Clinical Use of NSAIDs
Ajchara Koolvisoot, M.D.
Division of Rheumatology
Department of Medicine
Outline
• Clinical application & Practical use
Indication
Efficacy
Safety
• Practical approach & recommendation
Efficacy : Mechanism of Action
Action
Mechanism
1. Anti-inflammatory
COX-2
2. Analgesic & antipyretic
COX-2
3. Carcinoprotective
COX-2
4. Anti-platelet
COX-1 ( TXA2 )
Efficacy of Specific COX-2 inhibitor = Classical NSAIDs
Except : No antiplatelet effect
หญิงอายุ 48 ปี มีโรค HT มีอาการปวดหลัง
ตรวจพบมี OA change ที่ spine ท่ านจะสั่ งยาใด
• A. Indomethacin
• B. Naproxen
• C. Celecoxib
• D. Acetaminophen + orphenadrine
• E. Acetaminophen โดดๆ
หญิงอายุ 55 ปี พึง่ วินิจฉัยว่ าเป็ นโรค rheumatoid
arthritis ได้ ยา ibuprofen 600 มิลลิกรัมต่ อวัน
2 สั ปดาห์ ไม่ ดีขน
ึ้ ท่ านจะทาอย่ างไร
• A. ให้ยาเดิม แต่เพิม่ ขนาดเป็ น 1600 มิลลิกรัมต่อวัน
• B. เปลี่ยนเป็ น Indomethacin 75 มิลลิกรัมต่อวัน
• C. ให้ยาเดิม แต่ add prednisolone 20 มิลลิกรัมต่อวัน
• D. ให้ยาเดิม + แนะนาว่ารอยาออกฤทธิ์ก่อน และโรคเป็ นแบบนี้เอ
• E. ส่ ต่อ rheumatologist
Anti-inflammatory Properties
• Clinical application & characteristic :
No difference among all NSAIDs
Individual response
Drug properties - Dose & duration
Optimal Use of NSAIDs
• Is NSAID really needed ?
Which indication ?
Dose ?
Interval of Rx ?
• Any underlying disease ?
• Drug interaction ?
หญิงอายุ 48 ปี มีโรค HT มีอาการปวดหลัง
ตรวจพบมี OA change ที่ spine อย่ างเดียว
ท่ านจะสั่ งยาใด
• A. Indomethacin
• B. Naproxen
• C. Celecoxib
• D. Acetaminophen + orphenadrine
• E. Acetaminophen โดดๆ
หญิงอายุ 55 ปี พึง่ วินิจฉัยว่ าเป็ นโรค rheumatoid
arthritis ได้ ยา ibuprofen 600 มิลลิกรัมต่ อวัน
2 สั ปดาห์ ไม่ ดีขน
ึ้ ท่ านจะทาอย่ างไร
• A. ให้ยาเดิม แต่เพิม่ ขนาดเป็ น 1600 มิลลิกรัมต่อวัน
• B. เปลี่ยนเป็ น Indomethacin 75 มิลลิกรัมต่อวัน
• C. ให้ยาเดิม แต่ add prednisolone 20 มิลลิกรัมต่อวัน
• D. ให้ยาเดิม + แนะนาว่ารอยาออกฤทธิ์ก่อน และโรคเป็ นแบบนี้เอ
• E. ส่ ต่อ rheumatologist
Anti-platelet Properties
• Clinical application & characteristic :
Drug
Anti-platelet
Character
Classical
NSAIDs
++
Reversible
T1/2 dependent
COX-2
inhibitor
-
-
ASA
( low dose )
+++
Irreversible
ยาใดในกลุ่ม NSAIDs สามารถใช้ ในโรค
familial polyposis coli ได้
• A. Celecoxib
• B. Etoricoxib
• C. Indomethacin
• D. ASA
• E. All of above
Carcino-protective Properties
• Clinical application :
Disease Familial adenomatous polyposis
( FAP )
Choice
Most classical NSAIDs & ASA
COX-2 inhibitor : Celecoxib
Dose 200-400 mg BID
reduced number 28%, size 30.7%
( placebo 4.5% & 4.9% )
( NEJM 2000 June 29; 342: 1946-1951 )
Inhibited by NSAIDs
Apoptosis
Growth factor
Induced apoptosis
Angiogenesis
ยาใดในกลุ่ม NSAIDs สามารถใช้ ในโรค
familial polyposis coli ได้
• A. Celecoxib
• B. Etoricoxib
• C. Indomethacin
• D. ASA
• E. All of above
Adverse Effects
Diverse physical, chemical,
Inflammatory & mitogenic stimuli
COXIBS
COX-1
COX-2
Tissue specific isomerases
Prostanoids Prostacyclin
Endothelium
Kidney
Platelet
brain
Thromboxane A2
Prostaglandin D2
Platelet
Smooth m. vv.
Macrophage
Kidney
Mast cell
Brain
Airway
Prostaglandin E2
Prostaglandin F2α
GI
Uterus
Brain
Airway
Kidney
Smooth m.vv.
Smooth m vv.
Eye
Adverse Effects
• Gastrointestinal
> 10%
• Cardiovascular
• Renal & electrolytes
1-10%
• CNS
• Hematologic
• Dermatologic & hypersensitivity
• Hepatic
< 1%
Safety
Risk of Cardiovascular Events
NSAIDs & CVS : Mechanism
Platelet
COX-1
X
Arachidonic acid
NSAID
Thromboxane TXA2 Cox-2 inhibitor
Prothrombotic state
Endothelial
COX-2
X
X
Prostacyclin
PGI2
Antithrombotic state
ยา Coxibs ใด มีผลข้ างเคียงทาง CVS น้ อยทีส่ ุ ด
• A. ทุกตัวในกลุ่ม ทาให้เกิด thrombosis มากพอๆกัน
• B. Lumiracoxib
• C. Etoricoxib
• D. Celecoxib
• E. Parecoxib
Kearney PM, et al. BMJ 2006
Vascular events
1.42
( 1.13-1.78 )
Myocardial infarction
1.86
( 1.33-2.59 )
Coxibs increase risk of MI & vascular events > Placebo
Dose-Response Relationship of AMI risk
2.5
Diclofenac
> 150
2
Rofecoxib
> 25
Naproxen
> 1000
Celecoxib
> 200
1000
> 150
ac <=
g
> 200
= 200
0.5
Odds Ratio
Naproxen
< 1000
Diclofenac
< 150
en <=
mg
Celecoxib
< 200
b > 25
Rofecoxib
< 25
1
<= 25
1.5
COX-2 Inhibitors : Chemistry
Generic name
Chemistry
COX-2
• Celecoxib
Sulphonamide
30
• Valdecoxib
Sulphonamide
261
• Parecoxib
Sulphonamide
261
• Rofecoxib
Sulphonyl
276
• Etoricoxib
Sulphonyl
344
• Lumiracoxib
Phenyl acetic acid
433
Half-life & CV Risk
• Half-life :
Rofecoxib
Valdecoxib
> Celecoxib
Longer T1/2  More CV events
Coxibs & BP Effect
Effect of Time to CV events
• Within the first 10-30 days of Rx
• Cumulative effect with time
• Risk persists 30 days after discontinuation
ยา Coxibs ใด มีผลข้ างเคียงทาง CVS น้ อยทีส่ ุ ด
• A. ทุกตัวในกลุ่ม ทาให้เกิด thrombosis มากพอๆกัน
• B. Lumiracoxib
• C. Etoricoxib
• D. Celecoxib
• E. Parecoxib
Coxibs : Cardiovascular Risk
• Drug : Class effect ?
