Farmacotoxicologie Si Farmacoepidemiologie Generala

- Farmacologie general
S C O A L A P O S T L I C E A L A
D I M I T R I E C A N T E M I R
T G - M U R E S

I O A N R A D

FARMACOTOXICOLOGIE SI FARMACOTOXICOLOGIE SI
FARMACOEPIDEMIOLOGIE FARMACOEPIDEMIOLOGIE
GENERAL GENERAL
S U P O R T D E C U R S
( t e o r i e s i l a b o r a t o r
t e h o l o ! i " #
$ % % &
1
C U P R I N S
CAPITOLUL I
FARMACOTOXICOLOGIA GENERALA........................................................... 3
1.1. Aspecte introductie..........................................................................................3
1.!. E"ecte secund#re................................................................................................$ 1.!. E"ecte secund#re................................................................................................$
1.3. E"ecte to%ice......................................................................................................& 1.3. E"ecte to%ice......................................................................................................&
1.$. Re#c'ii #derse de tip (ut#)en..........................................................................* 1.$. Re#c'ii #derse de tip (ut#)en..........................................................................*
1.&. Re#c'ii #derse de tip ter#to)en.........................................................................+ 1.&. Re#c'ii #derse de tip ter#to)en.........................................................................+
1.,. E"ecte #derse de tip c#nceri)en......................................................................13 1.,. E"ecte #derse de tip c#nceri)en......................................................................13
1.-. Re#c'ii #derse de tip idiosincr#.ic /into0er#n'1 (edic#(ento#s12.................13 1.-. Re#c'ii #derse de tip idiosincr#.ic /into0er#n'1 (edic#(ento#s12.................13
1.*. Re#c'ii #derse produse de (edic#(ente i(unosupresie.............................!$ 1.*. Re#c'ii #derse produse de (edic#(ente i(unosupresie.............................!$
1.+. To0er#n'# /t#3i"i0#%i#2......................................................................................!- 1.+. To0er#n'# /t#3i"i0#%i#2......................................................................................!-
1.14. F#r(#codependen'# /dependen'# (edic#(ento#s12......................................!+ 1.14. F#r(#codependen'# /dependen'# (edic#(ento#s12......................................!+
1.11. Into%ic#'ii0e (edic#(ento#se.........................................................................3! 1.11. Into%ic#'ii0e (edic#(ento#se.........................................................................3!
1.1!. 5op#6u0 (edic#(entos...................................................................................3&
1.13. Re#c'ii #derse re.u0t#te 0# 7ntrerupere#F#r(#coter#piei..............................3& 1.13. Re#c'ii #derse re.u0t#te 0# 7ntrerupere#F#r(#coter#piei..............................3&
CAPITOLUL II
FARMACOEPI5EMIOLOGIA.............................................................................3+
!.1. Gener#0it1'i.......................................................................................................3+ !.1. Gener#0it1'i.......................................................................................................3+
!.!. Pre.ent#re# din punct de edere st#tistic # re.u0t#te0or unor studii priind !.!. Pre.ent#re# din punct de edere st#tistic # re.u0t#te0or unor studii priind
pre#0en'# 8i inciden'# re#c'ii0or #derse 9+:..........................................................$4 pre#0en'# 8i inciden'# re#c'ii0or #derse 9+:..........................................................$4
!.3. E0e(ente /Aspecte2 de studiu #0e procesu0ui epide(io0o)ic.......................... $1 !.3. E0e(ente /Aspecte2 de studiu #0e procesu0ui epide(io0o)ic.......................... $1
!.$. For(e0e #ctiit1'ii "#r(#coepide(io0o)ice.....................................................$3 !.$. For(e0e #ctiit1'ii "#r(#coepide(io0o)ice.....................................................$3
!.&. ;iste(u0 de "#r(#coi)i0en'1..........................................................................$& !.&. ;iste(u0 de "#r(#coi)i0en'1..........................................................................$&
<I<LIOGRAFIE....................................................................................................$- <I<LIOGRAFIE....................................................................................................$-

!
CAPITOLUL I

FARMACOTOXICOLOGIA GENERALA
'('( As)e"te itro*+"ti,e
Este r#(ur# "#r(#co0o)iei c#re studi#.1 #specte dierse 0e)#te de (#ni"est1ri
nedorite nocie re.u0t#te 7n ur(# #d(inistr1rii (edic#(ente0or 8i nu(ite 7n )ener#0 re#c'ii
#derse= d#r 8i #0te #specte 0e)#te de 0ips# de re#ctiit#te s#u r1spuns #0 or)#nis(u0ui 0#
#d(inistr#re# su>st#n'e0or (edic#(ento#se.
Or)#ni.#'i# Mondi#01 # ;1n1t1'ii de"ine8te reaciile adverse c# re#c'ii nedorite=
d1un1to#re 8i c#re #p#r 0# do.e ter#peutice.
5esi)ur= pentru #p#ri'i# re#c'ii0or #derse s#u # #0tor "or(e de (#ni"est#re c#re
"#c o>iectu0 de studiu #0 "#r(#coto%ico0o)iei= e%ist1 #nu(i'i factori favorizani= dintre
c#re #(inti(?
- po0i(edic#'i#@
- #d(inistr#re# de su>st#n'e (edic#(ento#se cu indic#'ii ter#peutice necunoscute@
- dier8i po0u#n'i /c3i(ici= "i.ici etc.2@
- st1ri "i.io0o)ice p#rticu0#re /s#rcin1= #01pt#re= Arst1 7n#int#t1= copii de Arst1 (ic1
etc.2@
- co(p0i#n'1 de"icit#r1@
- #0'i "#ctori /su>nutri'i#= "u(#tu0= consu(u0 de #0coo0= dro)uri etc.2.
Bn "unc'ie de (ec#nis(u0 incri(in#t 7n producere# 0or= re#c'ii0e #derse pot "i de (#i
(u0te tipuri= 8i #nu(e?
- re#c'ii #derse produse c# e"ecte secund#re #0e unui e"ect "#r(#co0o)ic de >#.1@
- re#c'ii #derse produse prin (ec#nis( idiosincr#.ic@
- re#c'ii #derse produse prin (ec#nis( i(uno0o)ic /re#c'ii #0er)ice2@
- re#c'ii #derse produse c# ur(#re # unei #d#pt1ri "i.io0o)ice= 8i #nu(e
sensi>i0i.#re s#u up regulation, 8i desensi>i0i.#re s#u down regulation.
Bn continu#re o( pre.ent# princip#0e0e (#ni"est1ri nedorite s#u ne#8tept#te c#re
"#c o>iectu0 de studiu #0 "#r(#coto%ico0o)iei.
3
1.2. Efecte secundare 1.2. Efecte secundare
Mec#nis(u0 de producere # e"ecte0or secund#re este de tip "#r(#codin#(ic.
Intensit#te# 8i "recen'# de #p#ri'ie # #cestor# este 7n )ener#0 dependent1 de do.1= "#ctoru0
"#ori.#nt "iind supr#do.#re#.
C# exemple de efecte secundare #(inti(?
- usc1ciune# )urii= d#tor#t1 reducerii secre'iei s#0i#re= prooc#t1 de
p#r#si(p#to0itice@
- 3ipotonicit#te di)esti1 s#u c3i#r constip#'ie= produs1 de p#r#si(p#to0itice@
- sindro( de >0oc#re e%cesi1 # ;.N.C. cu (#ni"est1ri depresie= produse de
si(p#to0itice etc.@
- so(no0en'1 produs1 de (edic#(ente depri(#nte #0e ;.N.C.= c# de e%e(p0u
3ipnotice@
- sindro( neuro0o)ic e%tr#pir#(id#0 produs de neuro0eptice0e c0#sice prin >0oc#re#
e%cesi1 # tr#ns(isiei neuron#0e dop#(iner)ice /5
!
2@
- sindro( #st(#tic />ron3oconstric'ie2 prooc#t s#u #)r##t de C-
#dreno0itice nese0ectie /propr#no0o02@
- insu"icien'1 c#rdi#c1 produs1 de (edic#(ente cu e"ect inotrop ne)#ti= c# de
e%e(p0u? C
1
#dreno0itice= #nti#rit(ice >0oc#nte #0e c#n#0e0or de sodiu /c3inidin#2
s#u de c#0ciu /er#p#(i02@
- #rit(ii re.u0t#te prin cre8tere# e%cit#>i0it1'ii (ioc#rdu0ui contr#cti0 /e"ect
>#t(otrop po.iti2= c# de e%e(p0u ?C
1
#drener)ice= )0ico.ide c#rdiotonice etc.@
- re#c'i# Der%3ei(er deter(in#t1 de c#ntit1'i0e (#ri de to%ine e0i- >er#te prin
(o#rte# (#si1 # spiroc3ete0or speciei Treponema
palidum 7n ur(# uti0i.1rii unor do.e (#ri de #t#c= din #nti>ioticu0
uti0i.#t@
- c#ren'e it#(inice #p1rute 7n ur(# tr#t#(entu0ui cu #nti>iotice cu spectru 0#r) de
tipu0 Tetraciclinei 8i "1r1 un tr#t#(ent #u%i0i#r cu it#(ine din co(p0e%u0 < s#u
#0te (od#0it1'i=
- )#strite 3iper#cide s#u c3i#r u0cer )#strointestin#0 c# re.u0t#t #0 #d(inistr1rii
(edic#(ente0or #ntiin"0#(#to#re nesteroidiene s#u steroidiene 7n ur(# >0oc1rii
prost#)0#ndine0or E
!
etc.
1.3. Efecte toxice 1.3. Efecte toxice
$
C# 8i 7n c#dru0 e"ecte0or secund#re= #cest tip de re#c'ii #derse cresc propor'ion#0
cu do.# #d(inistr#t1.
Acest tip de re#c'ii sunt "recente 0# perso#ne0e 3iperre#ctie= c#re sunt situ#te 7n
p#rte# stAn)1 # cur>ei G#uss= o>'inut1 7n ur(# 7nre)istr1rii pe un )r#"ic c#rte.i#n #
(odu0ui de #p#ri'ie # e"ectu0ui "#r(#codin#(ic= c# ur(#re # cre8terii trept#te # do.e0or.
5intre "#ctorii "#ori.#n'i pute( su>0ini# pe cei #(inti'i 0# 7nceput= 0# c#re pute(
#d1u)# su>st#n'e0e (edic#(ento#se cu to%icit#te intrinsec1 (#re 8i indice ter#peutic (ic=
c# de e%e(p0u? c#rdiotonice= #(ono)0ico.ide etc.
E"ecte0e to%ice pot "i u8o#re s#u )r#e= pAn1 0# e"ecte (ort#0e= 8i pot "i 7ntA0nite 7n
"unc'ie de (edic#(entu0 #d(inistr#t= 0# nie0u0 di"erite0or siste(e 8i #p#r#te din or)#nis(.
Bn continu#re se # pre.ent#= 7n (od succint= (odu0 7n c#re di"erite c0#se de
(edic#(ente pot pre.ent# e"ecte to%ice 0# di"erite nie0uri #0e or)#nis(u0ui= 8i #nu(e?
a) Medicamente cu efect toxic asupra S.N.C.
L# nie0u0 ;.N.C. pot #p1re# di"erite tu0>ur1ri de ordin neuro0o)ic s#u psi3ic= 7n
"unc'ie de (edic#(entu0 #d(inistr#t s#u de re#ctiit#te# indiidu#01 # p#cientu0ui tr#t#t= 8i
#nu(e?
- e"ecte psi3ice de tip psi3otic= 7n c#.u0 supr#do.1rii corticosteroi.i0or@
- (#ni"est1ri psi3otice= 3#0ucin#'ii= 0# #d(inistr#re# (edic#(ente0or
#ntiin"0#(#to#re nesteroidiene /A.I.N.;2@
- tu0>ur1ri de (e(orie 0# p#cien'ii tr#t#'i cu #ntico0iner)ice.
b) Medicamente cu efect toxic la nivelul aparatului cardiovascular
L# #cest nie0 pot #p1re#?
- 0e.iuni de)ener#tie 7n ur(# #d(inistr1rii #nti>iotice0or citost#tice
/ d#unoru>icin# etc.2@
- #rit(ii re.u0t#te 7n ur(# #d(inistr1rii de c#rdiotonice etc.@
- 0eucopenie 8i tro(>openie dup1 #d(inistr#re# de citost#tice@
- risc de tro(>oe(>o0ie s#u tro(>o.e d#tor#te cre8terii co#)u0#>i0it1'ii sAn)e0ui 7n
ur(# #d(inistr1rii de contr#ceptie peror#0e@
- (et3e()0o>ine(ie 7n ur(# #d(inistr1rii de su>st#n'e cu c#r#cter o%id#nt c#re
tr#ns"or(1 Fe
!E
3e(o)0o>inic 7n Fe
3E
in#cti din punct de edere #0 0e)1rii
o%i)enu0ui= c# de e%e(p0u? p#r#cet#(o0= "en#cetin1 etc.
- #ne(ie (e)#0o>0#stic1 prooc#t1 de #ntiepi0eptice de tip "enitoin etc.
c) eacii adverse de tip toxic la nivelul aparatului respirator
- #0eo0it1= "i>ro.1 pu0(on#r1 7n ur(# #d(inistr1rii de citoto%ice />0eo(icin=
cic0o"os"#(id1 etc.2@
- sindro( #st(#tic etc.
d) eacii adverse la nivelul aparatului di!estiv
&
- di#ree= co0ici= 3iperperist#0tis( prooc#t de (edic#(ente propu0sie= irit#nte #0e
(uco#sei tr#ctu0ui di)esti etc.@
- u0cer )#stric prooc#t de (edic#(ente0e c#re sti(u0e#.1 secre'i# #cid1 s#u
irit#nte= c# de e%e(p0u? #ntiin"0#(#to#re0e nesteroidiene etc.
e) eacii adverse la nivelul principalului or!an epurator "ficatul)
- cito0i.1 produs1 de (edic#(ente cu( sunt? ri"#(picin#= i.oni#.id#=
p#r#cet#(o0u0= #nti(#0#rice= IMAO= citost#tice etc.@
- ste#to.1 3ep#tic1 prooc#t1 de? tetr#cic0ine= corticosteroi.i etc.@
- )r#nu0o(#to.1 prooc#t1 de? c3inidin1= 3idr#0#.in1 etc.@
- c#rcino(-3ep#to-ce0u0#r produs de steroi.i #ndro)eni@
- sindro( de 3ep#tit1 irotic1 produs de? IMAO= 3#0ot#n etc.= c#re este r#r 7ntA0nit=
d#r 0et#0 7n procent de pAn1 0# !4F@
- ciro.1 G produs1 de (etotre%#t #d(inistr#t 7n c#ntit1'i (#ri@
- #deno( 8i tro(>o.1 supr#3ep#tic1 produs1 de contr#ceptie peror#0e@
- co0est#.1 intr#3ep#tic1 8i icter produse de? contr#ceptie peror#0e= estro)eni=
"enoti#.ine= #ntidi#>etice peror#0e= steroi.i #n#>o0i.#n'i etc.@
- 3ep#tit1 su>#cut1 8i #cut1 cu 0e.iuni cronice= produs1 de? p#r#cet#(o0=
ri"#(picin1= i.oni#.id1= su0"on#(ide= IMAO etc.@
f) eacii adverse de tip toxic produse la nivelul rinic#iului
L# nie0u0 rinic3iu0ui pot #p1re# di"erite tipuri de re#c'ii #derse 7n ur(#
#d(inistr1rii unor (edic#(ente= c# de e%e(p0u?
- crist#0uri# 7n ur(# #d(inistr1rii su0"#(ide0or cu e0i(in#re r#pid1@
- ne"rop#tii prooc#te de #(ino)0ico.ide= 7n speci#0= d#r 8i de une0e ce"#0osporine=
c# de e%e(p0u? ce"#0oridin#@
- tu>u0op#tii cronice 7nso'ite de po0iurie prooc#te de? tetr#cic0ine= s1ruri de 0itiu
etc.
!) eacii adverse de tip toxic la nivelul analizatorilor
!
1
) eacii adverse de tip toxic la nivelul oc#iului
L# #cest nie0 s-#u 7nre)istr#t e"ecte #derse de tip to%ic cu( sunt?
- )0#uco(= prin cre8tere# presiunii intr#ocu0#re 7n ur(# #d(inistr1rii de
)0ucocorticoi.i@
- retinit1 pi)(ent#r1 G prooc#t1 de neuro0eptice "enoti#.inice= c# de e%e(p0u?
tiorid#.in#= c0orpro(#.in# etc.
!
2
) eacii adverse de tip toxic la nivelul urec#ii
- tu0>ur#re# #u.u0ui pAn1 0# surdit#te= prooc#te de? #(ino)0ico.ide= )0icopeptide
/#nco(icin#2= diuretice c# "urose(id= #cid et#crinic 7n do.e (#ri@
- tu0>ur#re# ec3i0i>ru0ui 8i erti6 produse de #(ino)0ico.ide etc.
,
#) eacii adverse de tip toxic produse la nivelul sistemului muscular sau esutului
con$unctiv
- distruc'ii (uscu0#re /r#>do(io0i.e2 G produse de? #neste.ice )ener#0e de tip
3#0ot#n= #n#0)e.ice G #ntipiretice /p#r#cet#(o0= s#0ici0#'i2= #ntiin"0#(#to#re
nesteroidiene= #ntiin"0#(#to#re steroidiene= IMAO= cur#ri.#nte= neuro0eptice #nti
5
!
= #nti>iotice /penici0ine2 etc.@
- (iop#tii "1r1 (i#0)ie= produse de corticosteroi.i@
- (i#stenii G produse de po0i(i%ine= C->0oc#nte= #(ino)0ico.ide= >en.odi#.epine
etc.@
- (iop#tii cu (i#0)ii G produse de? "0uoroc3ino0one etc.@
- po0i(io.ite cu (i#0)ie produse de? #ntiu0cero#se #nti D
!
