9. mdn-Ketorolac AKHIR (no P).ppt

7/24/2019 9. mdn-Ketorolac AKHIR (no P).ppt

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Aznan Lelo

Dep. Farmakologi & Terapeutik,Fakultas KedokteranUniversitas Sumatera

Utara

2 A ril 2011 MEDAN A!N 2011 Medan


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Surgical Inflammatory Pain

functio

laesiarubor

calor

tumor

inflammation

acute chronic

pain


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Inflammatory mediatorand its actions

Mediator Pain Vascularpermeability

Vaso-dilatation

Chemotaxis

Histamine -

++ -

Serotonin -

+/- -

rady!inin +++

+++ -

Prosta-

glandin +

+++ +++

"eu!o-triene

-

- +++


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Classification of some ma#or

features of pain$ype %ura-

tionCharac-teristics

Cells &dapti'eresponse

(xamples

&cute Seconds Proportional

to the cause

Nociceptive Withdrawal,

escape

Contact with

hot surface

Sub-chronic

Hours todays

Hyperalgesia,Allodynia,Spontaneouspain

NociceptiveNeurogenic

Quiescence,Avoidance ofcontact withinjuredtissues

Inflaatorywound

Chronic !onths toyears

Hyperalgesia,Allodynia,SpontaneouspainAffectivecoponent

NociceptiveNeurogenic

Psychologicaland cognitive

Arthritis, CNSinjury,etastaticdisease


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)ocicepti'e Pain

" #$aples%

& Post-surgical

& etastatic 'one pain& usculos(eletal pain

& arthritic pain

" What to (now

& *esponds to )S&I%s and pioids


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,actors that modify post-

operati'e pain

)* Site, nature and duration of surgery*

+* ype and e$tent of incision*

-* Physiologic and psychologic a(eup ofthe patient*

.* Pre operative preparation of the patient*

/* Presence of coplications of surgery*

0* Anesthetic anageent*

1* Quality of perioperative care*

2* Preoperative treatent of painful stiuli *


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Pain Management

.oals of Pain Managemento 3elieve sufferingo Increase functional capacityo Iprove 4uality of life

ays to ad'ocate forPainManagement

o 5on6t use place'oso Proote pain education with all

disciplines


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Pathophysiology of acuteinflammatory pain

" Pain ediators released in acute

inflaatory pain

& 7rady(inin

& Prostaglandin

" #n8ye involved in prostaglandin

synthesis

& C9: ) ; C9:


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C0-1/C0-2 selecti'ity of )S&I%s

nonsele"tive

re#$%&'(2

%&'(2sele"tive

%&'(1sele"tive

re#$%&'(1

anti(in)ammation

anal*esi"NN+


10/28Warner et al. PNAS1999; 96: 7563-7568

C0-1 Inhibition at $herapeutic C0-2 Inhibition

in a Human hole lood &ssay

! " 6 8 1 1!

ro#e"oi-

NS(./

etodola"meloi"am

nimesulide"ele"oi-

tomoiproldi"lo#ena"

sulinda" sulpide

piroi"amme"lo#enamate

di)unisalni)umi" a"id

sodium sali"late#enopro#en

zomepira"

indometa"intolmetin

naproeni-upro#en

amproneketopro#en

aspirin

)ur-ipro#ensupro#en

ketorola"

# $n%iition '()-1 *%en '()-! in%iite+ 8#


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Willoug% D, et al. '()-1, '()-!, an+ '()-3 an+ t%e uture

treatment o /%roni/ in0ammator +ieae. 2an/et 355: 6"6-

&' potesized "entrall involvesin in)ammator pain


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=hu :, Con(lin 53, #isenach >C*

Preoperati'e Inhibition of Cyclooxygenase-1

in the Spinal Cord *educes Postoperati'e Pain

Anesth Analg ??%)-@?


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)g &7 $emple &7 Smith .7 (membolu 8

(arly analgesic effects of parecoxib versus!etorolacfollo9ing laparoscopic sterili:ation

a randomi:ed controlled trial7ritish >ournal of Anaesthesia, @+0B%2.0


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3eu'en SS, 7uvanendran A, Droin >S, Stein'erg 37*

Postoperati'e modulation of central ner'ous system

prostaglandin (2 by cyclooxygenase inhibitors after

'ascular surgery;Anesthesiology* )?.-B%.))


15/28

Current 'ie9 in selecting analgesic and

anti-inflammatory drugs

(fficacyindicationB Safety side effectB

)ot onlyEI to$icity

Cardiovascular to$icity 3enal to$icity 7leeding 7one healing ipairent etc

Suita'ility contra


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9

C9+H

9

acetylsalicylic acid

aspirin

H

N

9

acetainophen

ylenol

H9

C9+H

i'uprophen

!otrin, Nuprin

C9+H

(etoprophen

9rudis

9

C9+H

napro$en

Naprosyn, Alleve

(etorolac

oradol

9

!e9

HN

diclofenac

Catafla, Foltaren

Cl

Cl

C9+

N

C9+H

indoethacin

Indocin

N

9 Cl

C9+H

!e9

%emi"al stru"ture o#NSA!Ds


17/28

3etorolac tromethamine

a e'er of the pyrrolo


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Pharmaco!inetic Parameters =Mean < S%>

po7 im and i' doses of 3etorolac $romethamine

3oute of adinistration po i IvPharaco(inetic Paraeter )? g )/ g )/ g

7ioavaila'ility e$tentB )??K )??K )??K

a$

)inB .. L -. -- L +)MM )*) L ?*1MM

Ca$

+cglBGsingle dose ?*21 L ?*++ )*). L?*-+MM

+*.1 L?*/)MM

Ca$

cglBGsteady state 4id)*?/ L?*+0MM

)*/0 L?*..MM

-*?@ L)*)1MM

Cin-cglBGsteady state 4id ?*+@ L?*?1MM ?*.1 L?*)-MM ?*0) L?*+)MM

Cavg

.cglBGsteady state 4id ?*/@ L?*+?MM

?*@. L?*+@MM

)*?@ L?*-?MM

F'eta

/(gB ?*)1/ L

?*?-@

?*)1/, Choi #D, Dil HD*

3etorolac or fentanyl continuous

infusion for post-operati'e analgesia

in children undergoing

ureteroneocystostomy*Acta Anaesthesiol Scand* +?)) >anO//)B%/.


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5aw(ins N, 7arclay CA, Eardiner 3,

Drawc8es(i C5*

Safety of intra'enous use of

!etorolac in infants follo9ing

cardiothoracic surgery;Cardiol oung* +??@ e'O)@)B%)?/


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" Detorolac is an acidic and C9:

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9. mdn-Ketorolac AKHIR (no P).ppt