No
Individual properties ? :
Yes Dose-related
Dose
Molecule/Chemistry
Yes
Half-life
Yes
Effect to BP & sodium Yes
• Duration of Rx
Yes
Is Naproxen Cardio-protective ?
Versus placebo
Versus Coxibs
Risk of MI in Classical NSAIDs
Study
Relative risk
Relative risk
1.19 ( 1.08.1.31 )
Classical NSAIDs increase risk of MI > Placebo
ยา NSAIDs ใด
มีผลข้ างเคียงทาง CVS มากทีส่ ุ ดในกลุ่ม
• A. ทุกตัวในกลุ่ม ทาให้เกิด thrombosis มากพอๆกัน
• B. Diclofenac
• C. Ibuprofen
• D. Meloxicam
• E. Naproxen
Summary : Meta-analysis & Systemic Review
• Rofecoxib
• Celecoxib
•
•
•
•
Naproxen
Diclofenac
Piroxicam
Ibuprofen
< 25 mg/d
> 25 mg/d
> 400 mg/d
< 200 mg/d
RR
1.33* -1.73*
2.19*
1.56* -2.70*
1.0
0.92-0.97
1.40* -1.63*
1.06 ( 0.70-1.59 )
1.07-1.51*
Thromboxane Inhibition
( COX-1 mediated )
Prostacyclin Inhibition
( COX-2 mediated )
Diclofenac
Rofecoxib
Celecoxib
Etoricoxib
Lumiracoxib
Ibuprofen
Anti-thrombotic
More GI side toxicity
Prothrombotic
Less GI side effect
COX-2 Inhibitors : COX-Selectivity
ASA
Naproxen
ยา NSAIDs ใด
มีผลข้ างเคียงทาง CVS มากทีส่ ุ ดในกลุ่ม
• A. ทุกตัวในกลุ่ม ทาให้เกิด thrombosis มากพอๆกัน
• B. Diclofenac
• C. Ibuprofen
• D. Meloxicam
• E. Naproxen
EMEA : June 2005
• Coxibs should not be used in pts with established
CAD, stroke and/or peripheral arterial disease
• Caution when prescribing Coxibs in pt with
CAD risk ( HT, hyperlipidemia, DM, smoking )
• Use the lowest effective dose & shortest duration
• Warning of hypersensitivity esp. in first month use
GI Side Effects
Renal Side Effects
ชายอายุ 79 ปี เป็ น HT คุมได้ ดี BP 120/80 พึง่
ได้ รับยา Etoricoxib 1 สั ปดาห์ รักษา OA knee ซึ่งได้
acetaminophen ไม่ ดีขน
ึ้ มาพบท่ านเนื่องจาก ขา 2
ข้ างบวมกดบุ๋ม ไม่ มีอาการอื่น BP 140/100 ท่ านจะ
ปฏิบัติอย่ างไรเป็ นลาดับแรก
• A. ตรวจ U/A และ renal function ทันที
• B. ตรวจ LFT และ ดู albumin ในเลือด
• C. ยาเดิม เพิ่ม furosemide prn. และ follow up
• D. แนะนาว่ามันเป็ นเช่นนี้เอ เพราะเป็ น HT ให้ ดอาหารเค็ม
• E. ดยา Etoricoxib ทันที และ เขียนเป็ น drug list แพ้ยา
Renal side effect
• Incidence
up to 1-5%
• Risk
Volume-contracted states
Low cardiac output
Other condition compromised renal functions
Aging, septicemia, DM, premature baby etc.
NSAIDs & Renal Effect
Arachidonic acid
Coxibs
NSAIDs
COX-1
COX-2
PGE2
Sodium retention
• Peripheral edema
•  Blood pressure
•  Weight
• CHF (rarely)
PGI2
Hyperkalemia
Acute renal
failure
Others : Nephrotic syndrome
interstitial nephritis
Brater. Am J Med. 1999;107:65S.