/r#nitidin#2@
- tre(or= produs de neuro0eptice etc.@
- co0#)eno.1 0# indii.i #ceti0#tori 0en'i d#torit1 de"icien'ei de N #ceti0tr#ns"er#.1 7n
ur(# #d(inistr1rii de i.oni#.id1 etc.
i) eacii adverse de tip toxic la nivelul pielii
E"ecte0e to%ice 0# #cest nie0 sunt di"erite c# intensit#te= "iind de 0# ce0e (#i
si(p0e pAn1 0# ce0e (#i )r#e= c# de e%e(p0u? necro0i.# epider(ic1 to%ic1 etc.= une0e
c3i#r cu s"Ar8it 0et#0.
A"ec'iuni0e to%ice 0# nie0u0 pie0ii sunt 7ntA0nite cu "recen'1 (#i (#re 0# perso#ne
7n Arst1 8i 0# "e(ei. Bn continu#re se or pre.ent# cAte# dintre re#c'ii0e #derse de tip
to%ic cu (#ni"est#re 0# nie0u0 pie0ii= 8i #nu(e?
a. pruritul G po#te "i prooc#t de (edic#(ente c#? >#r>iturice= opi#cee=
contr#ceptie peror#0e etc.@
b. erupii cutanate c#re sunt de (#i (u0te "e0uri 8i pot "i prooc#te de? contr#ceptie
or#0e= steroi.i= >ro(uri= ioduri= #ntitu>ercu0o#se c0or#("enico0= #(ino)0ico.ide=
su0"#(ide= penici0in1= #nti3ist#(ini-ce #nti(#0#rice= "enitoin1= C-#dreno0itice=
"eni0>ut#.on1 etc.@
c. Eritem% c#re este de #se(ene# de (#i (u0te "e0uri 8i po#te "i prooc#t de?
>#r>iturice= #cid #ceti0s#0ici0ic= p#r#cet#(o0= tetr#cic0ine= penici0ine= su0"#(ide=
"enitoin1= pir#.o0one= s#0ici0#'i= >ro(uri= ioduri etc.
d. &orfirie G produs1 de? ri"#(picin1= su0"#(ide= )riseo"u0in1= >#r>iturice= "enitoin1=
#ndro)eni= estro)eni= contr#ceptie or#0e etc.@
e. 'ulbur(ri pi!mentare de di"erite cu0ori= produse de? #nti(#0#rice= citost#tice=
contr#ceptie or#0e= tetr#cic0ine= "enitoin1 etc.@
f. )lopecii= produse de? citost#tice /cic0o"os"#(id1 etc.2= contr#ceptie or#0e= retino0=
s1ruri de #ur= #ntitiroidiene= #ntico#)u0#nte etc.@
-
!. Necroliz( epidermic( toxic(= c#re po#te "i produs1 de >#r>iturice= c0or#("enico0=
ri"#(picin1= su0"#(ide= "eni0>ut#.on1 etc.
1.*. eacii adverse de tip muta!en 1.*. eacii adverse de tip muta!en
Re#c'ii0e #derse de #cest tip sunt re.u0t#t #0 #0ter1rii )enotipu0ui c#re= (#i r#pid s#u 7n
ti(p= d#u (odi"ic1ri "enotipice.
Modi"ic1ri0e )enotipu0ui pot re.u0t# 7n ur(# #c'iunii # di"eri'i "#ctori din (ediu0
e%tern= 8i #nu(e?
- "#ctori "i.ici= c# de e%e(p0u? r#di#'ii0e etc.@
- "#ctori c3i(ici? su>st#n'e (ut#)ene.
5intre "#r(#conii incri(in#'i 7n producere# re#c'ii0or #derse de tip
(ut#)en= #(inti(? (edic#(ente citost#tice= "un)icide etc.
1.+. eacii adverse de tip terato!en 1.+. eacii adverse de tip terato!en
;u>st#n'e0e cu e"ect ter#to)en #c'ione#.1 #supr# de.o0t1rii >io0o)ice
intr#uterine # "iin'ei u(#ne= #"ectAnd #nu(ite or)#ne= siste(e= 'esuturi
etc.= 7n "unc'ie de "#.# de de.o0t#re.
;u>st#n'e0e cu e"ect ter#to)en produc (#0"or(#'ii= cuAntu0 teraton deri1 din
0i(># )re#c1 8i 7nse#(n1 monstru.
Fo#rte (u0te (edic#(ente pot produce (#0"or(#'ii 0# "1t= c3i#r d#c1 pentru
or)#nis(u0 (#tern nu sunt to%ice.
P0#cent# este o (e(>r#n1 0ipidic1 cu pori (#ri= c#re este u8or per(e#>i01 pentru
su>st#n'e 0iposo0u>i0e cu GMRH1444= d#r d#torit1 pre.en'ei pori0or 8i # siste(e0or
(e(>r#n#re de tr#nsport #cti spre "1t pot penetr# 8i di"erite su>st#n'e 3idroso0u>i0e
po0#re s#u disoci#te. Riscu0 ter#to)en ce0 (#i (#re este 7n pri(e0e 3 0uni= d#r posi>i0it#te#
producerii re#c'ii0or #derse de tip ter#to)en e%ist1 8i 7n #0te "#.e #0e de.o0t1rii
intr#uterine.
E"ecte0e #derse #supr# procesu0ui reproducerii pot #e# 0oc 7n di"erite
"#.e de de.o0t#re 8i #nu(e?
a) Efecte adverse asupra !ameto!enezei
G#(eto)ene.# #re 0oc 7n or)#ne0e se%u#0e (#scu0ine 8i "e(inine. E%ist1 pu'ine
in"or(#'ii priind re#c'ii #derse produse de (edic#(ente c#re s1 #"ecte.e 7n #cest st#diu.
*
b) Efecte adverse asupra blasto!enezei
Ace#st1 et#p1 #re 0oc 7n pri(e0e ! s1pt1(Ani de 0# "ecund#re. ;u>st#n'e0e to%ice
c#re #"ecte#.1 .i)otu0 s#u >0#sto(eru0 7n #ce#st1 "#.1 #u e"ect 0et#0 #supr# #cestui#=
ur(And e%pu0.#re# #cestui#.
Bn #ce#st1 perio#d1 se di"eren'i#.1 din ce0u0e0e (u)ure0ui e(>rion#r dou1 str#turi=
8i #nu(e? endo>0#stu0 8i ecto>0#stu0= u0terior di"eren'iindu-se 8i (e.o>0#stu0.
c) eacii adverse asupra embrio!enezei
E(>rio)ene.# cuprinde perio#d# de ti(p din de.o0t#re# intr#ute-rin1 #
e(>rionu0ui cuprins1 7ntre s1pt1(Ani0e 3 8i *.
5i"erite0e su>st#n'e to%ice s#u (edic#(ento#se pot #"ect# e(>rio-nu0= #And c#
ur(#re?
- e"ect 0et#0 8i e%pu0.#re# e(>rionu0ui@
- s#u e"ect ter#to)en etc.
E"ectu0 ter#to)en po#te #e# 0oc #supr# di"erite0or or)#ne= 7n "unc'ie de perio#d#
7n c#re #"ect#re# po#te "i (#%i(1.
Bn perio#d# e(>rio)ene.ei= din ce0e trei (e(>r#ne se di"eren'i#.1
di"erite0e or)#ne= 8i #nu(e?
- din ecto>0#st? siste(u0 neros= te)u(ente0e@
- din (e.o>0#st? siste(u0 osos= 'esut con6uncti= (uscu0#r= #p#r#tu0
circu0#tor= ren#0 etc.@
- din endo>0#st? #p#r#tu0 di)esti= #p#r#tu0 respir#tor etc.
A"ect#re# (#%i(1 # di"erite0or or)#ne= siste(e s#u #p#r#te po#te
#e# 0oc 7ntr-un #nu(it inter#0 de ti(p= c# de e%e(p0u?
- ;.N.C. G 7ntre .i0e0e 1& G !&@
- oc3ii G 7ntre .i0e0e !$ G $!@
- urec3i0e G 7ntre .i0e0e !4 G 3,@
- )on#de0e G 7ntre .i0e0e 3- G $& etc.
Bn continu#re se or pre.ent# cAte# e%e(p0e de su>st#n'e contr#indic#te pentru #
"i #d(inistr#te "e(eii 7ns1rcin#te d#torit1 riscu0ui ter#to)en= 8i #nu(e?
- #ntineop0#.ice /(etotre%#t2 c#re pot produce (#0"or(#'ii cr#nio-"#ci#0e@
- #ndro)eni 8i pro)esteroni pot duce 0# (#scu0ini.#re# "1tu0ui "e(inin@
- estro)eni c#re pot duce 0# "e(ini.#re# "1tu0ui (#scu0in@
- )0ucocorticoi.i c#re pot d#? (#0"or(#'ii c#rdio#scu0#re= cr#nio-"#ci#0e= #0e
(e(>re0or etc.@
- (edic#(ente0e #ntiepi0eptice /"enitoin= #cid #0proic2 pot produce (#0"or(#'ii?
c#rdio-#scu0#re= cr#nio-"#ci#0e etc.@
+
- (edic#(ente0e #ntidepresie tricic0ice pot d# (#0"or(#'ii #0e (e(>re0or@
- 0itiu0 G (#0"or(#'ii c#rdi#ce@
- tr#nc3i0i.#nte0e >en.odi#.epinice@
- #ntico#)u0#nte cu(#rinice@
- deri#'i de it#(in# A /i.otretinoin#2
d ) Efecte adverse produse ,n perioada feto!enezei
Feto)ene.# este perio#d# de ti(p 7ncepAnd cu s1pt1(An# # IX-# 8i pAn1 0#
s"Ar8itu0 ie'ii intr#uterine. Bn #ce#st1 perio#d1 sunt posi>i0e ur-(1to#re0e tipuri de e"ecte
#derse?
- de"ecte "i.io0o)ice@
- tu0>ur1ri de 3isto)ene.1 #0e siste(u0ui neros@
- (#0"or(#'ii (inore #supr# #p#r#tu0ui )enit#0 e%tern@
- e"ect 0et#0 etc.
Bn continu#re se or pre.ent# cAte# )rupe de (edic#(ente contr#indic#te 0#
)r#ide /7n ti(pu0 s#rcinii2= d#torit1 poten'i#0u0ui "etoto%ic= 8i #nu(e?
- neuro0eptice "enoti#.inice - pot produce depri(#re respir#torie= sindro(
e%tr#pir#(id#0= sed#re etc.@
- #neste.ice 0oc#0e /0idoc#in#2 - produc depri(#re respir#torie= e"ect cronotrop
ne)#ti />r#dic#rdie2= conu0sii etc.@
- s#0ici0#'i - pot produce 3e(or#)ii@
- #ntitiroidiene /ioduri= c#r>i(#.o02 - pot produce 3ipotiroidis(@
- #ntidi#>etice peror#0e /to0>ut#(id#2 - pot produce 3ipo)0ice(ie@
- #ntico#)u0#nte cu(#rinice - risc de 3e(or#)ii@
- C-#dreno0itice - pot produce depri(#re respir#torie= >r#dic#rdie= 3ipo)0ice(ie etc.@
- c0or#("enico0 - sindro( cenu8iu@
- tetr#cic0ine - denti'ie #nor(#01= co0or#t1 7n )#0>en@
- #(ino)0ico.ide - pot produce ototo%icit#te (#ni"est#t1 prin surdi-t#te con)enit#01=
tu0>ur1ri esti>u0#re etc.@
- #nti(#0#rice@
- su0"#(ide - pot produce icter nuc0e#r= #ne(ii0e 3e(o0itice d#tor#te de"icitu0ui de
)0uco.o , "os"#tde3idro)en#.1 etc.
e ) Efecte adverse produse ,n perioada prenatal( -i obstetrical(
Medic#(ente0e c#re pot produce tu0>ur1ri 7n #ce#st1 perio#d1 sunt su>st#n'e0e
(edic#(ento#se cu e"ect ocitocic 8i toco0itic.
;u"erin'e0e produse 7n #ce#st1 perio#d1 pot #"ect# "etusu0 i(edi#t s#u t#rdi.
5intre (edic#(ente0e sti(u0#nte #0e (oti0it1'ii uterine c#re pot produce #ccidente
o>stetric#0e= c#? #ort= #s"i%ie= n#8tere pre(#tur1= #(inti(? ocitocin#= er)o(etrin#=
14
prost#)0#ndine= C
1
-#dreno0itice nese0ectie /propr#no0o02= pur)#tie de cont#ct
/#ntr#c3inon# etc.2= p#r#si(p#to(i(etice /neosti)(in#= pi0oc#rpin# etc.2 etc.
5intre (edic#(ente0e in3i>ito#re #0e (oti0it1'ii uterine= c#re pot produce
#ccidente o>stetric#0e= c# ini'iere# n#8terii= oprire# tr##0iu0ui= #(inti(? toco0itice
/i.o%uprin#2= C
!
-#dreno(i(etice /s#0>ut#(o0 etc.2= #ntiin"0#(#to#re nesteroidiene
>0oc#nte #0e sinte.ei prost#)0#ndinei PGT
!
/indo(et#cin= "eni0>ut#.on1 etc.2= #neste.ice
)ener#0e= depri(#nte #0e ;.N.C. /su0"#t de (#)ne.iu2= #n#0)e.ice opioide= c# de e%e(p0u?
(or"in# etc.
f ) Medicamente care pot produce efecte adverse asupra su!arilor
;u)#ru0 po#te "i #"ect#t de (edic#(ente0e uti0i.#te de (#(1 8i c#re sunt e0i(in#te
prin secre'i# 0#ct#t1.
Pentru # #6un)e 7n 0#pte0e (#tern su>st#n'e0e (edic#(ento#se tre->uie s1
tr#erse.e >#rier# sAn)eI0#pte= c#re este o (e(>r#n1 se(iper-(e#>i01 0ipidic1 cu pori
(#ri= per(i'And #st"e0 p1trundere# (u0tor su>-st#n'e nedisoci#te #tAt 0ipo- cAt 8i
3idroso0u>i0e.
5#torit1 pD-u0ui 0#pte0ui (#tern de J -= 7n 0#pte se pot concentr# su>st#n'e >#.ice.
Re#c'ii0e #derse (#ni"est#te 0# su)#r pot "i di"erite c# (ec#nis(= 8i #nu(e?
- c# e"ect secund#r #0 #c'iunii "#r(#codin#(ice princip#0e@
- (ec#nis( to%ic@
- (ec#nis( i(uno#0er)ic etc.
E%ist1 (edic#(ente c#re= 7n ti(pu0 #d(inistr1rii 0or tre>uie 7ntrerupt1 #01pt#re#=
8i #nu(e?
- #nti>iotice s#u c3i(ioter#pice c#? tetr#cic0in#= c0or#("enico0u0= #(ino)0ico.ide=
(etronid#.o0 /tu0>ur1ri neuro0o)ice= depri(#re (edu0#r12@
- #ntitiroidiene G pot produce 3ipotiroidis(@
- #ntiin"0#(#to#re nesteroidiene /indo(et#cin= #cid #ceti0s#0ici0ic2= c#re pot
produce? #cido.1= 3e(or#)ii= tu0>ur1ri respir#torii= conu0sii etc.@
- #n#0)e.ice-#ntipiretice deri#'i de #ni0in1 /p#r#cet#(o02= c#re pot produce
(et3e()0o>ine(ie@
- #ntico#)u0#nte or#0e G pot prooc# sAn)er1ri@
- )0ucocorticoi.i G pot produce insu"icien'1 corticosupr#ren#01 8i 7ncetinire#
cre8terii@
- opi#cee pot produce depri(#re respir#torie= dependen'1 etc.@
- pur)#tie0e #ntr#c3inonice pot produce di#ree@
- sed#tie0e pot d# so(no0en'1@
- #nti3ipertensie0e neurosi(p#to0itice /reserpin#2 pot d# dispnee= sti(u0#re#
secre'ii0or >ron8ice etc.@
11
Bn continu#re se or pre.ent# cAte# )rupe de (edic#(ente c#re pot supri(# 0#ct#'i#=
8i #nu(e?
- #0c#0oi.ii din er)ot />ro(ocriptin#2@
- contr#ceptie or#0e@
- estro)eni@
- diuretice /"urose(id2 d#torit1 3ipo3idre(iei@
- p#r#si(p#to0itice produc 3iposecre'ie e%ocrin1 etc.
1... Efecte adverse de tip canceri!en 1... Efecte adverse de tip canceri!en
E%ist1 su>st#n'e c#re pot induce pro0i"er#re# 8i de.o0t#re# ce0u-0e0or c#ncero#se.
Ti(pu0 de 0#ten'1 pentru #p#ri'i# tu(ori0or po#te "i uneori de !4 G 34 de #ni.
5intre su>st#n'e0e cu poten'i#0 c#nceri)en #(inti(? #(ine #ro(#tice= nitro.#(ine=
re.u0t#te 7n ur(# tr#ns"or(1rii #(ino"en#-.onei 7n pD-u0 #cidu0ui )#stric=
#.oco0or#n'i= #"0#to%ine produse de (uce)#iuri= su>st#n'e #0c3i0#nte /citost#tice2=
3idroc#r>uri po0icic0ice con'inute 7n "u(u0 de 'i)#r1 s#u 7n )udronu0 de c1r>une etc.
