1. Nonsteroidal Antiinflammatory Drugs (NSAIDs)
Medical Author: Omudhome Ogbru, Pharm.D. Medical Editor: Jay Marks, M.D.

2. What are NSAIDs and how do they work?
Drug with analgesic( without impairing consciousness ), antipyretic, and anti-inflamammatory effects
weak acids, PH 3-5, well absorbed from stomach and intestinal mucosa
protein-bound in plasma ( albumin),
metabolised in the liver

3. Prostaglandins
Prostaglandins : produced by the cells, promote inflammation, pain, and fever; blood clotting function of platelets; protect the lining of the stomach from damaging effects of acid.
two COX enzymes, COX-1 and COX-2. produce prostaglandins that promote inflammation, pain, and fever

5. What are NSAIDs and how do they work ?
NSAIDs block the COX enzymes , reduce prostaglandins, inflammation, pain, and fever are reduced.
COX-1 produced prostaglandins that support platelets and protect the stomach.
Reduced prostaglandins that protect the stomach and support blood clotting, so NSAIDs can cause ulcers in the stomach and promote bleeding.

6. For what conditions are NSAIDs used?RA OA
Infalmmatory arthritis, AS, psoriatic arthritis, Reter’s syndrome
Acute gout
Metastatic bone pain
Dysmenohhoea
Headache, migrain
Postoperative pain
Pyrexia ( fever)
Ileus
Renal colic

7. For what conditions are NSAIDs used?
Aspirin (also an NSAID) : inhibit the clotting of blood( platelet aggregation ) ,prevent strokes and cardiovascular attacks

8. Differences between NSAIDs
vary in potency, duration , eliminated from body, how strongly they inhibit COX-1
(tendency to cause ulcers and promote bleeding )
The more an NSAID blocks COX-1, the greater to cause ulcers and promote bleeding.

10. Differences between NSAIDs
Celecoxib (Celebrex), blocks COX-2 but little on COX-1, classified as a selective COX-2 inhibitor ,cause less bleeding and fewer ulcers.
Aspirin is a unique NSAID, the only NSAID inhibits clotting of blood for a prolonged period (4 to 7 days), ideal for preventing blood clots that cause heart attacks and strokes

11. Differences between NSAIDs
Most NSAIDs inhibit the clotting of blood for only a few hours
Ketorolac (Keto) is a very potent NSAID and is used for moderately severe acute pain that usually requires narcotics
Ketorolac (Keto) causes ulcers more frequently than other NSAID. Therefore, it is not used for more than five days.
Individuals who do not respond to one NSAID may respond to another.

12. Side effects of NSAIDs Cardiovascular
80% increase in AMI risk with newer COX-2
and high dose traditional NSAID
Heart failure risk
( with CHF history x10, without x2)

13. Side effects of NSAIDs Gastrointestinal
Direct irritation : acidic molecules
Indirect irritation: inhibit COX-1, reduce protective prostaglandins
S/S: nausea, vomiting, dyspepsia, gastric ulcer/bleeding, diarrhea
Duration of therapy, dose

14. Table: 各種NSAIDs對胃腸的影響
Drug*
High Risk
Moderate Risk
Low Risk
Aspirin (Bokey, Tapal) X
Celecoxib (Celebrex)
Diclofenac (Cataflam, Eunac)
Etodolac
Flurbiprofen
Ibuprofen
Indomethacin
Ketoprofen
Ketorolac (Keto)
Meloxicam **
Nabumetone
Naproxen (Anaprox)
Piroxicam
Sulindac (Weisu)
** Meloxicam risk increases with doses >7.5 mg.

15. Side effects of NSAIDs Renal
Decrease prostaglandins→ constriction of afferent arteriole → decreased renal perfusion
→alter renal function
S/S: salt and fluid retension, hypertension
Caution: NSAID with ACE inhibitor, diuretic
Rare: ARF, ATN, nephrotic syn.

16. Side effects of NSAIDs Others Allergy: shortness of breath
Asthma : a higher risk for serious allergic reaction
with a serious allergy to one NSAID are likely to have similar reaction to a different NSAID
photosensitivity

17. Combinational Risk
If COX-2 inhibitor taken, should not use a traditional NSAID concomitantly
With daily aspirin therapy, should use other NSAID carefully, they may block the cardioprotective effect of aspirin

18. During pregnancy
Not recommended during pregnancy, particular 3rd trimester
Cause early closure of fetal ductus arteriosus,
and fetal renal toxicity, premature birth
Acetaminophen ia more safe during pregnancy
In France, NSAID and aspirin is contra-indicated after 6 months of pregnancy