ชายอายุ 79 ปี เป็ น HT คุมได้ ดี BP 120/80 พึง่
ได้ รับยา Etoricoxib 1 สั ปดาห์ รักษา OA knee ซึ่งได้
acetaminophen ไม่ ดีขน
ึ้ มาพบท่ านเนื่องจาก ขา 2
ข้ างบวมกดบุ๋ม ไม่ มีอาการอื่น BP 140/100 ท่ านจะ
ปฏิบัติอย่ างไรเป็ นลาดับแรก
• A. ตรวจ U/A และ renal function ทันที
• B. ตรวจ LFT และ ดู albumin ในเลือด
• C. ยาเดิม เพิ่ม furosemide prn. และ follow up
• D. แนะนาว่ามันเป็ นเช่นนี้เอ เพราะเป็ น HT ให้ ดอาหารเค็ม
• E. ดยา Etoricoxib ทันที และ เขียนเป็ น drug list แพ้ยา
หญิงอายุ 29 ปี มีโรค SLE มี active arthritis ได้ ยา
chloroquine และ Naproxen 500 มิลลิกรัมต่ อวัน ต้ อง
ผ่ าฟันคุด 4 ซี่ ท่ านจะแนะนาอย่ างไร
• A. ดยา 24-48 ชม. ให้ acetaminophen แล้วผ่าได้เลย
• B. ลด dose 250 มิลลิกรัม/วัน ผ่าได้เลย ( จาเป็ นต้อ ใช้ยา )
• C. ดยา 24-48 ชม. และเปลี่ยนเป็ น prednisolone 20
มิลลิกรัม/วัน ผ่าได้เลย
• D. ดยา 5-7 วัน และเปลี่ยนเป็ น celecoxib 400 มิลลิกรัม/วัน
• E. ดยา 5-7 วัน ให้ผป.ทนปวดเอา
Hematologic : Bleeding
• GI
• Hemorrhagic stroke
• Intra / post-operative bleeding
Significant in
GU surgery
Tosillectomy
Underlying bleeding disorder
Discontinuation before surgery
ASA 7-10 days
NSAIDs 3-5 x T1/2
หญิงอายุ 29 ปี มีโรค SLE มี active arthritis ได้ ยา
chloroquine และ Naproxen 500 มิลลิกรัมต่ อวัน ต้ อง
ผ่ าฟันคุด 4 ซี่ ท่ านจะแนะนาอย่ างไร
• A. ดยา 24-48 ชม. ให้ acetaminophen แล้วผ่าได้เลย
• B. ลด dose 250 มิลลิกรัม/วัน ผ่าได้เลย ( จาเป็ นต้อ ใช้ยา )
• C. ดยา 24-48 ชม. และเปลี่ยนเป็ น prednisolone 20
มิลลิกรัม/วัน ผ่าได้เลย
• D. ดยา 5-7 วัน และเปลี่ยนเป็ น celecoxib 400 มิลลิกรัม/วัน
• E. ดยา 5-7 วัน ให้ผป.ทนปวดเอา
Other side effects
• Dermatologic & hypersensitivity reaction
Skin
Piroxicam, sulidac, mefenamate
Hypersensitivity ASA - asthma
• Central nervous system side effect
Headache
Indomethacin
Aseptic meningitis
Ibuprofen, sulindac, naproxen
Other Properties
• Potential application :
Closed patent ductus arteriosus
Alzheimer disease
Practical Approach
& Recommendation
Is an NSAID needed ?
Inflammation ?
No
Use non-pharmacologic
or other pharmacologic Rx
Yes
Yes
Is there a contraindication to NSAID ?
- Renal insufficiency ( CrCl < 30 )
- Allergic reaction
- Concurrent GI injury
No
Is there a reason that a classical NSAID cannot be used ?
- GI risk+ & Bleeding risk
No
Use classical NSAID
No
Yes
Use COX-2 inhibitor
( or classical NSAID + PPI+)
Is patient at increased risk for CV events ?
Select NSAID on the basis of GI risk
Yes
Avoid NSAID esp. COX-2 inhibitor
Quiz
ชายอายุ 66 ปี มีโรค angina pectoris ได้ ยา ASA อยู่
ล้ มสะโพกคราก 1 วัน ไม่ มีกระดูกหัก
ท่ านจะสั่ งการรักษาอย่ างไร
• A. เพิม่ ASA จาก 75 mg/d เป็ น 75 mg tid.
• B. เพิ่ม Naproxen 500 mg/d + Omeprazole
• C. เพิ่ม Naproxen 500 mg/d + off ASA
• D. เพิ่ม Celecoxib 400 mg/d
• E. ส่ PM&R ให้ทากายภาพบาบัด ให้ Parecoxib
ฉีดลดปวด prn
ชายอายุ 66 ปี มีโรค angina pectoris ได้ ยา ASA อยู่
ล้ มสะโพกคราก 1 วัน ไม่ มีกระดูกหัก
ท่ านจะสั่ งการรักษาอย่ างไร
• A. เพิม่ ASA จาก 75 mg/d เป็ น 75 mg tid.
• B. เพิ่ม Naproxen 500 mg/d + Omeprazole
• C. เพิ่ม Naproxen 500 mg/d + off ASA
• D. เพิ่ม Celecoxib 400 mg/d
• E. ส่ PM&R ให้ทากายภาพบาบัด ให้ Parecoxib
ฉีดลดปวด prn
หญิงอายุ 38 ปี แพ้ยาซัลฟา เป็ นโรค psoriatic
arthritis ปวดมากต้ องรับประทานยาแก้ ปวดหลายชนิด
หลังกินยามีผื่นทัว่ ตัว ยาใดน่ าจะเป็ นสาเหตุมากทีส่ ุ ด
• A. Etoricoxib
• B. Indomethacin
• C. Nimesulide
• D. Meloxicam
• E. All of above
หญิงอายุ 38 ปี แพ้ยาซัลฟา เป็ นโรค psoriatic
arthritis ปวดมากต้ องรับประทานยาแก้ ปวดหลายชนิด
หลังกินยามีผื่นทัว่ ตัว ยาใดน่ าจะเป็ นสาเหตุมากทีส่ ุ ด
• A. Etoricoxib
• B. Indomethacin
• C. Nimesulide
• D. Meloxicam
• E. All of above
ชายอายุ 19 ปี วินิจฉัยเป็ น ASA-induced asthma มี
acute tendinitis ท่ านจะให้ ยาใด
• A. Indomethacin
• B. Naproxen
• C. Etoricoxib
• D. None of above
ชายอายุ 19 ปี วินิจฉัยเป็ น ASA-induced asthma มี
acute tendinitis ท่ านจะให้ ยาใด
• A. Indomethacin
• B. Naproxen
• C. Etoricoxib
• D. None of above
Thank You For Your Attention
Recommendation
Prophylaxis of
NSAID-induced GI Side Effects
Supot Pongprasobchai, M.D.
Assistant Professor, Division of Gastroenterology,
Siriraj Hospital
NSAID-induced GI Side-Effects
Ulcer complications
1-2%
Ulcers
20%
Dyspepsia
25-50%
No lesion/Erosions
60-100%
Determination of Gastroduodenal Mucosal Integrity
Defensive vs Aggressive Factors
Acid
Pepsin
Mucus HCO3
Bile Alcohol
Blood flow PGs
Aggressive
Defensive
Pathogenesis of PU
Caused by NSAIDs
PGs
Acid
(acute)
Aggressive
HCO3 Mucus
(chronic)
Defensive
NSAID-induced Gastropathy
1-2% annually
1-2% annually
Strategies to Prevent
GI Complications of NSAIDs
 General
 Use least ulcerogenic NSAID, short duration
 Identify risk factors
 Low-risk :
 Moderate-risk :
 High-risk :
 Very high-risk :
no risk factor
1-2 risk factors
≥ 3 risk factors, use of ASA
or anticoagulant
previous ulcer complications
 Apply appropriate prevention
 Co-therapy with gastroprotective drugs
 Coxib
Which non-selective NSAID has lowest
GI side-effects?
