non opioid drugs

7/24/2019 Non Opioid Drugs

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NON-OPIOIDANALGESIC

A. M. Takdir Musba

Department of Anestesio!o"#$ Intensi%e Care and PainMana"ement

&a'u!t# of Medi'ine$ (asanuddin )ni%ersit#


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Good Drug in the RightDoctor

PHARMACODYNAMICMECHANISM OF ACTION

PHARMACOKINETIC

METABOLISM AND ELIMINATION


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NON OPIOID DRGS

N!NSAI

D!

CO"IB!P#r#cet#

$o%


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PA*ACETAMOL


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PARACETAMOL HISTORY

&'(') !*nthe!i+ed ,* Mor!e

&'-.) introduced /or $edic#% u!#ge

&-00) reintroduced #! #n #n#%ge!ic in S

Most popular and widely used drug for the rstline treatment of fever and pain

&-'0) intr#1enou! # 2ro3drug 2re2#r#tion)propacetamol

Recent introduction to the $#r4et o/ # re#d*3to3u!eintr#1enou! /or$u%#tion


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Mech#ni!$ o/ Action 5Still under discussion

Act peripherally and/or centrally ?

Which analgesic pathway mainly aected?

But) E+'a'# as no doubt

P#r#cet#$o% i! #n e6ecti1e #n#%ge!ic /or #cute2#in7 the incidence o/ #d1er!e e6ect! co$2#r#,%eto 2%#ce,o 8S, Le%e! I Co'rane *e%ie/0,.

Acute Pain Management: Scientic vidence! "rdedition! A#$%A! &'('


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Potenti#% $ech#ni!$! o/ #ction

Inhi,ition o/ CO" i!oen+*$e!

Inter#ction 9ith endogenou! o2ioid

2#th9#* Acti1#tion o/ !erotoninergic ,u%,o!2in#%

2#th9#*

In1o%1e$ent NO 2#th9#*

Incre#!e in c#nn#,inoid:1#ni%%oid tone


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T9o #cti1itie! o/ CO"3en+*$e


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Inhi,ition CO" i!oen+*$

Reducing #gent i! re;uired to con1ert CO"en+*$ /ro$ #cti1e to in#cti1e P#r#cet#$o%) # !u,!tituted 2heno%) #ct #! #

reducing #gent

Pero=ide3de2endent CO" inhi,iton

PCT i! not #cti1e #t 2eri2her#% !ite o/in?#$$#tion 8high 2ero=ide concentr#tion >),ut

#cti1e in the ,r#in 8%o9 2ero=ide concentr#tion>


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Peri2her#% 1! Centr#% e6ect

Se%ecti1e inhi,ition o/ CO" in CNS!u22ort h*2othe!i! PCT doe! not 2o!!e!!#nti3in?#$$#tor* e@c#c* !i$i%#r to

NSAID! Not #!!oci#ted 9ith g#!tric !ide e6ect

#nd inhi,ition 2%#te%et #cti1it*

CO"3. ) un%i4e%* to ,e the e%u!i1e t#rgeto/ PCT in hu$#n ti!!ue!


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Inter#ction 9ith endogenou! o2ioid2#th9#*) !erotoninergic #nd NOS !*!te$

Se%/3!*nergi!tic inter#ction ,et9een!2in#% d#n !u2r#!2in#%

Acti1#tion o/ de!cending o2ioid

2#th9#*! Centr#%%* #cting co$2onent o/

2#r#cet#$o% in1o%1e! !erotoninergic

inhi,itor* de!cending 2#th9#* Inhi,itor* nitric o=*de !*nth#!e 8 NOS >

1i# inhi,ited !u,!t#nce P3$edi#tedh*2er#%ge!i#


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S#/et* #nd to=icit* 2ro%e

S#/er th#n NSAID! S$#%% $inorit* %i/e thre#tening %i1er

inur*

To=ic $et#,o%ite N3#cet*%32,en+o;uinine i$ine 8NAFI>

P#r#cet#$o% o1erdo!e! !ignic#nt

c#u!e to=icit* Suicide #tte$2t!

nintention#% o1erdo!e!


