Skripta Iz Farmakologije

SKRIPTA IZ FARMAKOLOGIJE Koristiti tablice i slike iz Temeljne i klinike !armakolo"ije

Anđela V.

Sadržaj 1.POGLAVLJE - UVOD....................................................... ........................................................................................................................... ........................................................................ .... 1 2.POGLAVLJE - FARMAKODINAMIKA ..................................................... ....................................................................................................... .................................................. 7 3.POGLAVLJE - FARMAKOKINETIKA FA RMAKOKINETIKA ...................................................... ....................................................................................................... ................................................. 12 4.POGLAVLJE - METABOLIAM LIJEKOVA ....................................................... .............................................................................................. ....................................... 1! ".POGLAVLJE - UVOD U FARMAKOLOGIJU AUTONOMNOG #IV$ANOG %U%TAVA % U%TAVA ............................... 1& 7.POGLAVLJE - AGONI%TI KOLINERGI$NI' RE(EPTORA I IN'IBITORI KOLINE%TERAE ........................ ........................ 23 &.POGLAVLJE - BLOKATORI KOLINERGI$NI' RE(EPTORA ................................................... ..................................................................... .................. 27 ).POGLAVLJE * %IMPATOMIMETI(I...................................................... ....................................................................................................... ................................................. 3+ 1+.POGLAVLJE - BLOKATORI ADRENERGI$NI' RE(EPTORA ................................................................. 3! 11.POGLAVLJE * LIJEKOVI A LIJE$ENJE 'IPERTENIJE ..................................................................... ......................................................................... .... 3) 12.POGLAVLJE - VAODILATATORI I LIJE$ENJE ANGINE PEKTORI% ....................................................... ....................................................... 43 13.POGLAVLJE * LIJEKOVI A LIJE$ENJE ATAJENJA %R(A .................................................................... .................................................................... 47 14.POGLAVLJE * LIJEKOVI A LIJE$ENJE %R$ANI' ARITMIJA ................................................................ !1 1!.POGLAVLJE * DIURETI(I .......................................................................................................... ................................................................................................................... ......... !" 1".POGLAVLJE * 'I%TAMIN, %EROTONIN, ERGOT ALKALOIDI ............................................................... ............................................................... "1 17.POGLAVLJE * ANGIOTENIN ........................................................... ............................................................................................................. .................................................. "" 2+.POGLAVLJE * LIJEKOVI A LIJE$ENJE A%TME ...................................................... .................................................................................... .............................. "7 22.POGLAVLJE * ANK%IOLITI(I ANK%IO LITI(I I %EDATIVNI-'IPNOTI(I ........................................................................ ........................................................................ 72 24.POGLAVLJE * ANTIEPILEPTI(I A NTIEPILEPTI(I .......................................................................................... ........................................................................................................... ................. 7" 2!.POGLAVLJE * OPI ANE%TETI(I ........................................................................................ ........................................................................................................ ................ 7) 2".POGLAVLJE * LOKALNI ANE%TETI(I ........................................................................................... .................................................................................................. ....... &4 27.POGLAVLJE * RELAK%ATORI RELAK%A TORI %KELETNI' %K ELETNI' MIIA .................................................. ............................................................................... ............................. &7 2&.POGLAVLJE * FARMAKOTERAPIJA PARKIN%ONIMA PARK IN%ONIMA ....................................................................... ....................................................................... )1 2).POGLAVLJE * ANTIP%I'OTI(I I LITIJ ......................................................... .................................................................................................. ......................................... )! 3+.POGLAVLJE * ANTIDEPRE%IVI ......................................................................................................... ......................................................................................................... 1++ 31.POGLAVLJE * OPIOIDNI ANALGETI(I I ANTAGONI%TI.................................................... ANTAGONI%TI ..................................................................... ................. 1+4 32.POGLAVLJE * OPOJNE DROGE ................................................................. ........................................................................................................ ....................................... 1+) 33.POGLAVLJE * LIJEKOVI A LIJE$ENJE ANEMIJA I 'EMATOPOENI $IMBENI(I RA%TA ................... 114 34.POGLAVLJE * LIJEKOVI A LIJE$ENJE POREMEAJA KOAGULA(IJE KO AGULA(IJE................................................ 11) 3!.POGLAVLJE * LIJEKOVI A LIJE$ENJE DI%LIPIDEMIJA .................................................................... ...................................................................... .. 124 3".POGLAVLJE * NE%TEROIDNI PROTUUPALNI LIJEKOVI, ANTIREUMATI(I KOJI MODIFIRAJU BOLE%T, NEOPIOIDNI ANALGETI(I I LIJEKOVI A LIJE$ENJE ULOGA ................................................. .................................................................. ................. 12& 37.POGLAVLJE * 'ORMONI 'IPOTALAMU%A I 'IPOFIE .................................................... .................................................................... ................ 134

Sadržaj 1.POGLAVLJE - UVOD....................................................... ........................................................................................................................... ........................................................................ .... 1 2.POGLAVLJE - FARMAKODINAMIKA ..................................................... ....................................................................................................... .................................................. 7 3.POGLAVLJE - FARMAKOKINETIKA FA RMAKOKINETIKA ...................................................... ....................................................................................................... ................................................. 12 4.POGLAVLJE - METABOLIAM LIJEKOVA ....................................................... .............................................................................................. ....................................... 1! ".POGLAVLJE - UVOD U FARMAKOLOGIJU AUTONOMNOG #IV$ANOG %U%TAVA % U%TAVA ............................... 1& 7.POGLAVLJE - AGONI%TI KOLINERGI$NI' RE(EPTORA I IN'IBITORI KOLINE%TERAE ........................ ........................ 23 &.POGLAVLJE - BLOKATORI KOLINERGI$NI' RE(EPTORA ................................................... ..................................................................... .................. 27 ).POGLAVLJE * %IMPATOMIMETI(I...................................................... ....................................................................................................... ................................................. 3+ 1+.POGLAVLJE - BLOKATORI ADRENERGI$NI' RE(EPTORA ................................................................. 3! 11.POGLAVLJE * LIJEKOVI A LIJE$ENJE 'IPERTENIJE ..................................................................... ......................................................................... .... 3) 12.POGLAVLJE - VAODILATATORI I LIJE$ENJE ANGINE PEKTORI% ....................................................... ....................................................... 43 13.POGLAVLJE * LIJEKOVI A LIJE$ENJE ATAJENJA %R(A .................................................................... .................................................................... 47 14.POGLAVLJE * LIJEKOVI A LIJE$ENJE %R$ANI' ARITMIJA ................................................................ !1 1!.POGLAVLJE * DIURETI(I .......................................................................................................... ................................................................................................................... ......... !" 1".POGLAVLJE * 'I%TAMIN, %EROTONIN, ERGOT ALKALOIDI ............................................................... ............................................................... "1 17.POGLAVLJE * ANGIOTENIN ........................................................... ............................................................................................................. .................................................. "" 2+.POGLAVLJE * LIJEKOVI A LIJE$ENJE A%TME ...................................................... .................................................................................... .............................. "7 22.POGLAVLJE * ANK%IOLITI(I ANK%IO LITI(I I %EDATIVNI-'IPNOTI(I ........................................................................ ........................................................................ 72 24.POGLAVLJE * ANTIEPILEPTI(I A NTIEPILEPTI(I .......................................................................................... ........................................................................................................... ................. 7" 2!.POGLAVLJE * OPI ANE%TETI(I ........................................................................................ ........................................................................................................ ................ 7) 2".POGLAVLJE * LOKALNI ANE%TETI(I ........................................................................................... .................................................................................................. ....... &4 27.POGLAVLJE * RELAK%ATORI RELAK%A TORI %KELETNI' %K ELETNI' MIIA .................................................. ............................................................................... ............................. &7 2&.POGLAVLJE * FARMAKOTERAPIJA PARKIN%ONIMA PARK IN%ONIMA ....................................................................... ....................................................................... )1 2).POGLAVLJE * ANTIP%I'OTI(I I LITIJ ......................................................... .................................................................................................. ......................................... )! 3+.POGLAVLJE * ANTIDEPRE%IVI ......................................................................................................... ......................................................................................................... 1++ 31.POGLAVLJE * OPIOIDNI ANALGETI(I I ANTAGONI%TI.................................................... ANTAGONI%TI ..................................................................... ................. 1+4 32.POGLAVLJE * OPOJNE DROGE ................................................................. ........................................................................................................ ....................................... 1+) 33.POGLAVLJE * LIJEKOVI A LIJE$ENJE ANEMIJA I 'EMATOPOENI $IMBENI(I RA%TA ................... 114 34.POGLAVLJE * LIJEKOVI A LIJE$ENJE POREMEAJA KOAGULA(IJE KO AGULA(IJE................................................ 11) 3!.POGLAVLJE * LIJEKOVI A LIJE$ENJE DI%LIPIDEMIJA .................................................................... ...................................................................... .. 124 3".POGLAVLJE * NE%TEROIDNI PROTUUPALNI LIJEKOVI, ANTIREUMATI(I KOJI MODIFIRAJU BOLE%T, NEOPIOIDNI ANALGETI(I I LIJEKOVI A LIJE$ENJE ULOGA ................................................. .................................................................. ................. 12& 37.POGLAVLJE * 'ORMONI 'IPOTALAMU%A I 'IPOFIE .................................................... .................................................................... ................ 134

3&.POGLAVLJE * TIROIDNI 'ORMONI I ANTITIROIDNI LIJEKOVI ......................................................... ......................................................... 13& 3).POGLAVLJE * 'ORMONI KORE NADBUBRE#NE #LIJEDE I NJI'OVI ANTAGONI%TI ....................... 141 4+.POGLAVLJE * %POLNI 'ORMONI I NJI'OVI IN'IBITORI ................................................................. ................................................................. 144 41.POGLAVLJE * 'ORMONI GUTERA$E I LIJEKOVI A LIJE$ENJE EERNE BOLE%TI ......................... 1!+ 42.POGLAVLJE * LIJEKOVI % U$IN(IMA NA 'OMEO%TAU MINERALA KO%TI .................................... .................................... 1!" 43.POGLAVLJE * BETA-LAKTAM%KI I DRUGI ANTIBIOTI(I KOJI DJELUJU NA %TANI$NU %TIJENKU I MEMBRANU ........................................................... ............................................................................................................................... ............................................................................. ......... 1!) 44.POGLAVLJE * KLORAMFENIKOL, TETRA(IKLINI, MAKROLIDI, KLINDAMI(IN, %TREPTOGRAMINI I LINEOLID ............................................................................................................................................ ............................................................................................................................................ 1" ! 4!.POGLAVLJE * AMINOGLIKOIDI....................................................... AMINOGLIKOIDI...................................................................................................... ............................................... 171 4".POGLAVLJE * %ULFONAMIDI, TRIMETOPRIM I KINOLONI .............................................................. .............................................................. 174 47.POGLAVLJE * LIJEKOVI KOJI DJELUJU PROTIV MIKOBAKTERIJA ..................................................... ..................................................... 17& 4&.POGLAVLJE * LIJEKOVI PROTIV GLJIVI(A .................................................. ........................................................................................ ...................................... 1&1 4).POGLAVLJE * ANTIVIRU%NI A NTIVIRU%NI LIJEKOVI LIJEKOV I........................................................ .............................................................................................. ...................................... 1&" !+.POGLAVLJE * ANTIMIKROBNA %RED%TVA ........................................................... ...................................................................................... ........................... 1)2 !2.POGLAVLJE * LIJEKOVI PROTIV PROTOOA METRONIDAOL I TINIDAOL ................................... 1)3 !3.POGLAVLJE * ANTI'ELMINTI(I....................................................... ....................................................................................................... ................................................ 1)3 !4.POGLAVLJE * LIJEKOVI A LIJE$ENJE LOUDNI' BOLE%TI ............................................ ............................................................ ................ 1)! !!.POGLAVLJE * IMUNOFARMAKOLOGIJA ......................................................................................... ......................................................................................... 2+2 !&.POGLAVLJE * $E%TI TOK%I$NI %INDROMI ................................................................................... ....................................................................................... .... 2+" "2.POGLAVLJE * LIJEKOVI A LIJE$ENJE BOLE%TI PROBAVNOG %U%TAVA .......................................... 2+&

1.POGLAVLJE - UVOD Farmakologija /e Farmakologija /e 0nan /a e 5a6 8/e9a/e: e:/; 6a< na 5l=e 8a6e. Me>9na ?a<:al@/a /e > ?a<:al@/e /a e 5a6 6a<:a /e e /a@n0e  l/een/a 5le. Toksikologija /e Toksikologija /e > ?a<:al@/e /a /e 5a6 neCel/n: 8n9:a e:/; /e6a na 5l=e 8a6e. Farmakokinetika 8/e Farmakokinetika 8/e 8/e9a/ /ela na l/e, n<. a<9/a, 0l86an/e >. Farmakodinamika /el6an/e l/ea na /el, :e;an0:e nea l/e6a L/e6 / e na/e=e <e 8l/88/8 an<@ane ne, <@ane :le8le, :ale e>e  <ene, n8lene elne, l>e  8@l/;>@ene :le8le  e@0@en l/e6 8  a6n, 0na 0 na >a a>an l 6=e a:e<n; 9ena6e > 6aCn; ln; l/e>9a. VELI$INA I MOLEKULARNA MA%A L/e6 6a< M <7n l/a > M 1++ 8 </e >6l/n ele6n 8 6: >/el6an/8, > n a M < 6e: > 1+++ e e= a<5?8n>6e, 6an >e< aal6e, ;><?5ne. PRIN(IPI FARMAKODINAMIKE Un9 l/e6a <0la0e 0 >/el6an/a :le8le l/ea na a e l/e na06a agonist, agonist, a a /e a /e antagonist*slika1-3. Mle8la 0 e :Ce <a0a :8 krivulje doza-odgovor. doza-odgovor. Ne l/e6 a en0: ne >/el8/8 na en>@ene @ene 8
1

Ine<na 6e0na :/ea L/e6 e 6eC8 0a ne/el/9:ala0:a ne<n 6e0an/e @/el l/ea 88 na ln8 l5>n@ l/ea 8 9<8la9/ * al58:n. PRIN(IPI FARMAKOKINETIKE Da 5 >=l > 06n; 8naa l/ea, 6ena l/e6a e :<580=a > :/ea <:/ene9</e6a > :/ea a9/e:0a. PERMEABILNO%T * <la0a l/e6a <0 5l=e 5a</e?80/a <0 6>ene >/el/e, eene ?80/8 :le8la:al <en 0:eđ8 <6  eene 8na ne: l/e6:a. Difuzija kroz lipidni medij * a6na >?80/a :le8la <0 :e:5<8@e l>ne <88?80/: < 0:eđ8 :e:5@ene 6a<. Vel 5</ a6; en?9e/el8/e a:n, n90e e 5a6l/a 6e0an/e: :le8le 0a e9/al0/el6e na :e:5a 80<8/e 86laen/e @ >/ela :e:590a :@88/e 6el: :le8la:a e  l?5n: :le8la:a 8la0 8 an98, <en, 6a:n B12. En>90a /e 6e:a ele6an <9e. E@090a /e 5
2

FICK! "#K$ DIF%"I&' F96 0an >?80/e 8/e 5<0n8 a :le8la <0 5a</e<8 n9e/en(1(2, e?9/en e<:ea5ln l/ea, 6<=na, >e5l/na 5a</ea /e l/e 5a9. Tađe< a<9/a /e 5e5l/:Ca.    

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D?80/a <0 6>en :e>/ * l/6 l/ea 8 6> /e 6na  ionizaciji(polarnosti) :le8le,  /e< :le8le 6>e >/el8/8 a >l  <6lae ; na5/ene :le8le l/ea, 6aen =. Tađe< l>na l/6 :le8le /e 5n :e>/ * :n@ l/e6 8 la5e 5a0e  la5e elne. a a6e :le8le ' lne > :le8la e 5 n0 ne. A /e 0na P a l/ea  ' :e>/a, > :le8la /e e 5 n0
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' <n

R(OO -  ' ne<n

'en>e<n-'ael5a9;6a /e>na>C5a /e ln 5na a>a /e  l/ea 0:eđ8 /elen; >/el/aa 6n  '. N<. :n@ l/e6 e l5>n ?l<0a6an/e 5a<5naa. T e >@ađa /e< /e l/e la5a elna /a e >9/8, a a/ 5l e ne :Ce >?8n>. *slika1-6

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AP%ORP(IJA LIJEKA P8e6 a>:nal/en:a > 9l/n@ 6a  0a;/e6a/8  :/ea a9/e. Da 5 l/e 8=a 8 <6 ::n:n/el/ena a ln: <:/en/en@ l/ea /e bioraspolo,ivost. Ona6n/a, al /e a<9/a </a  :an/a. L/e6 <la0e <0 eliminaciju prvog prolaska, @>/e e 6e > l/ea :ea5l0đe 8 e:n8 9<8la9/8. na ne l/e6 :a/8 :al8 50a  n. El:na9/a <6@ <laa /e 05/e@n8a, al 8=a 0a, al > :Ce 0 @n@ 8a e >a/8 na 6a/ nan. $e e < > a9/enaa / 6na 0a l/e6e / 8 ln6 < 5n: e:e=n; 86a, 6a@ne 0a laln8 <:/en8. B<0na a<9/e 6  ><8/8 <:/ene  ?<8:8la9/e l/ea. Te<:alna <:/ena * ala9/a na C8 0a e:n8 <:/en8. A<9/a /e /a e5l/ne Ce, al el:na9/a <6@ a /e 05/e@n8a. P< <6 * 8/ee na a<9/8 n l/ea 8 <6  6ea6a n9e?80/a,  a e a<9/8.

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Kn9e/ena n9e/en n9e e 6ele lne l/ea <:/ene. Na8< :e :0a /e :an/, ><589/a :an/e lne l/ea e > n9e/en > n8le a al/n/e 8/an/e l/ea. P< <6 * 8 6a /e 6aCna >n9a 5<0ne 8na l/ea, a < <6 ne 8/ee na ln8 l/ea < 5< <<6l/ena 6a:0a, <9e, 585 ne >@ne >6l/n. Tl/6 * l/ea 8 68 8/ee na n9e?80/a 0 <6n; Cla e e 85<0a. Ne <@an:0a :a/8 6 aa6 l>a  8 n/:a 8 l/6 l/e6 / 8 ll85ln. Ka /el/8. Va?80/8 0 6a8la/el/a. Kl<6n e /a 6eCe 0a <ene eee<:nane >589/e l/ea. V > /e :/e< lne l/ea 8 /el8  n9e/el/9:a /ela 8 :an/e 6aCn 8 ?a<:ane9. Al e  :a 8 /el8 naa n/e@6 8na, al  ne ><8@ e?e 8 5n. Ne l/e6 nan đ8 8 e:n8 9<8la9/8. El:na9/a <6@ <laa /e e<6ae. Kn6e<0/a 8 :ea5le /e > el:na9/e. P<l/e6le6>a, :n>l 8 nea6n < <:/en  :a an8 a6n. Mn@ l/e6 8 a6n < <:/en, al :a/8 a6ne :ea5le5en0>a0en. !

