By : IG

Derifat asam asetic heterocyiclic Analgesic potent tapi anti inflamasi

moderatgol. NSAID menghasilkan efek

analgesi melalui penghambatan sintesis prostaglandin

Struktur kimia :

Sebagian besar NSAIDs bekerja sbg non-selective inhibitors dari enzyme cyclooxygenase,

Menghambat : cyclooxygenase-1 (COX-1) cyclooxygenase-2 (COX-2) isoenzymes.

Cyclooxygenase mengkatalisa formasi prostaglandins & thromboxane dari arachidonic

acid (itself derived from the cellular phospholipid bilayer by phospholipase A2).

Prostaglandins act (among other things) as messenger molecules in the process of inflammation. This mechanism of action was elucidated by John Vane (1927-2004), who later received a Nobel Prize for his work

Diindikasikan untuk manajemen nyeri jangka pendek (<5 hari)

Sangat berguna untuk manajemen nyeri post operatif yg segera

Efek analgesinya pada dosis terapi setara 6-12 mg morfin dgn onset yang sama (20-30menit) tapi durasi lebih panjang (6-8jam)

Bekerja di perifir dan tidak menembus sawar darah otak sehingga efek ke SSP minimal

Spesifik : tidak mendepresi pernapasan, mual, muntah,mengantuk.

Sering digunakan untuk manajemen nyeri operasi ortopedi dan obgyn tapi lebih jarang digunakan pada operasi intra abdominal

Menghambat agregasi platelet, memperpanjang bleeding time

Penggunaan jangka panjang bisa berakibat toksis ke ginjal (nekrosis papiler)

GIT bisa berakibat perdarahan dan ulserasi bahkan perforasi

Karena eliminasinya di ginjal tidak disarankan diberikan pd pasien dgn ggn fungsi ginjal

Kontra indikasi pada pasien yang alergi aspirin atau NSAID lainya

Pasien dg rwyt asma insiden hipersensitif terhadap aspirin meningkat (10%)polip nasal(20%)

NSAID

↑ Leukocyte-EndothelialInteractions

Capillary Obstruction

IschemicCell Injury

Proteases +Oxygen Radicals

Endo/EpithelialCell Injury

Mucosal Ulceration

Loss of

PGE 2 an

d PGI 2 m

ediat

ed in

hibition

of ac

id secre

tion an

d cytop

rotec

tive e

ffect Loss of PGI2 induced inhibition of LTB4 mediated

endothelial adhesion and activation of neutrophils

Dosis awal 60mg IM atau 30mg IV loading dose

Maintenance 15-30mg /6jamPasien usia tua perlu dosis

penyesuaian / pengurangan dosis karena fx ginjal menurun

Aspirin menurunkan protein binding ketorolac sehingga perlu dosis yang lebih besar.

Ketorolac tidak mempengaruhi MAC agen anestesi inhalasi serta tidak mempengaruhi hemodinamic pasien yang dibius

Ketorolac bisa menurunkan kebutuhan analgetik opiat post operatif

Non spesifik COX inhibitor (ketorolac, diclofenac dosis : 1mg/kgbb IV)

Selectif COX-2 inhibitor (parecoxib) punya toxicitas lebih rendah dan efek ke GIT yang lebih rendah,serta efek ke agregasi platelet yang lebih rendah pula dosis (20-40mg IV)

1. NSAIDs are effective analgesics for the acute pain of surgery, low back pain and renal colic (Level I*).

2. NSAIDs are effective adjunct to opioids (Level I).

3. NSAIDs given in addition to paracetamol improve analgesia (Level I).

I Evidence obtained from a systematic review of all relevant randomised controlled trials.

II Evidence obtained from at least one properly designed randomised controlled trial

III-1 Evidence obtained from well-designed pseudo-randomised controlled trials (alternate allocation or some other method)

NHMRC 1999

NNT (95%CI)Codeine 60 mg 16.7 (11-48)Paracetamol 1000 mg 3.8 (3.4-4.4)Morphine 10 mg (IM) 2.9 (2.6-3.6) Ketorolac 10 mg 2.6 (2.3-3.1)Ibuprofen 400 mg 2.4 (2.3-2.6)Diclofenac 50 mg 2.3 (2.0-2.7)Paracetamol 1G/ Codeine 60 mg 2.2 (1.7-2.9)Parecoxib 40 mg (iv) 2.2 (1.8-2.7)Lumiracoxib 400mg 2.1 (1.7-2.5)Diclofenac 100mg 1.9 (1.6-2.2)

Oxford acute pain league table www.jr2.ox.ac.uk/bandolier/booth/painpag/Ac

utrev/Analgesics/Leagtab.html

Small increased risk of thrombotic attacks.

Diclofenac (150 mg ) = etoricoxib. Ibuprofen 1200mg or below - no

increase of myocardial infarction.Naproxen - lower incidence of

thrombotic risk than coxibs.All NSAIDs - risk greater with high

doses, long term Rx.

Clinical anestesiology,G Edward MORGANJr, Fourt edition.2006 chapter 15 page 282-283

Pharmakology & physiology in Anesthetic practice,fourt edition, Robert K STOELTING, lipincot & walkins chapter 11 page 287-288