A.
B.
C.
D.
E.
Aspirin
Diclofenac
Ibuprofen
Indomethacin
Piroxicam
Relative Risk of
GI Complications with NSAIDs
Ibuprofen
1
Fenoprofen
1.6
ASA
1.6
1.8
Diclofenac
2.1
Sulindac
Diflusinal
2.2
Naproxen
2.2
2.4
Indomethacin
3
Tolmetin
3.8
Piroxicam
4.2
Ketoprofen
9.2
Azopropazon
Ketorolac
1
2
3
4
5
6
Relative risk
7
8
9
10
Henry D. BMJ 1996;312:1563-66
Strategies to Prevent
GI Complications of NSAIDs
 General
 Use least ulcerogenic NSAID, short duration
 Identify risk factors
 Low-risk :
 Moderate-risk :
 High-risk :
 Very high-risk :
no risk factor
1-2 risk factors
≥ 3 risk factors, use of ASA
or anticoagulant
previous ulcer complications
 Apply appropriate prevention
 Co-therapy with gastroprotective drugs
 Coxib
Risk Factors of
Ulcer Complications from NSAIDs
Prior GI events
2.5-4.8
Multiple NSAIDs
(including ASA)
2-4
2-3.5
Age (>65)
Anticoagulant
3
Steroid therapy
2
Co-morbid illness
2
H.pylori infection
2
1
2
3
4
Relative risk
5
6
Number of Risk Factors &
Incidence of Ulcer Complications
%
NNH 5
20
18
15
NNH 12
10
5
8
NNH 125
0.8
NNH 50
2
0
No Risk
Factor
1-2 Factors
3 Factors
4 Factors
Silverstein FE. Ann Intern Med 1995;123:241-9
Strategies to Prevent
GI Complications of NSAIDs
 General
 Use least ulcerogenic NSAID, short duration
 Identify risk factors
 Low-risk :
 Moderate-risk :
 High-risk :
 Very high-risk :
no risk factor
1-2 risk factors
≥ 3 risk factors, use of ASA
or anticoagulant
previous ulcer complications
 Apply appropriate prevention
 Co-therapy with gastroprotective drugs
 Coxib
Strategies to Prevent
GI Complications of NSAIDs
 General
 Use least ulcerogenic NSAID, short duration
 Identify risk factors
 Low-risk :
 Moderate-risk :
 High-risk :
 Very high-risk :
no risk factor
1-2 risk factors
≥ 3 risk factors, use of ASA
or anticoagulant
previous ulcer complications
 Apply appropriate prevention
 Co-therapy with gastroprotective drugs
 Coxib
Which co-therapy is most effective in
reducing NSAID-associated ulcer
complications?
A.
B.
C.
D.
E.
Misoprostal
PPI
H2-RA
Sucralfate
Rebamipide
Prophylaxis of NSAID-induced Gastropathy
Meta-Analysis
Serious GI
events
H2-RA
PPI
Misoprostal
No
No



Symptomatic No
ulcers
Endoscopic
ulcers



Mortality
No
No
No
(double dose)
Rostom A. Cochrane database of systematic reviews 2007
GI Side Effects of Coxib VS. ns-NSAID
Meta-analysis
Endoscopic ulcers
RR 0.26 [0.23-0.30]
Ulcer complications
RR 0.39 [0.31-0.50]
Ulcer complications
(ASA users)
RR 0.89 [0.52-1.53]
0.1
0.2
0.5
Favours coxibs
1
2
5
10
Favours ns-NSAID
Rostom A. Clin Gastroenterol Hepatol 2007;5:818-28
65 YO woman had Hx of UGIB following NSAID use 2
years ago
Now she requires NSAID for severe OA
What is the most appropriate
management?
A.
B.
C.
D.
E.
Ibuprofen + misoprostal
Ibuprofen + PPI
Coxib
Coxib + PPI
No NSAID/Coxib
Efficacies of Each Preventive Strategies in
Very High-Risk Patients
Chan FKL. NEJM 2001; 344: 967-73
Chan FKL. NEJM 2002; 347: 2104-10
Chan FKL. Lancet 2007; 369: 1621-6
NSAID + Hp eradication
COXib
NSAID + PPI
COXib + PPI
Prophylaxis of NSAID-induced Gastropathy
Recommendation
GI Risk
Low-risk
6 mo GI complications
rate (%)
0.8
• No risk factor
Moderate-risk
2
• 1-2 risk factors
High-risk
8
•  3 risk factors
• on anticoagulant
• on ASA*
Very high-risk
• Prior PU complication
18
Prophylaxis of NSAID-induced Gastropathy
Recommendation
GI Risk
Low CV Risk
High CV Risk
Low-risk
• No risk factor
Least ulcerogenic
NSAID, lowest
effective dose
Moderate-risk
• 1-2 risk factors
High-risk
•  3 risk factors
• on anticoagulant
• on ASA*
Very high-risk
• Prior PU complication
Chan FKL. AP&T 2004;19:1051-61
Prophylaxis of NSAID-induced Gastropathy
Recommendation
GI Risk
Low CV Risk
High CV Risk
Low-risk
• No risk factor
Least ulcerogenic
NSAID, lowest
effective dose
Moderate-risk
• 1-2 risk factors
High-risk
•  3 risk factors
• on anticoagulant
• on ASA*
Very high-risk
• Prior PU complication
Chan FKL. AP&T 2004;19:1051-61
Prophylaxis of NSAID-induced Gastropathy
Recommendation
GI Risk
Low CV Risk
High CV Risk
Low-risk
• No risk factor
Least ulcerogenic
NSAID, lowest
effective dose
Moderate-risk
• 1-2 risk factors
NSAID + PPI/MSP
Coxib
High-risk
•  3 risk factors
• on anticoagulant
• on ASA*
Very high-risk
• Prior PU complication
Chan FKL. AP&T 2004;19:1051-61
Prophylaxis of NSAID-induced Gastropathy
Recommendation
GI Risk
Low CV Risk
High CV Risk
Low-risk
• No risk factor
Least ulcerogenic
NSAID, lowest
effective dose
Moderate-risk
• 1-2 risk factors
NSAID + PPI/MSP
Coxib
High-risk
•  3 risk factors
• on anticoagulant
• on ASA*
Coxib + PPI/MSP
*NSAID + PPI/MSP
Very high-risk
• Prior PU complication
Chan FKL. AP&T 2004;19:1051-61
Prophylaxis of NSAID-induced Gastropathy
Recommendation
GI Risk
Low CV Risk
High CV Risk
Low-risk
• No risk factor
Least ulcerogenic
NSAID, lowest
effective dose
Moderate-risk
• 1-2 risk factors
NSAID + PPI/MSP
Coxib
High-risk
•  3 risk factors
• on anticoagulant
• on ASA*
Coxib + PPI/MSP
*NSAID + PPI/MSP
Very high-risk
• Prior PU complication
Coxib + PPI/MSP
Chan FKL. AP&T 2004;19:1051-61
Coxib in Patients with CV Risk
Important Issues
 Increased risk of thrombosis risk of Coxib
 Aspirin decrease GI safety of Coxib
 Aspirin is like another NSAID
Symposium:
Clinical NSAIDs Usage 12 Sep 2007
NSAIDs for Acute Pain
รศ.พญ.วิมลลักษณ์ สนัน่ ศิลป์
ภาควิชาวิสัญญีวิทยา
คณะแพทยศาสตร์ศิริราชพยาบาล
Vimolluck Sanansilp, Siriraj
Question 1
A 51-year-old man presents with a one-day
history of moderately severe low back pain that
began after lifting a heavy box. He has a
normal neurological examination. He has
epigastric pain off and on and has history of
allergy to sulfa.