1./. eacii adverse de tip idiosincrazic "intoleran( 1./. eacii adverse de tip idiosincrazic "intoleran(
medicamentoas() medicamentoas()
Into0er#n'# este un )en de re#c'ie #ders1 c#r#cteri.#t1 printr-un r1spuns
"#r(#codin#(ic #nor(#0 #tAt din punct de edere c#0it#ti= cAt 8i c#ntit#ti= #And 0#
>#.1 un de"icit en.i(#tic= c#re po#te c#r#cteri.# un indiid s#u c3i#r co0ectiit1'i.
Acest tip de re#c'ii #derse pot #e# dou1 tipuri de etio0o)ii?
- con)enit#01 /7nn1scut12
- s#u do>Andit1 etc.
1./.1. 0ntolerana con!enital(
Acest tip de into0er#n'1 #p#re 0# pri(# do.1 #d(inistr#t1 dintr-un (edic#(ent s#u
dup1 pri(e0e #d(inistr1ri. C#u.# deter(in#nt1 este o en.i(op#tie /de"icit en.i(#tic2 c#re
se d#tore#.1 unei #no(#0ii )enetice /)en1 #>sent12. Ace#st1 de"icien'1 en.i(#tic1 po#te "i
0#tent1 (u0t ti(p= dec0#n8#re# into0er#n'ei (#ni"estAndu-se 7n (o(entu0 7n c#re se
#d(inistre#.1 un (edic#(ent c#re este >iotr#ns"or(#t de c1tre en.i(# de"icit#r1 s#u
#>sent1.
Bn u0ti(ii #ni # #p1rut o nou1 8tiin'1 nu(it1 "#r(#co)enetic#= 8tiin'1 c#re studi#.1
#ceste #specte cu deter(in#re )enetic1.
1!
CAnd e%ist1 un teren pentru (#ni"est1ri idiosincr#.ice= pot "i eiden'i#te dou1 tipuri
de (#ni"est1ri= 8i #nu(e?
- (#ni"est1ri "#r(#cocinetice@
- (#ni"est1ri "#r(#codin#(ice etc.
1./.1.1. Manifest(ri idiosincrazice de tip farmacocinetic
M#ni"est1ri0e "#r(#cocinetice i.e#.1 deiere# de 0# tr#seu0 nor(#0
pe c#re (edic#(entu0 70 #re 7n or)#nis(= cu #"ect#re# unei# s#u (#i (u0tor et#pe
"#r(#cocinetice. Consecin'e0e #cestor (#ni"est1ri pot "i d#tor#te tipu0ui de distri>u'ie
respecti (et#>o0i.#re /r#pid1 s#u 0ent12 8i (odu0ui de e0i(in#re. Acest tip de (#ni"est1ri
sunt de dou1 "e0uri 8i #nu(e?
- "#r(#coter#pice= c#re pot conduce 0# ine"icien'1 ter#peutic1= cAnd (edic#(entu0
se #d(inistre#.1 0# su>iec'i (et#>o0i.#tori r#pi.i@
- "#r(#coto%ico0o)ice= cAnd (edic#(entu0 se #d(inistre#.1 0# su>iec'i
(et#>o0i.#tori 0en'i= cAnd cre8tere# concentr#'iei p0#s(#tice po#te #tin)e nie0uri
superio#re do(eniu0ui ter#peutic etc.
Bn continu#re or "i pre.ent#te princip#0e0e tipuri de en.i(op#tii respons#>i0e de
re#c'ii #derse de tip idiosincr#.ic cu (#ni"est1ri "#r(#cocinetice= 8i #nu(e?
a. Deficit de pseudocolinesteraz
Ace#st1 en.i(1 este >iosinteti.#t1 7n "ic#t 8i este 7ntA0nit1 7n p0#s(1. En.i(# #re
ro0u0 de # >iotr#ns"or(# (edic#(ente cu( sunt su%#(etoniu0 etc. 5#torit1 structurii
#nor(#0e # en.i(ei= c#p#cit#te# de (et#>o0i.#re # #cestei su>st#n'e este (ic1= conducAnd
0# cre8tere# do.ei p0#s(#tice de su%#(etoniu pAn1 7n do(eniu0 to%ic. Acest de"icit
en.i(#tic este 7ntA0nit cu "recen'1 crescut1 7n '1ri din Asi# Mic1= de e%e(p0u? Ir#n= Ir#K
etc.
b. Tulburri de acetilare
N-#ceti0tr#ns"er#.# 3ep#tic1 pre.int1 (#i (u0te "or(e po0i(or"e c#re di"er1 7n
priin'# ite.ei cu c#re se #ceti0e#.1 di"erite0e (edic#(ente 7n procesu0
>iotr#ns"or(1ri0or. 5in #cest punct de edere= perso#ne0e c#re pre.int1 #no(#0ii )enetice
de #cest tip se pot 7nc#dr# 7n dou1 )rupe= 8i #nu(e?
- perso#ne 0# c#re #ceti0#re# se "#ce r#pid@
- perso#ne 0# c#re #ceti0#re# se "#ce 0ent etc.
5istri>u'i# ce0or dou1 c#te)orii este dependent1 8i de #p#rtenen'# r#si#01=
procentu0 pri(ei c#te)orii "iind (#i ridic#t 0# r#s# )#0>en1= #6un)And pAn1 0# +4 F 7n
L#poni# s#u +& G 144 F 0# esc3i(o8ii c#n#dieni.
Prin #ceti0#re sunt (et#>o0i.#te di"erite (edic#(ente= c# de e%e(p0u? i.oni#.id#=
3idr#0#.in#= proc#in#(id#= "en#0#.in#= d#pson#= su0"#.o0in# etc.
13
Ti(pu0 de 7n6u(1t1'ire #0 i.oni#.idei= de e%e(p0u= este de ! G 3 ori (#i (#re 0#
#ceti0#re 0ent1= conducAnd 0# concentr#'ii p0#s(#tice de pAn1 0# 14 ori (#i (#ri 0# #ce#st1
c#te)orie de perso#ne. 5#torit1 #ceti01rii 0ente= procentu0 de i.oni#.id1 ne(et#>o0i.#t1
este de #pro%i(#ti 14 ori (#i (#re 0# #ceti0#torii 0en'i decAt 0# cei r#pi.i.
Ace#st1 #no(#0ie de >iotr#ns"or(#re #re ur(1to#re0e consecin'e "#r(#co0o)ice?
- do.e0e e"iciente (edii sunt ine"ic#ce 0# perso#ne din c#te)ori# #ceti0#tori0or r#pi.i@
- 0# #ceti0#torii 0en'i= i.oni#.id# 8i #0te (edic#(ente din #ce#st1 c#te)orie produc
re#c'ii #derse puternice.
Bn continu#re se or pre.ent# cAte# din re#c'ii0e #derse pre.ente 0# indii.ii
#ceti0#tori 0en'i= dup1 #d(inistr#re# unor (edic#(ente= c# de e%e(p0u?
- 0# i.oni#.id1 7n ur(# #socierii cu ri"#(picin# po#te s1 #p#r1 3ep#tit# i#tro)en1=
neurop#tii peri"erice= sindro( de 0upus erite(#tos etc.@
- 0# "ene0#.in1= re#c'ii 3ep#tice 8i 0# nie0u0 ;.N.C.@
c. Tulburri de oxidare
Mi #cest )en de tu0>ur1ri idiosincr#.ice sunt re.u0t#t #0 po0i(or"is(u0ui unor siste(e
en.i(#tice dependente de citocro(u0 P
$&4
.
Ace#st1 en.i(op#tie tip cu o%id#re 0ent1 este 7ntA0nit1 0# europeni 7n procent de + G
14 F.
5intre tu0>ur1ri0e en.i(#tice cu repercusiuni #supr# o%id1rii #(inti( ce0e
deter(in#te de?
c.
1.
Existena de forme polimorfe ale !idroxilazelor
5#torit1 e%isten'ei di"erite0or "or(e po0i(or"e #0e #cestei en.i(e= perso#ne0e 0# c#re
e%ist1 #ce#st1 #no(#0ie pot "i 7(p1r'ite 7n trei )rupe din punct de edere #0 ite.ei
procese0or o%id#tie deter(in#te pe #nu(ite su>st#n'e (edic#(ento#se= c# de e%e(p0u
de>risoNuin= 8i #nu(e?
- (et#>o0i.#tori 0en'i@
- (et#>o0i.#tori inter(edi#ri@
- (et#>o0i.#tori r#pi.i etc.
En.i(# i(p0ic#t1 7n (et#>o0is(u0 su>st#n'e0or #(intite este $-3idro%i0#.#.
E%ist1 (edic#(ente #se(1n1to#re de>risoNuinu0ui din punct de edere #0
po0i(or"is(u0ui en.i(e0or de c#re sunt (et#>o0i.#te= c# de
e%e(p0u?
- C-#dreno0itice /(etopro0o0= ti(o0o02@
- #ntidepresie tricic0ice /#(itripti0in# etc.2@
- sp#rtein# etc.
E%ist1 (edic#(ente cu po0i(or"is( di"erit de de>risoNuin 7n ce prie8te en.i(e0e
o%id#tie i(p0ic#te 7n (et#>o0i.#re= c# de e%e(p0u? "enitoin#= O#r"#rin#= to0>ut#(id# etc.
1$
c.
"
. #olimorfismul alc!ilazelor
E%ist1 su>iec'i 0# c#re (et#>o0i.#re# unor (edic#(ente c# p#r#cet#(o0u0 deine
#nor(#01= conducAnd 0# o cre8tere e%#)er#t1 # (et3e(o)0o>inei.
1./.1.2. Manifest(ri idiosincrazice de tip farmacodinamic
Re#c'ii0e #derse de #cest tip #u (#ni"est1ri "#r(#coto%ico0o)ice c#re pot "i de dou1
"e0uri?
- re#c'ii #derse di"erite de ce0e speci"ice #0e (edic#(entu0ui respecti@
- re#c'ii #derse di"erite din punct de edere c#ntit#ti= (#ni"est#te prin "recen'1 8i
intensit#te crescut1 c3i#r 0# #d(inistr#re# unei do.e (ici dintr-un #nu(e
(edic#(ent etc.
Bn continu#re se or pre.ent# princip#0e0e en.i(op#tii c#re i(p0ic1 (#ni"est1ri de
ordin "#r(#codin#(ic.
a) $eacii ad%erse de tip idiosincrazic rezultate prin deficit de glucozo-&-fosfat
de!idrogenaz '(-&-#D)
;unt cunoscute #pro%i(#ti *4 de #ri#'ii po0i(or"e #0e #cestei en.i(e.
Inciden'# indii.i0or #And #ce#st1 en.i(op#tie este (#i #0es 7n .on# 7n c#re este
r1spAndit1 (#0#ri#= #p#ri'i# #cestei de"icien'e po#te "i o (od#0it#te de #p1r#re 7(potri#
p#r#.itu0ui. Bn de"icien'1 en.i(#tic1= c#ntit#te# de )0ut#tion redus este (ic1= ro0u0 en.i(ei
este (en'inere# concentr#'iei nor(#0e 7n 3e(#tii. Bn de"icien'# de )0ut#tion redus este
de"#ori.#t1 de.o0t#re# proto.o#ru0ui= d#r totod#t1 se reduce 8i re.isten'# eritrocitu0ui 0#
su>st#n'e0e o%id#nte c#re or produce 3e(o0i.# #ccentu#t1= cu( #r "i?
- #nti(#0#rice= su0"#(ide #nti>#cteriene= to0>ut#(id= nitro"ur#ntoin etc.
Acest de"icit en.i(#tic este 7ntA0nit 0# #pro%i(#ti 3 F din
popu0#'i# )0o>u0ui.
De(o0i.# re.u0t#t1 7n de"icit en.i(#tic po#te "i redus1 s#u de propor'ii= re.u0tAnd
#ne(ie )r#1= uneori c3i#r cu consecin'e 0et#0e.
M#ni"est#ri0e c0inice # de"icien'e0or #r "i ur(1to#re0e?
- #ne(ie #cut1 3e(o0itic1@
- #ne(ie cronic1@
- icter "i.io0o)ic prooc#t 0# nou-n1scut etc.
b) $eacii ad%erse de tip idiosincrazic manifestate prin deficit de uridin-difosfat-
glucuroniltransferaz '*D#-glucuroniltransferaza)
5e"icien'# #cestei en.i(e #"ecte#.1 #tAt >iotr#ns"or(#re# prin )0ucuronocon6u)#re
# unor co(ponente endo)ene c# >i0iru>in#= #And consecin'e cre8tere# concentr#'iei
p0#s(#tice 8i #poi icter= cAt 8i # unor su>st#n'e (edic#(ento#se. G0ucuronocon6u)#re#
1&
este o >iotr#ns"or(#re # st#diu0ui II de (et#>o0i.#re # (et#>o0i'i0or re.u0t#'i 7n ur(#
(et#>o0i.1-ri0or din st#diu0 I.
;u>st#n'e0e (edic#(ento#se c#re su"er1 )0ucuronocon6u)#re sunt? su0"#(ide=
>#r>iturice= (or"ino(i(etice= #n#0)e.ice-#ntipiretiece= 3or(oni steroi.i etc.
c) +catalazia
Eritrocite0e con'in c#t#0#.o-en.i(e c#re c#t#0i.e#.1 re#c'ii de tr#ns"or(#re # #pei
o%i)en#te /D
!
O
!
2 7n #p1.
5in punct de edere #0 procentu0ui 7n c#re se )1se8te en.i(# 0# di"erite perso#ne=
e%ist1?
- indii.i #c#t#0#.ici@
- indii.i 3ipoc#t#0#.ici@
- indii.i nor(#0i etc.
L# perso#ne0e c#re (#ni"est1 #cest de"icit en.i(#tic= 7n ur(# cont#ctu0ui dintre
#p# o%i)en#t1 8i sAn)e nu re.u0t1 e"erescen'1. R1spAndire# #cestei #"ec'iuni este (ic1=
"iind 7ntA0nit1 7n une0e '1ri c#? E0e'i#= L#poni# etc.
d) $eacii ad%erse de tip idiosincrazic produse prin deficit de ,+D--
met!emoglobin-reductaz
Bn 0ips# #cestei en.i(e nu #re 0oc reducere# (et3e(o)0o>inei 0# 3e(o)0o>in1=
consecin'e0e "iind cre8tere# (et3e(o)0o>iei 0# #0ori cu !4 G &4 de ori (#i (u0t decAt 0#
indii.ii nor(#0i. Frecen'# en.i(op#tiei este (ic1= 8i #nu(e 0# #pro%i(#ti 1 F din
perso#ne.
;u>st#n'e0e (edic#(ento#se puternic o%id#nte sunt (et3e(o)0o>ini.#te= i#r prin
de"icit en.i(#tic= c3i#r 0# do.e u.u#0e ter#peutice pot re.u0t# (et3e(o)0o>ine(ii seere=
c#re #u c# re.u0t#t sc1dere# c#p#cit1'ii de o%i)en#re # 'esuturi0or= deo#rece
(et3e(o)0o>in# nu tr#nsport1 o%i)enu0= i#r c# si(pto(e c#r#cteristice sunt? dispnee#=
ci#no.# etc.
5intre (et3e(o)0o>ini.#nte #(inti(? deri#'i de #ni0in1 din c#te)ori# #n#0)e.ice-
#ntipiretice /p#r#cet#(o0= "en#cetin12= su0"#(ide= #nti(#0#rice etc.
e) $eacii ad%erse de tip idiosincrazic produse prin deficit de inducie de .-+/+
sintetaza !epatic
E%cesu0 en.i(ei este deter(in#t )enetic 8i este respons#>i0 de
#p#ri'i# por"irii0or 3ep#tice #cute.
Aceste su"erin'e sunt re.u0t#t #0 dere)01rii (et#>o0is(u0ui por"irinic= i#r c#
(#ni"est1ri pot "i /c# re.u0t#t #0 #cu(u01rii #cestor# 7n "ic#t2? di"erite tu0>ur1ri )#stro-
intestin#0e durero#se s#u di"erite tu0>ur1ri neuro0o)ice /nerite peri"erice2= tu0>ur1ri
psi3ice= "otoder(#to.e cut#n#te etc.
1,
;u>st#n'e0e (edic#(ento#se c#re produc induc'i# #cestei en.i(e pot d# 0# do.e
u.u#0e ter#peutice cri.e de por"irie. E%e(p0e de #st"e0 de (edic#(ente inducto#re
en.i(#tice sunt?
- #0coo0 eti0ic@
- 3ipnotice >#r>iturice= )0uteti(id# etc.@
- su0"#(ide= #ntidi#>etice /to0>ut#(id2@
- >en.odi#.epine /c0ordi#.epo%id2@
- #nticonu0si#nte /"enitoin#2@
- #n#0)e.ice-#ntipiretice /#(ino"en#.on#2@
- contr#ceptie or#0e@
- #nti(icotice /)riseo"u0in#2 etc.
f) -emoglobinopatii
De(o)0o>in# nor(#01 este "or(#t1 din $ 0#n'uri peptidice?
- ! 0#n'uri P
- ! 0#n'uri C
E%ist1 3e(o)0o>inop#tii 7n c#re #p#r 3e(o)0o>ine #nor(#0e cu to#te i(p0ic#'ii0e
"i.io0o)ice 8i "i.iop#to0o)ice c#re deri1 din #ce#st1 st#re p#to0o)ic1= c# de e%e(p0u?
- 3e(o)0o>in# QRric3 G #re 7n 0#n'uri0e C o (o0ecu01 de 3istidin1 7n0ocuit1 cu o
(o0ecu01 de #r)inin1. Ad(inistr#re# de (edic#(en-te din c0#s# su0"#(ide0or 0#
#ceste perso#ne po#te conduce 0# #nu(ite su"erin'e c#? #ne(ie prin 3e(o0i.1=
3iper>i0iru>ine(ie cu icter.
