NSAIDs (NON STEROIDAL

ANTI INFLAMMATORY
DRUGS)

By
Wiwik Kusumawati
 General Objective
After learning this topic, the students
understand about pharmacology (both
pharmacokinetic and
pharmacodynamic) of NSAIDs
SPECIFIC OBJECTIVE
The students understand the mechanism of
action of NSAIDs
The students know classification and select of
NSAIDs which have potential anti
inflammatory effect
The students know about side effect and can
chose of NSAIDs appropriately for the
patients who need anti inflammatory drugs to
overcome their problem (clinical indication
and contra indication)
OBAT AINS (=NSAIDs)
Analgesik Antiinflamasi Nonsteroid =
Nonsteroidal Anti-inflammatory Drugs
Generally, these drugs have analgesic,
antipyretic and anti inflammation
For specific condition such as acute or
chronic inflammation, osteoarthritis, arthritis
rheumatoid, etc. we must consider about the
potential inflammatory effect of NSAIDs
MECHANISM OF ACTION
NSAIDs inhibits prostaglandin synthesis
through inhibition of COX (Cyclo
oxygenase)
In clinical aspect, there are 2 types of
COX i.e. COX-1 and COX-2 which
different role in the inflammation
process
 COX-inhibitors = NSAIDs
the most widely used class of drugs
available as prescription & non-prescription (OTC)
Common mechanism of action (COX inhibition)
Different selectivity to COX-1 and COX-2
Common clinical indications
Analgesic (CNS and peripheral effect)
may involve non-PG related effects
useful when pain is accompanied by
inflammation
Antipyretic (CNS effect)
Anti-inflammatory (mainly by PG inhibition)
have various side effects
about 16,000 persons die every year due to NSAID used in US
 pain
redness heat

swelling hoarseness
COX-1 COX-2
PROSTAGLANDIN

COX inhibitor
 The evolution of NSAID
chemistry for the control of
pain
Coxib
Class
Acetic
Oxicam Acid Celecoxib
Class Class Rofecoxib
Propionic
Acid Valdecoxib
Salicylic Diclofenac Etoricoxib
Class Piroxicam
Acid Meloxicam Etodolac Parecoxib
Class Lumiracoxib
Ibuprofen
Aspirin ketoprofen

1853 1970- 1980- 1990- 2000-

traditional, classic, non-COXIB NSAID COXIB

The next slides will inform about general
classification of NSAIDs and discuss
more of NSAIDs which have potential
inflammatory effect
 Penggolongan
SALISILAT (aspirin, asetosal, diflunisal, dll)
PARAAMINOFENOL
(asetaminofen/parasetamol)
PIRAZOLON (dipiron/metampiron,
aminopirin, fenilbutazon, dll)
ASAM ORGANIK LAIN (ibuprofen, asam
mefenamat, indometasin, diklofenak, dll)
 SALISILAT
Aspirin, Asetosal, Diflunisal, dll.
Prototipe obat AINS
Efek analgesik, antipiretik, antiinflamasi
Efek antiinflamasi, urikosurik (dosis tinggi
:2-4 gram)
Efek antiagregasi trombosit (dosis rendah)
Efek keratolitik, astringent
REYE Sindrome
 SALISILAT
Absorbsi sempurna di lambung
Lama kerja 4 jam (4-6x/hari)
Ekskresi meningkat dengan alkalinisasi
urin
Iritasi saluran cerna (ulkus, perdarahan)
Pseudoalergi (Bronkokonstriksi)
 SALISILAT

Analgesik & antipiretik (300-600 mg 3x

sehari)
Nyeri disertai inflamasi (penyakit
inflamasi sendi/rheumatik), 3 6
gram/hari
Inflamasi sendi akut, 5 8 gram/hari
Pencegahan IMA
Topikal (metil salisilat)
 ASAM MEFENAMAT
Derivat asam fenamat
Efek analgesik kuat
Efek antiinflamasi lebih lemah
dibandingkan aspirin
Diberikan bersama dengan makanan
Kontra indikasi untuk ibu hamil dan
anak kurang dari 14 tahun
Lama pemberian tidak lebih dari 7 hari
 IBUPROFEN
Derivat asam propionat
Efek analgesik sama dg aspirin
Efek antiinflamasi lebih lemah
dibandingkan aspirin (lebih dari 2400
mg/hari 600 mg 4x/hari)
Metabolisme di liver
Waktu paruh 2,5 jam, ikatan protein
plasma 99 %
 IBUPROFEN
Efek samping di lambung lebih jarang
Efek samping : retensi cairan dan alergi
Pada penderita asma bronkial dapat
menimbulkan bronkokonstriksi
 DIKLOFENAK
Efek analgesik, antipiretik dan
antiinflamasi
Inhibitor sintesis prostaglandin yang
potensial
Absorbsi per oral baik
Kadar puncak 1-2 jam
Untuk penyakit inflamasi sendi kronis
Efek samping : gangguan lambung
 COX-2 inhibitors
COX inhibitor Administration Half-life
Specific
Celecoxib Oral 8-11 hr
Valdecoxib* Oral 8 hr
Parecoxib inj 8 hr
Rofecoxib* Oral 17 hr
Etoricoxib Oral 24 hr
Lumiracoxib Oral 3-6 hr
Preferential
Diclofenac Oral, inj., supp., topical 1.5 hr
Meloxicam Oral, inj., supp 20 hr
Nimesulide Oral 3 hr
this drug was voluntary withdrawn by pharmaceutical company, following official
request from FDA and EMEA, due to serious fatal adverse reactions
 MELOXICAM
Derivat oksikam, gol asam enolat
Efek antiinflamasi, analgesik, antipiretik
Kadar puncak 4-5 jam
Ikatan protein plasma 99,4 %
Kadar di cairan sinovial 40-50 %
Metabolisme dengan SP-450, T 15-
20 jam
 MELOXICAM
Indikasi : osteoartritis
Dosis 7,5 22,5 mg/hr
Meloxicam 7,5 mg/hr selama 1 bulan
resiko ES lebih rendah dibandingkan
piroxicam 20 mg/hr atau diclofenac 100
mg/hr
 NIMESULIDE
In vitro, menunjukkan selektivitas pada
COX-2
PO, mudah absorbsi
Kadar puncak 1-4 jam
Ikatan protein plasma 95 % T1/2 3 jam
Indikasi anti inflamasi jangka pendek
ES, saluran cerna, kulit, sistem saraf 5-
10 %
 ROFECOXIB
Selective COX-2 inhibitor yang poten
Selektivitas lebih besar dari celecoxib,
meloxicam, diclofenac dan indometasin
Dosis 12,5 mg/hr 25 mg/hr efektifitas setara
dengan ibuprofen 2400 mg /hr, diclofenac
150 mg/hr, naproxen 1000 mg/hr dan
celecoxib 200 mg/hr
Resiko ES gastrointestinal lebih ringan
(ulkus, perdarahan)
 Question
Why dont traditional NSAIDs be given
for the patient with renal disease?
What is the contra indication of COX-2
inhibitor? Can you explain why?