What analgesics would you offer?
1. Are NSAIDs an appropriate choice of
medication in this patient?
2. If so, which NSAIDs will you prescribe & why?
3. If not, why?
Vimolluck Sanansilp, Siriraj
Question 2
A 72-y-o man underwent an explor-lap with
bowel resection. He has Lt hemiplegia. He
gets IV morphine for postoperative pain relief
but still has pain score of 7-8.
1. Would you add any NSAIDs to enhance
analgesia for this patient?
2. If so, which NSAIDs will you prescribe & why?
3. If not, why?
Vimolluck Sanansilp, Siriraj
Question 3
A 70-y-o woman underwent Total Knee
Arthroplasty. Parecoxib 40 mg i.v. x 3 d,
etoricoxib 60 mg p.o. x 5 d. are prescribed.
POD 1, drainage = 400 ml blood, BP 120/70
mmHg, PR 96/min, urine output 460 ml/24 h.
POD 2, BP 180/100 mmHg, BUN 20, Cr 2.6,
edema 2+.
What do you think is(are) the problem(s)?
Vimolluck Sanansilp, Siriraj
NSAIDs and coxibs
• Non-selective NSAIDs and coxibs reduce pain
safely and effectively in many patients
• Neither are as safe as initially thought
• Both have similar cardiorenal profiles  should
be reserved for patients at low risk for cardiac
failure or thromboembolic events
• CV safety profile: coxibs are contraindicated in
patients with known atherosclerotic disease and
those at risk of CV thromboembolic events
Vimolluck Sanansilp, Siriraj
NSAIDs and coxibs
• Induced perioperative bleeding  small added risk
• Surgeons - reluctant to use NSAIDs in some types
of surgery:- endoscopic/microscopic or involving
the airway, head & neck, plastics, urology and
neurosurgery, where bleeding  interfere surgical
field / increase the level of risk
• Devoid of bleeding risk, coxibs = more safely, preor intra-operatively,
 analgesia + reduce strong opioid rescue pain relief
in postoperative period (opioid sparing effect)
Vimolluck Sanansilp, Siriraj
Vimolluck Sanansilp, Siriraj
• Act by inhibition of COX-2
• May be sufficient for moderate pain,
• An adjunct in a multimodal regimen to reduce
opioid requirements, to improve pain relief and
reduce opioid associated side-effects (:- N/V)
• Traditional non-selective NSAIDs associated with
GI complications: dyspepsia & gastric erosions 
serious ulcer bleeds and perforations
• COX-2 selective inhibitors (coxibs) was
developed to improve GI safety in long term antiinflammatory analgesic therapy
• Concerns over the CV safety of coxibs and
NSAIDs in some postoperative patients
• Recommendations and strict guidelines implemented for the use of coxibs, primarily for
long-term indications
• Efficacy and safety evaluation for the short-term
use, focusing on the issues relevant to the
surgical setting:- bleeding risk, and GI safety
International multicentre study of 1671 patients,
CV events (including myocardial infarction,
cardiac arrest, stroke and pulmonary embolism)
were significantly more frequent among the
patients given parecoxib and valdecoxib than
those receiving placebo.
Nussmeier NA, Whelton A, Brown MT, Langford RM, Joshi G, Verburg KM.
Safety of parecoxib and valdecoxib in the treatment of pain following
coronary artery bypass surgery. N Engl J Med 2005;352:1081—91.
462 patients, undergoing CABG, reported
proportionately more serious CVS sequelae in the
patients who received parecoxib/valdecoxib
postoperatively.
Ott E, Nussmeier NA, Duke PC, Feneck RO, Alston RP, Snabes MC et al.
Efficacy and safety of the cyclooxygenase 2 inhibitors parecoxib and
valdecoxib in patients undergoing coronary artery bypass surgery.
J Thorac Cardiovasc Surg 2003;125:1481—92.
By contrast, in a similarly designed study of 1050
non-cardiac major surgery patients, the group
randomised to receive parecoxib and valdecoxib
did not differ from the placebo patients in any of
the four safety categories: cardiovascular events,
renal events, surgical wound complications, and
GI complications.
Nussmeier NA, Whelton A, Brown MT, Langford RM, Joshi G, Singla NK et
al. Safety and efficacy of the cyclooxygenase-2 inhibitors parecoxib and
valdecoxib after noncardiac surgery. Anesthesiology 2006;104(3):518—26.
A combined analysis of 6979 patients in 19
cardiac and non-cardiac surgery studies (10
orthopaedic surgery, 5 gynaecological surgery, 2
general surgery, 2 CABG), in which parecoxib in
doses ranging from 20 to 80 mg was
administered, the CV thromboembolic event
rates were comparable to placebo [parecoxib
20—80 mg/day 1.0% (39/3821) and placebo
0.9% (27/3158)].
Schug S. Poster presentation. ESA; 2006.
• Choice of selective COX-2 inhibitor for the
acute pain setting is narrow.
• Both parecoxib and oral lumiracoxib are
licensed for the management of postoperative pain.
• Lumiracoxib being limited to orthopaedic
and gynaecological surgery.