- 3e(o)0o>in# D c#re #re $ 0#n'uri >et#. Perso#ne0e c#re #u #cest tip de
3e(o)0o>in1 sunt sensi>i0e 0# su>st#n'e o%id#nte= (#ni"est1ri0e "iind #pro%i(#ti
identice cu ce0e 7ntA0nite 0# #d(inistr#re# su0"#(ide0or 0# perso#ne cu
3e(o)0o>in1 QRric3.
!) $eacii ad%erse de tip idiosincrazic ca rezultat al deficienei genetice de
fenilalanil-0-!idroxilaz.
5e"icitu0 en.i(ei (en'ion#te conduce 0# "eni0cetonurie 7n ur(# (et#>o0i.1rii
"eni0#0#ninei 0# #cid "eni0piruic 8i "eni0#cetic= nu 7n tiro.in1. 5#torit1 #cestei de"icien'e de
(et#>o0i.#re= 0# >o0n#ii c#re #u #ce#st1 su"erin'1 tiro.in# deine #(ino#cid esen'i#0= "iind
neces#r1 introducere# #cestui# 7n or)#nis( prin #port e%o)en. L# rAndu0 s1u= tiro.in# este
tr#ns"or(#t1 de c1tre en.i(e0e corespun.1to#re 7n c#teco0#(ine 7n dop# 8i #poi 7n
dop#(in1= #dren#0in1 etc. Ro0u0 c#teco0#(ine0or 7n or)#nis( este "o#rte i(port#nt=
deo#rece sunt neurotr#ns(i'1tori etc. Pro>0e(# re.u0t#t1 7n ur(# #cestei de"icien'e este c1
#tAt "eni0#0#nin#= cAt 8i (et#>o0i'ii re.u0t#'i 7n ur(# o%id1rii sunt to%ici pentru ;.N.C.
1-
5e #cee#= cAnd e%ist1 #cest de"icit= pot re.u0t# de"icien'e (int#0e 0# copii=
(#ni"est#te prin ret#rd#re. Pro>0e(# po#te "i re.o0#t1 prin re)i( dietetic 0ipsit de
"eni0#0#nin1.
L# >o0n#ii cu #cest de"icit en.i(#tic #re 0oc o sensi>i0i.#re # receptori0or
#drener)ici /prin e%tern#0i.#re2= cee# ce d1 e"ecte 3ipertensie )r#e 0# #d(inistr#re# unor
do.e ter#peutice de c#teco0#(ine. Feno(enu0 este d#tor#t de"icien'ei unei c#ntit1'i
#dec#te de (edi#tori.
#) $ezistena la medicament pe fondul unei condiionri genetice
Re.isten'# 0# #c'iune# di"erite0or (edic#(ente este o re#c'ie #ders1 pe "ond
)enetic= c#re se (#ni"est1 printr-un r1spuns "#r(#codin#(ic nu0 s#u (u0t di(inu#t 0#
#d(inistr#re# (edic#(ente0or 7n do.e u.u#0e ter#peutice.
C# e%e(p0e de #"ec'iuni c#re se 7nc#dre#.1 7n #ce#st1 )rup1 #(inti(?
- r#3itis(u0 re.istent 0# it#(in# 5= >o#01 c#re presupune #d(inistr#re# de do.e
superio#re ce0or ter#peutice u.u#0e@
- re.isten'# 0# #ntico#)u0#nte0e cu(#rinice= c#re de #se(ene# se c#r#cteri.e#.1 prin
#>sen'# e"ectu0ui #ntico#)u0#nt 0# #d(inistr#re# do.e0or u.u#0e ter#peutice etc.
i) (laucomul cortizonic
L# unii >o0n#i= prin #d(inistr#re# de corticosteroi.i= 7n s#cu0 con6uncti#0 po#te
re.u0t# o cre8tere intens1 # presiunii intr#ocu0#re= conducAnd c3i#r 0# #p#ri'i#
)0#uco(u0ui. Mec#nis(u0 de producere # >o0ii nu este >ine cunoscut.
$) -ipertermia malign
Ace#st1 su"erin'1 po#te #p1re# 7n cursu0 #neste.iei )ener#0e= #And c# (#ni"est1ri?
3iperpire%ie= ri)idit#te (uscu0#r1 etc.= #And drept c#u.1 (odi"ic#re# c#p#cit1'ii de 0e)#re
# ioni0or de c#0ciu de c1tre (uscu0#tur# stri#t1.
1./.2. 0ntolerana dob1ndit(
1./.2.1. 2eneralit(i
Re#c'ii0e #derse c#re sunt 7nc#dr#te 7n #ce#st1 )rup1 sunt nu(ite 7n e%pri(#re#
curent1 #0er)ii 8i #p#r c# re.u0t#t #0 unei 3ipersensi>i0it1'i produse de #nu(ite su>st#n'e
(edic#(ento#se= #And un c#r#cter te(por#r s#u per(#nent.
Producere# re#c'ii0or #0er)ice presupune un (ec#nis( i(uno0o)ic c#re const1 7n?
- cont#ctu0 or)#nis(u0ui cu un (edic#(ent #0er)i.#nt= 7n ur(# c1rui# re.u0t1
#nticorpi /i(uno)0o>u0ine2= s#u produce o sensi>i0i.#re # 0i("ocite0or@
1*
- 8i un cont#ct u0terior #0 or)#nis(u0ui cu #cee#8i su>st#n'1= cont#ct c#re po#te duce
0# dec0#n8#re# re#c'iei #0er)ice.
;u>st#n'e0e c#re deter(in1 "or(#re# #nticorpi0or sunt?
- #nti)eni co(p0e'i? (#cro(o0ecu0e proteice= po0i.#3#ride etc.@
- 8i #nti)eni inco(p0e'i /3#ptene2= c#re pot "or(# #nti)eni co(p0e'i dup1 0e)#re# de
proteine etc.
Bn continu#re se or pre.ent# cAte# su>st#n'e din # II-# c#te)orie /3#ptene2 c#re
sunt i(p0ic#te 7n )ener#re# de re#c'ii de tip #0er)ic= 8i #nu(e? penici0ine /#(pici0in#2=
ce"#0osporine= su0"#(ide= proc#in#= #cid #ceti0s#0ici0ic= >#r>iturice= de%tr#ni etc.
E%ist1 situ#'ii 7n c#re se po#te produce 3ipersensi>i0i.#re# 7ncruci8#t1 /co-
sensi>i0i.#re2= c# de e%e(p0u p#r#cet#(o0u0= c#re po#te induce 3ipersensi>i0i.#re "#'1 de
su0"#(ide #nti>#cteriene= proc#in1 etc.
Ap#ri'i# re#c'ii0or #0er)ice po#te depinde de #nu(i'i "#ctori c#re "#ori.e#.1 #cest
tip de re#c'ii #derse= c# de e%e(p0u?
- "#ctori dependen'i de (edic#(ent /poten'i#0 #0er)ic intrinsec #0 (edic#(entu0ui 8i
"recen'# cont#ctu0ui cu or)#nis(u0@
- "#ctori dependen'i de or)#nis(= 7n c#re pute( #(inti? re#ctiit#te# indiidu#01
/(#i intens1 0# "e(ei2= c#0e# de #d(inistr#re cu inciden'1 crescut1 0# prep#r#te0e
#d(inistr#te topic pe pie0e 8i (uco#se etc.
Re#c'ii0e #0er)ice #u cAte# p#rticu0#rit1'i distincte 8i #nu(e?
- #>sen'# re0#'iei )r#d#te do.1Ie"ect /do.e "o#rte (ici pot produce #0er)ii )r#e2@
- or)#nis(u0 sensi>i0i.#t pre.int1 un con'inut ridic#t de #nticorpi= c# de e%e(p0u?
i(uno)0o>u0in# E /I)E2= #nticorpi ce pot "i pu8i 7n eiden'1 prin teste cut#n#te s#u
re#c'ii sero0o)ice etc.
1./.2.2. 'ipuri de reacii aler!ice 345
Re#c'ii0e #0er)ice se 7(p#rt= 7n "unc'ie de (ec#nis(u0 i(uno0o)ic i(p0ic#t= 7n p#tru
c#te)orii= 8i #nu(e?
a) $eacii alergice de tip 1 'tip anafilactic)
Aceste re#c'ii "#c p#rte din c#te)ori# #0er)ii0or de tip i(edi#t 8i #u 0# >#.1
cup0#re# #nti)enu0ui cu I
)
E= de pe supr#"#'# )r#nu0ocite0or >#.o"i0e= (#stocite0or=
dec0#n8And e0i>er#re# unor (edi#tori #i in"0#(#'iei= c# de e%e(p0u? 3ist#(in#=
prost#)0#ndin#= serotonin# etc. Ace8ti (edi#tori e0i>er#'i or #c'ion# pe receptorii speci"ici
situ#'i 0# nie0u0 di"erite0or or)#ne= re.u0tAnd?
- #0er)ii (inore c#? rinite #0er)ice= prurit= urtic#rie= ede( SuinNue etc.
- s#u #0er)ii (#6ore c# #st(u0 >ron8ic s#u 8ocu0 #n#"i0#ctic etc.
Medic#(ente0e c#re pot deter(in# re#c'ii #0er)ice de tip I sunt? penici0ine0e=
de%tro.#= #neste.ice 0oc#0e= #cid #ceti0s#0ici0ic etc.
1+
b) $eacii alergice de tip 11
Acest tip de re#c'ii #0er)ice de tip i(edi#t #p#r 7n ur(# "or(1rii de #nticorpi I)G
s#u I)D c#re #c'ione#.1 7(potri# unor co(ponente tisu0#re= e"ectu0 princip#0 "iind
citoto%ic.
M#ni"est1ri c0inice re.u0t#te 7n ur(# re#c'ii0or #0er)ice de tip II sunt?
- #ne(i# 3e(o0itic1 i(un1 /produs1 de penici0in1= ri"#(picin1= su0"#(ide=
"en#cetin1 etc.2@
- tro(>ocitopenie i(un1= produs1 de? su0"#(ide= ri"#(picin1= ti#.ide diuretice etc.@
- )r#nu0ocitopenie /produs1 de penici0ine= su0"#(ide= #(ino"en#.o- n1=
3ipo)0ice(i#nte= "eni0>ut#.on1 etc.2.
Tot 7n #ce#st1 c#te)orie pot "i 7nc#dr#te 8i 3ep#tit# cronic1 i(un1 produs1 de?
(eti0dop#= "eni0>ut#.on1 s#u 0upusu0 erite(#tos produs de #nti(#0#rice etc.
c) $eacii alergice de tip 111 234
;unt tot re#c'ii #0er)ice de tip i(edi#t= re.u0t#te 7n ur(# "or(1rii unor co(p0e%e
circu0#nte 7ntre #nti)eni 8i #nticorpii I)G 8i I)D= co(p0e%e c#re se "i%e#.1 7n #se0e (ici=
producAnd in"0#(#'ii #0e #cestor#.
M#ni"est1ri0e c0inice #0e #cestor procese sunt?
- >o#0# seru0ui= c#re po#te "i produs1 de penici0ine /"or(# ret#rd2= su0"#(ide etc.@
- eo.ino"i0ie pu0(on#r1= c#re po#te "i produs1 de? su0"#(ide= "ur#.o0idon1 etc.@
- )0o(eru0one"rit1 cronic1 G po#te "i produs1 de s1ruri0e de #ur@
d) $eacii alergice de tip 15 234
;unt #0er)ii 7ntAr.i#te d#tor#te sensi>i0i.1rii 0i("ocite0or T= c#re e0i>ere#.1
0i("oKin#= su>st#n'1 )ener#to#re de in"i0tr#te (onoce0u0#re.
M#ni"est1ri0e c0inice # #cestui tip de re#c'ii #0er)ice sunt?
- der(#tite de cont#ct= c#re pot "i produse de #(ino)0ico.ide c#? )ent#(icin#=
neo(icin# etc.@
- erite( po0i(or"= c#re po#te "i produs de? su0"#(ide= penici0ine= >#r>iturice=
i.oni#.id1= #cid #ceti0s#0ici0ic etc.
e) $eacii alergice autoimune 234
5in #ce#st1 c#te)orie #e( ur(1to#re0e tipuri de (#ni"est1ri de
tip #0er)ic?
- 3ep#tite #utoi(une G pot "i produse de su0"#(ide= i.oni#.id1= "enoti#.ine etc.@
- (i#stenii #utoi(une G pot "i produse de 5-penici0#(in#@
- #ne(ie 3e(o0itic1 #utoi(un1 G po#te "i produs1 de P-(eti0dop# etc.
f) 6oc alergic medicamentos 234
Este (#i "recent 0# perso#ne cu po0i(edic#'ie s#u #And di"erite su"erin'e= c#?
nero.e= tu0>ur1ri endocrine etc.
!4
Mocu0 #0er)ic (edic#(entos este ce# (#i )r#1 re#c'ie #0er)ic1= cu o "recen'1 de
(#ni"est#re 7n continu1 cre8tere.
Mocu0 #0er)ic po#te "i de (#i (u0te "e0uri= d#r #re 7n )ener#0 un de>ut r#pid= o
si(pto(#to0o)ie #0#r(#nt1= eo0u'ie r#pid1 8i un s"Ar8it c#re po#te "i e%itus /(o#rte2 s#u
rest#>i0ire prin interen'ie de ur)en'1 #supr# p#cientu0ui.
1./.2.3. Modalit(i profilactice de investi!are -i tratament a manifest(rilor de tip aler!ic
Pentru # preeni (#ni"est1ri0e #0er)ice i#tro)ene= se propun cAte# (1suri de ordin
pro"i0#ctic= 8i #nu(e?
- uti0i.#re# cu (u0t discern1(Ant # (edic#(ente0or cu poten'i#0 #0er)i.#nt ridic#t@
- eit#re# uti0i.1rii topice= cut#n#te s#u pe (uco#se # (edic#(ente0or "o#rte
#0er)i.#nte= c# de e%e(p0u? penici0ine= su0"#(ide etc.
C# (etode de inesti)#re # (#ni"est1ri0or de tip #0er)ic= e%ist1
ur(1to#re0e (od#0it1'i?
- #n#(ne.# #tent1 # >o0n#i0or@
- teste in itro /test de 3e(#)0utin#re p#si1 etc.2@
- teste cut#n#te /intr#der(ore#c'ie etc.2
C# (od de tr#t#(ent #0 (#ni"est1ri0or de tip #0er)ic se indic1?
- oprire# ur)ent1 # #d(inistr1rii (edic#(entu0ui@
- uti0i.#re# de (edic#(ente #nti#0er)ice /#nti3ist#(inice D
1
= #dren#0in1 s#u
corticosteroi.i #d(inistr#te i.. 0ent2.
1.6. eacii adverse produse de medicamente imunosupresive 1.6. eacii adverse produse de medicamente imunosupresive
1.6.1. 2eneralit(i
Re#c'ii0e #derse de #cest tip const#u 7n depri(#re# c#p#cit1'ii de #p1r#re# #
or)#nis(u0ui 7(potri# di"erite0or p#rticu0e cu ro0 #nti)enic. Bn ter#pie se uti0i.e#.1
(edic#(ente cu ro0 de (odu0#re # siste(u0ui i(unit#r.
Mec#nis(e0e i(p0ic#te 7n producere# re#c'ii0or #derse i(unosupresie pot "i
di"erite= 8i #nu(e?
- (ec#nis( "#r(#codin#(ic secund#r@
- (ec#nis( to%ic@
- (ec#nis( i(uno#0er)ic.
1.6.2. 'ipuri de reacii adverse produse de imunosupresive 345
!1
Bn continu#re or "i #(intite dou1 tipuri de re#c'ii #derse d#tor#te
i(unodepresiei= 8i #nu(e?
- #)r#nu0ocito.#= cu (#ni"est1ri c0inice #cute= cu o eo0u'ie r#pid1 spre e%itus@
- 8i de"icien'# i(unit#r1 0#tent1= o "or(1 cronic1 0#tent1 c#re po#te conduce 0#?
in"ec'ii "o#rte )r#e s#u tu(ori (#0i)ne.
1.6.2.1. )!ranulocitoza
A)r#nu0ocito.# po#te "i dec0#n8#t1 de nu(ero#se (edic#(ente= c# de e%e(p0u?
- #n#0)e.ice-#ntipiretice /pir#.o0on#= #ni0ide etc.2@
- #ntiin"0#(#to#re nesteroidiene@
- su0"#(ide= #nti>iotice 8i c3i(ioter#pice /penici0ine= ce"#0osporine= c0or#("enico02@
- #neste.ice )ener#0e@
- #ntiepi0eptice /c#r>#(#.epin1= "enitoin etc.2@
- neuro0eptice "enoti#.inice@
- #nti#rit(ice /propr#no0o02@
- #nti3ist#(inice D
1
8i D
!
@
- #ntitiroidiene@
- #ntidepresie tricic0ice@
- #nti3ipertensie /#0"#-(eti0dop# etc.2.
Tite.# de inst#0#re # >o0ii este dependent1 de (ec#nis(e0e i(p0ic#te 7n
producere# ei= (ec#nis(u0 i(uno-#0er)ic #And eo0u'ie "o#rte r#pid1.
Bn continu#re se # pre.ent# perio#d# de ti(p pAn1 0# de>utu0 >o0ii= produs1 de
di"erite (edic#(ente= 7n "unc'ie de (ec#nis(u0 de producere i(p0ic#t= 8i #nu(e?
- "enoti#.ine0e pot produce #)r#nu0ocito.1 prin (ec#nis( to%ic= ite.# de inst#0#re
"iind 3-1! s1pt1(Ani@
- (et#(i.o0u0 po#te prooc#= prin (ec#nis( i(uno0o)ic 0# p#cient nesensi>i0i.#t=
>o#0# 7n --14 .i0e@
- (et#(i.o0u0 po#te dec0#n8# >o#0# prin (ec#nis( i(uno0o)ic 0# perso#n1
sensi>i0i.#t1 7n ,-14 ore@
Pentru tr#t#(entu0 #)r#nu0ocito.ei se i(pun ur(1to#re0e (1suri?