19. Classification of NSAID

20. Acetic acid derivatives
Arthrotec (diclofenac/misoprostol)
Diclofenac (Voltaren® Meitifen,Formax ®)
Ketorolac (Toradol Keto, Painoff,Keto Inj,
Kop Inj )
Tolmetin (Tolectin ®)
Etodolac (Lodine ® Lonine )
Indomethacin (Indocin® Acemet )
Sulindac (Clinoril Unidac ®)

21. Carboxylic acid derivatives
Diflunisal (Dolobid ®)
Salsalate (Disalcid ®)

22. Enolic acid (oxicam) derivatives
Meloxicam ( Mobic ® Subic )
Piroxicam (Feldene Tonmax inj, Foglugen)
Tenoxicam ( Tencam, Sutondin )

23. Napthylkanone derivatives
Nabumetone (Relafen ® Relifex, No-ton )

24. Proprionic acid derivatives
Flurbiprofen (Ansaid ® Flufen,Lefenine, Flur Di Fen )
Ketoprofen (Orudis ®) Ketoprofen inj
Oxaprozin (Daypro ® )
Ibuprofen (Motrin ® Purfen ,Mac Safe syr, Arfen inj )
Naproxen (Naprosyn ® Napton)

25. COX-2 inhibitors Celecoxib (Celebrex ® ) Rofecoxib (Vioxx ® )
Valdecoxib (Bextra ® )

26. Dosage of NSAID

27. Diclofenac (Voltaren ® Cataflam ®)
Meitifen 75mg, Formax 75mg
Rheumatoid arthritis: mg/day orally in 2-4 divided doses Osteoarthritis: mg/day orally in 2-3 divided doses.
Maximum Daily Dose:  225 mg;  XR: 200 mg

28. Etodolac (Lodine ® ) Lonine 200mg
Acute pain: mg every 6-8 hours,
Rheumatoid arthritis, osteoarthritis: Initial: mg/day given in divided doses:
Maximum Daily Dose::  1200 mg

29. Ketorolac (Toradol ® ) Keto Inj 30mg, Kop Inj 30mg, Keto, Painoff 10mg
IM: 60 mg x 1 or 30 mg q6h (maximum daily dose: 120 mg).
 IV: 30 mg x 1 or 30 mg q6h (maximum daily dose: 120 mg).
Oral: 20 mg, followed by 10 mg every 4 to 6 hours (Max 40 mg/day)
Note: The maximum duration of treatment (for parenteral and oral) is 5 days.

30. Sulindac (Clinoril ®) Unidac 200mg
Adults: mg twice daily or mg once daily; not to exceed 400 mg/day.
Should be administered with food or milk.
Maximum Daily Dose :  400 mg

31. Meloxicam (Mobic ® ) Subic 7.5mg
Oral: Initial: 7.5 mg once daily; may increased dose of 15 mg once daily
maximum dose: 15 mg/day

32. Piroxicam (Feldene ®) Tonmax Inj 20mg, Foglugen 20mg
Adults: mg/day once daily
doses >20 mg/day have been used (ie, mg/day)
May be taken with food to decrease GI adverse effect.
Maximum Daily Dose :  20 mg
Dosing adjustment in hepatic impairment

33. Nabumetone (Relafen ® )
No-ton 500mg ,Relifex
1000 mg orally with or without food
may obtain more symptomatic relief from 1500 mg to 2000 mg per day (in two divided doses)
Maximum Daily Dose:  2000 mg

34. Flurbiprofen (Ansaid ® )
Flufen50 mg,Lefenine100mg, Flur Di Fen Patch 12mg
Inflammatory disease: mg/dose 3-4 times/day (maximum dose: 400 mg/day )

35. Tenoxicam Tencam 20mg, Sutondin 20mg, Tencam inj 20mg
Adults: mg/day ,1-2 times daily
Acute gout: 40mg x 2days, then 20mg qd

36. Ibuprofen (Motrin ® ) Purfen 400mg ,Mac Safe syr, Arfen inj 400mg
Inflammatory disease: mg/dose 3-4 times/day
Analgesia/pain/fever/dysmenorrhea: mg/dose every 4-6 hours (maximum daily dose: 1.2 g )
maximum dose: 3200 mg/day
in severe hepatic impairment: avoid use

37. Naproxen (Naprosyn ®) Napton 750mg
Rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis: mg orally twice daily
May increase to 1.5 g/day

38. Test Time
Q 1: which of the following NSAID in our hospital is the most COX 2 selective?
(1) no-ton (2) unidac (3) subic (4) lonine
Q 2: which of the following NSAID should not been used more than 5 days?
(1) lefenine ( 2) ketoprofen ( 3) sutondin
(4) painoff