Usual recommended dose for
Cox-2 inhibitors in postop. pain
Celecoxib
(Celebrex®)
200-400 mg/tab
Parecoxib
(Dynastat®)
40 mg/amp
Etoricoxib
(Arcoxia®)
60, 90, 120
mg/tab
Lumiracoxib
(Prexige®)
100, 400
mg/tab
first day: 400 mg
single dose
followed by 200
mg after 12 h if
needed,
then 200 mg b.i.d.
as needed
20-40 mg
IV/IM q 12 h
(short period)
(Can keep
diluted med in
room temp for
24 h)
120 mg
once daily
Leaflet:
400 mg
once daily not
exceed 5
consecutive
days
Vimolluck Sanansilp, Siriraj
…cancelled the registration of lumiracoxib
in Australia due to concerns that it may
cause liver failure.
…8 reports of serious liver adverse
reactions to the drug, including two deaths
and two liver transplants.
Vimolluck Sanansilp, Siriraj
NSAID Contraindications
 Dehydration
 Hypovolemia
 Nephrotoxic agents
 Anticoagulants
Vimolluck Sanansilp, Siriraj
NSAIDs and Asthma
• Study of stable asthmatics given diclofenac
orally (Short et al. 2000)
• Measured PEFR and FEV 1 pre- and post
administration
• 56% had drop in values but max 15%
• None had to increase their medication
• Suggest - acceptable in stable asthmatics
Vimolluck Sanansilp, Siriraj
Safety Information for COXIBs
• Contraindications
– Pregnancy and lactating women, Age < 16 y
– Patients with Sulfonamide allergy history
– Experienced angioneurotic edema, urticaria or allergictype reactions after taking acetylsalicylic acid or NSAIDs
or other COX-2 selective inhibitors
– Patients who undergone Coronary Artery Bypass Graft
(CABG) surgery
– Patients with IHD or stroke, CHF
– Currently GI bleeding / Active peptic ulceration
– Patients who have cardiovascular risks
– Patients with renal and hepatic impairment
Vimolluck Sanansilp, Siriraj
Back to basic analgesia
11th WCP at Sydney, 2005
•
•
•
•
Ibuprofen
Naproxen
Diclofenac
Ketorolac
• Combination drugs
– Opioid + NSAIDs
– Opioid + acetaminophen
– Tramadol + acetaminophen
• Intervention Rx
Vimolluck Sanansilp, Siriraj
NSAID-Induced
Upper GI Bleeds and Perforations
Rate of GI Bleeds and Perforations (per 1000 patient years)
3.1
Nabumetone
Ibuprofen
4.3
Indomethacin
4.4
5.6
Mefenamic Acid
6.5
Ketoprofen
6.7
Naproxen
7.8
Diclofenac
15.9
Piroxicam
0
2
4
McDonald TM, et al. BMJ 1997; 315: 1333-7.
6
8
10
12
14
16
Vimolluck Sanansilp, Siriraj
NSAIDs – for Acute Pain
•
•
•
•
•
•
Postoperative – mild to moderate pain
Orthopedic – acute low back pain1,2
Dental – periodontitis
Oral surgery – 3rd molar surgery
Gynecological – dysmenorrhea
Urological – renal colic
1 Griffin
et al. Do NSAIDs help in acute or chronic low back pain?
Am Fam Physician 2002;65
2 Tulder
et al. Non-steroidal anti-inflammatory drugs for low-back pain.
The Cochrane Database of Systematic Reviews 2000, Issue 2.
Art. No.: CD000396. DOI: 10.1002/14651858
Vimolluck Sanansilp, Siriraj
NSAIDs – When to give?
• Preoperative – premedication
preemptive analgesia
preventive analgesia
• Intraoperative
• Postoperative
Vimolluck Sanansilp, Siriraj
Preemptive analgesia
Noxious stimuli Initiating analgesic regimen
before onset of noxious stimuli
Neurons of dorsal horn
of spinal cord
“windup/central sensitization (process)”
Neurons of dorsal
horn of spinal cord
become “sensitized”
Level of pain
Limit subsequent pain
Vimolluck Sanansilp, Siriraj
Analgesic choices - based on level of pain
Strong opioid
severe
+/- adjuvant
+/- NSAIDs
Weak opioid
moderate +/- adjuvant
+/- NSAIDs
mild Non-opioid/NSAIDs
+/- adjuvant
Vimolluck Sanansilp, Siriraj
Multimodal Analgesia
₪Improved antinociception
Morphine
Codeine
Tramadol
due to synergistic/
additive effects
Potentiation
₪Reduce dose of each
analgesic
NSAIDs,2 agonist,
acetaminophen,
regional blocks
₪May reduce severity of
side effects of each drug
Kehlet H, Dahl JB. Anesth Analg. 1993;77:1048–56.
Vimolluck Sanansilp, Siriraj
Treatment for common menstrual
cramps (primary dysmenorrhea)
• Lie down at the first sign of pain
• Current recommendations = not only adequate rest and
sleep, but also regular exercise (especially walking)
• Nonpharm. strategies: heating pad, massage, yoga, etc.
For mild cramps: aspirin / acetaminophen, or
acetaminophen + diuretic
For moderate menstrual cramps: main agents are NSAIDs,
which lower the production of PG and lessen its effect:ibuprofen; naproxen sodium; and ketoprofen
http://www.medicinenet.com/menstrual_cramps/article.htm
Vimolluck Sanansilp, Siriraj
NSAIDs - Route of administration
•
•
•
•
Oral
IV
IM
Rectal suppository1
diclofenac (suppo) 50 mg x3 or placebo 1x3 during
the first 24 h postoperatively
 reduces the need for opioids significantly with
maintained or improved analgetic effect
 reduce negative side-effects of systemic opioids
1Olofsson.
Eur J Obstet Gynecol Reprod Biol 2000;88:143-6.
Vimolluck Sanansilp, Siriraj
NSAIDs - Route of administration
•
•
•
•
•
Oral
IV
IM
Rectal suppository
Peri- & intra-articular1
 Improve early analgesia and mobilization
vs contin. Fem. n. block in TKA under
spinal anesthesia
1Toftdahl
et al. Acta Orthopaedica 2007;78:172-9.
Vimolluck Sanansilp, Siriraj
NSAIDs - Route of administration
 Continuous intrawound infusion of diclofenac
• Oral
demonstrates a greater opioid sparing effect and
• IVbetter postoperative analgesia than the same
dose
administered
as
an
intermittent
intravenous
• IM
bolus during the first 24 h after surgery.
• Rectal suppository
• Peri- & intra-articular
• Local infiltration – single/continuous1
1Lavand’homme
et al. Anesthesiology 2007; 106:1220–5.