- oprire# i(edi#t1 # tr#t#(entu0ui@
- spit#0i.#re 7n c#(er1 steri01@
- tr#t#(ent de ur)en'1 cu #nti>iotice 7n do.e (#ri@
- tr#ns"u.ie de )r#nu0ocite@
- tr#nsp0#nt (edu0#r= 7n c#.u0 7n c#re #p0#.i# este ireersi>i01.
1.6.2.2. 7eficiena imunitar( latent(
Ace#st1 su"erin'1 po#te #e# c#u.e dierse= 8i #nu(e?
- in"est1ri ir#0e /DIT2@
!!
- su>st#n'e to%ice@
- di"erite st1ri c#ren'i#0e@
- (edic#(ente.
Bn continu#re se or pre.ent# cAte# (edic#(ente c#re produc de"icien'1 i(unit#r1
0#tent1 prin di"erite (ec#nis(e= 8i #nu(e?
#. Medic#(ente c# su0"#(ide0e= "enoti#.ine0e= #ntitiroidiene0e= c0or#("enico0u0= pot
produce #ce#st1 >o#01 prin #c'iune 3ipop0#.ic1-(edu0#r1 pe seri# #0>1 s#u )ener#01.
>. Medic#(ente c#? #0coo0= #neste.ice )ener#0e= neuro0eptice "eno-ti#.inice=
tr#nc3i0i.#nte >en.odi#.epinice= #nti>iotice /tetr#cic0in#= ri"#(-picin#= eritro(icin#=
cotri(o%#.o0= di)o%in# pot produce #ce#st1 de"icien-'1 i(unit#r1 prin depri(#re#
i(unit1'ii ce0u0#re.
c. Medic#(ente c#? #neste.ice )ener#0e= neuro0eptice "enoti#.inice= #ntiepi0eptice
/"enitoin#2= nicotin# 7n e%ces= strepto(icin#= pot produce de"icien'1 i(unit#r1 0#tent1 prin
depri(#re# i(unit1'ii u(or#0e /sc1dere# sinte.ei de #nticorpi2.
d. Antiin"0#(#to#re0e nesteroidiene= )0ucocorticoi.ii 8i citost#tice0e= pot induce
#ce#st1 su"erin'1 prin in3i>#re# sinte.ei proteice= 7n 0i("ocite etc.
1.6.3. Modalit(i de profilaxie a reaciilor adverse de tip imunodepresiv 345
Re#c'ii0e #derse i(unosupresie sunt "o#rte )r#e= d#torit1 eo0u'iei c#re se po#te
deru0# precu( s-# #r1t#t?
- r#pid1= i(inen'1 de (o#rte r#pid1= 7n c#.u0 8ocu0ui to%iin"ec'ios@
- s#u 0ent1= cAnd pot re.u0t# tu(ori (#0i)ne s#u #0te su"erin'e )r#e.
UinAnd cont de ce0e #"ir(#te= se i(pun= 7n pri(u0 rAnd= (1suri pro"i0#ctice= c# de
e%e(p0u?
- o >un1 cuno#8tere # (edic#(ente0or cu poten'i#0 "#r(#coto%ico0o-)ic
i(unodepresi@
- 0i(it#re# uti0i.1rii (edic#(ente0or c#re pot produce #cest tip de re#c'ii #derse@
- uti0i.#re# cu (u0t1 pruden'1 # #nti>ioter#piei pro"i0#ctice 7n c3irur)ie@
- 0i(it#re# pe cAt posi>i0 # #nti>ioter#piei 7n perio#d# copi01riei= perio#d1 7n c#re se
de.o0t1 siste(u0 i(unit#r@
- uti0i.1re# #nti>iotice0or s#u su0"#(ide0or nu(#i dup1 e"ectu#re# #nti>io)r#(ei@
- #sociere# (edic#(ente0or cu poten'i#0 i(unodepresi cu i(unosti(u0#nte 0#
>o0n#ii cu risc.
1.4. 'olerana "ta#ifilaxia) 1.4. 'olerana "ta#ifilaxia)
!3
Acest tip de (#ni"est#re const1 7ntr-o sensi>i0it#te sc1.ut1 # or)#nis(u0ui 0#
#c'iune# di"erite0or (edic#(ente.
To0er#n'# po#te "i de dou1 tipuri?
- 7nn1scut1 /con)enit#012@
- s#u do>Andit1.
1.4.1. 'olerana ,nn(scut(
Po#te "i de (#i (u0te "e0uri= 8i #nu(e?
- tolerana de specie= c# de e%e(p0u? iepure0e= to0ere#.1 #tropin# d#torit1 "#ptu0ui
c1 posed1 #tropinester#.#= o en.i(1 c#re (et#>o0i.e#.1 #cest #0c#0oid@
- s#u tolerana de grup G cAnd #nu(ite popu0#'ii pre.int1 un #nu(it de"icit
en.i(#tic cu repercusiuni #supr# (et#>o0i.1rii di"erite0or (edic#(ente.
1.4.2. 'olerana dob1ndit(
Acest tip de (#ni"est#re const1 7n sc1dere# e"ectu0ui (edic#(entu0ui 7n ur(#
#d(inistr1rii repet#te= "iind neoie de cre8tere# do.ei pentru o>'inere# #ce0or#8i e"ecte.
To0er#n'# do>Andit1 este de dou1 "e0uri= 8i #nu(e?
- #cut1 /t#3i"i0#%ie2@
- cronic1 /o>i8nuin'12.
1.4.2.1. 'olerana acut(
To0er#n'# #cut1 const1 7n sc1dere# trept#t1 # e"ectu0ui produs de (edic#(ente prin
#d(inistr1ri repet#te= 0# inter#0e scurte de ti(p. Acest tip de to0er#n'1 #re ur(1to#re0e
c#r#cteristici?
- "eno(enu0 este reersi>i0= dup1 7ntrerupere# tr#t#(entu0ui@
- to0er#n'# se inst#0e#.1 r#pid@
- e"ectu0 se di(inue#.1 trept#t= pAn1 0# disp#ri'ie@
- dur#t# e"ectu0ui este scurt1= dup1 7ntrerupere# tr#t#(entu0ui.
T#3i"i0#%i# #re ur(1toru0 (ec#nis( de producere?
- epui.#re# s#u s#tur#re# unor receptori@
- desensi>i0i.#re# receptori0or prin intern#0i.#re /doOn re)u0#tion2.
E%e(p0e de (edic#(ente c#re pot d# t#3i"i0#%ie sunt?
- e"edrin#= C
!
-#dreno(i(etice= nitri'i or)#nici coron#rodi0#t#tori etc.
!$
1.4.2.2. 'olerana cronic( "obi-nuina)
To0er#n'# cronic1 const1 7n sc1dere# e"ectu0ui su>st#n'e0or (edic#(ento#se dup1
#d(inistr#re# repet#t1= "iind neces#r1 cre8tere# do.ei pentru o>'inere# #ce0ui#8i e"ect.
5#torit1 o>i8nuin'ei= or)#nis(u0 po#te s1 suporte 0# un #nu(it (o(ent c3i#r do.e to%ice
"1r1 pro>0e(e. Un tip de o>i8nuin'1 este (itrid#tis(u0= nu(e c#re ine de 0# Mitrid#tes=
re)e0e Pontu0ui= c#re # e%peri(ent#t o #st"e0 de to0er#n'1 cronic1 do>Andit1.
To0er#n'# cronic1 #re ur(1to#re0e c#r#cteristici?
- se inst#0e#.1 0ent@
- este neces#r1 cre8tere# trept#t1 # do.e0or@
- "eno(enu0 este reersi>i0 dup1 o perio#d1 de ti(p (#i 7nde0un)#t1.
Mi 7n c#.u0 #cestui tip de to0er#n'1= (ec#nis(u0 "#r(#codin#(ic este
desensi>i0i.#re# receptori0or prin doOn re)u0#tion.
Acest tip de to0er#n'1 po#te "i d#t de su>st#n'e (edic#(ento#se= c#? 3ipnotice
>#r>iturice= #)oni8ti opioi.i etc.
1.18. 9armacodependena "dependena medicamentoas() 1.18. 9armacodependena "dependena medicamentoas()
1.18.1. 2eneralit(i
F#r(#codepende'# po#te "i de"init1 c# st#re# psi3ic1 s#uI8i "i.ic1 c#re se inst#0e#.1
7n or)#nis( c# ur(#re # consu(u0ui #>u.i= ne6usti"ic#t= dintr-o su>st#n'1
(edic#(ento#s1= ducAnd= 7n "unc'ie de di"eri'i "#ctori= 0# inst#0#re# unei neoi de #
consu(# su>st#n'# respecti1 7n (od continuu s#u periodic.
F#r(#codependen'# #p#re cAnd 7n conte%tu0 e%isten'ei perso#nei #p#r #nu(ite
circu(st#n'e "#ori.#nte= dintre c#re #(inti(?
- (ediu0 socio-cu0tur#0 #0 perso#nei@
- p#rticu0#rit1'i0e psi3o-so(#tice indiidu#0e@
- uti0i.#re# de su>st#n'e c#re produc "#r(#codependen'1.
1.18.2. 9aze ale farmacodependenei
Bn "unc'ie de perio#d# de ti(p 8i de #0'i "#ctori pre.ent#'i #nterior= se po#te inst#0#
"#r(#codependen'#= c#re #re (#i (u0te st#dii= pe c#re 0e o( pre.ent# 7n ordine# #p#ri'iei
dup1 #d(inistr#re# de su>st#n'e c#re d#u "#r(#codependen'1= 8i #nu(e?
a# Dependena psi!ic
Acest tip de "#r(#codependen'1 const1 7n dorin'# indiidu0ui= de.o0t#t1 pe un "ond
psi3ic #0ter#t= de # procur# su>st#n'# incri(in#t1= uti0i.And orice (od#0it#te posi>i01 cu
scopu0 de # 7n01tur# discon"ortu0 psi3ic 8i de # cre# sen.#'i# de >ine= 7n po"id# "#ptu0ui c1
!&
indii.ii respectii cunosc >ine consecin'e0e #cestui "#pt 7n p0#n person#0= "#(i0i#0 8i
soci#0= cAt 8i preederi0e 0e)#0e c#re 0i(ite#.1 uti0i.#re# #cestor su>st#n'e cu scop
protector #supr# entit1'i0or #(intite #nterior.
b# Tolerana G # "ost studi#t1 #nterior 8i repre.int1 st#re# #d#pt#ti1 #
or)#nis(u0ui= (#ni"est#t1 prin sc1dere# e"ectu0ui su>st#n'ei respectie 0# #d(inistr#re#
repet#t1 # unor do.e si(i0#re= pentru o>'inere# #ce0or#8i e"ecte "iind neces#r1 cre8tere#
do.ei. ;c1dere# e"ectu0ui este re.u0t#tu0 di(inu1rii re#ctiit1'ii neuroni0or 0# #nu(ite do.e
din su>st#n'# #d(inistr#t1.
"# Dependena fizic
Este st#re# p#to0o)ic1 c#re este eiden'i#t1 7n (o(entu0 7ntreruperii #d(inistr1rii
unei su>st#n'e c#re cree#.1 dependen'1= s#u 0# o reducere se(ni"ic#ti1 # do.e0or.
5ependen'# "i.ic1 este eiden'i#t1 prin #p#ri'i# sindro(u0ui de #>stinen'1 s#u ser#6.
Mec#nis(u0 inst#01rii #cestui tip de dependen'1 const1 7n 3ipersensi>i0i.#re# unui siste(
c#re este dependent "unc'ion#0 de siste(u0 #supr# c1rui# #c'ione#.1 dro)u0= c# de
e%e(p0u?
- 0# #d(inistr#re# opioide0or sunt sensi>i0i.#'i receptorii #drener)ici= prin re)0#re
#scendent1 /up re)u0#tion2= deo#rece neurotr#ns(isi# #drener)ic1 este (odu0#t1
de neurotr#ns(isi# prin opioide endo)ene c#re in3i>1 e0i>er#re# de c#teco0#(ine=
- s#u= 7n c#.u0 >#r>iturice0or= sunt sensi>i0i.#'i receptorii )0ut#(#ter)ici # c1ror
(odu0#re este re#0i.#t1 de siste(u0 GA<A prin in3i>#re# e0i>er1rii #cidu0ui
)0ut#(ic= 7n ur(# sti(u01rii 7nde0un)#te # neurotr#ns(isiei in3i>ito#re.
Bn c#.u0 dependen'ei "i.ice= sindro(u0 de #>stinen'1 este c#r#cteri.#t #tAt prin
tu0>ur1ri psi3ice= cAt 8i so(#tice.
*# Toxicomania /psi3oto%icit#te#2 este tipu0 de into%ic#'ie cronic1= c#r#cteri.#t
prin ce0e trei tipuri de dependen'1 de"inite #nterior= 8i #nu(e? "i.ic1= to0er#n'#= psi3ic1=
conducAnd 0# tu0>ur1ri (#6ore de co(port#(ent de ordin psi3ic 8i e)et#ti= #st"e0 7ncAt
tr#t#(entu0 #cestei su"erin'e este di"ici0= presupunAnd condi'ii speci#0e pentru re#ducere 0#
st#re# nor(#01.
E%ist1 di"erite tipuri de to%ico(#nie= #ceste# "iind c0#si"ic#te dup1 (#i (u0te criterii?
d
1
2 5up1 nu(1ru0 su>st#n'e0or #d(inistr#te?
- (onoto%ico(#nii= cAnd s-# #d(inistr#t o sin)ur1 su>st#n'1@
- po0ito%ico(#nii= cAnd to%ico(#ni# #p#re c# ur(#re # #d(inistr1rii 7nde0un)#te #
(#i (u0tor su>st#n'e eu"ori.#nte.
d
!
2 Bn "unc'ie de su>st#n'# #d(inistr#t1?
- to%ico(#nii (inore= ce0e prooc#te de? >#r>iturice= 3ipnotice= tr#nc3i0i.#nte=
#0coo0 etc.
- to%ico(#nii (#6ore= ce0e prooc#te de stupe"i#nte.
!,
1.18.3. Substane care pot provoca farmacodependen(
Bn continu#re o( #(inti c#te)orii de su>st#n'e c#re pot cre# #cest sindro(= 8i
#nu(e?
- depresie ;.N.C. /#0coo0= 3ipnotice= sed#tie= tr#nc3i0i.#nte2@
- opioide= sti(u0#nte #0e ;.N.C. /#("et#(in#= coc#in# etc.2@
- 3#0ucino)ene /3eroin#= L;52@
- c#n#>is@
- so0en'i or)#nici o0#ti0i /#ceton#= tetr#c0orur# de c#r>on= to0uen etc.2.
1.18.*. Norme le!islative privind farmacodependena
5#torit1 consecin'e0or ne)#tie #0e to%ico(#niei pe p0#n (ondi#0= s-#u 0u#t (1suri
prin or)#ni.#'ii c#re re)0e(ente#.1 re)i(u0 #cestor su>st#n'e= 8i #nu(e?
- Conen'i# unic1 #supr# stupe"i#nte0or= e0#>or#t1 de O.N.U.@
- Conen'i# unic1 #supr# su>st#n'e0or psi3otrope= e0#>or#t1 de O.N.U.
L# nie0u0 Or)#ni.#'iei N#'iuni0or Unite "unc'ione#.1 ur(1to#re0e co(isii c#re
re)0e(ente#.1 circu0#'i# su>st#n'e0or incri(in#te 7n to%ico(#nii?
- Co(isi# pentru stupe"i#nte@
- O.I.C.;. /Or)#nis(u0 Intern#'ion#0 de Contro0 #0 ;tupe"i#nte0or2@
L# nie0 europe#n e%ist1?
- Centru0 Europe#n de (onitori.#re pentru (edic#(ente 8i #dic'ie 0# (edic#(ente=
cu sediu0 0# Lis#>on# /1++$2@
- Centru0 Europe#n de in"or(#re #supr# (edic#(ente0or 8i #dic'iei 0# (edic#(ente.
Bn Ro(Ani#= circu0#'i# stupe"i#nte0or este re)0e(ent#t1 de preederi0e Le)ii nr.
-3I1+,+= cu #0te co(p0et1ri u0terio#re.
1.11. 0ntoxicaiile medicamentoase 1.11. 0ntoxicaiile medicamentoase
1.11.1. 2eneralit(i
Into%ic#'ii0e (edic#(ento#se sunt st1ri p#to0o)ice re.u0t#te prin #d(inistr#re# 7n
(od #ccident#0 s#u oit # unor su>st#n'e to%ice.
!-
Into%ic#'ii0e pot "i= 7n "unc'ie de (odu0 7n c#re #p#r= 7(p1r'ite 7n? into%ic#'ii #cute
/cri(e= sinucideri= into%ic#'ii #ccident#0e2 s#u cronice /to%ico(#nii= dop#6 (edic#(entos
etc.2.
Into%ic#'ii0e #cute pot "i c0#si"ic#te= 7n "unc'ie de do.# #d(inistr#t1 8i eo0u'i#
c0inic1 # st1rii p#cientu0ui= 7n?
#.Into%ic#'ii supr##cute= 7n c#.u0 7n c#re sunt in)er#te do.e superio#re ce0or 0et#0e.
Eo0u'i# #cestui tip de into%ic#'ie este r#pid1 /(inute= ore2 spre e%itus= d#c1 nu se
interine "o#rte ur)ent.