Ne l/e6l/, n8 :>?9/el8/8 > e ne 0l8e. El:na9/a l/e6a * 80 >08 l/ea, 5<0na el:na9/e 0a>n/e >0eneana a6n; :le8la 0 <6a l /ela >?9a0ea:, el:na9/a <6e :le8le :ea5l0:: n/e  a   8na. a l/e6e / e ne :ea5l0na 8Cen 8na. Fenl5en0a:n /e  a 6/el6an/e l/ea a @6< >a /e 5<0na el:na9/e <<9nalna n9ea n9ea @6< >a 5<0na el:na9/e /e nanna  ne6na  n9e@ađa a>a l/e 0a :e;an0:e el:na9/e < n9e ln@ nea lnea/el/9:a Nan a<9/e 8 9<8la9/8, :n@ l/e6 <la0e <0 <589/e a nan @a </8 ?a08 el:na9/e. Mae:a, 6 e :Ce :8l/el/a :>el: * <6  ea /e
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2.POGLAVLJE - FARMAKODINAMIKA Fa<:a>na:a e 5a6 >/el6an/e: l/ea na 5l= e:, > e ?a<:anea 5a6 >/el6an/e: 8a6a na l/e. P<n9 ?a<:a>na:e 6</e>e 0a 6e, > 0l a9/enaa a e9?n: 5le:a. RE(EPTORI 0eceptori 8 e9?ne :le8le 8 5l=: 8a68  /:a l/e @ađa/a / : >a 5 :@l a e 6eC8 a l/e: >a 5 >=l > <:/ene ?8n9/e. Mn@ en?9@ađa/ / 0an/e 8ne l/ea, e :n@ l/e6 8 la?9e neenla-9la0a. Ne n:  e?e<, n<.<0nna0a> n08ln  nna9elln a >@6< >n /e +iperbola, a>a a/ >n a6: 8 l@a<a: 8a6 <68l/a /e sigmoidna   /e>na6l/8/e :ae:a >n 0:eđ8 >0e  8na *slika2-1. 'fikasnost('ma4)  potentnost('C56 ili 'D56) e 06>e 0 6; >aaa. A 8 :an/ E( !+ l ED!+ enn l/ea /e 6ea. K0I!%.&' D$# K$C'T0#CI&' I %3I$K# I !'"#$&' #7$IT# M@8e /e 0:/e< a 5 e: lan >n a  >n 0:eđ8 l/ea  8na. Kn9ea 5 e 6e0al !+ na :an/  /e 6e a?ne l/ea a /e :@8e  0:/e< 6e88n 5</ a e > :n:8: >0e 0a e9?n >@6< 8 6a@ /e>n9a 8 8la9/ >5/e: 6ann8 <68l/8 >0a-8na*slika2-16. N<.l/e6 0a nCa6an/e laa :@8 e <8a6a :/e0e 
a9/enaa. Ka>a e na9<a na @@6< na >08 8 85 a l@a<:: >0e /a /e a>:n<5/e: 8:8la6n8 6ann8 <68l/8 >0a-8na, na/e=e sigmoidnog 5la. redi8nja potentnost('D56)9 sredi8nja toksična doza(TD56) i (,ivotinje) sredi8nja letalna doza(.D56) e >5/8 0 6a6; e6a. Je< /e e@ e9?n@ e?ea <06l/n >0a-8na n/e 8 6e0 a ED !+ > <68l/e n9.l/ea-8na, 6ann: <68l/: e ne >0a-8na >a/e n?<:a9/e  6a</a9/a:a na /el/6 l/ea 8 8la9/,  a /e 6a</a9/a :ala <68l/a /e <:a. D&'.T!0$T('FIK#$T) D/el60a l/ea /a 6ela. E?an /e >: l/ea  e?n9/ a<9/aln a@n :a/8 :an/8 :a:aln8 >/el6a 5 >=l > >n8 l/ea  8na, > 8na na/e=e >la0 na !+ :a:aln@ 8na, a  >0a /a  /e 0a  8n; 0a-8na :/e 0 <68l/e n9.l/ea-8na  0 6anne <68l/e >0a-8na, al >56en na. P0I3%!$I 0'C'PT0I P<86n @ađa 8l n8 6 /e a e 8e n9e. A /e 'C56 manji od Kd, n>a <86n n@ > >6a :e;an0:a. P<6, 6</e:e a6a9/e e?e8Ce ne@  5</a >8n; e?e<; :le8la. P<86 <86n; a e 6eC8 l/e-ea 6a an/a * a6n  na6n. U >868 l@an>a, 868 l@an>a, a08/8 >a ne
 e na06a konstitutivna aktivnost. Puni agonist /e l/e 5an 8 8n a6a e 6eCe 0a 6l/na 6a n9e6> > a6 :an/ 8na a 0a 6e el8, neutralni antagonisti e 6eC8 a : a?ne: 0a R   Ra an/e,  n86ne a6n. O5/e e a@n 6eCe l na  :/e, 6eC8 e 0a a@na e 6ea6a<68l/a 8 >en, al :a:aln 8na /e /e>na. A /e n9e6l/n 6ela, :Ce 8 8n 0a:/en ana@na  8 8n a6en/e>n a /e <86n n a /e <86n a /e <8@a/8 :le8l8 e 5 ?a<:al=; ana@na /e< e n 6eC8 a  :/e a  l/e /e@ n;5laa9/a a>0:e<a<l, / el<8@e <6ne :eale. P: e 6eCe a ??<:  <@an??a:a / 8 n;5< lnee
)

TERAPEUT%KI INDEK% I TERAPEUT%KI RA%PON Terapeutski indeks /e :/e< TD !+ 0a8na. Pa6l/a <9/en8 @8a :a /a 6el8 n8 >08  :n@ :an/8 e?e6n8 >08. Al n/e <an 8 e. D terapeutski raspon, 6=e ln 6aCan, 8/e 0e 0:eđ8 :n:alne e?e6ne >0e  :n:alne ne >0e. %IGNALNI ME'ANIMI Ka>a e a@n 6eCe 0a a:n na, DAT. Mn@ ana<:9 9l/a/8 nan: a6 /e e?e< :e;an0a: 8n8a< an9e  a6l/a/8 lan8 l/e-?805lne<>n ;<:n,NO <la0e :e:5/el8/e na n?9/el8/e na <0n na08 /a /e na :e:5a e l/e 6eCe9n JAK e a66> > ??<l0a9/e %TAT :le8la, ne a>a 88/8 > /e0@?9<8@e a@ene5en0>a0en na GABA-a6n: anal8. Mle8le anala >/el8/8 a enla 9la08 6> > a6a9/e G <ena a n > a6a9/e a>enla 9la0e. *tablica2-1

1+

REGULA(IJA RE(EPTORA Re9e< e >na: @ađa 8 8@:>an. $ea l nanna 0lCen a@n:a @6 Qa>a Q-a90: 8 8 an9e,  a e lne > a@na. Kan/e e   > <=n/e ne; een9/aln; 8aa l; ?a@6
11

3.POGLAVLJE - FARMAKOKINETIKA Fa<:anea 6a 8/e9a/ 5l=@ 8a6a na l/e. P<9e 8 a<9/a, ><589/a  el:na9/a l/ea. P<:/ena >aaa  ?a<:ane9 >06l/a6a 00e  n9e. N 8 66 86/e:aa9/en n9e/ele  6:a9l/n <@an  5<0ne el:na9/e. O6e 6e ?8n9/e 8 6<8@e >6/e e :@8 > :8 2 <:a/eleV>  ln6en 0a 6a l/e  a9/ena, al e </ene 6</e>n 0 8la9/e :@8 < 0a 0/eleV> 6e08/e ln8 l/ea 8 /el8  n9e
&.!$ '(&$ / 0'(/ 1

I0 n/e 8 8n an, 0a e na06a prividnim. L/e / e 8 8n 0a> /e>na 6l8:en8 la0:e4 eCne /ela. V > l/e6a / e 6eC8 0a <ene la0:eal58:n :@8 5 <:/en/en 8 l8a/8 5le /e<8@8 a V > :Ce 5 8n 6e ne@ aln 6l8:en /ela. K.I0'$ Kl
3#"!$ (4!$'( 1

a l/e / /e >e <0 el:na9/8 <6: : le ? 9lea??e<8@ ?l  a :a:8: ? ;e al 5l> ?l  ;e <@an ? el:nan. Klna aa9e8 ela: @ l/ea 8 <@an. Kl8 <6. U 6: l8a/8, 5le l ne ><8@ 12

l/e6 / :ea/8 < <6 :@8 :a /a >n8 na 5le a:@ <@ana el:na9/e. a l/e6e / 8 n8l: : el:na9/e, l  (L. Ka  l:. MCe e > 0 05 )

678 - 12

Ble, @>ne  ><8@e 6a</a5le e :/en/a/8 l/ele. Pl86/e el:na9/e e nee <:/en a e 5/e 6</e>n :an/e. N<.a>a e l>an <:/en <an: 5len8. Pl86/e el:na9/e ><8@ a &7*)+ ?  ea>-ae 9n9enn@8;a5le ?<: ;e ea>-ae e??e9 ;8, 3*4 ;al?-l6e ? >n@ a a 9nan e a>eS8ae  <>89e ;e e??e9  5e ee9e> a ea> ae ; a e9?e> n@. /I0#P.;I!T B0e /a >đe > e:e 9<8la9/e. Be?n<8@: <8a:a, 5nae 5@ađa 8 >:a 6<8@: ?a<:a. Da 5 8l/8l  e ?a5/e: #%C(povr8inu ispod krivulje koncetracija-vrijeme).*slika3-4 'KT0#KCI&# I0l86an/e l/ea <@an: e :Ce @le>a a e <la0 <0 a/ <@an. Nan 8a6e 08 60a n9ee@n8 :n:alne ne n9e8@; e<>a <:/ene e >0e >a0a e < >a e V > na8n l/e:. I>ealn lan 13

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V> n/e 8 6/ ?<:8l. B<0na >008 >0a  /e>n9 6na6n <:/ene 8 <nn/ e0e l/ea 5 e n: l 6=e 8a >ne6n. B</ >ne6n; >0a e > :n:alne en aln, l e >a/e 6ea >0a 8 >8C: ne<6al:a l :an/a >0a 8 e=: ne<6al:a. A /e a e :an/e  e=e >0e l/ea :a 5 e 05/e@l <6an/e. U>a0a A e e0a : 6el, 6ela >0a e :
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Ne:a la0a /a 6elaV > :n@ 6e > 6l8:ena <6, >0a e :a6a la@an >a 5 05/e@l n 05@ /a 6el; 9e<589/e. TERAPEUT%KI RA%PON Te0n lne l/ea / e >a/e ne<:enn, > :n:alna na n9e 1!:@L. na 0a @ a9/ena ea/e 6a l86/e @ l/ea.

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4.POGLAVLJE - METABOLIAM LIJEKOVA %6 <@an0: 8 0lCen   ; >/el6an/a :n@; en>@en; 85an9, e6l89/a /e nalCn 0l86an/8. ATO JE /IT0#$F01#CI&# NU#NA Mn@e an9e /e >/el8/8 a 8la0 0a ee:a; nan a<9/e. Ia nee a/8 6e  n; en; 8 /el8. Ban > a6; <9ea. T /e 6aCan :e;an0a: 8 /e: /el a >/el6an/e :n@; l/e6a, al 8 ne: l8a/e6:a  0a a6a9/8 <l/e6a. Mn@ l/e6 8 a0e :/e=6e ?8n9/e, redukcija, deaminacija  +idroliza. O6 en0: 8 nađen 8 6el: n9e@6 l/e6a :ea5l06aH C l C, ele6n e :Ce 6>/e, a  enan:e< 8 :ea5l0a/8 e en>@en 88 :an/e ll85ln: ne@ <@naln l/e. En0: ?a0e II n8 /a ele6n. L/e6 / e :ea5l0
1!

DETERMINANTE BRINE BIOTRAN%FORMA(IJE BIOTRAN%FORMA(IJE B<0na 5a na9a. O6e 6a</a9/e 8 05@ @ene; l 05@ 8/e9a/a l/e6a. a nee l/e6e, @>ne l 5le :@8 0nan 8/e9a na :ea5l0a:. U l/8>, l /e 5an a: > ne; l/e6a8na <6@ <laa na al;l /e 6e 8 :8=a<8@8 <88, 6ena l/e6a :Ce n>8989/e en0:a 8 /e<  l8:a  :Ce 6ea :ea5l0a: ne; l/e6a. Je< /e 5<0na 5ee<:nana l0a/n0lneelnee 6a/ <9e  <9e e 056a /a 5<0,   /e>na >0a 6@ ne8<:88la/el6an/e ! :n8a. :n8a. P</en 1 5a 5a > 2!++ :a a5n<:alan 5l 6@ en0:a / :ea5l0 /e>ne >0e :Ce   ><8@ a:n a ;> e :ea5l0 / :a/8 :an/ aa9e a9ela9/e< a9ela<, :a/8 <>8l/en/e  ne >@60e 6; l/e6a. %< a9ela< e 89/a /e a9/e 9<:a P4!+ 8 /e<  ?a@689ana >a 5 e @la :a:alna n>89/a l 6a e 689/8 :ea5l0:a l/e6a 8 karbamazepin9 fenobarbital i rimfampicin. rimfampicin. I$*I/ICI&# '$"I1# Na/6/e<6an/ n;5< :ea5l0:a l/e6a 8 amiodaron(benzofuran)9cimetidin9 furanokumarini(sok grejpa)9 antifugalni azoli9 ritonavir. ritonavir.*tablica4-2 %a:85la n;5< 8 l/e6 / 8 :ea5l0l, n<n, n <n, <nlan, e5a<5al, al8<nl, ?l8<en  <la9el8na:; ?a89/a <a <6 8 <@an / :ea5l0
1"