Vimolluck Sanansilp, Siriraj
NSAIDs - Route of administration
• Oral

adm. of COX-1, but not COX-2,
• Intrathecal
IV
specific inhibitors given on postoperative day 1
• IM
has analgesic effects in an incisional model of
• postoperative
Rectal suppository
pain in rat.
• Peri- & intra-articular
• Local infiltration – single/continuous
• Intrathecal (COX-1)1
1Zhu
et al. Anesth Analg 2005;100:1390 –3.
Vimolluck Sanansilp, Siriraj
Before prescribing NSAIDs,……weigh risks vs benefits
Cost
GI
CVS
Benefits
Vimolluck Sanansilp, Siriraj
Oral Analgesics for
Acute Nonspecific Pain
• The safest NSAID is ibuprofen in doses of 400 mg
• Higher doses may offer greater analgesia but with
more adverse effects
• Other NSAIDs fail to demonstrate consistently
greater efficacy or safety than ibuprofen
• Coxibs provide equivalent efficacy to traditional
NSAIDs but lack a demonstrable safety advantage
for the treatment of acute pain
Vimolluck Sanansilp, Siriraj
Oral Analgesics for
Acute Nonspecific Pain
Direct comparative studies between NSAIDs
and acetaminophen (1,000-mg dose) :
 more effective than acetaminophen in some
situations (e.g., dental and menstrual pain)
 equivalent analgesia in others (e.g.,
orthopedic surgery and tension headache).1,2
1. Scott D, Smith C, Lohmander S, Chard J. Osteoarthritis. Clin Evid 2003;(9):1301-26.
2. Hyllested M, Jones S, Pedersen JL, Kehlet H. Comparative effect of paracetamol,
NSAIDs or their combination in postoperative pain management: a qualitative review.
Br J Anaesth 2002;88:199-214.
Vimolluck Sanansilp, Siriraj
Oral Analgesics for
Acute Nonspecific Pain
Traditional NSAIDs
EFFICACY
• Dysmenorrhea1 :
ibuprofen=naproxen > acetaminophen/aspirin
• Postpartum perineal pain2 :
ibuprofen > acetaminophen+codeine+caffeine
1. Zhang WY, Li Wan Po A. Efficacy of minor analgesics in primary dysmenorrhoea: a
systematic review. Br J Obstet Gynaecol 1998;105:780-9.
2. Peter EA, Janssen PA, Grange CS, Douglas MJ. Ibuprofen versus acetaminophen
with codeine for the relief of perineal pain after childbirth: a randomized controlled
trial. CMAJ 2001;165:1203-9.
Vimolluck Sanansilp, Siriraj
Oral Analgesics for
Acute Nonspecific Pain
Traditional NSAIDs
SAFETY AND ADVERSE EFFECTS
• Ibuprofen  excellent GI safety profile, not
different from placebo (dose 800-1,200 mg/d)1
• Higher doses of naproxen and ibuprofen 
increased GI side effects similar to other NSAIDs2
1.Kellstein DE, Waksman JA, Furey SA, Binstok G, Cooper SA. The safety profile
of nonprescription ibuprofen in multiple-dose use: a metaanalysis. J Clin
Pharmacol 1999;39:520-32.
2.Bansal V, Dex T, Proskin H, Garreffa S. A look at the safety profile of over-thecounter naproxen sodium: a meta-analysis. J Clin Pharmacol 2001;41:127-38.
Vimolluck Sanansilp, Siriraj
Oral Analgesics for
Acute Nonspecific Pain
COX-2 Selective NSAIDs
EFFICACY
• Theoretically, provide analgesia = traditional
NSAIDs without many of the side effects
• Meta-analysis of celecoxib, showed fair to good
efficacy for postoperative pain with an NNT of 4.5
(95% CI, 3.3 to 7.2) compared with placebo1
1. Barden J, Edwards JE, McQuay HJ, Moore RA. Single dose oral celecoxib for
postoperative pain. Cochrane Database Syst Rev 2004;(3):CD004233.
Vimolluck Sanansilp, Siriraj
Oral Analgesics for
Acute Nonspecific Pain
COX-2 Selective NSAIDs
SAFETY AND ADVERSE EFFECTS
• Greater numbers of thrombotic CV events
• May impair renal function and have no benefit
over traditional NSAIDs in this area
• In elderly patients with hypertension - may be
associated with edema and ↑ BP1
1. Whelton A, White WB, Bello AE, Puma JA, Fort JG, for the SUCCESS-VII Investigators.
Effects of celecoxib and rofecoxib on blood pressure and edema in patients > or = 65 years of
age with systemic hypertension and osteoarthritis. Am J Cardiol 2002;90:959-63.
Vimolluck Sanansilp, Siriraj
Oral NSAIDs in the Treatment of Acute Pain
Medication
Efficacy*
Max dosage per day
Recommended
Ibuprofen (400 mg initially)
Good
2,400 mg
Naproxen (Aleve)
Good
1,376 mg
Alternative choices
Diclofenac (Voltaren)
Good
150 mg
Piroxicam (Feldene)
Good
20 mg
Ketorolac (Toradol)
Good
40 mg
Meclofenamate (Meclomen) Good
400 mg
Meloxicam (Mobic)
Good
7.5 mg
Nabumetone (Relafen)
Good
2,000 mg
COX-2 inhibitors
Fair to
good
Celecoxib (Celebrex),
400 mg
* Poor: number needed to treat (NNT) > 6, Fair: NNT = 3 – 6, Good: NNT = <3
Sachs. Oral analgesics for acute nonspecific pain. Am Fam Physician 2005;71:913-8
Vimolluck Sanansilp, Siriraj
Analgesic Side effects
class
Dosage
Comment
No
evidence
that any
one NSAID
is more
effective
than
another
NSAIDs
GI,
platelet
function
inhibition,
renal
dysfunction
400 mg ibuprofen
safest inexpensive
choice;
decreases some
adverse GI events
with misoprostol 800
mg, H2 blockers,
and PPI
Selective
COX-2
inhibitors
Renal
dysfunction;
hypertension;
thrombotic
events
Once or twice per
Expensive
day, only advantage
over most traditional
NSAIDs for acute
pain
Sachs. Oral analgesics for acute nonspecific pain. Am Fam Physician 2005;71:913-8
Vimolluck Sanansilp, Siriraj
Recommendation
Label
Acetaminophen in doses up to 1,000 mg is the initial choice for
most mild to moderate acute pain.