>.Into%ic#'ii #cute propriu-.ise= cAnd p#cientu0 # in)er#t do.e de su>st#n'1
superio#re do.e0or ter#peutice /do.e to%ice2= eo0u'i# >o0n#u0ui depin.And "o#rte (u0t de
pri(u0 #6utor #cord#t.
c.Into%ic#'ii su>#cute= re.u0t1 7n ur(# #cu(u01rii 7n or)#nis( # unor su>st#n'e
(edic#(ento#se d#torit1 supr#do.1rii= #tAt prin #d(inistr#re= cAt 8i d#torit1 unor pro>0e(e
0# nie0u0 or)#ne0or epur#to#re.
1.11.2. Simptomatolo!ia ,n intoxicaii acute medicamentoase 32*5
Bn c#. de into%ic#'ii #cute= sunt (onitori.#'i ur(1torii p#r#(etri c#re preced o >un1
interpret#re # re.u0t#te0or inesti)#'ii0or pentru # #6un)e 0# conc0u.ii corespun.1to#re= 8i
#nu(e?
a) 7tatusul 7.,.8.
Acest p#r#(etru este in"0uen'#t 7n (od di"erit de #nu(ite c0#se= 8i #nu(e?
- sti(u0#nte0e ;.N.C. G produc e"ecte #0e sti(u01rii= c#? #)it#'ie= tre(or= eu"orie=
ce"#0ee= de0ir= conu0sii etc.
- >0oc#nte0e ;.N.C produc? #stenie= so(no0en'1= (i#stenie= co0#ps= co(1 etc.@
- sti(u0#re ini'i#01 ur(#t1 de in3i>i'ie produs1 de? #ntico0inester#.ice= #tropin1=
#ntidepresie tricic0ice etc.
b) Tensiunea arterial 9i pulsul
5i"erite0e c#te)orii de (edic#(ente pot in"0uen'# tesiune# #rteri#01
8i rit(u0 c#rdi#c 7n di"erite (oduri= c# de e%e(p0u?
>
1
2 Dipertensiune #rteri#01 8i t#3ic#rdie /#ntico0iner)ice= coc#in#= deri#'i de
#("et#(in12@
>
!
2 Dipotensiune #rteri#01 8i t#3ic#rdie /neuro0eptice "enoti#.inice= #ntidepresie
tricic0ice= teo"i0in#= #nti3ipertensie cu e"ect peri"eric@
>
3
2 Dipotensiune cu >r#dic#rdie /C->0oc#nte= >0oc#nte #0e c#n#0e0or de c#0ciu= #)oni8ti #i
receptori0or P
!
presin#ptici etc.2.
c) Frec%ena respiratorie
!*
E%ist1 ur(1to#re0e (odi"ic1ri #0e "recen'ei respir#torii= 8i #nu(e?
- t#3ipnee= c#re este produs1 de (edic#(ente c#re produc #cido.1 (et#>o0ic1
/s#0ici0#'i etc.2@
- dispnee= uneori c3i#r cu scurte perio#de #pneice= produs1 de opioide etc.
d2 Temperatura corpului.
Acest p#r#(etru este in"0uen'#t de (u0te (edic#(ente c#re #c'ione#.1 #supr#
;.N.C.= c# de e%e(p0u?
- do.e to%ice de #("et#(in1= #tropin1= 3or(oni tiroidieni pot prooc# "e>r1@
- (#6orit#te# depri(#nte0or ;.N.C.= c# de e%e(p0u? >#r>iturice= opioide= #0coo0
proo#c1 3ipoter(ie etc.
e) Diametrul pupilei
Acest p#r#(etru po#te d# indicii #supr# tipu0ui de into%ic#'ie 7n ur(1to#re0e
(oduri= 8i #nu(e?
- (io.1 /(ic8or#re# di#(etru0ui pupi0ei2 este produs1 de (edic#(ente c#? opioide=
#ntico0inester#.ice= p#r#si(p#to(i(eti-ce etc.@
- (idri#.#= produs1 de p#r#si(p#to0itice= #("et#(in1 etc.
"2 Tranzitul digesti% G po#te "i (odi"ic#t 7n ur(1to#re0e (oduri?
- tr#n.it #cce0er#t 7n into%ic#'ii cu co0ino(i(etice= propu0sie etc@
- s#u tr#n.it di(inu#t 7n into%ic#'ii cu p#r#si(p#to0itice= opioide etc
g) +spectul epiteliilor 'piele 9i mucoase)
Aspectu0 epite0ii0or po#te d# uneori indicii #supr# etio0o)iei into%ic#'iei= c# de
e%e(p0u?
- ci#no.# po#te su)er# o (et3e(o)0o>ine(ie@
- icteru0 po#te su)er# o 3ep#tit1 #cut1@
- usc1ciune# )urii= te)u(ente usc#te= pot su)er# o into%ic#'ie cu p#r#si(p#to0itice
etc.@
- 3ipersecre'i# )0#nde0or sudorip#re s#u # #0tor )0#nde e%ocrine= po#te su)er# o
into%ic#'ie cu #ntico0inester#.ice s#u p#r#si(p#to(i(etice.
1.11.3. Modalit(ile de intervenie a personalului medical ,n intoxicaii acute cu
diferite substane
Conduit# de ur)en'1 presupune ur(1torii p#8i?
a# :suri pentru asigurarea meninerii funciilor %itale= c# de e%e(p0u?
- respir#'ie #rti"ici#01@
- enti0#'ie (ec#nic1@
- (#s#6 c#rdi#c e%tern@
!+
- #d(inistr#re# de su>st#n'e si(p#to(i(etice etc.= pentru (en'inere# "unc'ii0or
respir#torii@
- o%i)enoter#pie= d#c1 este c#.u0.
b# :suri de ;mpiedicare a absorbiei toxicului ;n mediul intern al organismului= c#
de e%e(p0u?
- sp101turi )#strice@
- prooc#re de o(1@
- #d(inistr#re de pur)#tie etc.
"# :suri prin care este grbit eliminarea toxicului?
- (odi"ic#re# pD-u0ui 7n (od corespun.1tor= 7ncAt s1 se re#0i.e.e disociere#
e0ectro0itic1 # su>st#n'ei 8i s1 "ie 7(piedic#t1 #>sor>'i# tu>u0#r1 din urin# pri(#r1
etc.
*# -emodializa, d#c1 este c#.u0@
e) +dministrarea unui antidot general sau specific.
PAn1 0# o>'inere# re.u0t#te0or de 0#>or#tor 7n ur(# inesti)#'iei pe #nu(ite 0ic3ide
>io0o)ice etc.= se po#te #d(inistr# un #ntidot )ener#0= cu( #r "i c1r>une #>sor>#nt etc.
5up1 descoperire# to%icu0ui= se # recur)e 0# un #ntidot speci"ic.
1.12. 7opa$ul medicamentos 1.12. 7opa$ul medicamentos
5op#6u0 (edic#(entos const1 7n uti0i.#re# de su>st#n'e (edic#(ento#se pentru #
(1ri r#nd#(entu0 7n #ctiit1'i sportie s#u inte0ectu#0e. E%ist1 conen'ii intern#'ion#0e
c#re co(>#t dop#6u0 pe considerente de ordin etic= 8i #nu(e?
- Co(itetu0 Intern#'ion#0 O0i(pic /C.I.O.2 din #pri0ie 1+*+@
- Conen'i# pentru dop#6 din c#dru0 Consi0iu0ui Europei din ;tr#s>our). Bn
Ro(Ani#= conen'i# 7(potri# dop#6u0ui este r#ti"ic#t1 prin Le)e# nu(1ru0 1-1
din 1++*.
In continu#re se or pre.ent# 7n (od succint )rupe0e de (edic#(ente uti0i.#te 8i cAte#
su>st#n'e din "iec#re )rup1 c#re uti0i.#te produc dop#6 8i #nu(e?
#. ;ti(u0#nte ;.N.C.? #("et#(in#= e"edrin#= coc#in#= #("epr#(on#= stricnin#=
(eti0"enid#t etc.
>. An#0)e.ice (or"ino(i(etice? codein1= (or"in1= de%tropropo%i"en= petidin1=
dionin1= 3eroin1 etc..
c. ;teroi.i #n#>o0i.#n'i? (eti0testosteron= n#ndro0on= testosteron etc.
d. C->0oc#nte? #teno0o0= (etopro0o0= o%preno0o0= prop#no0o0 etc.
e. diuretice? "urose(id= spirono0#cton1= c0ort#0idon1 3idroc0orti#.id1= #cet#.o0#(id1
etc.
34
1.13. eacii adverse rezultate la ,ntreruperea 1.13. eacii adverse rezultate la ,ntreruperea
farmacoterapiei farmacoterapiei
..12.1. 2eneralit(i
CAnd se 7ntrerupe >rusc #d(inistr#re# unui (edic#(ent dup1 o #d(inistr#re
7nde0un)#t1= pot re.u0t# re#c'ii #derse= uneori cu (#ni"est1ri c0inice )r#e= de.o0t#te pe
"ondu0 #d#pt1rii "i.io0o)ice # p#cien'i0or respectii 0# #)resiune# (edic#(ento#s1.
L# 7ntrerupere# >rusc1 # unui tr#t#(ent (edic#(entos pot #p1re# ur(1to#re0e
tipuri de re#c'ii #derse?
- re#c'ii #derse re.u0t#te prin 7ntrerupere# unui tr#t#(ent cu #nt#)oni8ti
"#r(#co0o)ici@
- re#c'ii #derse re.u0t#te prin 7ntrerupere# unui tr#t#(ent cu #)oni8ti
"#r(#co0o)ici@
- 8i re#c'ii #derse re.u0t#te pe "ondu0 unei insu"icien'e "unc'ion#0e.
'('-.1.1. eacii adverse rezultate prin ,ntreruperea tratamentului
cu anta!oni-ti farmacolo!ici345
Acest tip de re#c'ii se de.o0t1 pe "ondu0 receptori0or #nt#)oni.#'i de #nu(ite
su>st#n'e (edic#(ento#se= sensi>i0i.#re produs1 7n ur(# unui proces de e%tern#0i.#re #
receptori0or respectii.
C# e%e(p0e de re#c'ii #derse re.u0t#te printr-un #st"e0 de (ec#-nis( #(inti(?
- re#c'ii #derse re.u0t#te 0# 7ntrerupere# tr#t#(entu0ui cu #nti3ist#(inice D
!
/r#nitidin1= ci(etidin1 etc.2= c#re pot conduce 0# #)r##re# u0ceru0ui )#stro-
intestin#0 pAn1 0# per"or#re@
- re#c'ii #derse re.u0t#te 0# 7ntrerupere# tr#t#(entu0ui cu C-#dreno0itice
/propr#no0o02= c#re pot conduce 0# 3ipertensiune #rteri#01 s#u #n)in1 pector#01@
- re#c'ii #derse re.u0t#te 0# 7ntrerupere# tr#t#(entu0ui cu #ntico0inester#.ice
centr#0e /#tropin1= tri3e%i0"enidi0 etc.2= c#re pot conduce 0# tu0>ur1ri
e%tr#pir#(id#0e etc.
Mec#nis(u0 i(p0ic#t 7n producere# re#c'ii0or #derse de #cest tip este cre8tere#
nu(1ru0ui de receptori disponi>i0i prin e%tern#0i.#re# 0or 0# supr#"#'# (e(>r#nei 7n ur(#
>0oc1rii #cestor tipuri de receptori ti(p 7nde0un)#t 8i "i%#re# #)onistu0ui "i.io0o)ic pe un
nu(1r (#si de recep-tori 7n (o(entu0 7ntreruperii (edic#'iei >0oc#nte= re.u0tAnd #st"e0
e"ecte e%#)er#te. Mec#nis(u0 producerii este prin sensi>i0i.#re# receptori0or.
1.13.1.2. eacii adverse rezultate prin ,ntreruperea tratamentului cu a!oni-ti
farmacolo!ici345
Acest tip de sindro( #p#re c# re.u0t#t #0 7ntreruperii #d(inistr1rii /7n ur(# unui
tr#t#(ent de 0un)1 dur#t12 cu su>st#n'e (edic#(ento#se din c#te)ori# #)oni8ti #i
31
receptori0or "#r(#co0o)ici #p#r'inAnd unui siste( (odu0#tor s#u in3i>itor #0 unei #0te
neurotr#ns(isii.
C# e%e(p0e de #)oni8ti din #ce#st1 c#te)orie #(inti(?
- (edic#(ente (or"ino(i(etice c#re sunt #)oni8ti #i receptori0or opioi.i V 8i K= 8i
c#re (odu0e#.1 neurotr#ns(isi# #drener)ic1@
- (edic#(ente >#r>iturice s#u >en.odi#.epinice c#re sunt #)oni8ti #i
neurotr#ns(isiei GA<A= neurotr#ns(isie (odu0#to#re pentru neurotr#ns(isi#
)0ut#(#ter)ic1 s#u #drener)ic1.
L# 7ntrerupere# #d(inistr1rii #cestui tip de #)oni8ti #p#re sindro(u0 de #>stinen'1=
de retr#)ere= (#ni"est#t prin supr#sti(u0#re# neurotr#ns(isii0or (odu0#te de c1tre
(edic#(ente.
Mec#nis(u0 i(p0ic#t 7n #cest sindro( este ur(1toru0?
(edic#(ente0e de tip #)onist /(or"in1 etc.2 sti(u0e#.1 receptorii din siste(u0 (odu0#tor
s#u in3i>itor= 7n c#.u0 (or"inei siste(u0 opioid s#u siste(u0 GA<A. Bn ur(# sti(u01rii
receptori0or (odu0#tori 7n siste(e0e #(intite= este depri(#t1 e0i>er#re# (edi#toru0ui 0#
nie0u0 3eterosin#psei 7n siste(u0 (odu0#t #drener)ic s#u )0ut#(#ter)ic. Co(pens#tor= 7n
siste(u0 (odu0#tor #re 0oc e%tern#0i.#re# receptori0or cu o cre8tere # cA(pu0ui
receptori0or prin (ec#nis( 3etero Wup-re)u0#tionX. Bn (o(entu0 7ntreruperii (edic#'iei
#)oniste= pe siste(u0 (odu0#tor #re 0oc o e%#cer>#re # "unc'ion1rii siste(u0ui (odu0#tor=
#And consecin'e0e c0inice #0e #)oni.1rii #cestui# de c1tre neurotr#ns(i'1toru0 endo)en.
1.13.1.3. eacii adverse rezultate pe fondul unei insuficiene funcionale 345
Acest tip de re#c'ii #derse pot #p1re# pe "ondu0 unor insu"icien'e "unc'ion#0e #0e
unei )0#nde endocrine= re.u0t#te 7n ur(# #d(inistr1rii de 3or(oni pe c#0e e%o)en1.
Func'ion#re# )0#nde0or endocrine= c# de e%e(p0u corticosupr#ren#0e0e= este coordon#t1 de
concentr#'i# s#n)uin1 # produsu0ui "in#0 de 0#n' (et#>o0ic /3or(oni corticosteroi.i2 prin
retrocontro0 /"eed->#cK2 po.iti s#u ne)#ti= 7n ur(# #c'iunii #cestor# 0# nie0u0
c3e(oreceptori0or din 3ipot#0#(us 8i 3ipo"i.1.
Pe >#.# concentr#'iei s#n)uine de 3or(on circu0#nt= 3ipot#0#(u-
su0 secret1 neuro3or(onu0 3ipot#0#(ic /CRF2= 3ipo"i.# 3or(onu0 /ACTD2= c#re #u ro0 de
contro0 # "unc'ion1rii endocrine # corticosupr#ren#0ei.
Bn ur(# #d(inistr1rii de corticosteroi.i ti(p 7nde0un)#t= se reduce secre'i# de
corticosteroi.i #i )0#ndei corticosupr#ren#0e= (ec#nis(u0 "iind diri6#t prin "eed->#cK
ne)#ti de 0#n'u0 3ipot#0#(o-3ipo"i.#r. L# 7ntrerupere# >rusc1 # #d(inistr1rii
corticosteroi.i0or= #p#re "eno(enu0 de insu"icien'1= "eno(en (#ni"est#t pAn1 0# repunere#
7n "unc'ie # )0#ndei peri"erice 0# un #0t nie0= desi)ur diri6#t prin #ce0#8i (ec#nis(= de
c1tre centrii nero8i c#re contro0e#.1 "unc'ion#re# )0#ndei. Pentru perio#d# de ti(p
3!
neces#r1 pentru #d#pt#re# )0#ndei endocrine 0# noi0e condi'ii= #p#re "eno(enu0 de
insu"icien'1 "unc'ion#01= c#r#cteri.#t prin re#c'ii #derse c#r#cteristice c#ren'ei 3or(on#0e.
a) :edicamente care declan9eaz tulburri la oprirea brusc a administrrii lor
5in #ce#st1 c#te)orie pute( #(inti? (edic#(ente #ntiepi0eptice />#r>iturice=
>en.odi#.epine2= #ntip#rKinsoniene= #nti3ipertensie /c0oni-din#2= #nti#st(#tice /C
!
#dreno(i(etice2= #nti#n)ino#se /C
!
#dreno0itice2= #ntiu0cero#se prin (ec#nis(
#nti3ist#(inice D
!
= #ntico0iner)ice centr#0e= corticosteroi.i= opioide etc.
Medic#(ente0e din #ce#st1 c0#s1 nu se 7ntrerup niciod#t1 >rusc= ci 7ntrerupere#
tr#t#(entu0ui #re 0oc dup1 reducere# trept#t1 # do.e0or #d(inistr#te.
b) :edicamente care pot pro%oca tulburri la oprirea brusc
5in #cest )rup pute( #(inti?
- (edic#(ente neuro0eptice@
- tr#nc3i0i.#nte />en.odi#.epine2@
- 3ipnotice /)0uteti(id2@
- si(p#to(i(etice #soconstricto#re peri"erice /decon)estion#nte n#.#0e2@
- sed#tie />ro(uri2 etc.