BIOTRAN%FORMA(IJA BIOTRAN%FORMA(IJA LIJEKOVA U TOK%I$NE METABOLITE Mea5l0a: l/e6a n/e nn: a na6a9/: l/e6a. Ne l/e6 e <8@e a6ne <>8e :ea5l0:a. A 8 6 <06> n, :Ce > > 05l/n; =een/a 8 ne: l8a/e6:a. VaCan <:/e< /e paracetamol a>a paracetamol a>a @a e 80:e 8 6el: >0a:a.*slika4-5 A9ea:n?en e n/8@:  8l?a:a 8 @80 /a /e 0a:a, ?a0a II :ea5l0:a e ea P4!+ * G%'@l8an  l/ea a <ln: @<8a:a na een9/aln: <en:a /e<8@@ 8l?;><ln@ >nna, 8l?aa  @l8ana :@8 5 :ale, = a9/ena >6> > ;ean  8 n<:aln: >0a:a a8< en0:aeanl :@8 6ea n a9ea:n?ena /e< 6ea6a/8 :ea5l0a: ?a0e I 6=e ne@ ? a0e II, a  n/:
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!.POGLAVLJE - UVOD U FARMAKOLOGIJU AUTONOMNOG AUTONOMNOG "IV#ANOG SUSTAVA A#% /e 6en: nena:/e C6an@ 8a6a  n A#%-a /e @la6n 8 0a n?<:a9/e 0 (N%-a e. N/e@6a 2 @la6na >/ela 8 parasimpatički i simpatički #;. #;. *slika6-1 Ene< C6an 8a6E#% /e l8a8n:an  l9 :/ene<@ le8aA8e<5a9; le8aA8e<5a9;  85:80n@ le8aMene< le8aMene< n =al/8 en0<e n?<:a9/e  n/; :<e n?<:a9/e. Mn@ /e a?e/el8/8 na n/;. Pa e@:enaa?->. . %:aa ne. Vena :a; @an@l/a /e l96a a/el8 a5>:nalne a<e. Vena aale > :C>ne. 5@ la9/e @an@l/a, 8@a. O5@6ael8 <6n; Cla, e ne  >/el6an/a ne8</el8/8 8 >/el6an/8 a8n:n; l/e6a. *slike6-3 i 6-4 K.I$'07I3K# $'%0T0#$1II&# #cetilkolin(#c+) /e #cetilkolin(#c+) /e <:a</ acetil-Co#:;n></  kolina0 kolina0 06anann@ <<8Cen@  :/e;8<:a!#T :/e;8<:a !#T. . O6a/ <9e e :Ce n;5
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O8=an/e a9ellna * 8=an/e la0 > ?80/e :e:5=en a 5 an/e ?8n9/e a9ellna * >/el6an/e a9ellna e n<:aln >>a :ea5l0:: 8 a9ea  ln :8 en:a acetilkolinesteraze 8 acetilkolinesteraze 8 na/ 8n. O6 <>8 e 6l/n ele6n. Ia :le8le 58ln8: na 8 /a 6ele  /a < >?8n>a:a  6/e<6an 6a0>laa9/: :a: 6lan:a 8 elen: :=:a, n 0l88/8 a9elln. Da:n /e 6a0>laa< 8 585a:na  n<l<la0a e n;5a:n e </:a 8 a> >a:na > a:na  n >/el6an/a * >a:n  n >/el6an/a /e 8n  8n ><8@a/. D?80/a  6a/8 >/el6an/e. I06an nae 8ne 6 8 e 0l88/8. Anal0: 24-an@ 0l86an/a metanefrina9 !1#(vanilmandelična kiselina) e kiselina) e :Ce 0:/e< 8n 6a/a@n08 ?e<:9:a. In;59/: MAO e 6ea6a lna aela:na   :a e
L/e6 / 5l<8@e , ne8<e> , 6a< P, ne8<en0n, :aan. Gla6na 8l@a : /e modulacija nae <8@: naa:a. KARAKTERI%TIKE RE(EPTORA Re9e< 8 A#% 8 lna:n   a9elln. E?e a6a9/e 6; el,@la :=, e. 3 >6<e 8 6aCne 8 e<?e6<e 8 l96<a /e na/6aCn/ >a:n an 8<đen <:/e< 8 / e 6a @an@l/a 80<8/e 6n <:/e<. %ln, n8n 6< <9a :a 8<đen <a:1++-11+:n 8 l8a/8 ne>aa A#%. Ka e e 6e 6</e>n <:/en6ea l :an/ a e @an@l/ 5l@6< /e la@an a 0na: / 8a6 /e >:nanan. I 0/en9a  n8a</aln 6< 8 >:nann ne<6
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aa 5a>6a 8a6a, a 8lan/e: >:nann@ a:nann@ :a@ 8a6a, </a0:  a;a<>/:. NEURONI KOJI NI%U NI ADRENERGI$NI NI KOLINEREGI$NI ($#$C) Nea C6ana 6lana 8 a8n:n: e?e<: 6:a ne a08/8 ;e:/8 a@6< 80<6an 8<n:a /e >en?9e<@na, 0na 8=a/8 e>e a <:ae, a 6a< P, /a e 8=a/8. O6a 6lana e na06a/8 en0 e a6ne  8 enn a@n 8 :n@: a8n:n: 6:a, @la :=. MJE%TA DJELOVANJA LIJEKOVA 5@ 6=e /el6a. On 8l/88/8 (N% 9ena >/el6an/a. Na/ele6n/e >/el6an/e /e a l/e >/el8/e na n/e. *tablica6-5 Mn@ <<>n  ne n :a/8 6aCne e?ee na a8n:n8  :a8 C6an8 ?8n9/8. INTEGRA(IJA AUTONOMNE FUNK(IJE F8n9nalna ne@@ađa :8 :e;an0a:a negativne povratne sprege  6aCna /e 8 >@6@ene  e@0@ene A#% 08l<8@: na, e>a  ><8@; 6a< 8 nađen. P@en: 6a<: e >@ađa na 6: C6an: 6lan:a. Pna :>8lae<@n; /e /e nna 
=n; 86a. Kn<la <6n@ laa a 5a<e<n ;<:naln: 8a6: /e /a 6aCna. *slika6-7 O6 ;:ea :e;an0: >n/ a<e</ la na e6/a9/a > >n 80<8/e <:/ene 8 A#% a6n  ln e<n ;<:na. O6e <:/ene 8 /a 6aCne 8 >@6e 8 585 8/e9a/e: al>e<na. O6 :e0a6l/n /a >a 6la>a/8 8/e9a/ ne; l/e6a. N<.elaa<:a a ;>/a5a<e  le<8@: l/e6:a. FARMAKOLOGIJA OKA O e a/ > :n@; 6a a a8n:nn: n<l:.*slika6-9 /en9a /e > laa<8  aa9/8 a, /e <:a n<l: :8a<n; 9e. %6a > 6;
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$.POGLAVLJE - AGONISTI KOLINERGI#NI% RE&EPTORA I IN%IBITORI KOLINESTERAE Kln::e l/e6 8 l/e6 / :/el8/8 izravno a/a/8 e a ln/el8/8 neizravno :a/8 lne e?ee a  0/el8/8 a@n al n >/el8/8 n;5a/8 >/el6an/e en>@en@ a9ellna. Kln::e9 e a/e > 2 @la6ne >6<e 0a6n  :e >/el8/8 l 0/el8/8 0/ele e na ne / >/el8/8 na :8a<ne l nne ee<8@e @<8e <<>n; alal>amuskarin9 pilokarpin9 nikotin9 lobelin. O6 l/e6 e /el6an/a  ?a<:ane9. Kla?a9/a 1uskarinski agonisti 8 parasimpatomimetici, / ! >6a :8a<n; :na9/ @an@l/e l ne8<:88la<8@8 <88 /e ele6n ana@n 0a 2 nna /el6an/a :8a<n; an /e 0a 1B i 1= /el6an/e: naa/8 >a9l@l9e<lDAG  n0l-1,4,!-<??aIP3. DAG :>8l/el6an/e <en na0e (, > IP 3 80<8/e 8=an/e (a 0 8n8a<ann; enla 9la0: a /e @ađa e depolarizacija an9a a >6l/n 6, EP%P <=< e na aa :e:5 n; na ne8<:8la
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D/el6an/e na 6a  <@ane *tablica7-3 Va0>laa9/anCen/e <6n@ laa n/e a@6<n/e <80<en a/el6an/e ln::ea 80<8/e 6a0>laa9/8. O6 >/el6an/e /e eln@ </ela'D0F9 $ 8 Cla:a, = e >@ađa :8 neinervirani+ muskarinski+ eln: an9a:a. %nCen la a6/el6an/e: na <9e. Male lne >/el8/8; :8a<n; ln::ea 80<8/8 a;a<>/8, > aa<>/8. E?e ln::e; l/e6a a ne a/el6an/a nne @an@l/e :8la9/e 6e  a8:n/ ne<6a9/ <@ana  6a. K<6ne Cle 8 >:nann :a ne<6 >:nann: a/el6an/a. Nna ne8<:88la/el8/8: l/e6:a 8Cena a6a9/a :a a nn:  <@an??a:a. Klna <:/ena Nel 5le < > /aane lne<@e a6n, @la8:, %/<@en6 n><:, :an/a a/el8/8 nn a@n e ne <e 8 e/el8/8 l/e6 e <e a /e . !areniklin  /e n6 nn a@n / /e a<9/aln a@n  :an/8/e Cel/8 0a nn: 8 6na. Tn na6  :: 0a9/e, 5<n;n<9/a, a0n/ne Cl/e0>e, >=n 8,GI e  6a0>laa9/a. Naa/e <la0na 5a<>/a, /: a /e l/e <:/en/en n e nala0e 8 ne: @l/6a:a,  <69 8 a,  >ela<0a9/a ne8<:88la > ?a98la9/a  ae
24

$'I"0#!$I #7$ITI %ne ne0a/8 8 2 6<eH karbamati i organofosfati. $eostigmin  /e < a<5a:aa, > parationne9> /e < <@an??aa. Tn@ lana edrofonij, al;l /el6an/a. Me;an0a: >/el6an/a I a<5a:a  <@an??a 8 n;5< / e 6eC8 0a lnee<l0 :le8le. Kiseli dioa<5a:an n  ??an n e l5ađa/8 :n@ </e,  6 < >9/el/6an/e <l08 en>@en@ a9ellna,  a /aa6a >/el6an/e a9ellna. KARBAMATI Nan ;><l0e, a<5a:an n e l5ađa 8 e<>8 > 2 > & a. ORGANOFO%FATI O<@an??a 8 >8@ >/el8/8 l/e6, n 6a<l0e, aa ??aa e l5ađa 8 e<>8 > nel >ana > nel /e>ana. O/el: 05@ ne0e n6; en0:a. Una In;59/: lnee/el6an/e a9ellna 8 naa:a @>/e e l5ađa ?0l=. na, ne0/el8/8. In;5< lnee/el6an/e 8 6:a /a n8 ne<6/e e a9elln n<:aln ne l5ađaan9e en>ela. KLINI$KA PRIMJENA Karbamati9 neostigmin9 fizostigmin i piridostigmin e <e 8n 6=e ne@ <@an??a. L/een/e :aene @ ne>ela0e, 8 >/a@n0 :aen/e, 8 >?e6/e :Ce 5 e=a. P<:/ena /el8/8e@ ln::eae><?n/ :Ce 5l/=a na@8 :=a 8 :/aenn/ <0, a /= 6=e @<=a 8 lne<@n/ <0. TOK%I$NO%T U0 e/el8/8 l/e6e5n <@an??a 8 5n 05@ l8a/ne 0lCen n: lna:a 8 e9>:a. Na/n/a:a; ne l/ee. Nan an>a<>ne 0a=e 6aln; 0na6a, <8l/e /e an:8a<n l/e atropin, al n ne:a >/el6an/a na nne 0na6e n. Ona e l/e :a; nan 6e0an/a 0a lnee
0na6e n. A 8 ??a 6e0an 0a en0: 8@, l/e6 0a /el8/8. na6 <6an/a 8  a  > 0/el8/8; l/e6a, a 6: 0n:a:aH 6a0>laa9/a /e an/a  </eđa, 5a<>/a /e ea, (N% :8la9/a ea a <@an??a:an68l0/e, 8an/a  <9a. P<l/e6, :a<>/a, ea9/aelen; :=a, (N%, la<:a9/a, al6a9/a, 0n/en/e.

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'.POGLAVLJE - BLOKATORI KOLINERGI#NI% RE&EPTORA Ana@n lne<@n; /el6an/8>a l 5l/ele  selektivnosti 0a e9?ne M a8 e. Vena l/e6a /e nee9?na. M8a<n 5la< e >/ele  na 5a0 n/;6; 9l/n; <@ana(N%, , 5<n;, GI 6l/n ll85ln >a 5 <=l l>ne 5a</en9a ll85ln /e <8n l >8n kvarterne amino grupe na :le8l l/ea. Na5/ene :le8e 8 6=e lan8 5a</e<8, a <6-:0a 5a</e /e nađen 8 A<a 5ella>na  ><8@: 5l/a:a. Je< /e tercijarni amin, a<n /e <58<8@e <@ane, >/el:n e :ea5l0 ne<:/en/en 8<n:. Pl8C6 :8 /e 2 aa, a /el6an/a 4-& a, a 8 8 72 aa  >8Ce. FARMAKOKINETIKA DRUGI' BLOKATORA MU%KARIN%KI' RE(EPTORA U ?a:l@/, aln >/el6an/e:@8n >a 8đe 8  nan n/86ne <:/ene  /el6an/a 8 6aCn 8 >ne 5a</e/el6an/a 8 (N%-8 6 l/e6 :a/8 6a<ea :an/e <la0a <0 <6:0a 5a</e<8. Bla< :8a<n; /el8/8 a kompetitivni antagonisti n/;6 5l/el6an/e 5lae lna9/a, :an/en/e 5le 6a8la/el6an/a /:  :an/en/e: a<6en<8lal/6 </e e<?e6a98la< e??e9 a ;ee n9l8>e an nal ln@ ? ;ea< 5 9en 5 ;e a9;9a<>a an> >e9 a<6en<98la< 9n>89n :e ;a 8l> 5e 9e> ?<: e<;ee. M1 ele6n l/e6 8 ele6n 0a @a<nenaln 
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KLINI$KA PRIMJENA (N% kopolamin /e an>a<>na ean /e > na/e?e6n/; >8n;. P/  e<:aln ?lae<. /enztropin9 biperiden9 tri+eksifenidil 8 an:8a<n l/e6 / e <e 8 a<nn6/. Ia n8 >/el6< a le6>a, 6 l/e6 a/8 <n a a9/en ne >@6a8. Ben0<n e nea> < an/8ne6l/ne :=ne n</a0e. U0<8/8  9lle@/8n;59/8 9l/aa9/8. T/el6an/a atropin-72;, +omatropin-24;, ciklopentolat-2-12;, tropikamid-+.!-4;. %6 6 l/e6 e >5< a<58@ < 0a :an/6an/e e=n: 8e6:a /e: @enea 5 0a06a 5<n;>laa9/8 8 a:  KOPB<nna <89/a l8na 5le. Ia n/e e?e6an a Q a@n, /8  <an8 a<:/8 8 /el/6; a9/enaa. I:a :al 8naa 5la8l/e >/el6an/e. (RIJEVA Bla< :8a<n; ?enlaa  lea 8 8n6/. MOKRANI MJE'UR ksibutinin i tolterodin e <e 8 la5/e: 98  0a :an/en/e a0:a :/e;8 a a 5ee, :a> a a ;ae<.%8; a 5a<8, 9<6en a 9la, l8> a l58a< An:8a<n >/el6an/e :Ce >6e > 6aCn;  en9/aln an; 8naa. Bla>a e<:/e98  >/ena>. O<6an/e a<n: e na06a 8; a 5a<8 /e< 0n/en/e, al6a9/a  la<:a9/a 8 0a8a6l/en. U:/e/a /e ea, a /aa a;a<>/a  a<:/e 8 l8a/8 0 8 0a/e>n :: 0a 6e >5ne 8ne. Tn 8 (N%-8 8l/88/e e>a9/8, a:ne0/8, >el</8: l ;al89na9/e  n68l0/e. U 6e 2&

8ne 8 6/e<6an 8l/8en 9eneel</ > a</;. K> 6el; >0a, 5ll/6, al 6 n/e e  e= e l/e. Dlaa9/a 8an; <6; Cla na <8a:a, @la6, 6@ađa < 6el: >0a:aa<n 9<6enl,  ne0na /e :e;an0a: 6@ 8na. KONTRAINDIKA(IJE O6 l/e6 e  >/ena> 05@ an > ;e<e<:/e, > 5a a @la8:: 0a6:a. P= /e a?ne :e @<8e 0a ??< 6e > a?nea a6n@ :/ea en0:a 0a ??<, 6 l/e6 e 6eC8 0a n;5<  0a:/ene en0:8l n/e >=l > aa 8 6 a6n en0: : e < 0a a9/ene 0lCene ne9>:aa
2)

(.POGLAVLJE ) SIMPATOMIMETI&I %:a::e9 e a/e > /a 6aCne @<8e l/e6a /a e < 0a a<>6a8la=ne  ><8@e 5le. P>/el/en 8  n/;6: >/el6an/8 a?ne8 0a  l Q /el6an/a0/el8/8 neizravno. D<8@ nan ne0/el6an/a /e > kokaina i triciklički+ antidepresiva n n;5a:na 8 C6an: 0a6<=e9:a  a 6ea6a/8 na8 a6n l5đen@ a :ea5l0:aW5la>a (OMTael--:ela0a :a :al 0/el6an/e ne0/el8/8; :a::ea / 80<8/8 8=an/e ;/el6an/a A>/ele na   Q /ele na >@<8e. *tablica9-3 #drenalin /e < a@na / >/el8/8 na 6e >6e /el8/8 na 6e a:n a l/e 8 n/: >0a:a a60e   @en a@n a>a:n 8 aela:n / e 5<0 :ea5l0a e 8e 0 C6an; 0a6<=eaa, >:a; e 6@ađa a e <:/ene a l/e. O6 a@n :a/8 /el6an/e. Ka>a e >a/8 a@en: 8Ce ne@ aela:n. Tiramin e 5<0 :ea5l0/el8/8 a e GS a6/e>n9a 6@ <ena a6a :e:5/el6an/e na al9/e anale :Ce @
2 RE(EPTORI H? receptori >/el8/8 enla 9la0e enla 9la08 6> > 6ean/a n9eenla 9la08 /el8/8 /el6an/a, la@an 6; 9ena:na 8 ne: >a:ne<@n: 86:a. Pna6l/a/8a <:/ena a:?ea:na /el6an/a >a:na 8 6en<8/8  ><8@: /e0@0e a:?ea:na :@8 >6e > an0n, a@a/a. P0a/:. OKO Dlaaa< 8le@la := </a0:. U/e9a/ na a:>a9/8 /e :n:alan. O9an/e ne 6>9e e :Ce /aa neele6n:  a@n:a, a l/e>9: :an/en/a n@ađa 9e. BRON'I Gla := 5<n;a e 8=a na >/el6an/e Q 2 a@na. O6 l/e6 8 na/<n/ <6 5<n;a0:a. GA%TROINTE%TINALNI TRAKT U GI 6> > 8=an/a @la; :=a.  2 ele6n a@n :an/8/8 ee 8 9</e6:a. GENITOURINARNI TRAKT U <88 :/e;8/el8/8 8 n/el8/8 8 n 80<8/8 /aan/e n8a ?nene, al e e >0e 80<8/8 0nan8 a;a<>/8.

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VA%KULARNI %U%TAV * :nann: a<>/8. H? a@n * a klonidin 80<8/8 6a0n<9/8 a>a e <:/ene nlaa9/8 8 ;lann: 5a0en8  5850a:a >a:n a60a:a   a Q 1  Q2 :nn: >/el8 <9a, > 5a Q l/6,  /aan/e <ane na@e nn a<>6a8la/el8/8 na H i EB  5a<:n 5ea 8n9:a na <9e, a a<>/:. *slika9-6 A /e /8. %ele6n H agonist(fenilefrin) 8 ele6n E agonist(izoproterenol) 86/e 85<0a6a 8l. D/al <6n la /e > 8/e9a/e: e<?e/al ne<6al >/el/a. A>/al@ /e >a 8/e9a/e: Q 1 /al@  laa 8la  05@ @a /e > 8/e9a/e:    Q
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KLINI$KA PRIMJENA ANAFILAK%A * adrenalin /e l/e 05n: l/een/8 ana?la@ =a /e< /e 8n6 ?0l= ana@n :n@; :e>/a 0a:/en a an;a:n9:a l <e<>:a al n n8 n 5l08 8n6 n 5<0 a a>ane n>a9/e 0a <:/en8 8 na<le/a, e?9a aCn/eAD'D,  8 ne: l8a/e6:a :<=a6l/en/e. Ann <:/e/ea, 6/eC5a  ;l=a 8@<n : a9/en:a. O6 l/e6 e <=a6a/8 0a >@>8 a6an/a  0a >0an/e a 5 0a06al :></a08, :an/l 6<5eC /n9e  n@e/8 05@ <a9/e l ale<@/e. O6 l/e6 ne 80<8/8 9lle@/8. #drenalin  l/e dipivefrin 8 e </e <l aln 0a @la8:. N6 H? agonisti / e <e 0a @la8: 8 apraklonidin i brimonidin, n :an/8/8 <06>n/8 ne 6>9e. BRON'I * Q a@n, e5n E? selektivni a@n 8 l/e6 05/el8/8 Q 2 ele6n a@nalbuterol9 metoproterenol9 terbutalin e ne /el8/8 Q 2 ele6n a@n, salmeterol i formoterol 0a/e>n a <e<>:a e <e 0a <?la8. KARDIOVA%KULARNI U$IN(I %an/a 8 /:a /e Cel/an 6ean < <6 * 8 a8n: <an: 0aa/en/8  ne: 6:a =a, 6ean <an 0l/e6  < <6 08 /a e :Ce <. %an/a 8 /:a /e Cel/n :an/en/e <6n@ <a l 6ean/e <6n@ laa * HB agonisti 8 <n 0a 0a06an/e 6a0n<9/e. T 8l/88/e laln ;e:a >/el6an/e a>/el6an/e :a8a >6l/n 6.  a@n e e :/e=a/8 a laln: anee9:a >a 5 :an/l @85a aneea 0 ><8/a <:/ene. K<nna <ana ;en0/a 05@ ne>an@ :a@ n8a e :Ce l/e efedrinom l n6: 
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GENITOURINARNI TRAKT * E? a@nritodrin9 terbutalin nea> <e 0a an/e a, al :8la9/a <9a :Ce 5 @85na 0a :a/8  >/ee. Nee<>n <88aln l/e6, 5la< al9/e6; anala  :a@ne0/ e <e 0a 68 n>a9/8. D8@ >/el8/8  <e 0a 8<na a</;  en8 >/e9e. O6 >/el6an/e /e a e <:/ene e:. U e<?e</, =en 8n9 8 05@ /aa6an/a 8naa /e nae :a/8H a, :C>an 8>a<, 8l:nae: l <6a /a8 (N% n, 0a6n  >0. U :al: >0a:a 8H ne<60a, ann na=an/e  n68l0/e. Pe<?e/el8/8. na  1 a@n 80<8/8 ;e<en0/8, Q 1 a@n 80<8/8 n8n8 a;a<>/8  a<:/e. Q 2 a@n 80<8/8 a n/e>an > 6; l/e6a n/e a6<=en ele6an, < 6el: >0a:a Q 1 ele6n l/e6 :a/8 Q2 8na  50 al; :a::ea.