B
The first-line NSAID for safety, efficacy, and cost is ibuprofen in
doses of 400 mg.
A
For moderate to severe pain, consider narcotic acetaminophen
or narcotic ibuprofen combination.
B
Tramadol, propoxyphene, and codeine provide inferior analgesia A
to other recommended agents.
COX-2 inhibitors provide analgesia equal to NSAIDs at greater
cost and may be reserved for patients who have a history of GI
bleeding and have failed treatment with acetaminophen.
B
A = consistent, good-quality patient-oriented evidence;
B = inconsistent or limited-quality patient-oriented evidence;
C = consensus, disease-oriented evidence, usual practice, opinion, or
case series.
Sachs. Oral analgesics for acute nonspecific pain. Am Fam Physician 2005;71:913-8
Vimolluck Sanansilp, Siriraj
Acute and Postoperative Pain
A. Managing pain in the older patient:
• NSAIDs and COX-2 inhibitors in older
people requires extreme caution
• Acetaminophen is the preferred non-opioid
analgesic
Charlton J E, editor. Core Curriculum for Professional Education in Pain. IASP Press, Seattle 2005.
Vimolluck Sanansilp, Siriraj
Acute and Postoperative Pain
B. Managing acute pain during pregnancy:
• Use of NSAIDs during pregnancy does not
seem to increase the risk of adverse birth
outcome, but  ↑risk of miscarriage.
Charlton J E, editor. Core Curriculum for Professional Education in Pain. IASP Press, Seattle 2005.
Vimolluck Sanansilp, Siriraj
Acute and Postoperative Pain
C. Managing pain in the puerperium
(perineal pain, breast and nipple pain):
1.Acetaminophen and rectal NSAIDs – effective in
perineal pain after childbirth.
2.Acetaminophen and NSAIDs – equally, but only
modestly, effective in treating uterine pain.
3.Acetaminophen and several NSAIDs, in
particular ibuprofen, seem safe non-opioids in
lactation.
Charlton J E, editor. Core Curriculum for Professional Education in Pain. IASP Press, Seattle 2005.
Vimolluck Sanansilp, Siriraj
Acute and Postoperative Pain
D. Abdominal pain of nonsurgical origin:dysmenorrhea, renal and biliary colic,
and irritable bowel syndrome:
1.Analgesics do not interfere with the diagnostic
process in acute abdominal pain.
2.NSAIDs – superior to opioids in the treatment of
renal colic.
3.Onset of analgesia is fastest with IV NSAIDs in
renal colic.
4.NSAIDs + vitamin B1 – effective in the treatment
of primary dysmenorrhea.
Charlton J E, editor. Core Curriculum for Professional Education in Pain. IASP Press, Seattle 2005.
Vimolluck Sanansilp, Siriraj
Acute and Postoperative Pain
E. Pain associated with acute orofacial
conditions:- sinusitis and oral ulceration:
1.NSAIDs and coxibs provide better analgesia with
fewer adverse effects than acetaminophen,
acetaminophen/opioid combinations,
acetaminophen/tramadol combinations,
tramadol, or weaker opioids after dental
extraction.
2.Aspirin and NSAIDs increase the likelihood of
reoperation for post-tonsillectomy bleeding.
Charlton J E, editor. Core Curriculum for Professional Education in Pain. IASP Press, Seattle 2005.
Vimolluck Sanansilp, Siriraj
Acute and Postoperative Pain
F. Pain management of acute headache
including migraine, cluster headache and postdural puncture headache (PDPH):
1.Aspirin-metoclopramide is effective in Rx of
migraine with mild symptoms.
2.Addition of caffeine to aspirin or acetaminophen
improves analgesia in acute tension-type
headache.
3.Ibuprofen + acetaminophen are effective in the
treatment of migraine with mild symptoms.
4.Simple analgesics:- aspirin, acetaminophen, and
NSAIDs, either alone or in combination, are
effective in the treatment of episodic tension-type
headache.
Charlton J E, editor. Core Curriculum for Professional Education in Pain. IASP Press, Seattle 2005.
Vimolluck Sanansilp, Siriraj
Acute and Postoperative Pain
G. Acute musculoskeletal pain:
1.Understand that topical + oral NSAIDs improve
acute shoulder pain.
2.Treat pain with acetaminophen; if it is ineffective,
NSAIDs may be used.
Charlton J E, editor. Core Curriculum for Professional Education in Pain. IASP Press, Seattle 2005.
Vimolluck Sanansilp, Siriraj
Acute and Postoperative Pain
H. For nonselective NSAIDs and
acetaminophen, know:
1. Different routes & dosage (:- oral, IV, rectal).
2. How to modify doses or withhold NSAIDs in presence
of comorbidity (CHF, renal disease, ulcer disease,
coagulopathy).
3. How to select particular NSAIDs to lessen risk of
specific side effects (:- nonacetylated compounds for
platelet sparing; nabumetone to lessen gastrointestinal
blood loss).
4. There is a “plateau effect” = dosage increases beyond
the recommended range increase the incidence of side
effects but do not improve analgesia.
Charlton J E, editor. Core Curriculum for Professional Education in Pain. IASP Press, Seattle 2005.
Vimolluck Sanansilp, Siriraj
Acute and Postoperative Pain
H. For nonselective NSAIDs and
acetaminophen, know:
5. Efficacy + utility of NSAIDs when administered
via intra-articular, topical, local infiltration routes
6. Pharmacokinetic profiles of the NSAIDs
7. Controversies concerning NSAIDs and
orthopedic surgery
8. Efficacy of NSAIDs for acute pain: aspirin,
ibuprofen, diclofenac, piroxicam, naproxen, and
ketorolac
Charlton J E, editor. Core Curriculum for Professional Education in Pain. IASP Press, Seattle 2005.
Vimolluck Sanansilp, Siriraj
Acute and Postoperative Pain
I. For the COX-2 inhibitors, know:
1. Structural differences between the agents and
conventional NSAIDs.
2. Selectivity for the COX-2 enzyme between
different agents.
3. Comparisons between COX-2 inhibitors and
nonselective NSAIDs in terms of analgesic
activity and side-effect profile.
4. The pharmaco-economic impact of COX-2
inhibitors.
5. Opioid-sparing effects.
6. Controversies concerning COX-2 inhibitors
Charlton J E, editor. Core Curriculum for Professional Education in Pain. IASP Press, Seattle 2005.
Vimolluck Sanansilp, Siriraj
Vimolluck Sanansilp, Siriraj