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P%#!$# concentr#tion

Mini$u$ 2%#!$# concentr#tion /or#n#%ge!i# #nd #nti32*re!i! 12-32$g:L

Potenti#% he2#toto=icit* 142 $g:L

Medi#n do!e th#t 9i%% de1e%o2ed #cute%i1er /#i%ure i! gr#$!

)ntravenous (* mg/+g , mg/- and

detecta.le in %SS at * minutes)ntravenous ( gr (0 mg/- in &' minutes1ral ( gr large and unpredicta.levaria.ility 2 su.therapeutic

plasma conc0 in 3' min 4


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The Met#,o%i!$ o/ Acet#$ino2hen #ndNAPI 2roduction

N Eng% Med ' u%* &(7 .0-8.>5 '0-


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Ri!4 /#ctor PCT3induced he2#toto=icit*

E=ce!!i1e do!ing Incre#!ed P30 #cti1#tion

Decre#!ed g%uth#tione#1#i%#,i%it*

Chronic !e1ere eth#no% #,u!e


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E6ect in co#gu%#tion /unction


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Se1er#% !tudie! #,out !#/et* u!e o/ PCT

#o evidence in the literature of an increased ris+ ofhepatoto5icity in chronic liver disease with therecommended doses

Ben!on GD) et #%) A$ Ther 07&5&..3&

Alcoholic patients treatment with gr/dayfor three consecutive days did not developincrease in serum transminase or othermeasures of liver in6ury

Ku6ner EK Et #%) BMC Med (70.5&.

1nly minor eect in on renal function! doesnot aect %178( en9ym

Ko22ert


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P#in re%ie/ #/ter IJ #nd Or#%%*

Mo%%er) S Sindet P Briti!h ourn#% o/ An#e!the!i# 0 7

- 80>5 '


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Intr#1enou! P#r#cet#$o%

F#!ter on!et #n#%ge!i#

Predict#,%e 2%#!$# concentr#tion#chie1ed

Route o/ choice 9hen or#% #d$ini!tr#tionno 2o!!i,%e

IJ 2#r#cet#$o% 9#! #n e6ecti1e #n#%ge!ic

#/ter !urger* 8 Le1e% II)Acute Pain Management: Scienticvidence! "rdedition! A#$%A! &'(' >


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P#r#cet#$o% e1idence

In the !#$e do!e!) 2#r#cet#$o% 9#! %e!! e6ecti1e#nd o/ !%o9er on!et 5 rect#% or#%%* intr#1enou!

IJ 2#r#cet#$o% 9#! #n e6ecti1e #n#%ge!ic #/ter!urger* 8Le%e! II,.

There i! no e1idence th#t 2#tient! 9ho h#1e de2%etedg%ut#thione !tore! 8eg 2#tient! 9ho #re $#%nouri!hed) or9ho h#1e cirrho!i!) he2#titi! C or hu$#n i$$unodecienc*

1iru! HIJ> #re #t incre#!ed ri!4 o/ %i1er d*!/unction 9hene=2o!ed to ther#2eutic do!e! o/ 2#r#cet#$o% 8Ben!on et #%)0 Gr#h#$ et #%) 07 O!cier Mi%ner) ->


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Non3Steroid Anti In?#$$#tor* Drug!


