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Focus on Parecoxib
Eddy Rahardjo
Pain Continues to be Undertreated
Postoperative pain U.S1,2
100%
1993 (n=135)
1999 (n=250)
82%
77%
80%
60%
Patients
49% 47%
40%
.
23%
19% 21%
20% 18%
13%
8%
0%
Any Slight Moderate Severe Extreme
Pain Pain Pain Pain Pain
4 Feb 2003
National Patient Safety Foundation
(created by AMA, reported on 9 Oct 1997)
• Specific pain
• Acute pain – Backpain
– Postoperative pain – Myofascial pain
• Chronic pain – Herpetic Neuralgia
• Cancer pain – Complex Regional
Pain Syndrome
• etc
– Neuropathies
– Headache
– Post Dural Puncture
Dispersi kompleksitas berbagai jenis nyeri
Nyeri post-op
Nyeri kanker
Nyeri khronis
Analgesia
Anestetika
Opioid
NSAID
COX-2 Inhib
paracet
Anestetika
Opioid
NSAID
COX-2 Inhib
paracet
Hierarchy of analgesia
University of Southern California
Los Angeles County Trauma Center
N O N O
C H3 CH 3
Hydrolysis
(-)
S O 2N C O C H2 CH3 SO 2 NH 2
Na+
Hydroxylation
(3A4, 2C9)
Glucuronidation
10 ---
-
-
-
NSAIDs
-
5 ---- parecoxib
- morfin
- Ceiling effect
- anestesia
- Pada titik ini, menambah dosis tidak
0 menambah analgesia, hanya
menambah komplikasi
NSAIDS can kill, indeed
• Seorang laki 35 th operasi laminektomi L1-3
• Postop diberi resep 6 ampul Ketorolac,
dosis 30 mg x 3 (dr A)
• Hari ke 2 pindah ruangan, Ketorolac diteruskan
3 x 30 mg (dr B)
• Hari ke 10 postop pasien shock, melena 2000 ml
(ternyata masih terus diberi Ketorolac 3 x 30mg)
• Masuk ke ICU selama 7 hari, resusitasi cairan,
transfusi masif sebanyak 20 unit darah
Profile of parecoxib
• 40mg IM ~ morphine 12mg IM ~ ketorolac 60mg IM1,2
• 40mg IV > morphine 4mg IV ~ ketorolac 30mg IV3
• Preoperative* administration: provides postoperative pain relief4
• Onset of action: 7 to 13 minutes8
• Duration of effect: consistent with twice daily dosing8
• Contraindicated in treatment of postoperative pain following
coronary artery bypass graft (CABG) surgery
1Malan TP Jr, Gordon S, Hubbard R, Snabes M. The cyclooxygenase-2-specific inhibitor parecoxib sodiumsodium is as effective as 12 mg of morphine administered
intramuscularly for treating pain after gynecologic laparotomy surgery. Anesth Analg. 2005;100:454-460.
2Daniels SE et al. Clin Ther. 2001;23:1018-1031.
3Rasmussen GL et al. Am J Orthop. 2002;31:336-343.
4Desjardins PJ et al. Anesth Analg. 2001;93:721-727.
5Hubbard RC et al. Br J Anaesth. 2003;90:166-172.
6Malan TP Jr et al. Anesthesiology. 2003;98:950-956.
7Wender RH et al. ASRM. 2001.
8parecoxib sodiumSmPC.
Postoperative Efficacy in Orthopedic Surgery:
Elderly Patients
1.6
more relief
Pain Intensity Difference (Mean)
1.4
* *
1.2 *
1.0 *
* *
0.8 *
* *
0.6 P-40 single dose
0.4
Ketorolac
less relief
0.2
Morfin 4 mg
0.0
-0.2
0 1 2 3 4 5 6 7 8 10 12
Hours Postdose
Measured as Time
- Specific Pain Intensity Difference (Categorical)
*P <0.05 statistically significantly
different from morphine 4 mg.
1
Hubbard RC et al. Anesthesiology. 2001;95:A807.
2
Data on file. Clinical Study #020. July 31, 2000. Pfizer, New York, NY.
Derajat nyeri postop berbeda-beda
• Abdominal Procedures
– Pain after major and upper abdominal operations is severe
– Combined regimen of epidural local anesthetics and opioids
plus systemic NSAIDs or COX-2 inhibitors is
recommended.[9]
• Prostatectomy
– Pain is usually not severe and may be treated with systemic
opioids combined with NSAIDs or COX-2 inhibitors and
acetaminophen.
Opioid-Sparing Effects on PCA Morphine
40 mg IV bid
0
Percent Reduction In Morphine Use
- 10
P-40 iv single dose vs morphine alone
- 20
-27.8%
- 30 *
Mean morphine consumption was placebo, 43.5 mg; DYNASTAT 20 mg bid, 36.7 mg; DYNASTAT 40 mg bid, 31.4 mg.
PCA morphine was available within 140 minutes following surgery.
1Hubbard RC et al. Br J Anaesth. 2003;90:166-172.
Conventional NSAIDs and COX-2 Inhibitors
"Although the risk that an individual patient would have a heart attack or
stroke related to Vioxx is very small, the study that was halted suggests
that, overall, patients taking the drug chronically face twice the risk of a
heart attack compared to patients receiving a placebo," Dr. Crawford
said in a news release.
Nominal
stimulus
Modulation
Pain General Anesthesia
Ascending
input Dorsal root
ganglion
Spinothalamic
Peripheral
tract
nerve
Peripheral
nociception
nociceptors
Ascending
input Dorsal root
ganglion
COX-2
Opioid
inhibitor
Spinothalamic
Peripheral
tract
nerve
Peripheral
nociception
nociceptors