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1*.POGLAVLJE - BLOKATORI ADRENERGI#NI% RE&EPTORA L/e6 5la<   Q a>/el/en  n/;6/ ele6n. O6 l/e6 8 antagonisti i parcijalni agonisti. /.K#T0I H #D0'$'07I3$I* 0'C'PT0# P>/ela  5la8@@ 8na * fenoksibenzamin, /a :al /e  1 ele6an. Re6e<05ln, 8@ 6</e:e 8na *  4& ; * /e< e 6eCe 6alenn 0a a e 80:a <8@ 1 ele6n 5la< >/el8/8 &-24 ;. Me;an0a: >/el6an/a Fenoksibenzamin e 6eCe kovalentno 0a   8. D<8@ l/e6 8 :e6n ?a<:al= ana@n * 0na n/;6 8na e :Ce 6l/n a@na. O6a 8. NE%ELEKTIVNI BLOKATORI O6 l/e6 80<8/8 6>l/68 5la>8  a>a  6a8la/8 05@ :an/en@ a<e</@ laa. O6a a;a<>/a :Ce 5 /aa 05@ 8/e9a/a na  2 6>l/6 a9/enaa / <:a/8  5lan na  6el; >0a a> :an/en/a laa@ađa a ?enle?<n:  n 6> a nee6an 8na l/e6a > /; /e  5la>a n8/a6a?ena0n, an;a:n9.

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%ELEKTIVNI  BLOKATORI P= prazosin  n/e@6 anal0 5l8la/8 ne@ neele6n  5la< /e: nCa6an/a <6n@ laa. O6 l/e6 :a/8 6aCan 8na na @lae :=e <ae. KLINI$KA PRIMJENA NE%ELEKTIVNI  BLOKATORI O6 l/e6 :a/8 @a6a n/e@6 <=en/e /e: l/een/a a<9n>n@ 8:/el6an/e, <:/ena ?enla:na e < 8 a6: l8a/e6:a. P06e > 05l/ne ;e<en0/e 05@ n>/el6an/a na :a8. O6a6a ;e<en0/a >5< n: >6> > ;e<en0/e, 6a/ ?en:en e l/e ?enla:n:. Rana8>6 n><:a0a: a<e<la 8 <:a nea> ?8n9/8. %ELEKTIVNI  BLOKATORI Prazosin9 doksazosin i terazosin e <e 8 l/een/8 ;e<en0/e. O6a/ HB 5la<, tamsulosin e < 8 n<l eCan@ :8l/en/e n/;6; 5la<; 8naa. Na/6aCn/a :an?ea9/a  /e <aa ;en0/a  8 l8a/8 neele6n; l/e6a /a. Ta;a<>/a  /e </eđa  8n 5laCa > 1 ele6n; 5lalaa9/e 8ne / n8 /:. O0a :ala  80:a e </e a6an/a.

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/.K#T0I E #D0'$'07I3$I* 0'C'PT0# %6 Q 5l< / e <e ln 8 kompetitivni farmakolo8ki antagonisti.*tablica10-2 P< /e propranolol. L/e6 8 6/ @<8 8 >/el/en  Q 1 ele6n, a<9/aln/ a6n a@na, laln: anee: 8n8  ll85ln. RE(EPTOR%KA %ELEKTIVNO%T EB ele6nQ1 5l<8@; l/e6a. O6 6/6 /e n 8 l/een/8 a:aan 8 l/een/8 a:aa<8@8 =n: 5le:a. LOKALNI ANE%TET%KI U$INAK Laln anee 8na8na a5l0a9/e :e:5aa a e Q 5la< <:/ene aln 8 , /e< :an/8/8 0a=n timolola  ><8@; Q 5la l/ea > l/ea. 'smolol /e /el8/8 ee< Q 5la< / e <:/en/8/e a8l/e@ >/el6an/a. #cebutolol9 atenolol9 nadolol 8 :an/e ll85ln ne@ al Q 5la<  0a e= 8la0e 8 (N%. U$INAK I KLINI$KA PRIMJENA Vena >/el6an/a Q 5lae :a@ 8na e /e /a =<a. L/een/e @la8:a 6<8@; l/e6a.*tablica10-3 Ka<>6a8laa e  :<ale. .abetalol9 karvediol i metoprolol 8 e5n <n 0a a/ 8na. Fe<:9: e nea> l/e :5n 6ele lne a>
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TOK%I$NO%T Ka<>6a8la8Cea 8na Q 5la>e 6; l/e6a,  8 5a<>/a, a<6en<8la=n: 5le:a :@8 >5 e=e a:ane naa>a/e. Ee<:enaln, Q 5la< :an/8/8 ea9/a, 8:<  <:/ene na. #tenolol9 nadolol  ><8@ :an/e ll85ln Q 5la< ne:a/8 8na 8 (N%-8, /e< la5/e <la0e 5a</e<8 <6-:0a. %e8lna >?89/a /e </a6l/ena > ne; a9/enaa.

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11.POGLAVLJE ) LIJEKOVI A LIJE#ENJE %IPERTENIJE An;e<en06 :a/8 /el6an/a, >8laa9/8  n;59/8 an@en0na. Ne>a6n /e 8 68 @<88 l/e6a >>an  n;5< 2+ l8a/e6a ;e<en0/e /e e8n>a  585e  nel ><8@; </e; aa, /. primarna l een9/alna ;e<en0/a. %a@ 6=en@ <6n@ laa e e:el/ na >n9a:a <6n@ laa.*slika6-7  O6a /el6an/a an@en0na. NaCal, 5a<@6< a >@6< e :Ce /8  diureticima l in+ibitorima angiotenzina0a e  l. *slika11-4 DI%0'TICI D8/e /e< 8 6aCn 8 l/een/8 ;e<en0/e. O6 l/e6 :an/8/8 <6n la a = :an/8/8 6l8:en <6  6/e<6an >8 8 <:/e >8n/8, e=8  :al@n8 ;e<en0/8. K:e0a8a, :a:aln an;e<en06n 8na e Ce < >0a:a :an/:a > n; /e 8 86a8lan@ l 6=e > na6e>en;H n8 6ena, 8l, na@a na/el/en  :/e8 >/el6an/a.*slika11-2 L/e6 / 80<8/8 en00a9/8 5a<n; /e6a a alal> 6e 6ea6a 6a@aln n8 8n. I1P#T.ITICI # 0'DI$&I1 D&'.!#$&'1 H? selektivni agonisti(klonidin9 metildopa) 80<8/8 :an/en/e :a@ 8na a = a6a /e <l/e, n e n  :el>a nCa6a/8 <6n la, a = :an/8/8 8>a@6< /e n na 80<8/e e=8 ;e<en0/8. O6 e :Ce 0e ln>na l <:/en: H blokatora(fentolamin). 3)

Mel>a nea> 80<8/e ;e:al=8 :8nn, /a e :Ce >eea9/8 * :el>a 6=e < e0a:a. Bla< @an@l/a - Nn 5la< @an@l/a 8 /a 8n6, al 05@ e=; n8/a6a e ne <e. /.K#T0I PT7#$7.I&KI* I1P#TI3KI* ;I!3#$I* "#!0'T#K# L/e6 / :an/8/8 0al;8 n@6< /e e. U 6el: >0a:a  n 8  /a e?an al :a/8 e=e n8/a6e. Re0e<n e nea> < 8 :al: >0a:a a >>aa ><8@: l/e6:a. G6ane>n e ne < 8 R'. Re0e<n 8la0 8 (N%, a @6ane>n ne. O5a :a/8 >8@/el6an/e>an-/e>n. Na/n/a n8/a6a ena 8 <aa ;en0/a  e8alna >?8n9/a. 7vanetidin < $'Tn6n 8n nena. /.K#T0I #D0'$0'C'PT0# HB selektivni blokatori(prazosin9 doksazosin9 terazosin) 8 8:/e <nne ;e<en0/e 05@ @6/e.  1 ele6n 5la< :a/8 :an/e n8/a6e > neele6n;  5la0a. On 5en@ne ;e<la0/e <ae. E blokatori e >a <e 8 l/een/8 ;e<en0/e. P< /e propranolol, a <n 8  atenolol9 metoprolol i karvedilol. P<6n :an/8/8 8>aana :an/8/8 6a8la<8@ 8na /e :C>a laa6n >/el6an/e. Tea,  :an/8/e 'DL, = :Ce :a en9/alne n8/a6e. EB selektivni blokatori a :an/e 8na 8 (N%-8 :a/8 n  neele6n:  6=e ll85ln: l/e6:a.

4+

!#"DI.#T#T0I L/e6 / >la/el8/8 na @lae :=e laa< >/el8/8 6> > ;e<la<0a9/e, 5la>a al9/e6; anala,  a6a9/a D1 >a:n; @6< 0a nee 6a0>laa /e /a. *ID0#.#"I$ I 1I$KIDI. O6 a</ 6a0>laa< :a/8 6e 8na na a<e<le ne@ 6ene. On 0a <nn8 <:/en8. *idralazin >/el8/e eln; an9a. Ia, </e e < 8 6: >0a:a /e< /e /a an, 0na 8na /e @@6<a;a<>/a, e, ::e e<e:a0n@ l88a, / 8 8 <:/ene. Ia, l88 80<6an ;>a < >0a:a :an/: > 2++:@>an. 1inoksidil /e /a 8n6,  e:a <:/ena /e l /e <l/e, n/e@6 :ea5l minoksidil sulfat 6ala 8l/88/e @6<a;a<>/a, e, ;<080a:, ala9/e, an@0ne :en/e. 5@ ;<080:a, :n>l e < aln 0a l/een/e an><@ene ale9/e. /.K#T0I K#.CI&KI* K#$#.# Bla< al9/; analanifedipin9 verapamil9 diltiazem 8 8n6 6a0>laa< n 0a <nn8 <:/en8. !erapamil i diltiazem :an/8/8 8>a8n 8 /= amlodipin9 felodipin9 isradipin. U0<8/8 la5 :e0a@6<, a e 8n 6=e <e ne@ ;>l. Me;an0a: >/el6an/a  n 8 5/a=n/en 8 12.@la6l/8. $IT0P0%ID9 DI#"KID I F'$.DP#1 O6 alaa< e <e 8 ;e<en06n: <0a:a. $itroprusid /e /el/6 na 6/el, /el8/enel :n8a  :/el6an/a /e a 8l/88/e /8,  a n?80/a ana, a8:8la9/8 9/an>a l 9/anaa 8 <6. Diazoksid /e >e<6a a0>a / ne:a >8/el8/e nel a. Da0> 6ae. A6a9/a DB >a:n; laa9/8 a<e<la.

41

O6a/ l/e e <:/en/8/e n?80/:. I:a /el6an/e1+ :n  < e 0a ;e<en06n8 <08. I$*I/IT0I 0'$I$-#$7IT'$"I$-#.DT'0$K7 %T#!#(0##) D6/e @la6ne @<8e antagonista angiotezina su #C'an@en0n n6e<0l >e>a08, 80<8/8 :an/en/e lne an@en0na II  al>e<na, a 6ea6a/8 ln8 en>@en; 6a0>lann.*slika11-5 A(E n;5< :a/8 :al8 6/e<6an neCel/en; 8naa < n<:aln: >0a:a: 8 <8>n  0a06a/8 :n:alan :e0a@6<. A(E n;5< 8 <n > <an@ 0aa/en/a, >/a5eea  ;e<en0/e. Tn A(E n;5 a9/enaa a /e: <6Cln: 5le:a 585/a5e 585a6n /e <8@ 5la< 8 8n6 8 nCa6an/8 <6n@ laa a  A(E n;5<,  n/;6a n /e 8 </e: 0a06an/8 a=l/a. Ia, 80<8/8 n an@en0na II. Tn 8l/88/8 @la65l/8  >/ae<naan@en0n II :8le<na  80<8/8 zadr,avanje kalija. A8:8la9/a al/a e :Ce <:/e a a9/en :a =een/e 5858e al/. U 6: 86/e:a, n9e
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12.POGLAVLJE - VAODILATATORI I LIJE#ENJE ANGINE PEKTORIS An@na e< a6l/a 5l, <a 05@ <ane ;e:/e. Bl /e lal0 e =< 8 66/e @la6ne a a 8 :a<>. PATOFIIOLOGIJA ANGINE Ae<le<na an@na * lana an@na. P6e0ana /e a ae<:a0n: la6:a / >/el:n 0ael/8/8 /e>n8 l 6=e <naa e 6ea <9a/e: 6/eC5an/a, <89/a <a  ne>6l/an > a :< >6> > @ađa 8 1+ l8a/e6a. R/e /e  @> 5l a>, a  /e: na. Va0ana an@na :Ce na6a 8 nea5ln8 an@n8. Nea5lna an@na * <: * aa/a / 8 a  :aa 0a :. Na/6aCn/a >n9a /e nae <ane /ene6ea nae * 6ea een /e > l; >ee<:nan <n 88n/ nae /ene /e< a /e 6ea ?8Ce 8 l/ nae. Dal/e, < 6e: ?/ala /e an l ?a< / /e n<l8Cena la 6ea6a 6l/n: >: a naa. O6 e :Ce 6a nanaH 6ean/e: >a a  :an/en/e: 9naln l/e6 uključuju nitrate9 blokatore kalcijski+ kanala i E blokatore. %6 n :an/8/8 
kalcijski+ kanala :@8 6ea > a :an/en/e: a0:a > 6a0ane an@ne. Te ><8@;, ;na an@laa  a e <  nna:8 /e na/6aCn/ > n8Cne >/el6an/a > 1+-2+:n85ln@6aln > &-1+ae<:aln. 5@ l/een/a a8n; naa>a/a  na, / :a 6a0>laa6n >/el6an/e * a n>a </e :nn/el6an/e. 5@ 6ele en0:e a6n 8 /e<, 5nna:9. Izosorbid dinitrat /e >8an 8 85ln@6aln:  8an 0a /el8/8 6a0>laa<  < e 0a an@n8 n;ala9/:, al >ana e </e <:/en/8/e. Me;an0a: >/el6an/a * >en<8=6 >NO, / :8l<8@@ @lana 9GMP, 05@ @a naa/e e??<l0a9/e la; lana9a :0na.*slika12-2:a  >/el6an/e a na</e6 n<<8> Una na a<>6a8la6> > 6en>laa9/e, /a e/el:n 0a6/alne <nalaa9/e a<e</a <>n 6ean/8 e/e9/e  >al/n/e: :an/en/8 <9a. Vene 8 na//el/6/e, a<e</e :an/e, a<e<le na/:an/e /el/6e. Dlaa9/a 6ena >6> > :an/en/a >/al@ <9a  en0/e 6laana. Dlaa9/a a<e</a >6> > :an/ena e<?e<ne 6e88n: :an/en/8 nae /ene,  <=n/e a. na,  /e <:a<8/8. U 6a0an/ an@n e :an/8/e a0a:  6ea6a < <6. N/a  6eana n
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Una na ><8@e <@ane * na 5 5l ln <n. In nea5lne an@ne :an/8/e a@a<>n 5l l/een/a a8ne an@nalne 5l /e 85ln@6alna a5lea l /el6an/a 1+-2+ :n. I0<5> :nn/el6an/e: 3+:n. O/el8/e 4-" a, 05@ 9<8lne<:alna <:/ena :Ce >an/e ?laea 5 6@6< na 6a0>laa9/8. On 8l/88/8 a;a<>/8 5a<laa9/a 6ena, /e6a/8a @la65l/a 05@ 6a0>laa9/e :enn@ealn; a<e</a. N/el8/8 a sildenafilom  ln: l/e6:a <6 e?8n9/e. O6 l/e6 n;5ee8C8/e e@ađa  8 @la: :=:a <6n; Cla. Ka 6l/n: e/el6an/e 8 <6an/8 9/an>:. Nna 8 e:// n>8</<06>n/a el06a. Na/e=a 5le  /e 5la 5le ne>/el/a, = /e na0:/enn na  neana e/e: 6en>a 05@ 6a0>laa9/@ 8na  6e0ane a;a<>/e  @la65l/e 6a@ ne>/el/a. D/el6an/e n<a > <6an/a 9/an>: * n 9/an>a e 5<0 6eCe a Cel/e0: 8 9<: >a0, = >6> > 5la >a6n@ :ea5l0:a  anne :<. % ne@ Cel/e0 0 9<: >a0e. N< n6e<<5ala:n: 5l: 6a:na B12. /.K#T0I K#.CI&KI* K#$#.# P/ nel l/e6a,  8 nifedipin9 diltiazem i verapamil. %6 8 /el6an/a * 5la< al9/; anala 5l/el8/8 na ne8<<8@e 6e al9/; anala. 4!