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NsNSAID

E=hi,it # !2ectru$ o/ #n#%ge!ic) #nti3in?#$$#tor*)#nti2%#te%et #nd #nti2*retic ,*inhi,ition CO" en+*$e

Mo!t co$$on%* 2re!cri,ed #n#%ge!ic $edic#tion!in the 9or%d i0e0 Metami9ole! etorolac!;iclofenac! etoprofen

Many used as the sole method of treatment mildto moderate pain

4


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Non3S2ecic NSAID e@c#c* e1idence

Sing%e do!e! o/ n!NSAID! #re e6ecti1e inthe tre#t$ent o/ 2#in #/ter !urger*

8 Derr* et #% - Le%e! I,

N!NSAID! #re in#de;u#te #! the !o%e#n#%ge!ic #gent in the tre#t$ent o/!e1ere 2o!to2er#ti1e 2#in 8E%i# et #%)0 Le%e! I ,

Ad1er!e e6ect! o/ NSAID! #re !ignic#nt

#nd $#* %i$it their u!e


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A*AC(IDONATE

CO5-1 CO5-3

prosta"!andins prosta"!andins

Con!tituti1eQ E=2re!!ed5

GI $uco!# Kidne*! P%#te%et! J#!cu%#r

endothe%iu

Induci,%eQ E=2re!!ed5

Site o/inur*

CNS

Ad1er!e e6ect due toNon3!e%ecti1e CO"3& #nd CO"3 inhi,itor


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NSAID! #nd Ren#% Function

or4eto2ro/en 8Lee A et #%) ( Le%e! I,.

NSAID! #nd Co=i, h#1e !i$i%#r #d1er!e e6ect onren#% /unction Le%e! I ,


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NSAID! #nd B%eeding

In $et#3#n#%*!e! o/ ton!i%%ecto$* in ,oth #du%t #nd2#edi#tric 2#tient!) n!NSAID! 9ere /ound to incre#!ethe ri!4 o/ reo2er#tion /or ,%eeding 8NNH - to >8. Le%e! I, ,ut !urgic#% ,%ood %o!! 9#! not

!ignic#nt%* incre#!ed 8Moiniche et #%) . Le%e! I, Loo4ing #t !tudie! in chi%dren on%*) there 9#! no

incre#!e in the ri!4 o/ reo2er#tion /or ,%eeding #/terton!i%%ecto$* 8C#rd9e%% et #%) 0 Le%e! I,.

A/ter # 1#riet* o/ di6erent o2er#tion!) the u!e o/n!NSAID! !ho9ed # !ignic#nt incre#!e in ri!4o/!e1ere ,%eeding /ro$ to &( 8E%i# et #%) 0Le%e! I,.


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NSAID! #nd GI %cer

A %#rge c#!e3contro%%ed !tud* u!ing # gener#% 2r#cticed#t#,#!e identied & '- 2#tient! o1er *e#r! 9ith# r!t e1er di#gno!i! o/ #n u22er GI u%cer or ,%eeding#nd co$2#red the$ 9ith $#tched contro%! 8Hi22i!%e*3

Co= et #%) 0 Le%e! III-6,.

!ignic#nt%* reduced the incidence o/ n!NSAID3re%#ted2e2tic u%cer di!e#!e 8T#rgo9ni4 et #%) ' Le%e! III-3,.


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Se%ecti1e CO3 Inhi,itor


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Se!e'ti%e CO5-3 inibitor

L#rger $o%ecu% 9ith !ide ch#in tted theh*dro2hi%ic !ide o/ CO"3 i!o/or$ ,ut didnot t CO"3& i!o/or$

CO"3 in 2eri2her#% #nd centr#% ner1e!*!te$

A! # 2#rt o/ $u%ti$od#% #n#%ge!i#

O6er !ignic#nt #d1#nt#ge! o1erN!NSAIDS 9ith reg#rd to !e1er#% #d1er!ee6ect 8 not in ren#% /unction >


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CO"IB e1idence

Co=i,! #re e6ecti1e in the tre#t$ent o/#cute 2o!to2er#ti1e 2#in 8N, Le%e! ICo'rane *e%ie/0>

Co=i,! 9ere #! e6ecti1e #! n!NSAID! inthe $#n#ge$ent o/ 2o!to2er#ti1e 2#in8Ro$!ing Moiniche) Le%e! I,.

