetone, nimesulide, rofecoxib)?????
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• (?) ??????60????????
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• ?. ??????????????????????????,
  ??????????????????, ????????????(misoprostol)

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???????????
Brand Name Company Generic BNHI Daily cost
Voltaren 100mg SR Novartis Diclofenac 12.4 12.4
Napton 750mg CR ???? Naproxen 19.8 19.8
Relifex 500mg GSK Nabumetone 11.5 23
Lonine 200mg ?? Etodolac 8.7 17.4 26.1
Nimed 100mg ???? Nimesulide 8.1 16.2
Mobic 7.5mg BI Meloxicam 17.8 17.8 35.6
Vioxx 25mg MSD Rofecoxib 33.4 33.4
CELEBREX 200mg Pfizer Celecoxib 28.9 28.9
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COX-2??

• Rofecoxib (Vioxx) ???(9/2004)
• Celecoxib (Celebrex)
• Valdecoxib (Bextra) ???(4/2005)
• Parecoxib (Dynastat) IV or IM injection
• Arcoxia
• Prexige

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NSAIDs?????

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• ?????400??????,??????????2.5?
• ?????800?????3.4?

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• ????(Alternate Medicine)

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?????????(Pedicle Screw Fixation)?????

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1999-2000???????

• 1999????????????120???
• ??????45?(??22?)
• ????14?(??7?)
• ????????13?(??9?)
• ???????????11?(??7?)
• ????6?(??5?)
• ????27?

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• 1998-1999????????????(14)
• 1999???13???,??2??????????
• ??????(interbody fusion device)??????????(structur
  al allograft products)?????????????
• ?????????(???????) ???????????????????????????????
  ?

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?????????????????(1986-2001) 3244 ?

• . ?????? Disectomy 441
• ????? Laminectomy 549
• ?????? Lumbosacral fusion 2254
• ????? Non-instrumented 516
• ???? Instrumented 1738

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• ??????Disc arthrodesis
• Total disc replacement
• Disc arthroplasty
• Artificial intervertebral disc prosthesis
• Disc regeneration

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?????????????????

• Lumbar Disc Disease
• Instrumentation or Not
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Post-laminectomy Slippage
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Dysplastic Spondyloptosis L5S1Fusion in Situ
with hip spica(12y/o,F)
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• ???????????????????(?????),???????????????????????
  ,??????

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Distraction Instrumentation Sagittal imbalance
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Settling after Long Fusion
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• ?????????(ALIF)
• ?????????(PLIF)

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