Download Nonsteroidal Antiinflammatory Drugs (NSAIDs)

Nonsteroidal
Antiinflammatory Drugs
(NSAIDs)
Medical Author: Omudhome Ogbru, Pharm.D.
Medical Editor: Jay Marks, M.D.
What are NSAIDs and how do they
work?
Drug with analgesic( without impairing
consciousness ), antipyretic, and antiinflamammatory effects
 weak acids, PH 3-5, well absorbed
from stomach and intestinal mucosa
 protein-bound in plasma ( albumin),
 metabolised in the liver
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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
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What are NSAIDs and how do they
work ?
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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.
For what conditions are NSAIDs
used?
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RA
OA
Infalmmatory arthritis,
AS, psoriatic arthritis,
Reter’s syndrome
Acute gout
Metastatic bone pain
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Dysmenohhoea
Headache, migrain
Postoperative pain
Pyrexia ( fever)
Ileus
Renal colic
For what conditions are NSAIDs
used?
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Aspirin (also an NSAID) : inhibit the clotting
of blood( platelet aggregation ) ,prevent
strokes and cardiovascular attacks
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.
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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
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Differences between NSAIDs
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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.
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)
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
Table: 各種NSAIDs對胃腸的影響
High Risk
Moderate Risk
Low Risk
Drug*
Aspirin (Bokey, Tapal)
X
Celecoxib (Celebrex)
X
Diclofenac (Cataflam, Eunac)
X
Etodolac
X
Flurbiprofen
X
Ibuprofen
X
Indomethacin
X
Ketoprofen
X
X
X
Ketorolac (Keto)
X
Meloxicam **
X
Nabumetone
X
Naproxen (Anaprox)
Piroxicam
X
X
Sulindac (Weisu)
X
** Meloxicam risk increases with doses >7.5 mg.
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.
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
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
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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 contraindicated after 6 months of pregnancy
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Classification of NSAID
Acetic acid derivatives
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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 ®)
Carboxylic acid derivatives
Diflunisal (Dolobid ®)
 Salsalate (Disalcid ®)
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Enolic acid (oxicam) derivatives
Meloxicam ( Mobic ® Subic )
 Piroxicam (Feldene Tonmax inj, Foglugen)
 Tenoxicam ( Tencam, Sutondin )
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Napthylkanone derivatives
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Nabumetone (Relafen ® Relifex, No-ton )
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)
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COX-2 inhibitors
Celecoxib (Celebrex ® )
 Rofecoxib (Vioxx ® )
 Valdecoxib (Bextra ® )
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Dosage of NSAID
Diclofenac (Voltaren ® Cataflam
®)
Meitifen 75mg, Formax 75mg
Rheumatoid arthritis: 150-200
mg/day orally in 2-4 divided doses
Osteoarthritis: 100-150 mg/day orally
in 2-3 divided doses.
 Maximum Daily Dose: 225 mg; XR:
200 mg
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Etodolac (Lodine ® )
Lonine 200mg
 Acute pain: 200-400 mg every 6-8
hours,
 Rheumatoid arthritis, osteoarthritis:
Initial: 600-1200 mg/day given in
divided doses:
 Maximum Daily Dose:: 1200 mg
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.
Sulindac (Clinoril ®)
Unidac 200mg
 Adults: 150-200 mg twice daily or 300400 mg once daily; not to exceed 400
mg/day.
 Should be administered with food or
milk.
 Maximum Daily Dose : 400 mg
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
Piroxicam (Feldene ®)
Tonmax Inj 20mg, Foglugen 20mg
 Adults: 10-20 mg/day once daily
 doses >20 mg/day have been used (ie, 30-40 mg/day)
 May be taken with food to decrease GI adverse
effect.
 Maximum Daily Dose : 20 mg
 Dosing adjustment in hepatic impairment
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
Flurbiprofen (Ansaid ® )
Flufen50 mg,Lefenine100mg, Flur Di Fen
Patch 12mg
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Inflammatory disease: 50-100 mg/dose 3-4
times/day (maximum dose: 400 mg/day )
Tenoxicam
Tencam 20mg, Sutondin 20mg, Tencam inj
20mg
 Adults: 20-40 mg/day ,1-2 times daily
 Acute gout: 40mg x 2days, then 20mg qd
Ibuprofen (Motrin ® )
Purfen 400mg ,Mac Safe syr, Arfen inj 400mg
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Inflammatory disease: 400-800 mg/dose 3-4 times/day
Analgesia/pain/fever/dysmenorrhea: 200-400 mg/dose every
4-6 hours (maximum daily dose: 1.2 g )
maximum dose: 3200 mg/day
in severe hepatic impairment: avoid use
Naproxen (Naprosyn ®)
Napton 750mg
• Rheumatoid arthritis, osteoarthritis, and
ankylosing spondylitis: 250-500 mg orally
twice daily
• May increase to 1.5 g/day
T
est
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
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