Preo2er#ti1e co=i,! reduced 2o!to2er#ti1e

2#in #nd o2ioid con!u$2tion #ndincre#!ed 2#tient !#ti!/#ction 8Str#u,e et#%) 0 Le%e! I,

PCT N!NSAID CO"IB 9ith OPIOID 5 the


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PCT) N!NSAID) CO"IB 9ith OPIOID 5 thee1idence

decrease in & h morphine consumption when paracetamol! #SA);! or%178& inhi.itors are given in addition to P%A morphine after surgery!

with no clear diference between them. Similarly! the .enets in terms of reduction in morphine8related

adverse eects do not strongly favour one of the three non8opioid

analgesics0

PCT N!NSAID CO"IB co$,in#tion 5 the


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P#reco=i, #nd #cet#$ino2hen e6ecti1e%* reduce 2o!to2er#ti1e o2ioidre;uire$ent! #/ter th*roid or 2#r#th*roid !urger* The co$,in#tion o/the!e drug! i! not #!!oci#ted 9ith # /urther reduction in o2ioidcon!u$2tion

Po!to2er#ti1e #n#%ge!i# 9ith 2#reco=i,) #cet#$ino2hen) #nd the co$,in#tion o/ ,oth5 #r#ndo$i+ed) dou,%e3,%ind) 2%#ce,o contro%%ed tri#% in 2#tient! undergoing th*roid !urger*

Geh%ing) et #% Briti!h ourn#% o/ An#e!the!i# & 8>5 (&( 8& >

Hu$#n !tudie! 8 nU&> ) &-- 2t! ) The NSAID! u!ed 9ere i,u2ro/en 8n@4!diclofenac 2n34! +etoprofen 2n"4! +etorolac 2n (4! aspirin 8n(4! teno5icam 2n

(4! and rofeco5i. 2n(40The combination o paracetamol and NSAID was more efective th#n2#r#cet#$o% or NSAID #%one in '0 #nd o/ re%e1#nt !tudie!) re!2ecti1e%*

Co$,ining P#r#cet#$o% 8Acet#$ino2hen> 9ith Non!teroid#% Antiin?#$$#tor* Drug!5 Au#%it#ti1e S*!te$#tic Re1ie9 o/ An#%ge!ic E@c#c* /or Acute Po!to2er#ti1e P#in

C%i6 K S Ong) et #% 8Ane!th An#%g &7&&5&&(->

PCT) N!NSAID) CO"IB co$,in#tion 5 thene9 e1idence

Co$,ined 2#reco=i, $g i1 #nd 2#r#cet#$o% & gr 2ro1ide!#ddition#% #n#%ge!ic e6ect 9ith ,etter 2o!to2er#ti,e !#ti!/#ction in2#tient undergoing n#terior cruci#te %ig#$ent con!truction

E%!ei/* V et #% S#udi ourn#% o/ An#e!the!i#) Jo% 0 i!!ue &) &&

% i hi,i


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c*c%oo=*gen#!e inhi,itor

Ibuprofen

NabumetoneEtodolac

Dexketoprofen

DiclofenacMeloxicam

NimesulideCelecoxib

Rofecoxib

Valdecoxib

Acetosal IndomethacinPiroxicam

DualCOX

inhibitor

preferentiallyCOX-2

selective

inhibitor

COX-2selectiveinhibitor

COX-1selectiveinhibitor

preferentiallyCOX-1

selective

inhibitor

COXIB

GITIncidence

CV Incidence


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E@c#c* An#%ge!ic

#um.er needed to treat 2##4 for at least *'> pain relief over to @ hours compared with place.o in third molar e5tractiontrials0

Briti!h Dent#% ourn#% 8B#rden ) et #% Br Dent 7&-(5(3&&>


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PCT) NSAID!) CO"IB!