Mi 0# #cest )rup de (edic#(ente este >ine c# do.e0e s1 se reduc1 trept#t.
c) :edicamente care se presupune c ar determina tulburri la oprirea brusc
5in #cest )rup #(inti(? #nore%i)ene= #ntico#)u0#nte or#0e.
Mi 0# 7ntrerupere# tr#t#(entu0ui cu (edic#(ente0e (en'ion#te este
i(port#nt s1 "ie 0u#te to#te (1suri0e pentru # 7ndep1rt# posi>i0e0e re#c'ii #derse de
#cest tip.
CAPITOLUL II
FARMACOEPIDEMIOLOGIA FARMACOEPIDEMIOLOGIA
2.1. 2eneralit(i 2.1. 2eneralit(i
Procesu0 epide(io0o)ic (edic#(entos este un "eno(en re#0= (oti pentru c#re
(edic#(entu0= c# "oc#r epide(io0o)ic tre>uie 0u#t 7n studiu= #st"e0 #p1rAnd o nou1 r#(ur1
# "#r(#co0o)iei= cu denu(ire# de "#r(#coepide(io0o)ie= #ce#st# "iind o 8tiin'1 de )r#ni'1
7ntre "#r(#cie 8i epide(io0o)ie.
F#r(#coepide(io0o)i#= c# r#(ur1 cu c#r#cter #p0ic#ti # "#r(#co0o)iei= este
>#.#t1 pe "#r(#coto%ico0o)ie 8i studi#.1 contr#indic#'ii0e 8i prec#u'ii0e 7n pr#ctic#
"#r(#coter#pic1= respecti "#r(#co)r#"ic1.
F#r(#coepide(io0o)i# #re ur(1to#re0e c#te)orii de o>iectie= 8i #nu(e?
33
#. O>iectie cu c#r#cter )ener#0= c# de e%e(p0u?
- studiu0 dec0#n81rii= (#ni"est1rii 8i sist1rii >o0i0or produse de (edic#(ente@
- instituire# unor (1suri corespun.1to#re #tAt din punct de edere pro"i0#ctic= cAt 8i
cur#ti= 0e)#te de procesu0 epide(io0o)ic (edic#(entos.
>.O>iectie p#rticu0#re
5intre o>iectie0e p#rticu0#re #0e #cestei r#(uri #(inti(?
- studiu0 tipuri0or de re#c'ii #derse r#port#te 0# di"erite condi'ii= 7n conte%tu0 7n c#re
#u #p1rut= c# de e%e(p0u? c#te)orie de Arst1= .on1 )eo)r#"ic1= )rup# "#r(#co0o)ic1
etc.@
- studiu0 (odu0ui 7n c#re cre8te procentu0 re#c'ii0or #derse 8i #0 into%ic#'ii0or 7n
core0#'ie cu consu(u0 de (edic#(ente@
- studiu0= respecti instituire# unor (1suri prin c#re s1 "ie de"#ori.#t procesu0
epide(io0o)ic (edic#(entos@
- respect#re# contr#indic#'ii0or 8i prec#u'ii0or= respecti instituire# ce0or (#i dr#stice
(1suri de ordin "#r(#coter#pic 8i "#r(#co)r#"ic@
- e0#>or#re# unor 0e)i )ener#0e priind procesu0 epide(io0o)ic (edic#(entos.
2.2. &rezentarea din punct de vedere statistic a rezultatelor 2.2. &rezentarea din punct de vedere statistic a rezultatelor
unor studii privind prevalena -i incidena reaciilor adverse 345 unor studii privind prevalena -i incidena reaciilor adverse 345
Bn ur(# studii0or deru0#te 7n #cest scop= s-# #6uns 0# ur(1to#re0e conc0u.ii?
- 7ntre 3 G - F din nu(1ru0 tot#0 de >o0n#i spit#0i.#'i #u #6uns 7n #ce#st1 st#re critic1
d#torit1 unui proces epide(io0o)ic (edic#(entos@
- 7ntre & G 3& F dintre >o0n#ii intern#'i 7n spit#0 #cu.1 di"erite tipuri de re#c'ii
#derse@
- procentu0 de re#c'ii #derse cre8te propor'ion#0= cu nu(1ru0 de (edic#(ente
#d(inistr#te conco(itent@
- e%ist1 di"eren'e (#ri 7ntre (edic#(ente priind e"ecte0e "#r(#co-to%ico0o)ice@
- din nu(1ru0 tot#0 de re#c'ii #derse 7nre)istr#te= e%ist1 (edic#(ente uti0i.#te do#r 7n
procent de 1 F /din tot#0u0 (edic#(ente0or uti0i.#te2= d#r procentu0 re#c'ii0or #derse
produse de #ceste# se ridic1 0# 34 F din tot#0@
- din tot#0u0 (edic#(ente0or c#re produc re#c'ii #derse= 0ocu0 de 0e#der este ocup#t
de #(pici0in1= dup1 c#re un 0oc i(port#nt 70 ocup1 contr#ceptie0e or#0e@
- prin #d(inistr#re# unui sin)ur (edic#(ent s-# 7nre)istr#t un nu(1r de 1, F re#c'ii
#derse@
- prin #d(inistr#re# de 14 (edic#(ente conco(itent= procentu0 # crescut 0# 144 F@
- s-# const#t#t c1 un procent de nu(#i 1 F din (edic#(ente #u "ost i(p0ic#te 7n
#pro%i(#ti $4 F din c#.uri0e 0et#0e dec0#r#te@
3$
- c#u.e0e ce0e (#i "recente de decese d#tor#te re#c'ii0or #derse produse de
(edic#(ente sunt ur(1to#re0e? 3e(or#)ii 8i u0cer#'ii di)estie /corticosteroi.i= AIN;
etc.2= 3e(or#)ii cu #0te 0oc#0i.1ri /#ntico#)u0#nte2= #ne(ie #p0#stic1 /c0or#("enico02=
8oc #n#"i0#ctic /penici0ine2= in"ec'ii /i(unosupresie2= 0e.iuni 3ep#tice /i.oni#.id12
etc.
2.3. Elemente ")specte) de studiu ale procesului epidemiolo!ic 2.3. Elemente ")specte) de studiu ale procesului epidemiolo!ic
2.3.1. 7efiniie
Procesu0 epide(io0o)ic (edic#(entos este repre.ent#t de tot#0it#te# tu0>ur1ri0or
produse 7n or)#nis(= cu i(p0ic#'ii econo(ico-soci#0e= re.u0t#te 7n ur(# (#ni"est1rii
re#c'ii0or "#r(#coto%ico0o)ice #0e unei su>st#n'e (edic#(ento#se.
2.3.2. Etapele procesului epidemiolo!ic
Procesu0 epide(io0o)ic #re ur(1to#re0e et#pe?
a) Debut
Ace#st1 et#p1 #re 0oc de o>icei 0# introducere# (edic#(entu0ui 7n ter#pie@
b) E%oluie= c#re po#te "i #scendent1 s#u descendent1 8i este dependent1 de c#ntit#te# de
su>st#n'1 (edic#(ento#s1 in)er#t1= cAt 8i de #nu(i'i "#ctori c#re pot "i deter(in#n'i
s#u "#ori.#n'i@
c) 7tingerea focarului epidemiologic
Ace#st1 "#.1 #re 0oc 7n (o(entu0 sco#terii (edic#(entu0ui respecti din ter#pie.
Bn continu#re o( pre.ent# cAte# su>st#n'e c#re #u dec0#n8#t procesu0
epide(io0o)ic 7n #nu(ite .one )eo)r#"ice= cAt 8i (odu0 7n c#re s-# so0u'ion#t procesu0
respecti= c# de e%e(p0u?
c
1
G T#0ido(id#= tr#nc3i0i.#nt c#re # produs (#0"or(#'ii 7n #nu(ite .one din Europ# de
est= procesu0 epide(io0o)ic constAnd 7n in3i>#re# procese0or de cre8tere #0e >r#'u0ui 8i
#nte>r#'u0ui= #"ect#re# producAndu-se 7n ti(pu0 ie'ii uterine= re.u0tAnd copii cu >r#' 8i
#nte>r#' "o#rte scurt. ;tin)ere# "oc#ru0ui # #ut 0oc prin sco#tere# (edic#(entu0ui din
ter#pie.
c
2
G Acidu0 #ceti0s#0ici0ic= (edic#(ent #n#0)e.ic-#ntipiretic= d1 re#c'ii #derse di)estie
/sindro( u0ceros etc.2. 5up1 descoperire# e"ectu0ui #nti#)re)#nt p0#c3et#r 0# #d(inistr#re#
7n do.e (ici= d#r prin "o0osire# continu1 procesu0 epide(io0o)ic (edic#(entos
7nre)istre#.1 o cre8tere.
3&
c
3
G A(ino"en#.on#= #n#0)e.ic G #ntipiretic de tip pir#.o0on1 #re di"erite re#c'ii #derse=
c# de e%e(p0u?
- (odi"ic1ri de tip #0er)ic@
- 0eucopenie@
- "#ori.#re# c#nceru0ui )#stric prin e0i>er#re# de nitro.#(ine etc.
Bn ur(# #cestor o>ser#'ii= 0# reco(#nd#re# Centru0ui de F#r(#coi)i0en'1 #0
O.M.;.= #cest (edic#(ent s-# scos din ter#pie 7n (u0te '1ri= i#r 7n #0te '1ri se e0i>ere#.1
do#r pe >#.1 de prescrip'ie (edic#01. C# ur(#re # #cestor (1suri= procesu0 epide(io0o)ic
indus de #(ino"en#.on1 7nre)istre#.1 o p#nt1 descendent1.
2.3.3. 9orme de manifestare a procesului epidemiolo!ic medicamentos
M#ni"est#re# #cestui proces po#te #e# 0oc 7n di"erite (oduri= 8i #nu(e?
- spor#dic= procesu0 se (#ni"est1 r#r@
- ende(ic= (#ni"est#re# procesu0ui epide(io0o)ic este 0e)#t1 de o #nu(it1 .on1= de o
#nu(it1 popu0#'ie= se (#ni"est1 per(#nent= d#r "recen'# de #p#ri'ie este (ic1@
- epide(ic= procesu0 epide(io0o)ic se (#ni"est1 0i(it#t c# ti(p s#u re)iune
)eo)r#"ic1= d#r "recen'# de #p#ri'ie # >o0ii este (#re@
- p#nde(ic= un tip de epide(ie c#re #"ecte#.1 un teritoriu )eo)r#"ic s#u popu0#'ion#0
(#re= uneori e%tin.Andu-se 0# nie0u0 )0o>u0ui p1(Antesc.
2.3.*. 9actori care declan-eaz( procesul epidemiolo!ic medicamentos
F#ctorii incri(in#'i 7n dec0#n8#re# procesu0ui epide(io0o)ic (edi-c#(entos sunt
7(p1r'i'i 7n dou1 )rupe= 8i #nu(e?
a) Factori determinani
5intre "#ctorii deter(in#n'i #(inti(?
- i.oru0 epide(io)en= c#re este dependent de structur# c3i(ic1 # su>st#n'ei
(edic#(ento#se c#re dec0#n8e#.1 re#c'i# #ders1@
- 8i p#rticu0#rit1'i0e >io0o)ice #0e popu0#'iei sensi>i0e= unde se pot #(inti@ re#ctiit#te#
indiidu#01= structur# )enotipu0ui= di"erite st1ri p#to0o)ice etc.
b) Factori care fa%orizeaz apariia procesului epidemiologic medicamen-tos
5intre #ce8ti "#ctori #(inti(?
- consu(u0 e%#)er#t de (edic#(ente= (#ni"est#t #tAt prin do.e0e #d(inistr#te= cAt 8i
prin "recen'# #d(inistr1rii@
- di"erite #socieri (edic#(ento#se ur(#te de inter#c'iuni@
- #0i(ent#'ie@
- .on# c0i(#teric1@
3,
- "#ctori socio-cu0tur#0i /nie0 de tr#i= stres= nie0u0 educ#'iei s#nit#re etc.2 etc.
2.*. 9ormele activit(ii farmacoepidemiolo!ice 2.*. 9ormele activit(ii farmacoepidemiolo!ice
For(e0e #ctiit1'ii "#r(#coepide(io0o)ice pot "i de dou1 tipuri?
- #ctiit1'i de preenire # procesu0ui /pro"i0#%i#2@
- 8i #ctiit1'i de co(>#tere # procesu0ui epide(io0o)ic (edic#(entos.
2.*.1. )ctivitatea profilactic(
Acest tip de #ctiit#te const1 7n?
- cuno#8tere# #(1nun'it1 # re#c'ii0or #derse= contr#indic#'ii0or 8i prec#u'ii0or c#re
sunt neces#re # "i 8tiute 7nc1 7n#inte de introducere# 7n ter#pie # (edic#(entu0ui@
- "i%#re# c#dru0ui 0e)is0#ti de e0i>er#re= depo.it#re 8i circu0#'ie # (edic#(ente0or cu
poten'i#0 "#r(#coto%ico0o)ic@
- o educ#'ie s#nit#r1 #dec#t1 etc.
Re"eritor 0# (o(entu0 #p#ri'iei re#c'ii0or #derse #0e unor (edic#(ente= e%ist1
ur(1to#re0e dou1 tipuri= 8i #nu(e?
- re#c'ii #derse cunoscute 7n#inte de #utori.#re pe pi#'# (ondi#01@
- re#c'ii #derse depist#te dup1 introducere# 7n ter#pie.
2.*.1.1. eacii adverse depistate ,nainte de autorizare
Re#c'ii0e #derse de #cest tip pot "i 7(p1r'ite 7n dou1 )rupe?
- re#c'ii #derse prei.i>i0e G dependente de do.1= dur#t# #d(inistr1rii etc.@
- 8i re#c'ii #derse i(prei.i>i0e= independente de do.1= 8i #nu(e? re#c'ii0e de tip
#0er)ic 8i idiosincr#.ice.
5intre e%e(p0e0e de re#c'ii #derse de #cest tip #(inti(?
- #ne(i# #p0#stic1= re.u0t#t1 7n ur(# tr#t#(entu0ui cu c0or#("enico0@ - #ne(i#
3e(o0itic1 G re.u0t#t1 7n ur(# #d(inistr1rii de #nti(#0#rice 0# >o0n#i #And
de"icient1 en.i(# )0uco.1 , "os"#tde3idro)en#.# G-, P5.
M1suri0e pro"i0#ctice c#re se i(pun 7n c#.u0 re#c'ii0or #derse cunoscute sunt?
- prescriere# de do.e (ini(e e"ic#ce@
- (onitori.#re# concentr#'iei p0#s(#tice 0# (edic#(ente0e (et#>o-0i.#te de siste(e
en.i(#tice c#re pre.int1 po0i(or"is(= c# de e%e(p0u 7n c#.uri0e? i.oni#.idei=
su0"#(ide0or= 3ipo)0ice(i#nte0or= propr#no0-o0u0ui etc.@
- #n#(ne.# #(1nun'it1 # >o0n#i0or= pentru depist#re# unor eentu#0e sensi>i0i.1ri
#nterio#re.
2.*.1.2. &rofilaxia reaciilor adverse necunoscute
3-
Cuno#8tere# 7ntre)u0ui pro"i0 "#r(#coto%ico0o)ic #0 (edic#(entu-0ui 7n#inte de
uti0i.#re# 7n ter#pie nu este posi>i01= deo#rece?
- sunt re#c'ii #derse c#re nu se pot eiden'i# 7n c#dru0 cercet1rii pe #ni(#0e de
0#>or#tor= c# de e%e(p0u? #(e'e#01= )re'uri= inso(nie= depresie etc.@
- e%ist1 re#c'ii #derse cu inciden'1 nou1@
- e%ist1 deose>ire priind e"ecte0e ter#peutice 0# o( "#'1 de #ni(#0e /e%. c#.u0
t#0ido(idei 2 etc.
5in punct de edere st#tistic= s-# o>ser#t c1?
- #pro%i(#ti &4 F dintre re#c'ii0e #derse o>ser#te sunt eiden'i#te nu(#i 7n ur(#
#d(inistr1rii 0# o(@
- e%ist1 re#c'ii #derse cu inciden'1 r#r1 8i c#re sunt eiden'i#te 0# 1I14 444 Y 1I&4
444 din indii.ii tr#t#'i cu o #nu(it1 su>st#n'1 (edic#(ento#s1= c#re sunt depist#te 7n
ur(# #ctiit1'ii de "#r(#coi)i0en'1@
5eo#rece situ#'i# se pre.int1 #st"e0= este neces#r s1 "ie 0u#te ur(1-to#re0e (1suri?
- (onitori.#re# #tent1 # (edic#(ente0or nou introduse 7n ter#pie@
- uti0i.#re# cu (u0t1 pruden'1 # (edic#(ente0or nou introduse@
- neuti0i.#re# (edic#(ente0or nou introduse pentru tr#t#(entu0 )r#ide0or 8i copii0or
pAn1 0# Arst# de 1& #ni.
2.*.2. )ctivit(i de combatere a procesului epidemiolo!ic medicamentos 345
Acest tip de #ctiit#te presupune?
- depist#re# cAt (#i r#pid posi>i0 # re#c'ii0or #derse 8i into%ic#'ii0or (edic#(ento#se@
- di#)nostic#re# corect1 # re#c'ii0or #derse 8i into%ic#'ii0or produse de di"erite
(edic#(ente.
Actiit#te# de co(>#tere # procesu0ui "#r(#coepide(io0o)ic este or)#ni.#t1 7n
c#dru0 siste(u0ui de "#r(#coi)i0en'1= c#re presupune 7nre)istr#re# 8i r#port#re# tuturor
re#c'ii0or #derse s#u # into%ic#'ii0or i#tro)ene o>ser#te.