Una  lna <:/ena * 5la< al9/; anala n  ><8@ >;><<>n 80<8/8 6e8 6a0>la9/8, = 80<8/e :a a<>/8  6ea6a ?n e <  8 a8n: naa>a/:a an@ne. U e=/ ae<le<n/ an@n, 6 l/e6 8 e5n <n a e :5n/8, :@, :C>an 8>a<  Rena8>6 n><:. Tn * 5la< al9/; anal :@8 80<6a na9/8, e:, :8nn8, 9<6enl l9a, :a@l9a. O05l/n/ neCel/en 8n9 8 0aa/en/e <9a, AV 5l, >e a/a. Un9 6; l/e6a :a/8 anan@naln >/el6an/e, :an/en/e <ane ?/ale  a/:a. Un6 8 8 /a  6eana n
4"

13.POGLAVLJE ) LIJEKOVI A LIJE#ENJE ATAJENJA SR&A %<an 0aa/en/e naa/e a>a <an :n8n 6l8:en ane ne>6l/an 0a <58 /ela :. O=een/e <ane n/el/en 8 < @<8e  9l/8  >/el6an/8. PATOFIIOLOGIJA aa/en/e <9a /e 05l/na 5le a 6: :<ale:. Te:el/n ?0l= >e?e /e :an/en/e <an@ :n8n@ 6l8:ena, e :: >ne/e  8:a a 8 n?a<8 :a<>a. $e /e 6e0an a <nn: ;e<en0/:, 5le:a 0alaa, 5le:a <na:a/a. U /e>n/ aa  /e :an/en/e na@e n<8@/ e5l/an/8 l ><8@: <:/ena:a 6en<8la / @6a/ale e/e9/a ?a/al 0aa/en/e. U al: l8a/e6:a /e </e  :5na9/ l@  >/al@ 0aa/en/a. Ra06/ <an@ 0aa/en/a /e aan a8n: <an: >e:e0a9/: 6e0an: a l8n: l e<?ee::a. %:an/en/e 8>a@6@6< na l/e6e. Ka>a e :an/ 8>a8Ce e 6lana na /ale. Una 8  B /e :an/e 8n6 05@ 6ean/a a = /e 6e0an a @6< /ela na :an/en <an :n8n 6l8:en /e /a 6aCan  6an  /e :a: 8a6:  e<n 8a6:. *slika13-2 Gla6n >@6< 8H a;a<>/a * e 8 585e:  l8n8 n@e/8  :aCe <>8Cen/8 6laana na /ale. Ka<>:e@al/a  /e </ :e0a@6<, 6an :a8:  an@en0n: II. Ia 6 6 :e0a@6< :@8 <68@<n @<=a6a 0aa/en/e. A0a /e an >@6<,  6an aela:n:a, an@en0n: II  al>e<n:. %TRATEGIJA TERAPIJE Fa<:al=a ee :8 >8e :8 A(E n;5elaa<:a  8 l: 0aa/en/8, 0@ala. 47

Da0an /e >a ana@n an@en0na, ne Q-5la<, ana@n al>e<na<nlan, ele8@<n <an 8na. Ta0 @6a 5 e a8n 0aa/en/e <9a 8/el8/8: n<n: l/e6:a 8 Q a@na l n;5eelaa<:a. K<nn 0aa/en/e e l/e a >885< le<?8n9/a le. Ne<>, an@ na<8a, :a 6a0>laa9/  >8a6n @l0> a>n8 /e0@<8 a lan: <en:  a9:a =ee@al /e< ; nel >la0 0 68na@ na<a>@al. Digoksin /e < @<8e. D@n :a /el6an/a * <:a/el6an/a /e a e l5ađa 80<8/e 6ean/e n9e n;59/e NaK ATPa0e e 6>e  na :e;an/  ele<n/ ?8n9/ <9a. D@al :>?9/ale  le, 6ean/e: :n8n@ 6l8:ena,  6ean/e: e@6ea <9e ?8n9n@6< * 6ean/e PR ne<6ala, 05@ :an/en/a 5<0ne a<6en<8lal/6  8=an/e T-6ala 8 e 8n9 na EKG. Una na a</  AV 6< 8 a8Cen/e @6a /e <8na a</a ?5<la9/a = e@ađa an/e.

4&

Tn >@6< - 6ean/e :ae a6n, 05@ 8n8a<ann@ @ala. Un8a<ann n: >ela<0a9/a:a, /e :@8 0a06a e/8 l ?5<la9/8 8 5l /e: >/el8 <9a. U 6en<8l:a, ea e 0:/en/8/8 a n<:aln: 89a/:a 8 :/e<8 1H1, a/ <a: e 06e 5@e:n/a. *slika13-6 KLINI$KA PRIMJENA Kn@e6n 0aa/en/e <9a * >@al /e 9naln 06n n<n l/e /e < 0a l/een/e <nn@ 0aa/en/a <9a. Ia, lna a :an/8/e ::e, al ne <>8C8/e C6. D<8@ l/e6>8laa< 8 /e>na 8n6, :an/e 8n6  ne <>8C8/8 C6. P= /e l8C6 /a >8@, 6 l/e6 e 0naa/n a8:8l08C 8 AV 6<8, a >a /e 6en<8lae >6l/n na 0a 8n6 8n/en/e  05a96an/e. I  >@al 8/e6a 0a:a. Ale@na  :Ce 6ea n9e@na a e >0a ne <la@>. Tn >@ala, @6 a<:@en /e 6eana 05@ ;al/e:/e, ;:a@ne0/e:/e  ;e<al9/e:/e. D8, / 8 86/e 8l/8en 8 l/een/e 0aa/an/a <9a, :@8 0naa/n n0 n9e@ala. P6@ala :Ce :an/ n9e@ala 8 a<:/e, :8nna, 6a e :@8 >@>. K<nn <6an/e /e <>8Cen/e e0e > <an@ an8 > >6/e >0e >@ala  <:/en: @6a0@al: 80<8/e 0naa/n8 n;59/8 6 <an; a9e:ae a6; a9/enaa. P<8/ela <6 >@na * 8 0n:n 8n6a > <6an/a a 6: a<>a6n: @l0>:a.

4)

O%TALI LIJEKOVI A LIJE$ENJE KONGE%TIVNOG ATAJENJA %R(A DI%0'TICI * 8 <6a ln/a e/al 0aa/en/e <9a. Furosemid /e 6e:a 8n6 l/e 0a nen :an/en/e @e/e l8a  e=; e>e:a 6e0an; a a8n: 0aa/en/e: <9a  0a 8:/e<l<a0>a e nea> >6l/n 0a 5la@ <nn 0aa/en/e. pironolakton i eplerenonana@n al>e<na :a/8 6l/ne >8@<ne 8ne  :@8 :an/ :<n > <nn@ 0aa/en/a. #$T#7$ITI #$7IT'$"I$# * 6 l/e6 :an/8/8 :<5>e  :<ale > <nn@ 0aa/en/a <9a. On e a>a :an a >85n 0a <nn 0aa/en/e 05@ leaa ?8n9/a le. I$*I/IT0I FFDI'T'0#"'(/IPI0IDI$I) * inamrinon i milrinon 8 @la6n a6n9 6e @<8e l/e6a / e </e <:/en/8/8. O6 l/e6 6ea6a/8 n9eeelaa9/8, = /e na/6aCn/ 6l/n 6: >0a:a /aa6a/8 /el/6 ne>  :<ale. !#"DI.#T#T0I * elaa<:a nitroprusidom i nitroglicerinom e e < 0a a8n n@e6n 0aa/en/e. P<:/ena 6a0>laaelaa<:a :Ce 5 >/e e/el8/e laa9/e, a :a  >8 /e 0naa/n an 0a 585 >5< >@6alaa
!+

14.POGLAVLJE ) LIJEKOVI A LIJE#ENJE SR#ANI% ARITMIJA %<ane a<:/e e e /a6l/8/8 > a9/enaa a /e: 5le:a <9a. Na/e= 8 80< :< > a9/enaa a n?a<: :a<>a l e<:naln: 0aa/en/e: <9a. Na/05l/n/a 8 :an?ea9/a n >@ala  e 8 6e0ane a anee0/:, ;e<a/8 8 e @<8a, al 6ena :a :al8 ea9/8,  a>a /e :@8e < e el/6  :=a 6en<8la.*slika14-1 N<:aln 6al/6 0a;/e6a/8 a9/e en9/ale0a6e  al/e6:, al9/:, na</: anal:a / naa/8 > <:/ee?n6>n9 <:a  a5n<:alna <6>l/6 >6a :e;an0:a 6a/a%VT, 6en<8la/aVT, 8n>8la9/a a</aUA, 6en<8la/a  8 <a>e e neVT-T>P. *slika14-7  VT-T>P /e 6en<8la89<8@: l/e6:a, :/en/a 5l a9/@ en9/ala  <>8C8/e ZT ne<6al. N<:alna ele<na a6n 8 <an/ an9 * ann a9/ en9/al <a0an na l9 14-1 8 /el8 <9a, <8/a na</a >:nela<0a9/: ?a0: a9/@ en9/ala  na/6aCn/a /e >ee<:nana 5<0ne <6>l/6. Nan 8C e<> na6a9/e. U AV 6<8, / 6  <8/ al9/a, <8/a al9/a >ela<0a9/8  5<0n8 <6>l/6 <0 AV 6<. K<0 la a9/@ en9/ala >:n 6ene :9a6n;  na</8 /e ?8n9/a /el6an/8 l/e6a / e 6eC8 0a na</e6e anale. F8n9/a <n :al 5l8 a9/@ en9/alaal 8 /a 5n 0a >/ena na. Ana<:9 >/el8/8 na /e>n8 l 6=e > < 6aCne <8/e l na Q-a>8l
Kla?a9/a l/e6a * ana<:9 8 la?9/el8/8. P>/el/en 8 8 e< @<8e l8 @<8a
1.5la< na</e6; anala 2.5la< Q-a>en0n, al/, :a@ne0/ 70%P# B - /.K#T0I $#T0I&KI* K#$#.# L/e6 8 @<8 1 8 >/el/en na 5a0 8na na >8Cn8 a9/@ en9/ala. G<8a 1A l/e6a<ana:> <>8C8/e a9/ en9/al. G<8a 1B l/e6al>an /el6:a <an@ 6a. G<8a 1( l/e6a?lean> ne:a 8na na /el6an/a %6 l/e6 8 @<8 1 8n 8 ;e:n:  >ela<06>ne <:a a  <9e 6e  anal:a na</a. Na/ele6n/ l/e6@<8a 1B :a/8 0naan 8na na na</e6e anale 8 ;e:n: 68, al 0ane:a<6 8na na n<:alne an9e. Kna /e otvoren ili inaktiviran ne@ a>a /e 8Ce 6ela<0/e, l 6 /e /e ela<0:a<n, lan @<8e 3, ađe< :a 8na @<8e 1A. O6 l/e6 :a/8 8na na a</e  6en<8la0a:a 8<8/8 <6đen/e 8 AV 6<8. U8C: ZR%. D>an l/e6 1A @<8e 5l8C8/8 a9/ en9/al  , 80 86>na <:a. A:>a<n :a lan 8na na <8/8 na</a  :a na/>8C 8na <>8Cen/a a9/@ en9/ala5la>a <8/e al/a. .I&'K!I B/ * .idokain /e < 6e @<8e  < e nan :a ele6n 8na na ;e:n 6 l >ela<0. O6 l/e6 :a/8 :al 8na na n<:alne an9e, a :a /a :al 8na na EKG. Fenn, anele, e :Ce < 0a l/een/e a<:/a 05@ >@ala. !2

.I&'K!I BC * Flekainid /e < 6e @<8e l/e6a. O6 l/e6 ne:a/8 8na na >8Cn8 a9/@ en9/ala 8 6en<8l8 l na ZT ne<6al. %naCn 8<8/8 <8/8 na</a, :@8 8< <6đen/e 8 a</8  an9a:a 6en<8la. P<>8C8/8 ZR%. P<a?enl, :a  la58 Q 5la:> e < 0a 6e 6<e a<:/aHa<:/e a</a  6en<8la na/5l/e >@6an  >0 :a/8 lan 8na al e e < 0a a<:/e /e: a8ne ?a0e n?a<a :a<>a. P<ana:> :Ce 80<6a ;en0/8@6 a>a e < an 80<8/e 9n;n0a:@la65l/a, 6<@la69a, 08/an/e 8 8=:a >en :an/8/e l@na  :Ce 6ea n9e :a 0naa/an 8na an:8a<na  :Ce an8 <an 0aa/en/e. %6 l/e6 6e @<8e 0a06a/8 n6e a<:/e. T<a>e >e ne /e 6e0ana a n>n:  al: l/e6:a / <>8C8/8 a9/ en9/al. 'e<al/e:/a 5n /aa6a n l/e6a @<8e 1A. L/een/e 09an /e <an 0a a8ne ;e:ne 6en<8laa. D/el8/e na a<:/e 8 a</8 /e>n a 8 80<6ane >@al:. Melen :a lan 8na  <:/en/8/e e an e <:/en/8/e nn. L>an  :elen nea> 80<8/8 ne n laln@ aneea:8la9/a (N%a, n68l0/e a<>6a8lae @<8e 1A. 'e<al/e:/a /aa6a a<>n. LIJEKOVI 1( * ?lean> /e 8n6 0a a<:/e a</a  6en<8la, al /e >5  <>n /e6 :a/8 na/6e <0 0a06an/a a<:/a<a<:9. O6 l/e6 e <e 0a e<0enne a<:/e /e ne >@6a<8@e l/e6e. Tađe< :a/8 ne 8ne a laln anee9. 'e<al/e:/a /aa6a a<>n.

!3

70%P# ?  /.K#T0I E-#D0'$'07I3$I* 0'C'PT0# Propranolol i esmolol 8 < 6e @<8e. N/;6 :e;an0a: 8 a<:/a:a /e <:aa Q 6>na <:a. AV 6< /e e5n /el/6 na Q 5laa na</; anala na <9e, al 6 /e </e < ln: n9ea<n@<8a 3 :a/8 8na Q 5la>e. Klna <:/ena  n * e:ll, /el8/8 Q 5la< 0a n a9/enaa / 8 :al n?a< :a<>a. O6 l/e6 @86/e @>ne  >8Ce nan n?a<a. Tn Q 5la a9/enaa a a<:/a:a  a9/en:a a al: 5le:a. Pa9/en a a<:/a:a e=e e. Pa:en <=en/e 6; l/e6a :an/8/e <@en9/8 ?aaln; a<:/a 8 6: an/8. 70%P# =  /.K#T0I K#.I&'!I* K#$#.# Dofetilid i ibutilid 8 n a6n9 @<8e 3. otalol /e an 0:e< /e 8n6 Q 5la<, a 5a 0:e8C8/e a<n8 al /e :an/e 8n6  :an/e an. Me;an0a:  8na * 0na @<8e 3 /e <>8Cen/e a9/@ en9/ala. U0< :e /e 5la>a al/e6; anala / 8 >@68Cen/e a9/@ en9/ala 8Cen/e: e?e6n@ 5l/a  :an/8/e :@8n >@6/8. %all, 58l>, >?el>  a:>a<n 0a06a/8 6a/ 8na 8 < 6: an9a:a <9a, n/;6 >/el6an/e na EKG-8 e 6> a <>8Cen/e ZT ne<6ala. Klna <:/ena  n * all /e >8an  0a e >e ne a<:/8 a  0na6e e 8 n8ne 5a</>e  a:e. I58l>  >?el> e <e 0a 8n>8la9/8 a</a  ?5<la9/8 a</a. Na/6aCn/a n  /e n>89/a <a>e >e ne. A:>a<n * /e <an > 6ene a<:/a  :a 6 ana<:a. Bl5<8@e l/e6e, n a e < 05@ 6/e 8n6. A:>a<n 80<8/e >e0e 8 <Cn9  C, >?8n9/8 =n/ae, aa<n, anal@ a:>a<na, >5
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70%P# >  /.K#T0I K#.CI&KI* K#$#.# !erapamil /e <. Diltiazem /e ađe< 8n6 ana<:. N?e>n  al >;><<>n n8 <n a ana<:9, 0a /e< n08/8 <6n la l >a 0a06a/8 :e0ala0e: 8 8n6 0a a<:/e /e <la0e <0 6 6n  al9/8AV 6<. O6 l/e6 80<8/8 6n8  8e8C8/8 e?e6n 5l/e. Klna <:/ena  n * 8n6 8 8 n6e<0/ a;a<>/e AV 68n 8  0a a a;a<>/e 6en<8la. A:>a<n :a 8:/ee al9/; anala. RANI ANTIARITMI(I #D'$"I$ * /e n<:aln <8an 8 /el8, al a>a e <:/en/8/e 8 6el: >0a:a nen0n /e 0n:n 8n6 8 8 a<0:alne 8/e,  05@ /a :ale n l/e /e 05/el6an/a ne @ne/a. K#.I& * 86>ne <:a,  n; = 8 @ala. 'al/e:/a /e 6e0ana a 6ean: n9>en9/: a<:/a, @6 > 5a /e <:a/8 >@al. O5@al:. Un6 /e  0a <a>e >e ne a<:/e.

!!

1+.POGLAVLJE ) DIURETI&I %6a e@:en ne?<na * <:aln 0a6/en 858l, >e5el 80la0n aln 0a6/en 858l  a5@<8e >8e. Una >86>l/6 0 ?8n9/e e@:ena ne?<na na / >/el8/8. TRAN%PORTNI ME'ANIMI BUBREGA I GRUPE DIURETIKA B85e 8 8/el8/8 na e e@:ene :a/8 /el6an/a. Vena >8/el8/e a l8:nalne e<na<nlan  elee<na 8 9la0:. PROK%IMALNI AVIJENI TUBUL U 6: e@:en8 e >@ađa 0:a a  na</e6@ 5a<5naa. O6a/ 858l  /e >@6an 8an l/e ne >/el8/e na > >a. U 858la6/en 6e ne  an 0a 8@ađa 8 9/el: <:aln: 858l8, a 6ena 8e<6a 8l?na:>a. Me;an0a: >/el6an/a /e n;59/a a<5an;><8@: 6:a  @9e. A9ea0la:> 5l8 a5la0 6ea lna na</a, > na</a e 8a /e >8ana. !"