B %an ;ent Assoc &''&C @3234:,@83&


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Other #du1#nt #n#%ge!ic 5 not u!t theP#r#cet#$o%) NSAID!) CO"IB!


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De7ametasone

Anti3in?#$$#tor* #ction reducing %oc#% ti!!ue 2re!!ure#nd re%e#!e o/ 2otent 2#in $edi#tor!

Direct e6ect! on 2#in neuron! #nd rece2tor! neuro2e2tide re%e#!e) inhi,it !ign#% tr#n!$i!!ion in C ,er!)#nd !ti$u%#te the !ecretion o/ endogenou! endor2hin!

Direct e6ect! on ,%ood c#2i%%#rie! 2er$e#,i%it* #nd1#!odi%#t#tion

Benet #/ter or#% !urger*) ton!i%%ecto$*) %u$,#r di!c !urger*)%#2#ro!co2ic cho%ec*!tecto$*) #rthro!co2ic !urger* #nd %ungre!ection 8Gi%ron) 7 Keh%et) (>

De=#$eth#!one co$2#red 9ith 2%#ce,o) reduce! 2o!to2er#ti1e2#in) n#u!e# #nd 1o$iting) #nd /#tigue 8Le%e! II, AN8CA 3212

De=#$eth#!one de$on!tr#ted do!e3de2endent e6ect! on ;u#%it* o/reco1er* De=#$eth#!one & $g 4gW&reduced o2ioid con!u$2tionco$2#red 9ith de=#$eth#!one 0 $g 4gW&) 9hich $#* ,e

,eneci#% /or i$2ro1ing reco1er* O%ie1er# D) et #% Dr0 B0Anaesth0 2&'((4 (', 2"4: "@&8",(0


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Gabapentin and Pre"aba!in as9prote'ti%e premedi'ation.:Ca2+

Ca2+

Ca2+Ca2+

Ca2+

Curr Drug T#rget - Aug7& 8'> 5(&3.. Douri M) et #%

Gabapentin and pre"aba!in for te a'ute post-operati%e pain mana"ement. As#stemati'-narrati%e re%ie/ of te re'ent '!ini'a! e%iden'es

G#,#2entin #nd 2reg#,#%in reduce 2#in #nd o2ioid con!u$2tion #/ter!urger* in con/ront 9ith 2%#ce,o) ,ut co$2#ri!on! 9ith other !t#nd#rd2o!t3o2er#ti1e regi$en! #re not !u@cient

Br An#e!th && A2r7&8>503 Vh#ng ) et #%E+'a'# of pre"aba!in in a'ute postoperati%e pain; a meta-ana!#sis.

In thi! !*!te$#tic re1ie9) 9e e1#%u#ted r#ndo$i+ed) contro%%ed tri#%! 8RCT!>/or the #n#%ge!ic e@c#c* #nd o2ioid3!2#ring e6ect o/ 2reg#,#%in in #cute2o!to2er#ti1e 2#in

&& 1#%id RCT! th#t u!ed 2reg#,#%in /or #cute 2o!to2er#ti1e 2#in

Perioperative pregabalin administration reduced opioidconsum tion and o ioid-related adverse efects ater sur er .

A nu$,er o/ $et#3#n#%*!e! h#1e !ho9n th#tperioperativegabapentinoids improved analgesia8#t re!t #nd 9ith$o1e$ent> #nd reduced postoperative opioid consumption),ut incre#!ed the incidence o/ !ed#tion co$2#red 9ith 2%#ce,o8 Le%e! I ,. Hur%e* R) Ho KY) et #% 8> Tii22#n# EM) et #% 8(>


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NEROPATHIC DRG

ALGORITHM FOR NEROPATHIC PAIN


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Gi%ron) I et #% CMA 7&(0503(0

ALGORITHM FOR NEROPATHIC PAINMANAGEMENT PRIMARY CARE


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Anti Neuro2#thic Drug 5Pre!cri2tion con!ider#tion


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non opioid drugs

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