Re#c'ii0e #derse re.u0t#te 7n ur(# #d(inistr1rii (edic#(ente0or pot "i de (#i
(u0te "e0uri din punct de edere #0 )r#it1'ii= 8i #nu(e?
- u8o#re= c#re nu presupun #d(inistr#re# de (edic#(ente #ntidot s#u #0te (1suri
ter#peutice@
- (oder#te= c#re i(pun (odi"ic#re# tr#t#(entu0ui 8i pot pre0un)i ti(pu0 pAn1 0#
indec#re@
- seere= c#re necesit1 7ntrerupere# tr#t#(entu0ui= pe 0An)1 #0te (1suri ter#peutice c#re
se i(pun@
- 0et#0e= c#re deter(in1 (o#rte# >o0n#u0ui.
3*
Bn "unc'ie de c#te)orii0e de re#c'ii #derse se i(pune un tr#t#(ent cAt (#i
#dec#t= 8i #nu(e?
- 7n c#.u0 re#c'ii0or #derse independente de do.1 tre>uie ne#p1r#t sist#t tr#t#(entu0 8i
totod#t1 eit#re# unei e%puneri 7n iitor@
- 7n c#.u0 re#c'ii0or #derse dependente de do.1= se reduce c#ntit#te# #d(inistr#t1
pAn1 0# 0i(ite0e (ini(e posi>i0e= #st"e0 7ncAt s1 se o>'in1 un e"ect "#r(#coter#pic.
2.+. Sistemul de farmacovi!ilen( 2.+. Sistemul de farmacovi!ilen(
Acest siste( este or)#ni.#t 0# nie0 (ondi#0 8i n#'ion#0 7n ur(1toru0 (od?
- e%ist1 un sediu centr#0 7n c#dru0 O.M.;. /Or)#ni.#'i# Mondi#01 # ;1n1t1'ii c#re
"unc'ione#.1 din 1+,*@
- e%ist1 re'e0e n#'ion#0e de F#r(#coi)i0en'1 7n c#dru0 di"erite0or '1ri= c#re tri(it
in"or(#'ii O.M.;. priind re#c'ii0e #derse depist#te 7n ur(# #d(inistr1rii unor
(edic#(ente.
Ro0u0 sediu0ui centr#0 din c#dru0 O.M.;. este de # pre0ucr# in"or(#'ii0e pri(ite de
0# re'e0e0e n#'ion#0e 8i # 7ntoc(i #nu(ite r#po#rte= c#re sunt tri(ise re'e0e0or n#'ion#0e=
c#re 0# rAndu0 0or i#u 3ot1rAri priitor 0# #nu(ite pro>0e(e de ordin
"#r(#coepide(io0o)ic.
Bn Ro(Ani# siste(u0 de "#r(#coi)i0en'1 este or)#ni.#t 7n >#.# unui ordin #0
Ministeru0ui ;1n1t1'ii 8i cuprinde ur(1to#re0e entit1'i?
- Co(isi# Medic#(entu0ui= c#re "unc'ione#.1 7n c#dru0 Ministeru0ui ;1n1t1'ii@
- Centre 7n teritoriu 0# nie0u0 Uniersit1'i0or de Medicin1 8i F#r(#cie@
- Nuc0ee de F#r(#coi)i0en'1 0# nie0u0 c0inici0or uniersit#re 8i spit#0e0or 6ude'ene.
F#ctorii u(#ni i(p0ic#'i 7n #ctiit#te# de "#r(#coi)i0en'1 sunt? (edici=
"#r(#ci8ti= cAt 8i person#0u0 te3nic #u%i0i#r.
Actiit#te# siste(u0ui de "#r(#coi)i0en'1 const1 7n depist#re#= e%#(in#re#=
7nre)istr#re# re#c'ii0or #derse produse de (edic#(ente.
O>iectie0e #ctiit1'ii de "#r(#coi)i0en'1 sunt?
- o>ser#re# cAt (#i r#pid1 8i co(p0et1 # re#c'ii0or #derse produse de (edic#(ente@
- cuno#8tere# (1suri0or pro"i0#ctice 8i (od#0it1'i0or cur#tie speci"ice pentru "iec#re
tip de re#c'ie #ders1 etc.
Metode0e de inesti)#re 7n "#r(#coi)i0en'1 /FT2 sunt?
- "#r(#coi)i0en'1 prin (etod# spont#n1= c#re const1 7n r#port1ri indiidu#0e re#0i.#te
de (edici= "#r(#ci8ti s#u #0te perso#ne@
3+
- "#r(#coi)i0en'1 prin (etod# intensi1= c#re const1 7n studii >ine or)#ni.#te de c1tre
ec3ipe de speci#0i8ti #supr# unui nu(1r (#re de perso#ne= c# de e%e(p0u? to'i
>o0n#ii intern#'i 7ntr-un spit#0= 7ntr-o #nu(it1 perio#d1 de ti(p.
F#r(#coi)i0en'# 0# sc#r# unei popu0#'ii= c#re const1 7n 7nre)istr#re# re#c'ii0or
#derse o>ser#te 7n ur(# unui consu( cunoscut de (edic#(ente= 7n c#dru0 popu0#'iei
respectie.
.I.LIOGRAFIE .I.LIOGRAFIE
1. A0e%#ndrescu LZ)i# Elemente de semiologie 9i farmacologie= Editur# Fund#'iei
$om<nia de :<ine= !44- @
2. A0ecu M.= A0ecu ;i0i#= $eacii alergice la medicamente= Ed. Medic#01= !44!@
3. <en)# G3.= =iologie celular 9i molecular= Editur# 5id#ctic1 8i ped#)o)ic1
<ucure8ti=1+-,@
*. <o6i'1 M.= ;1ndu0escu R.= Ro(#n L.= Opre#n R. - +naliza 9i controlul medicamentelor
To0.1= Editur# Inte0credo 5e#= !44!
+. <o6i'1 M.= ;1ndu0escu R.= Ro(#n L.= Opre#n R. - +naliza 9i controlul medicamentelor
To0.!= Editur# Inte0credo 5e#= !443
$4
.. Cinc# Rodic#= Popoici M#rine0# 8i co0#>.= 8urs de Farmacologie= Editur# Mirton=
Ti(i8o#r#= !44,
/. Cotr1u M.= ;t#n T.= Pop# Lidi#= Pred# I.= [incses.-A6t#Z M#ri#= To%ico0o)ie= Ed.
5id#ctic1 8i Ped#)o)ic1= <ucure8ti= 1++1@
6. Criste# Aure0i#-Nico0et#=Teodorescu ;i(on#= P#r#sc3i-<ucur L#ur#= Petri01-Cio>#nu
A0e%#ndr#= 5#rie Tioric# - 8ercetri farmacologice experimentale pri%ind aciunea
diluiilor !omeopate de 8!amomilla la ni%elul sistemului ner%os central - F#r(#ci#=
<ucure8ti= 1++$= ,! /1-!2= p. 1!-1&.
4. Criste# Aure0i# Nico0et#= - Farmacologie general= Editur# 5id#ctic1 8i Ped#)o)ic1=
<ucure8ti= 1++*
18. Criste# Aure0i# Nico0et#= - Farmacologie= Note de curs= Editur# Medic#01= <ucure8ti=
1+++
11. Criste# Aure0i# Nico0et#= Tratat de farmacologie= Edi'i# 1= Editur# Medic#01=
<ucure8ti= !44&
12. Criste# I.= Terapia durerii= Editur# Medic#01= <ucure8ti=1++,@
13. Cucuiet ;orin# - Farmacologie= !44- I;<N +-*-+-3--,,&-$3-4 G UMF - TG.
MURE;
1*. Cup#rencu <.= P0e8c# Lu(ini'# G+ctualiti ;n farmacologie 9i fiziopatologie= Editur#
5#ci#= C0u6-N#poc#= 1++&@
1+. Cup#rencu <.= Ti(#r M.= T!e farmacological receptors= !
nd
edition= G0ori# Pu>0is3in)
Douse= C0u6-N#poc#= 1++*@
1.. 5#nciu Fe0ici#= [orZ M.= Lupu'iu Geor)et#= 7tructur c!imic= Editur# 5#ci#= C0u6-
N#poc#=1+*3@
1/. 5i#conu E. 8i Nec3i"or M.= +ntibiotice betalactamice= Ed. Po0i)r#"ic1= C0u6= 1+**
16. 5i#conu E.= Nec3i"or= M.= +ntibiotice betalactamice= Editur# Te3nic1= <ucure8ti= 1+*&
14. 5inu=T.= Pop#-Criste# E. Tru'i#=E.= Popescu= A.= =ioc!imie medical= Ed. :edicala
=ucure9ti, 133&>
28. 5o>rescu. 5.= Farmacodinamie= Editur# 5id#ctic1 8i Ped#)o)ic1= <ucure8ti=1+--@
21. 5o>rescu= 5.= Farmacoterapie= Ed. Medic#01= <ucure8ti= 1+*3
22. 5o>rescu= 5.= Farmacoterapie practic= o0.I 8i II = Ed. Medic#01= <ucure8ti= 1+*+
23. 5o>rescu= 5.= (erontofarmacologie= Editur# Mond#n= <ucure8ti 1++&@
2*. 5o)#ru T. M#ri#= T#ri C.E.= 8ompendiu de farmacologie general= Editur# UniersitZ
Press= !443@
2+. 5o)#ru T. M#ri# Fes.t G.= T#ri C.E.= M1ru8teri M.= Farmacologie Experimental=
U.M.F. T)-Mure8= 1++*@
2.. Fu0)#= I.= Farmacologie= Editur# Medic#01= <ucure8ti= !44$
$1
2/.Font#ine L#nine= Tra%aux prati?ues de p!armacologie= Uniersite Li>re de <ru%e0es=
Institute de P3#r(#cie= Edition 1++&-1++,@
26. G0i)or Tir)ini#= Tudor Rodic#= Popoici M#rine0#= 8urs de farma-cologie= o0. I.
Lito UMF 1++3.
24. G0i)or Tir)ini#, 8urs de farmacologie, o0. II Lito UMF 1++$ @
38. D1u0ic1 I.= Fiziologie uman= Editur# (edic#01=<ucure8ti=1++,
31. D#'ie)#nu E0en#= 5u(itrescu E0en#= ;teco.# C#(e0i#= Moru8ci#) L.= 8!imie
terapeutic= o0.I.= Editur# Medic#01= <ucure8ti= !44, @
32. Ionescu C.= =iotransformarea medicamentelor= Editur# Medic#01 Uniersit#r1 \Iu0iu
D#'ie)#nuX C0u6 GN#poc#= !44!@
33. Ionescu-T#ro= M.= =iologie celular= Editur# 5id#ctic1 8i Ped#)o)ic1 <ucure8ti= 1+-,@
3*. [#t.un) G.<.= =asic @ 8linical #!armacologA= ei)3t ed.= !444= -&$-*43
3+. [0##sen C.5.=/edited >Z2= 8asaret and Doull s TosicologA-T!e =asic 7cience of
#oisons, ,
t3
Editions= McGr#O Di00= !441@

3.. L#ndrZ= ].= Gies L.P.= #!armocologie molBculaire-:Bcanismes dCaction des
mBdiateurs et des mBdicaments. Edition Arnette= P#ris= 1++3@
3/. Leucu'#= ;.= 1ntroducere ;n biofarmacie= Editur# 5#ci#= C0u6-N#poc#=1+-&@
36. Leucu'#= ;.= Pop= R.5.= Farmacocinetic, Editur# 5#ci#= C0u6-N#poc#=1+*1@
34. Leucu'#= ;.= Farmacocinetica ;n terapia medicamentoas= Editur# Medic#01=
<ucure8ti= 1+*+@
*8. Leucu'#= ;.= :edicamente 5ectorizate= Editur# Medic#01= <ucure8ti= 1++,@
*1. Leucu'#=;.= 'e#nolo!ie farmaceutic( industrial(= Ed. 5#ci#= !441@
*2. Leucu'# ;orin, =iofarmacie si farmacocinetica= Ed. 5#ci# !44!
*3. Lo)3in Fe0ici#= Toxicologie general= Editur# Medic#01 Uniersit#r1 ^ Iu0iu
D#'ie)#nuX C0u6-N#poc#= !44!@
**. [#t.un) G.<.= =asic @ 8linical #!armacologA= TII
t3
edition= App0eton _ L#n)e=
;t#("ord Press= Connecticut=U;A= 1++*@
/0( M#no0escu= E.= Farmacologie= Editur# 5id#ctic1 8i Ped#)o)ic1= <ucure8ti= 1+*$@
*.. M#%i(i0i#n=C.= Io#n 5.M.= (enetica medical= Editur# Medic#01= <ucure8ti=1+*,@
*/. Mitre# T#si0escu Nicu0in#.Lupu0e#s# 5.= Andrie8= A.= Mi0ic# Enoiu= =iote!nologii
utilizate ;n prepararea medicamentelor= o0. I. Editur# Medic#01=!441@
*6. Mo'oc= I.= 7tructura moleculelor 9i acti%itatea biologic= Editur# F#c0#= Ti(i8o#r#=
1+*$@
*4.Mun)iu =O.C.= +lgeziologie general= Editur# Po0iro(= I#8i= 1+++@
+8.Mun)iu =O.C.= P#e0iu= M.= P#e0iu Fr#)#= =ioc!imie - D abordare farmacologic=
Editur# Po0iro(= I#8i= 1+++@
$!
+1. Mun)iu= C. O.=/red.2= Elemente de farmacologie fundamental= Editur# U.M.F.
^Gr.T.Pop#X= I#8i= 1++&@
+2. Mure8#n An#= :edicaia ;n boli cardio%asculare1 Ed. Medic#01 Uniersit#r1 WIu0iu
D#'ie)#nuX= C0u6-N#poc#= !44&@
+3. MZceK D.= Farmacologie ilustrat= Editur# C#00isto= !444.
+*. Pop#= I.= Toxicologie= Ed. :edicala =ucuresti, 13EF@
++. Popescu= L.M.= Mi%ic3= F.= =iologie celular= Edit.Uni. WC#ro0 5#i0#X <ucure8ti=
1++,
+.. Popoici Iu0i#n#= Lupu0i#s# 5.= Te!nologie farmaceutic1 Ed. Po0iro(= I#8i= !441@
+/. Popoici= L.= D1u0ic1= I.= #atologia 7istemului ,er%os 5egetati%= Editur# Medic#01=
<ucure8ti= 1+*!@
+6. Popoici M#rine0#= (!id de studiu ;n Farmacologie= Editur# Mirton= Ti(i8o#r#= !44,@
+4. Popoici M#rine0#= 5u(itr#8cu=T.= 5. An#= Io#n# An#= C3eere8#n Ade0in#=
Mut#=N.= Mipo8 ;i(on#= Len)Ze0 5#n#= M#0i'# Io#n#= <#r#c <e#trice= (!id practic de
farmacologie= Edi'i# # III-#= Editur# Mirton= Ti(i8o#r#= !44$@
.8. R#icu= P.= (enetica general 9i uman= Editur# Du(#nit#s= <ucure8ti= 1++- @
.1. R#n)= D. P.= 5#0e= M.M.= #!armacologA, !
nd
edition.C3urc3i00 Liin)stone=1++1 @
.2. Resti#n=A.= Medicin# ci>ernetic1= Editur# 5#ci#=C0u6-N#poc#=1+*3 @
.3. Rosetti-Co0'oiu M#ti0d#= O'e0e#nu= 5.= =iocatalizatorii ;n practica medical 9i
farmaceutic=Editur# Medic#01 <ucure8ti=1+*4 @
.*. Rusu= T.= <#r#n= T.= <r8te#nu ````=5.5.==iomembrane 9i patologie. Editur# Medic#01
<ucure8ti=o0.I 1+**=o0.II 1++1 @
.+. ;i(ionoici= M.= CArste#= A0.= T0#descu=T.= 8ercetarea Farmacologica si
#rospectarea :edicamentelor= Ed. :edicala =ucuresti, 13FG@
... ;c3orderet= M.= #!armacologie- Des concepts fondamentaux aus applications
t!erapeuti?ues= Edition Frision Roc3e=P#ris= ;0#tKine Genee= 1++!@
./. Rac. Istan= (AHgAszerformulIlIs= Medicin# [bnZKi#dc= <ud#pest= 1+*$@
.6. ;#n-M#rin#= I.= 5#nciu= I.= Nede0cu= A0.= +natomia 9i Fiziologia Dmului, Editur#
5id#ctic1 8i Ped#)o)ic1= <ucure8ti= 1+-+@
.4. ;#r#)e# =M.= Tratat de fiziopatologie= Editur# Ac#de(iei= <ucure8ti= o0. I=1+*&=o0.
II=1+*-= o0.III 1++$@
/8. ;t1nescu=T.= ;##po0 E.= 1ncompatibiliti medicamentoase= Editur# Medic#01=
<ucure8ti=1+*4@
/1. ;troescu=T.= Const#ntinescu Cocioei I.= Fu0)# I.= Ciu>ot#ru= R.= 1ndreptar pentru
prescrierea medicamentelor= Editur# A00= <ucure8ti= 1++-@
/2.;troescu= T.? =azele farmacologice ale practicii medicale. Ed. Medic#0#= <ucuresti=
1++*.
$3
/3. ;troescu= T.= =azele Farmacologice ale practicii medicale= Ed.Medic#01= <ucure8ti=
1+++= Edi'i# # ,-#
/*. ;troescu= T.= =azele Farmacologice ale practicii medicale= ed.# TII-#= Ed.Medic#01=
<ucure8ti= !441
/+. ;urdu0escu= ;t.? Farmacologie generala. 8urs si lucrri practice pentru :edicina
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Farmacotoxicologie Si Farmacoepidemiologie Generala

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