I0l86an/e 5a<5naa 8 n8 6>98 n@ le8a /e :an/en. U 8, :Ce e  <n nCen/e n0a l698 ne @ e <:/en/8/e 8n 8 dorzolamid i brizolamid 0a aln8 <nn8 <:/en8. Tađe< e <e 0a 8e: e<6aa 8l?na:>a. Alal0a9/8 8<na :Ce 80<6a 6a5/8 a9ela0a:>, alal0a9/a 8<na a >e 8 n9e/ena,  >@6e<6a 8l?na:>a. 'takrinska kiselina /e >e<6a ?en9ene elne, al >/el8/e na  nan a al. D8a. O6 >8/el8/8 >8@ađa 4 aa nan <:/ene. Una * 'enle6a el/a /e >@6a 0na 8na >0a >88a a /e @l:e<8lae:a e 5<0 0l88/e. %5n /e e 6ena 8<na 66alen; anaM@2,(a2,  a 6ea6a/8 0l86an/e 6; na. Ea<na elna :n:aln >/el8/e a 8<08< a /e 6l8:en <6 > a5la0 6ela lna na</a, >la0  > 6el@ 0l86an/a al/a  <na = :Ce /el8/8  a 6a0>laa< 8 l8:a. !7

P<a@lan>n 8 6aCn 8 >a /e ne0a <a@lan>na n;58a. Klna <:/ena * na/6aCn/a <:/ena >8e:a0n; an/a0aa/en/e <9a, a9e. Pe5n 8 <n 0a a8n 8l:nae:, 8 /e: 6a0>laa9/a l8a @ e <e 0a ;e<en0/8 a ;e<en0/a ne >@6ae, al 05@ 6@ /el6an/a n8 5a= <n. R/eđa al 6aCna <:/ena /e 0a l/een/e e=e ;e<al9/e:/e05@ :al@nea. O6 an/e e l/e a 6el: >0a:a ?8<e:>a a n?80/:  ele<l:a. D8la0e > a56a8la6>e >  </e 80<8/8 ale<@/e 0 l8:ena 8 an9e ; >8@6 n<l: an@ ;<:na. Ve e<6a 8l?na:>a. Ta0> 8 /el8/8 "-12 a, 8n >8Ce ne@ >8a /e n;59/a Na(l- aln: 0a6/en: 858l8. Una * < 8n/ >0, a0> <06>e 8:/e8a. MCe e /a6 ;ale:/a :ea5la alal0a. %:an/en/e 8 :an/8/8 0l86an/e 6>e, = :Ce 80<6a ;6le:/8 ;na</e:/8. Tađe< nC8/8 <6n la, :a:aln 8na nCa6an/a laa e >@ađa < >0a:a :an/: ne@ 0a :a:aln 8na >8na 8 585a. Ka>a e <e a >88a9/a /e ;e<en0/a, 8 /e: /e n/;6 >8@ >/el6an/e  8:/ee:a > 8:/e<8@a n>a9/a, a e 8a e < 0a ne?<l/a08  ne?<@en >/a5ee n>8. Tn * </e e /a6l/8/e :a6na >88 >/a5ea ne; 5a e 6ea6a n9e
elne;e<8<9e:/a  l>a;ee:/a-LDL. Ta0> 8 8l?na:> a / :@8n ale<@/e n/ e@:en ne?<na /e 0a>n/e :/e e<n:*slika15-5, e<>n: ;<:n: / e l8 8 < na>585e. O6a/ e@:en /e >@6e<n 6=en. Rea<9/a na</a e >@ađa na: @85: al/a  6>6; na. na a5?a9/e 8<na  0a>n/e :/e 0l86an/a al/a. Re9e< al>e<na  anal na</a 8 9l/e6 >8e al/. Rea<9/a 6>e e >@ađa > n<l: AD'6a0  >/el8/8 a ?a<:al= ana@n al>e<na 8 a5e<na, 6 l/e6 :an/8/8 e/el8/8 e eeln; na</e6; anala 8 a5/el6a  la /el6a24-72 aa. A:l<>  <a:e/el8/8 12-24 aa. Una * 6 l/e6 6e @<8e 6ea6a/8 l6; na. M@8 80<6a +iperkalijemijsku metaboličku acidozu. Klna <:/ena * <=en/e al/a 05@ <nne e:a l >85< >@6ae  >8e al/ 8 /e>n/ a5le. Al>e<n0a: /e 6aCna n>a9/a 0a <nlan, ađe< e /a6l/8/e 8 0aa/en/8 <9a, a <nlan  ele ne :/8 <:/en a 8le:en:a al/a. Oal ana@n al>e<naA(E n;5<, ARB, <ne a5n<:aln, @ne:a/8  anan><@en 8na. Ele<n 8na. 1TKI DI%0'TICI 1anitol, < :; >8n ?l<8 05@ :@ 8na. Gla6n :/e 6@ 8na /e <:aln 0a6/en 858l, @>/e e 6ena 0:e @ađa. Rea<9/a 6>e /e :an/ena  8 la0n: /el6a na a6 na</. Manl :an/8/e 6l8:en :0@a  !)

n8 0 an9a, lan 8na e >@ađa 8 8. Klna <:/ena * : >8a /e < <6 8 585:l0e. Manl e < 0a nCa6an/e ne 0 an9a :Ce 80<6a ;na</e:/8  8l:nae:. Ka e 6>a 0l88/e, naa/e ;e  <:/en/8/8 e ae 0 a5enla 9la08 en; anala na l8:naln8 :e:5e0:a5eea n>8a. a ne?<@en 5l >a5eea e < e, a0>  >8/el:n na>:/e=a :an/a n9e<a5ee8. ANTAGONI%TI * AD' ana@n e <6e >/el6an/8 AD'  al; e>a / >/el8/8 na V 2 e l8e >e  an8 ;na</e:/8. O6a/ n><: ne>@6a  al 80 /a8 n. Tn * 80 <86 AD' l >e0:e :Ce 0a06a ;na</e:/8. Vele >0e 6; e>a > ne; 5a 80<8/8 ;e<en0/8. Kn6aan :Ce 80<6a >e:/eln0a9/8 a e ;na</e:/a l/e 
"+

1!.POGLAVLJE ) %ISTAMIN, SEROTONIN, ERGOT ALKALOIDI A8a> 8 en>@ene :le8le a :n: ?a<:al=: 8n: / ne a>a/8 8 @<88 9naln; a8n:n; :le8la. *istamin i serotonin!-;><<a:n!-'T 8 na/6aCn/ a8a>n a:n. E<@ alal> 8 ;ee<@ena 8na l/e6an8 a8a> / a:na   na  ;@6< ale<@/e  :a/8 6aCn8 a?0l=8 8l@8 8 ale<@/: <n8, 8<a</, an@e>e:8. Tađe< :a 6aCn8 8l@8 8 n<l 0l86an/a elna 8 Cel8>98  a ne8<9n. Re9e<  8n9 D6a 8/8 6en8 e<?e@6<, /e lan <:/e< >/el6an/a ;a:na /e 6an @6< 8l/88/e :al8 9<6en8 8 8 9en<8 ne<:alne n/e9/e ;a:na <8Cen8 9<6en: e>e::. *B receptor * 7 6e0an <8@ @lan9. Tn >@6< /e 5l  6<5eC Ce, 5<n;n<9/a, 6a0>laa9/a80<6ana  NO. Kalaelne an9e 80 l5ađan/e NO  ><8@; 6a0>laa6n; 6a< e ne:a. O6 8n9 e >@ađa/8 /e: ale<@/; /el6an/e /e :an/en/e l5ađan/a ;a:na 0 :a9ane@a6na 6/el6an/e /e 8la9/8 ;a:ne<@e ne8< receptor * 8 lal0@6<.

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#$T#7$ITI *B 0'C'PT0# P/e >6/e @ene: a8n:n; a6n /e difen+idramin. N6/ l/e6 <6e @enea6n9 8 klorfeniramin i ciklizin. D<8@a @enea6l/ena a cetirizinom9 feksofenadinom i loratidinom, /e :n@ :an/e lll85lna a 8n :an/e e> n6/; l/e6a /e 12-24 aa. Me;an0a:  8na * ' 1 5la< 8 kompetitivni antagonisti '1 /ea na :8a<ne 5la/el6an/e  na e na @<0n9a  8<a</a. Difen+idramin9 dimen+idrinat9 ciklizin9 i prometazin e <e 0a l/een/e 5le  <e ea9/8. %e>a9/a /e </ea > l/e6a ><8@e @ene e /a6l/8/8 > ne; a9/enaa /e: <:/ene l/e6a <6e @enea  a> <:ea0na>e<6a ?en/a0na :Ce 80<6a <a8 ;en0/8. Ine@ađa/8 0:eđ8 a</; an;a:nna  ><8@; e>a0en, al;l. L/e6 / n;5n/a < :a/8 :an/e neCel/en; 8naa ne@ 9:e>n. On 8 0a:a, a >a >/el6an/e /e>ne >0e 58>e 12-24 aa. Me;an0a:  8na * ' 2 ana@n kompetitivno blokiraju '2 ;a:ne 8 ' 1 l a8n:n; n e
Klna <:/ena * 6 l/e6 :an/8/8 ::e >8>enaln@ en@ 8l8a, 85<0a6a/8 9/el/en/e  0a >ne6n, > n / e na6l/a/8 e :@8 n: >0: </e a6an/a. ' 2 5la< 8 8n6 8 85<0an/8 9/el/en/a  <:8, / /e a0e  n8 8n6 a n;5< <ne 8:e. Tađe< e <e 0a l/een/e @a<e0?a@ealne n /e n;5< en0:a / :ea5l0<@en 8na. Ran>n  al ' 2 :a/8 :an/ n;5<n 8a6. #7$ITI '0T$I$# %e<nn e ne089/aa<9n>n n><: e :Ce >/a@n9<n>l 9ene elne!-'IAA 8 8<n8. %e<nn /e ne8<8l 8 <:59:a. D a>a /e <6en 14 /el8/e na 5-*TBD /e 8/8 na8 n;59/8 :8 6eane <6>l/6 al/a.*tablica16-3 Pe<?e8/8 ea9/e  n;59/e 8ne 8 :n@: @la: :=:a. O6 8/8 na8 ea9/8 8 (N%-8  n/el8/8 n al/a, nCen/e 9AMP. O6 /el8/8 8 6a0>laa9/, <l/e68  5<n;n<9/ 05@ a<9n>n@ 8:<8/8,  8 e<?e8/8 ea9/8  
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5-*TBD #7$ITI * umatripan, /e < 6; l/e6a. $aratripan  ><8@ <an 8 ln 8:a<an8. On 8 <6a ln/a l/e6a 0a a8ne :@a0 >a /e a5<:aln e<nna 6e0ana a :::a @la65l/e. O6 l/e6 8 8an  0a a 8 a<9/aln a@n 6; <: * e<nn  a@n !-'T 0a:a 8 6e0an a 6<89:, 8n: na elene :=e  a<>6a8la l/ean 8 6laCn: Ca<9a:a, ne 8 >@6e:/8 e<@0:a6an/e@ 6/ea. Vena e<@ alal>a 8 agonisti H adrenoreceptora i 5-*T receptora. Tađe< 8 ne a@n >a:n;  8 >/el/en 8 3 6ele >@<8e 0a6n  68 l <@an8 na / <:a/el8/8.*tablica 16-7  K<6ne Cle * e<@ alal> <06>e <>8Cen8 6a0n<9/8 06a. Je< 8 a<9/aln a@n :@8 5l 80<8/8 naCne n <đa/. 'rgonovin /e <. T/e: <8>ne, n6l/na >a 80<8/e 5aa/. Ran/e 8 <8>n :aene 8 0e e<@ alal>a >a 5 80<6ale n <<>n; e<@ alal>a  > dietilamid lizergične kiseline(.D), al ne  > ee<6aa. Ia /e L%D :an !-'T 2 5la< 8 e<?ea:ne  8 a@n ln >a:n8 / n;5e<6a, >/el8/8 na >a:ne D?  e<@ alal>:a 0a l/een/e :@e /a8  >8@a la9ene.

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'e<<lane:/a  a<nn0a: * bromokriptin i pergolid e <e 0a :an/en/e l8en/a <lana. Tađe< :an/8/e 6eln8 <lan:a. O6 l/e6 e <e 0a l/een/e a<nn6e 5le. TOK%I$NO%T Va8la8Cena 6a0n<9/a :Ce  a e <e >8@ :@8 80<6a ne5n8 ;e<la0/8 6e06n@ 6a. O6a ?5<la0/a :Ce 5 8 a<>/aln  :Ce 80<6a ;><ne?<08<89/a 8 ne; a9/enaa a a<9n>n: 8:<:, a e a6l/a >a 6e /a6e 8 80<6ane a@n: 8n: na e<nne ne. Una na :0a * ;al89na9/e lne ;0 8 80<6ane L%D,  nea> :e0e<@>.

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1$.POGLAVLJE ) ANGIOTENIN Va0a6n e> 8 a8a> a naCn: >/el6an/e: na @lae :=e  ><8@a 6a. On 8l/88/8 6a0n<9/8, 6a0>laa9/8. Ana@n 6; e>a l en0:a / ; <06>e :a/8 6aCn8 ln8 8l@8. Va0a6n e> >/el8/8 a ne8< >/el8/8  0 9<8leae>   :8 an@en0n n6e<a0a. Una  lna 8l@a An@en0n II /e naCan 6a0n<< a<e<la  :8le<na. On >e<na 80<8/e 0a>/el6an/a ;ee<6/a/8 8/e 6a0>laa9/8 8n: :/e:a. N/e@6a lna 6aCn /e 8 :e =  /e a?0l= n 8 ne: 5l9:a ;e<en0/e  a06an/8 <9a. $a 8 n<:aln/ ;e<en0/  n/ 80<6an/ n: n9en n;5< na an@en0n II AT 1 5
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2*.POGLAVLJE ) LIJEKOVI A LIJE#ENJE ASTME A:a /e 5le a=n; 8e6a  na6l/a/8; laa<laa< 8l/88/8 :a::ee @6 Q 2-ele6ne a@ne, :8a<ne ana@ne, :elanne,  5la, a5l0a< :a9a  <8-I@E <8/ela. Ana@n le8<ena @/a<8@; an9a 8l/8en; 8 :8nl= >@6<. O6 :e>/a< 8 le8<en (4  D4, e e:a :e>/a< a le8<en B 4 <6lae 8alne an9e. Na 6> > <nne 8ale. K<nna 8ala 6> ;e<an; 6a<an@en, ;a:n, :8a<n a@n, <an  ;la>n@ 0/el: 05@ 6a@aln; =n: 8e6:a,  8 kortikosteroidi9 kromolin i nedokromil (in+ibiraju oslobaLanje medijatora). D8@>/el8/8 E? agonisti :@8 5l/=a >@6< na <e<>e. Protu-Ig' protutijela ne e <n 0a <nn8 e e <e  a>/el8/8 l/e6, salmeterol i formoterol 8 >8@>/el8/8 Q 2ele6n a@n. O6 l/e6 e <:/en/8/8 n;ala9/: l ne58l0a<:. In;ala9/a <:/ena :an/8/e e:n8 >08 neCel/ene 8ne > 8  6</e:e :@88/e e?e6n8 >08 laln na @lae :=e >=n; 8e6a. %a</ l/e6 :a/8 6</e:e  al:ee<l  ?<:e<l >/el8/8 12 a  >8Ce. Q a@n :8lenla 9la0a  6ea6a/8 n9elaa9/:. Klna <:/ena * :a::e9 8 <6a ln/a e/el8/8 :a::e9salbutamol 8 l/e6 05e 5<n;a0:a. Una : /el8/8 l/e6 salmeterol9 formoterol e <e 8 <?la, 8 e:8 /e <an 8na > 12 a l >8Ce, ne <e e 0a a8ne e0>e /e< : 8Ce >a n8 >/el6a. A e <e a: 6ea6a/8 "7

:<n, > a e <e a <e<>:a 5l/=a6a/8 n<l8 a:e. a 6en8 a9/enaa, /el8/8 Q a@n 8 na/8n6/ 5<n;>laa<  a=a6a/8 C6e 8 a8n/ a:. Pa9/en a KOPB ađe< <e > n/;, al / <0 > 6ee n. Tn * 0a:a 6 l/e6 :a/8 /a 8na na Q 1 a e <:/en/8/8 n;ala9/:, ea /e a;a<>/a. A e l/e6 <e e :@8 e /a6 a<:/e. M@8e /e 6a/el8/8e :a::ee. Pa9/en a KOPB e :a/8 6 n/; a<:/e /a6l/8/8  8 n<:aln: >0a:a. 1'TI.K#$TI$I Melann 8 >e<6a 8<na. T< 6aCna :elanna e nala0e 8 5l/a:a  :@88/8 :8la6n 8na 3 a ?ena6a, e?lna/, e5<:naa. Teofilin /e /e>n lan 6e @<8e / /e 5an 8 l/een/8 a:e. O6a/ l/e  nel n/e@6; anal@a 8 8n 8 a l. Te?ln /e >8an 8 5<0  < l5ađa/8: 5l9:a. El:n5na/6e 8 :la>; a>le9enaa, 8=en/86e 8 8=aa, e 689en0na 8 (N%-8  ><8@>/e, al 6e0an 6@ >/el6an/a a 5<n;>laa9/: n/e >a0ana. M@8e /e >a 5<n;>laa9/a /e 80<6ana ne: a0an: 8n:. Una - 8 a:, 5<n;>laa9/a /e na/6aCn/ e/a?laa9/a, 6=en/e <6n@ laal5ađan/e: na9/a 0a 8an 6a/ l/e n/e @8a9/e, 6a/ 8na /e 006a8la
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1%K#0I$KI #$T#7$ITI A<n  al <<>n 5ella>nna alal> 8 e <l @>na:a 0a l/een/e a:e, al 8 a>a 0a:/en/en ipratropij bromidom, 6a<ee<6a / /e <06e>en 0a n;ala9/8 <:/en8. Ka e 6a/ l/e <:/en/8/e 8>an/e: :a /a :al e:n 8na. Tiotropij /e >8@ >/el8/8 anal@. Ka>a e 8>a;n8, =n: 8e6:a  8n6 /el6an/e a  /el8/8 :8a<n 5la<. Una * :8a<n ana@n a/8 5<n;n<9/8 > ne; a:aa/e9e  8 :n@; a9/enaa a KOPB. Ne:a/8 naa6 8na na <nn8 8al8 a:e. Klna <:/ena *  /e>ne > >6/e  < 6;. a a8n 5<n;a0a:, 8 0na 5l/ Q a@n. Ia, 8 KOPB 8 an:8a<n9 6=e 8n6  :an/e n. Tn * = e 6 l/e6 <:/en/8/8 0=ne 8e6e  :n:aln a<5a e <:/ene 8 0a:a, /a6l/8/e e n lna a<n8 &.@la6l/e. a Q2 a@na ne 80<8/8 na</ <:@la  nedokromil 8 0a  8 @<:n: <:/en/en: >0a:a /el6an/a 6; l/e6a /e /alaa9/e, al :@8 <:l @6< 8ala na an@en. Una * :a/8 a: laln 8na. Ka>a e <:/ene <:l e <e 8 a: @6 > >/e9e. One  nne a <:lna e <e 0a el8>n8 @<0n98, a =n: 8e6:a. U ne: l8a/e6: /e </a6l/ena ale<@/a na l/e.

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K0TIKT'0IDI %6 <e<> 8 en9/aln <n 8 e=/ a:3).@la6l/e. Ia 05@ 6/e n, e: e <e <nn a: a ><8@a e/el8/e. a a5el:ea0n, 58>en>, >ea:ea0n, ?l8nl>, flutikazon /e @8a /e <6a ln/a l/een/a 8:/e e=e a:e. a e= n aa>a/ a:e e <e n prednizon9 metilprednizolon. K<e<> :an/8/8 ne08 ane elne a ??la0: A 2  n;589@6< Q a>=n: 8e6:a. Una * @l8<> e 6eC8 0a neGRE 8 /e0@<, = a 8 naCn 5<n;n<<  8>/el8/8 8 an/e: 8aln: >@6<8. Klna <:/ena * n;ala9/a @l8<>a /e <:/e >/e9e 8l ne >@6aa ne6n: >0: n0na, a n>a a >ne6n8 n;ala9/8. a e= naa>a/ a:e, a a=a6a/8 C6  5l/e >/el8/8 ne@ 8 5n/ a:. Tn * ea 8a :Ce >6e > 8585a. $e=e, <:/ene 8 ?l< <?a<na >/a0:. A /e 585a e :Ce :an/ <:/en: e<8@ >an. Bna e:na n /e ana 8 3).@la6l/8  ea /e a /e e:na e8Ce > 2 /e>na, a 8 e=/ na6l/a/8/ a:. $ea n;ala9/a e<>a > >/e9e :Ce 8< e@n8 n<:aln8 6n8. #$T#7$ITI .'%KT0I'$# O6 l/e6 /el6an/e le8<ena. N8 8n6 a <e<> 8 e=/ a:. Bla<  receptora, 6 l/e6 8 e a:e. Tn  /e :ala. In;5< !-l@ena0e * zileuton /e n8 eln8 8 le8<ene. O6a/ l/e 
 /e 5<n;a0a: / naa/e nan <5a6l/an/a a<na > /e>na9a / 89/8 e0an>a 8 le8<ene a /e 8 9@ena0e 5l
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22.POGLAVLJE ) ANKSIOLITI&I I SEDATIVNI-%IPNOTI&I %e>a6n ;n9 <a>a/8 e:/ ;ee<@en/ @<8 l/e6a /a 6ena 0a06a e>a9/8 (N%-a 6n  >0. Na/6aCn/a >@<8a 8 benzodiazepini, n a6n9 ><8@; >@<8a, a barbiturati, 589/a * 6ena e>a6n;-;na 8 ll85ln  >5< e a<55< >5889/8 anee0/e. Una 8 (N%-8 enala e a <589/: l/ea 0 :0@a 8 ><8@a >5< <<6l/ena 6a, 8 elen; :=a. D<8@ l/e6 / 5<0 8la0e 8 (N% 8 eszopiklon9 zaleplon i zolpidem. Mea5l0a:  0l86an/e * e>a6n ;n9 e :ea5l0a0ena e 58@: l86/e: el:na9/e. Nan nel >ana <:/ene ne; l/e6adiazepam9 flurazepam, a8:8la9/a a6n; :ea5la :Ce >6e > a9/e. .orazepam i oksazepam <la0e e@6/el6an/e zolpidema. B?a0n l5ađan/e 0l>e:a <>8C8/e n/e@6 l86/e 8 la0:. "aleplon e /= 5e;> >a0:  9<: P4!+(P3A4. 'szopiklon e :ea5l0a6n;-;na 6a< nel a 0aleln ] 0l>e: ^ <a0la: ^ e0ln > >8Ce > 3+ al<>a0e>, la0ea:, ?en5a<5al. ME'ANIAM DJELOVANJA /'$"DI#"'PI$I * a0enaB an/ <. B  7#/## n n anal :a<:le8lan@ :lea, ena:e ! >/e>n9a /e :a/8 6aa 4 :ene. VaCna 0?<:a GABA A  ? HB9 ? E?9 i B? >/e>n9a, 8 6/ 0?<: 6e06n :/e 5en0>a0ena e nala0 0:eđ8 HB i ? >/e>n9e. Ia, 5en0>a0en e 6eC8  0a ><8@e GABAA 0?<:e /e e a/e >  2, 3,  ! >/e>n9a. Ve0an/e 5en0>a0ena 0a06a n;59/ 8na GABA, = e >@ađa l/6 0a l<>ne ne. *slika22-6 Ben0>a0en 6ea6a/8 ?n; anala. Flumazenil 0a8a6l/a 8na 5en0>a0ena na (N%,  la?9a/e,  n 8 n6e<0n a@n. 72

/#0/IT%0#TI * :an/8/8 ne88l/ene :C>ne, /aa6a/8  <>8C8/8 n;59/ 8na GABA-e  @l9na. Ba<58<8/a :/ea ne@ 5en0>a0en. Fl8:ane0l n/e ana@n n/;6@ 8na. Ba<588C8/8 6n; anala. Tađe< 5la0en /e< e 6eC8 0a 5en0>a0ena, 6 l/e6 e 6eC8 a: 0a 7#/## /e>n9:. N/;6 8na 0a8a6l/a ?l8:a0enl. FARMAKODINAMIKA Una 8 (N%-8 6ene e>a6n;-;na 6  >0.*slika22-1 %e>a9/a * 6 l/e6 6e @<8e :a/8 8na e>a9/e  anl0e. Anl0a /e 8@la6n: 6e0ana a :an/en: ;: >e0n;59/: na=an/a. U C6n/a, 6ena e>a6n;-;na  a0n: n8 na=an/e. 'n0a * e>a6n ;n9 8 a6an/e  <>8C8/8 a6an/e. REM an /e 5n 0a:a a>a e la0 > /a6e 68l/en/a REM-a. Una na ?a0e na /e </eđ > n6/; ;na 8 0alelna  0l>e:a. Anee0/a * < 6: >0a:a 6ene a</; e>a6n;-;na, :Ce > > @85a 6/e, a a:ne0/:  8na a:ne0/a /e e=a > benzodiazepina ne@ al; e>a6n;-;na. Anee0/a e :Ce 0a06a 5a<58a0en:amidazolam. Ann68l06n 8n9 * 6ena 5a<58a0en 8 6el: >0a:a n;5a9/8. %ele6n ann68l06n 8na :a/8 a: ne l/e6 fenobarbital9 klonazepam. Vele >0e na/:a, 8 6: l8a/e6:a e>a9/a /e <na. Relaa9/a :=a * e >@ađa a 6el: >0a:a 6ene e>a6n;-;na. Ia, diazepam /e  < nC: >0a:a 8n6 0a e9?na ana an/a, 8 9e8l/ene :C>ne * 6ele >0e e>a6n;-;na, @6 al;la  5a<58e8l/en/ :C>n, = >6> > an/a, ;en0/e, :an/6an/a a<>6a8la0
73

Tle@6@ađa e a>a e e>a6n-;n9 <e <nn 8 6: >0a:a. K<Cna le@> 0:eđ8 e:/ @<8a. P;a 6n e /a6l/8/e > 6ene ;na  :an?ea 5 e :an/la an0n. F0l=a/elena 6n >6> > n><:a 8e0an/a 8l e l/e @ađa/8 e=e > /el8/8; l/e6a. l>e:, 0aleln  e0ln 0a06a/8 :an/e ::e 8e0an/a ne@ 5en0>a0en. Klna <:/ena An0n * benzodiazepini 8 l/e 05a/a ane. Ia /e e= <9/en 8e<n@ l/ea na> ><8@:, alprazolam i klonazepam 8 8n6/ > ><8@; 5en0>a0ena 8 >8@<n: l/een/8 ane  ?5/a. Pa0en, ea0la:, ?l8<8@: 0e e <e > a</; a9/enaa / 8 /el/6/ na 8na e>a9/e (N%-a. %a>a e <e zolpidem9 zaleplon i eszopiklon 0a l/een/e nean9e /e< :a/8 5<0 na8 na a :n:aln: :ean/e: ?a0a na, 80 :n:aln8 :a:8eee@ >ana ne@ 5en0>a0en. %e>a6n-;n9 n an/e:. Oala ea0endiazepam9 midazolam e <e a >/el6 <la anee0/e. %e9/alna 8a0ea:. D8@ >/el8/8 5en0>a0enl<>a0e>, >a0ea: e <e 0a n<l8 ::a 8e0an/a > 5a 6n;  al;l8  ><8@: e>a6n:-;n9:a. TOK%I$NO%T P;:?8n9/a * 8l/88/e @n6ne ne6na e>a9/a. O6 neCel/en 8n9 8 e= > 5en0>a0ena / :a/8 a6ne :ea5le a >8@: l8C6:diazepam9 flurazepam, al e :@8 /a6  > /e>ne >0e /el8/8; 5en0>a0ena triazolam. D0a e>a6n;-;na : a</; a9/enaa, /e< 8 6=e /el/6 na l/e6e / 80<8/8 ;:?8n9/8. K> a6; a9/enaa ne6na e>a9/a 6ea6a <0 > a>6a  ?a0en 8 6el: >0a:a 80<8/8 ane<@n8 a:ne0/8,  0a ; <:nal9 <e 0a e8alne naa>e. l>e:  n6/ ;n9 80<8/8 :an/8 ;:ean,  ne:a/8 aa6 e?e a:ne0/e. Ia, 6 l/e6 0a l/een/e @ađa/. 74

D>ana >e@ađa a>a e e>a6n-;n9 80:a/8 a ><8@: l/e6:a 0 e @<8e, al;ln: :a, an;a:n9:a, an;: l/e6:a, >n: anal@e9:a, <9l: an>ea6ne-;ne. P0a6n:-;n9:a 80<8/e e=8 6a8lae alko+ola9 barbiturata9 karbamata ne@ 5en0>a0ena l n6/; ;na0l>e:. L/een/e 0a;/e6a n<l8 >=n; 8e6a  a 8ne >e 5en0>a0ena, e0lna, 0l>e:a  0alelna. D<8@ neCel/en 8n9 * barbiturati i karbamatine 5en0>a0en e0n, 0l>e:, 0aleln n>896e > 6=e<8e ne9e/el6a1 /e>an  < e 0a l/een/e @ene/a, an. 0amelteon * a6 nean9: l :::a 8e0an/a. O6a/ l/e :ea5l089 ?l86a:n(P1A2  ?l8na0l (P2() 6ea6a/8. NeCel/en 8n9 8 6<@la69a, 8:<, en><ne <:/enenCen ee<n  6=en <lan.

7!

24.POGLAVLJE ) ANTIEPILEPTI&I Ele/a /e @<8a <nn; n><:a / 8l/88/8 na6l/a/8e naa>a/en68l0/e * :C>ana >?8n9/a @9a an; ne8<na. Un6 anele9 ele6n :an/8/8 6a68 a5n<:aln8 ne8<n8 a6n. Ia /el6an/a  n/;6/ 8n6 <6 e9?n; elen;  6; l/e6afenitoin, > n>6>8aln; a9/enaa /e 6aCn 0a >5< a<55<8 5e ne <8@e 896l/ne 0a n<l8 n68l0/a. Ne anele9 n>896>8aln; /el6an/e:  >8@: 8=an/e: 8 >8n. Mea5l0a: ?enna  /e nelinearan nea el:na9/e a 8 n8l , 0:eđ8 8:/e0a. L/e e 6eCe 0a <ene la0:e)7-)&, n9en@ ?enna 8 la0: e 6ea6a 05@ l/e6a / e 5. Mea5l0a: ?enna e 85<0a6a 8 <8n l/e6a / n>89<8@: l/e6:a 9:e>n, 0na0>. %a: ?enn n>89<8@; anelea * a<5a:a0ena, lna0ea:a, la:<@na. Fosfenitoin /e 5l ?enna l/6 8 6>  < e a89<8@e aneleelna0ea:, la:<@n, 6al<na elna. Val<na elna, <?en  <lean>:9n n;5
7"

!#.P0I3$# KI'.I$# %e na/ee a ?enn: 0a 6e0n :/e na <en:a la0:e,  n;5a, ?enna, ?en5a<5ala  la:<@na. B<8@: l/e6:a. Topiramat <la0 /ea9/:. ME'ANIAM DJELOVANJA Oen 8na anelea /e n8 na6l/a/8e a9/e en9/ale 8 elen: Ca<=:a :0@a. /lokada natrijevi+ kanala * < e/el6an/e /e 6n  5<0n?8Cen/e na65l/a. Fenobarbital i valproična kiselina :a/8 lan 8na < 6: >0a:a. 7#/#-vezana ciljna mjesta * benzodiazepini e 6eC8 0a e9?ne n anala :a<:le8laa0ena, ?n; anala /e 6eana, 0na 6 l/e6 :aC8 n;5<ne 8ne GABA-e. Fenobarbital  ><8@ barbiturati ađe< :aC8 n;5<8@: :/e na 8l/en: 6n; anala. GABA a:n8 >/el6an/a GABA-e. !alproična kiselina @a n;5a/. %lan 8na :a  valproična kiselina. D<8@ :e;an0: * 6al<na elna 0a06a ;e<la<0a9/8 :e:5n: anal:a, ađe< >/el8/e a ana@n na @l8a:an: a0en * e>a9/a, le6le, @n6na >?8n9/a, :a:l/en, aa/a, >n * <5a6ne :en/e, lea<@/a, @la65l/a, <:/ene na=an/a La:<@n * :a@l9a, aa/a, :8nna, , Le6ea9/a, 8:<, a@a9/a, aen/a, ;al89na9/e 77

Fen5a<5al * e>a9/a, @n6ne :en/e, ;e89/a /e6le, e>a9/a, ;e<la0/a >en, ;<080a:, ane:/a, e<?e89/a /ean/e e,  2@>., n;59/a /e/e9a :a/ /e 80:a/8 anelee :a/8 6ean <0 n@enaln; :al?<:a9/a. De?e ne8a 8 6e0an a 6al<n: eln:, a<5a:a0en e 6e08/e a :,  ?ealn ;>ann n><: /e 6e0an a ?enn:. P0e0 > >ean/a. L/een/e /e <:a 0a0en:a. Tn * 6al<na elna :Ce 80<6a ?aaln8 ;ean > >/e9e :lađe > 2 @>.  a9/enaa / 80:a/8 6=e anelea >/e>n:. La:<@n :Ce 80<6a %e6en-Jn;n n><: l n8 e>e<:aln8 ne<l08. %n><: 8e0an/a *  l/een/a ann68l06:a e : een >a 5 e 05/e@la 6eana ? l/e6a 0a a<9/alne l @enea/e.

7&

2+.POGLAVLJE ) OPI ANESTETI&I Oa anee0/a /e an/e ae/el6an/e /e 8n 5/el6an/e e>a6n;;na. %a>/ anee0/e M>e/el8/8  C8 >858 anee0/8 6e:a 5<0. K> a</;  :al </; aneea, 9naln e 8/8 ?a0e anee0/e, @>/e e 6ean/e: >0e  6e e /a6l/8/e a:ne0/a, 6/e /e =eena al ne 0@85l/ena. Faza ?eksitacija * a9/en /e 8 58nl8  8058đen, /a6a a:ne0/e, /aan an/e  /e nean/e /e <:n, <6n la /e >medularna depresija * a9/en 6a8lae/a@n:, ea9/a /e e;na /a :5n858 anal@e0/8 80 0a>@65e. a eCne <8<=e 0a;6ae, <l anee0/e 8l/88/e n890< 6aln; 0na6a /e :e>a <9/ene >85ne anee0/e /e: e0< :C>ane ?8n9/e, /e e;na 5a0e/el6an/a 8l/88/e 8na na anale na ne:a l <en:a :e:56an8 n;59/8 na GABA A n/: > 6: n9e
@l9n /el/6 na <;n 8 /= /e>n :/e >/el6an/a n;ala9/; aneea. Ne8<n 8 /el6:a :0@a 8 @ađa </e ne@ n;59/a ne8<na 8 9+alotan9 izofluran9 sevofluran. On e <:/en/8/8 a ln6, n/;6 a<9/aln la 8 n;al<8@: 6:a /e :/ea<>n la n;al8=n >8l 8 n;al nel ?anae,  5 anee 8na. L/e6 a n: a<9/: e?9/en: <6Hln>8=n >8l 5naa6a/8 ne@ n a 6e: l/6 8 <6;alan.*slika25-3 Pa<9/ e?9/en n;ala9/; aneea 8 8 a5l9 2!-2. KON(ETRA(IJA ANE%TETIKA U UDA'NUTOM RAKU * 6 a<9/aln la l/ea 8 l8:a /en n9ea 5 anee @a an: 6:. T 0na  >a  /e a <589/: l/ea 0 :0@a 8 <6  el:na9/: l/ea <0 l8a. P< <=en/8 l/e6a a n: a<9/: e?9/en: <6Hln 5 anee0/e ne@ > aneea a 6: l/6=8 8 <6. *alotan i metoksifluran e :ea5l0
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a /e n. Mn:alna al6elaa<>n@ 5ln@ > !+ a9/enaa. %6a anee :a >n 6a<5, a<>6a8la>an; l/e6a. P<9/ena 6</e>n MAK-a a08/e 0a->@6< 0a n;ala9/e aneee. K> n6<đena>  a</; a9/enaa MAK /e nC ne@ > a>le9enaa  >a e < nel aneea >/e>n:, n/;6e MAK 6</e>n e 056e > 6ean/a n6e > /a6e =l/a-6al :lea  <0a/a :=a. Ia du8ični oksidul :a 6 MAKn8 na@8 aneea, a a08/e /a8 anal@e0/8  8na a:ne0/e. Un9 na a<>6a8laea  :an/8/8 :n8n 6l8:en <9a, > izofluran9 sevofluran 80<8/8 e<?elaa9/8. Du8ični oksidul  al; n;ala9/; aneea >e<:. Vena n;ala9/; aneea nCa6a <6n < 8 /e<  585 na a<:@ene 8ne aela:na. Un9 na >=n 8a6 * 80<8/8 6ean/e ?an/a, al :an/8/8 6> > 6ean/a n9e@6< na ;/8 a  85aneee n9ean/e. Vena n;ala9/; aneea 8 5<n;>laa<, al desfluran <a;a a n/e <an 0a n>89/8 anee0/e. TOK%I$NO%T U a9/enaa a ;6le:/: =:  ><8@: <8<=: @6<. Mea5l0:: metoksiflurana9 enflurana i sevoflurana naa/8 ?l8<>n n  :@8 80<6a =een/e 5858Cene anee0/e. P<>8Cena 0lCen du8ičnom oksidulu :an/8/e a6n :enn-na0e  :Ce 80<6a :e@al5lan8 ane:/8. O/el/6 a9/en :@8 a e anee9 <e 0a/e>n a ne8<:88la
nen<l6> > a0:a :=a, ;e<e<:/e, a9>0e, a;a<>/e, ;e<en0/e. a l/een/e e < dantrolen, 80 l/een/e ::a. INTRAVEN%KI ANE%TETI(I /#0/IT%0#TI Tiopental i meto+eksital 8 /a ll85ln, = @8 :n8e/e>an <la0a <0 e:n8 9<8la9/8. O6 l/e6 e <e 0a n>89/8 anee0/e  0a 8a <589/: 0 :0@a 8 ><8@a >5< <<6l/ena 6a *slika25-6, al :ea5l0a: 8 /e< /e ean/a  9<8la9/e = :an/8/8 < <6 8 :0@8 :@8 :an/ nn a n;ala9/: anee9:a  nn: anal@e9:a. Pea (N% 8na /e </ ne@ enal,  >8l/e >/el8/e. P/a6l 8 e l8a/e6 e=e eean/a. Fl8:ane0l 85<0a6a  :>a0la:a  ><8@; 5en0>a0ena. K'T#1I$ O6a/ l/e <06> an/e >9/a6ne anee0/e 8 /e: a9/en a/e < 6/e al /e aan ?en9l>n8P(P, / :a ;a6na 6/6a. O6a/ l/e /e :8la< a<>6a8la6e > 6ean@ n ea:na /a6l/8/e e >e0</ena9/a, ea9/a, ;al89na9/e /e e :@8 :an/ </eea0ena. PIID$I #$#.7'TICI Fentanil i sufentanil e <e 0a/e>n a ><8@: >e8=n >8l, 5en0>a0en > a9/enaa / ne 5 :@l n <n@ =a = 8/ee na >an/e. Naln n=a6a >ean/a 80<6an@ 6: l/e6:a. Ne8<leanee0/a /e an/e anal@e0/e  a:ne0/e /e naa/e a>a e ?enanl < 0a/e>n a >8=n: >8l:. #lfetanil i remifentanil 8 e <l 0a n>89/8 anee0/e. O ><8@; >a 05@ 5<0@ :ea5l0:a eena 5<0 a  n/el8/e ane:e,  8l/ nan <>8Cene n?80/e. O6a/ l/e /e > alne n8Cene e>a9/e > a9/enaa na ne06n/ <5. U0<8/e 0naa/n8 &2

;en0/8 /e: n>89/e anee0/e, <:aa 0a n/e@68 el:na9/8 8 >an :e;an0: : :ea5l0:a /e,  :an/e 5l :/e n/e9/e l/ea. 'T1ID#T De<6a :>a0la / 5<0 n>89an/a  :a /el6an/a. O6a/ l/e n/e anal@e,  n/e@6a <:a a9/enaa a l:=n: 8Cena <:/ena 80<8/e 8585a.

&3

2!.POGLAVLJE ) LOKALNI ANESTETI&I Lalna anee0/a /e an/e 5la>e en0<8/a /ela 8 :0a. Laln anee9 ne @<88 e:/ ln; 6a<ee<  a:> / 5la e <:/en/8/8 n/e9/: na 9l/n ><8/e l aln anee 8na /e a: na lal0<8/e<Cn9a, <8a, a a>a e >a/8 n<8@a 6a. Ke:/a 6/6a Vena laln; aneea 8 ee<benokain9 prokain9 kokain9 tetrakain l a:>lidokain9 bupivakain9 prilokain9 ropivakain /e>na6n; >e<6aa 5en0ena. P>@<8e laln; aneea e 5a08l/n n: n0n@ <na'. %8an/ n0a9/e /e ?8n9/a K a l/ea  ' lne. B8>8 >a ' 6a e ?0l=; 7.4:Ce 5 ".4 8 n?9a 8/e8 na :/e< n0/el8/8; laln; aneea e a<5<8/8 :an/en < <6. O6 e :Ce  a <:/en: 6a0n</el6an/e 05@ n;59/e 6/el8/8 l/e6bupivkain9 ropivakain9 tetrakain ađe< n8 6n  >>an/ <:/en 6a0n< 6<=n; C6a9a a e <:/en na 6<=n8 :80ne :e:58n a: 8 aln: 5l8, lidokaina i tetrakaina. Laln anee9 ee< e :ea5l0<l0: 9<8llnee e :ea5l0/el: :<:: 0en0:: 9<: P4!+. Pl8C6 l>ana  <lana 8 <le 1.! a. B86aan  <6aan e na/>8Ce >/el8/8 a:>n laln anee9 a l8C6: 3.!4.2 aa. D?8n9/a /en; laln; aneea6ean <0 n. A9>?a9/a 8<na e n0a9/8 laln; aneea,  a/ n0ela<0a9/8 :e:5la0e 8 na a n8 :e:5a 5 8=la 8 9la0:8, n>a nen0
l/ea </e Ce a 5 >/el6a ne@ n0la0a > <8@ a: 8na l/ea. A?ne la0 : na, 6lana a 6e: ?an/a e </e 5l <:/e<8 6lana, :/eln0a9/, 8eal >an/a, ana:/ la9/. *tablica26-3 Genea/8 5e5el: C6an: 6lan8 8 5l=8 /e< 8 </e 0lCena 6e: n9e0an/e /el6an/a na >a:n  ><8@8 na8 8/el6an/a e :Ce 85<0a <:/en: natrijeva bikarbonata, / 6ea6a ln8 l/ea 8 nen: 5l8. A<an :a na/5/el6an/a. Laln anee9 e <e 0a naln8 anee0/8  0a <06>n/8 a8n:ne 5la>e 8 ;e:n: 86/e:a. %88na n?80/a. Pna6l/an/e e>86e > a;?lae. Inn 0a l/een/e ne8<a; 5ln; ><:a. TOK%I$NO%T (N% * na/6aCn/ n 8n9 6ene laln; aneea 8 8 (N%-8. %6 8 5n 0a ea< 9ena9/e, ne:6a8lae
Ka<>6a8lalaa<. K> a9/enaa a /e: a<>6a8la
n9e6a 0:ean. 0opivikain 80<8/e a<>n < 8a 5l6a8la<@a, >la0 > e=e ;e<en0/e, :C>an; 8>aa. D<8@ n 8n9 * prilokain e :ea5l0e:e0a9/8 > a9/enaa a <an:  l8n: 5le. Laln anee9 ee< e :ea5l0n laln anee9. U 6: n9ea0ea:: l enal:. P:aCe  ;e<6enla9/a :. Nea>, ne8<:88la6a8la :@8 8:</e > n/e.

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2$.POGLAVLJE ) RELAKSATORI SKELETNI% MIIA L/e6 8 6: @la6l/8 >/el/en 8 8 >6/e /el8/8 na ne8<:8lae aa 5 la=al <8<=e 8e  a6l/an/e /el8/8 8 (N%-8, <e e 0a :an/en/e a5n<:aln@ n8a :=a 05@ ne8<l=; 5le l 5le nae. $'%01%K%.#0$I /.K#T0I Kna n/8 8eln ne8<:88lael0a<ela<0an8 5a</e<8. L/e6 / e :ea5l0/el6an/e1+-2+ :n ne@ n / e el:n/el6an/e 3! :n. U0 /ean/e '?:ann6a el:na9/a  <06> laudanozin / < 6: n9ean0na. Me;an0a: >/el6an/a * ne>ela0/el6an/e a9ellna na :</ 0a6<=n/ l. *slika27-6 D/el8/8 a ana@n, 0na 5la>a e :Ce 8n8 >6l/n: ln: a@na. On e na/e8 a a9elln: na 8. P-ean9 enan   n ;e 8<n@ ;e ean8 ?a>e l. *tablica27-2 Vel :=a5>:naln, >/a?8, al e /el6a. Dela0 >6/e :le8le a9ellna 6e0an; na na >0a >/el8/e nel :n8a. Bla>a /e >8Ca > a9/enaa / :a/8 6a</an8 lnee8 dibukainom. A9ellnee<l0
Me;an0a: >/el6an/a * 89nlln >/el8/e a nn a@n  >ela<0ela<0a9/a /e 6e0ana a <0an/e:  ?a98la9/a:a:@8 e 05/e :al: >0a:a ne>ela<0ne ela<0a9/e 0a6<=ne le, nn8ela<0a9/a 8l/en >a/e n?80/:, 8na 89nllna e :/en/a 0 nn8ela<0a9/eblok IG faze 8 een8 ela<0a9/8blok IIG faze. U>an/e 5la>e * >/el6an/e ne>ela<0a 6ean/e: n9e@:na. % ><8@e ela<0a/8 5l 89nlln:. TOK%I$NO%T Re0e ne8<:88la > a an8<n/ la5 5l/8. T858@>  a :e8<n:, a<8@ n6/ ne>ela<0a8</, e8<n/, <8<n/ ne:a/8 a8n:n 8na n 8na na l5ađan/e ;a:na.*tablica27-3 %e9?n 8n9 89nllna * ene, e<?e?8n9/e, :=ne ><?/e. P6ean/e laa 8 Cel8>98 05@ ?a98la9/a :Ce 80<6a 68C8/8 ne8<:88la8. R/ea nea 858n: ;e<e<:/:. Ran 0na 6@ an/a /e nan59  ana<:9 :@8 /aa  <>8C >/el6an/e ne8<:88la
&&

Un9 5le  a/el6an/e l/e6a * a</ a9/enX7! @>na  n a :aen: @/el6an/e ne>ela<00a : ; a9/enaa. O5 5le @an 8>a< 8 6e0ane a a5n<:aln 6: <8@: l8a/e6:a, a8na 0l/e>a l 8ala :=a >6> > a0:a  5l,  aa6 a0a: e :Ce :an/ >/el8/8 8 (N%-8  8 /e>n: l8a/8 na a:8 :=n8 an98. T 8 diazepam5en0>a0en, baklofenGABA a@n, tizanidin<>an ln>n8, dantrolen>/el8/e na a<la0:a n/; <8@. /otulinum toksin n/9 a9/enaa a :8ll: le<0:. Me;an0a: >/el6an/a * a0:l9 >/el8/8 a0ea:  0an>n >/el8/8 na n.*slika27-11 Bal?en >/el8/e a GABA B a@n na /el6an/e GABA-e. Da0ea: /aa6a n;59/8 GABA-: n, /e :>a0ln / lan ln>n8, / /e a@n  2 n. All 3 ><8@ 89e ;e n9 88 ? ;e <:a< nal :ne8<n. Dan<len >/el8/e na an9e elen; :=a  :an/8/e 8=an/e al9/a 0 a<la0:a@ n e<:
8n6 0a l/een/e :al@ne ;e<e<:/e, an<len e <:/en/8/e na9/a 05@ >a0ea:a /e 8n :an/a ne@ > al; e>a6n;-;na < >0a:a /e @8a9/8 ne@ >a0ea:, a lean/e l/een/a 5 e . T0an>n :Ce 80<6a 8 la5, an, 8;a 8a  ;en0/8. Dan<len 80<8/e la5 :=a al :an/8 e>a9/8 ne@ >a0ea: l 5al?en. [a9/en a a06an/e: 5858l/en >/el6an/e :6a8</a  89nllna .I&'K!I "# .I&'3'$&' #K%T$7 P#"1# K'.'T$I* 1IIQ# Mn@ l/e6 e <e 0a l/een/e a8n@ a0:a nan 0l/e>e :=aciklobenzaprin9 metokarbamol9 orfenadrin. Vena 8 e>a6 l >/el8/8 na :C>an >e5l. (l5en0a<n,  /e < 6e @<8e l/e6a, >/el8/e na :C>an >e5l, 6/e<6an :ean/e: lna; a6n  an:8a<n >/el6an/e. MCe 80<6a n?80/8, 6>ne ;al89na9/e. N/e>an > 6; l/e6a n/e 8n6 8 l/een/8 a0:a 05@ 9ee ne.

)+

2'.POGLAVLJE ) FARMAKOTERAPIJA PARKINSONIMA Pa?0l@/a * a<nn0a:a?8n9/8 8 5a0aln: @an@l/:a  6e0an: :C>an: <88n elen; :=a, ane0/al 5ne0/a, l9e 8 :ae, a a<nn0a: * /e ne0naa ></ela  /a6l/8/e e nan !+ @>ne. Pal=e aa:na 8 <a8:8  >e@enea:ne<@n; ne8<na 8 n@<</aaln: 88 / n<:aln n;5a:n; an;59/a a>enla 9la0e. %:an/en/e n<:alne >a:ne<@ne ne8<6> > a:na  a9ellna 8 6an ane >a:ne 0a:a, rezerpin 80<8/e lne ::e, :an/8/8 >a:n 8 :0@8. MPTP1-:el-4-?enl-1,2,3,"-e<<>n, /e n8<06> ne>8=ene <06>n/e :ee<>na, 80<8/e a:ne<@n; ne8<na 8 n@<</aaln: 88. LIJE$ENJE PARKIN%ONIMA %a:ne a6n 8 :0@8, :an/en/e :8a<ne lne<@ne a6n, l 5/e. Ia / 6=e 6<a >a:n; a:n :a :al8 5a le6>a. O6a a:nelna 8la0 8 :0a a:n, /a /e <8na 8 :0@8  :n@: 6:a. Le6>a e 5n >a/e a karbidopom, l/e: / ne <la0 <6-:0a 5a</e<8 al n;5a->ea<5la0e 8 e<?e8Cen, 8n6e 8 :an/e >0e le6>e  :a :an/e e<?ea 85laCa6a 0na6e a<nn0:a, e5n 5ne0/8  l/e>n8 ne5l/en,  :an/8/e <0 > :<. Ia, l/e ne l/e a<nn0a:,  /el/6 6a<6an/e 5le. Kln >@6< na l/e :Ce 6  60<8@: l8a/e6:a /a6l/8/e e n-?? ?en:enaa 8 /e: e 8n8a< nel a 0:/en/8/8 5l/a 05l/:a 5l/=ane )1

ne0/e, nea> ??-e<> :@8 >@6a5l/e ne 80:an/a l/e6a :an/8/e ne 8ne, al ne ?l88a9/e ln@ >@6n a le6>: :Ce :an/ ?l88a9/e ln@ >@60 l/ea. Ga<nenaln 8n9 8 an/el/en: >0a:a. Tlee. $ea /e <aa ;en0/a, @6 /e: ea l/een/a. Oal a<>6a8la/a, ala, a<:/e</e. Dne0/e naa/8 8 &+ a9/enaa, na/e=e 8 aln; >/el6a 8 >6a. B;e6el80/e, ;al89na9/e, >ea /e n9 a9/enaa a ;0:. #7$ITI DP#1I$KI* 0'C'PT0# /01K0IPTI$ Je e<@ alal>. On >/el8/e a parcijalni agonist na >a:n: D? a:n; ne8<alne ?8n9/e. B<:<n e < a a:aln l/e, 8 :5na9/ a le6>: anlne<@n: l/e6:a. O neCel/en 8n9 8 anne0/a, <aa ;en0/a. Be;a6 5<:<na ne@ n6/; l/e6a 8 n?80/a, ;al89na9/e, >el80/e. %a>a e l/e 8n :an/e < 0a l/een/e a<nn6e 5le, 05@ n6/; ne-e<@ >a:n; a@na. P0#1IP'K. O6a/ ne-e<@ :a a?ne na >a:ne D= n a le6>: 8 80na6al/ 5le. P<:/en/8/e e ne6n,  el:n?8n9/ >0a e :ne0/a. Menaln el80/a, ;al89na9/e, :8l06n 8 e= > e. U </e: l8a/e6:a, :Ce e /a6 nen<la9/a /e > a9/enaa a a6n: e: 8l8:, ;0a:a, l ne>a6n: n?a<: :a<>a. P/el8/e ne8<<e6n /e< >/el8/e a ;6aa 6>6@ e<>a.

)2

0PI$I0. J= /e>an ne-e<@, 6a/ l/e :a /a a?ne 0a >a:n D? n a le6>: 0a :an/en/e ?l88a9/a >@6aa/e 3 8a >ne6n, al / 5l a <>8Cen: >/el6an/e: / e 80:a /e>n:. Rn<l e :ea5l0<8@ l/e6 / e :ea5l0a9/e 8 lne a:n; e ane0/e 8 a9/enaa a :0a:n: eana ane:e9:atrimetobenzamid /e ne;>an. I$*I/IT0I 1$#1I$KID#"' elegilin i rasagilin 8 ele6n n;5< :na:n>a0e tipa /, 5l en0:a / :ea5l0a:n*slika28-5 %ele@ln e < a le6>: 8 l/een/8 a<nn0:a. Raa@ln /e /a  :Ce e < a :ne:. NeCel/en 8n9  nea0e 8 nean9a, <:/ene ne0/e, @a<nenalne :en/e, ;en0/a. K:5na9/a 6; l/e6a a :ee<>n: el</e:  :<. %ele@ln /e 6e0an a e<nn: n><:: a>a e < a ele6n: n;5<:a n6ne ;a 8 3-O-:el>a3OMD. P6eana n9e@6<: na le6>a, 0a /e< e a 6a< na/ee a le6>a 0a a6n </en 8 (N%. Enean >/el8/e a: 8 e<?e</. O6 l/e6 e <e a >>aa le6>a-a<5>a, :an/8/8 ?l88a9/e, 5l/=a6a/8 >@6< na l/e, <>8C8/8 n e<>. NeCel/en 8n9, >/el: 6e0an a 6e: n9ea, 8 >ne0/a, @a<nenalne :en/e, <aa ;en0/a. P0e le6>e < en: 80:an/8 n;5
)3

#1#$T#DI$ On 5l/=a6a >a:ne<@n8 ne8<a:na l n;59/: 6a:na. Tađe< 5lne0/8, <@>n, ana. Tađe< :a an6e:e, / 8/el6an/e ne8<na 8 </a8:8, 5ln, al :a/8 :al 8na na 5ne0/8. K<e e a >>ana ealne ::e 05@ an;a. Tn 8 (N% /e an, neaCn/a, n?80/a, ;al89na9/e. Pe<?e a<na. O6 l/e6 /aa6a/8 8ne0/8 80<6an8 <nn: 8
)4

2(.POGLAVLJE ) ANTIPSI%OTI&I I LITIJ An;9ne8<le9 e <e 0a l/een/e ;0?a:ne  n6/ an;9 :a/8 6 a?ne na 5-*T? e<nne el80/e e :@8 5l/=a. NaCal <nn l/een/e@>na:a /e   e=e n > ne; a9/enaa. Blan/; @>na 6e 6=e e <e n6/ an;9  ann68l06. #$TIPI*TICI Vele >@<8e an;a 8 fenotijazini(klorpromazin9 flufenazin9 tioridazin)9 tioksanteni(tiotiksen) i butirofenoni(+aloperidol)G N6 an;9, ;ee<9le <885< a<5a9/a  >e:ela9/a  :a/8 >8@ l8C6 a e :@8 /e>n: >ne6n 80:a. U ne: l8a/e6:a, l/e6 / n;58C l8C6 an;a. Me;an0a: >/el6an/a Da:ne<@na e</a ;0?a /e a:na 8 e9?n: ne8<n: 8e6:a :0@a. O6a e</a e 5a0a:ne <8@ >a:n a@na:?ea:n, le6>a /aa6a/8 ;0?a:n; /el6:a :0@a nel/en; ;0?6l/a6a 8 8n /e< an;9 8 a: >/el:n 8n6 > 6ene a9/enaa  0a = :n@ 8n6 l/e6 :a/8 6e a?ne na ><8@e a:ne<@n; :ena. D 2 enla 9la08. Tee D 2 alne >?8n9/e.

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D<8@ <8@e a  a> i 5-*T? 6ela > e<nne<@ne e</e. N6/ an l/e6 80<8/8 :an/e ealn; >?8n9/a. O: ;ale<>la, 6 an;9 8 ne/ :/e< 5la >a:n;  ealna a6n, 85e<n?8>58la8l-e<6en<8laa >a:n; e <8@: 8e6:a, 8 ealna >?8n9/a  ;e<<lane:/a. %< 6 an;9 5le/e, ;al89na9/e, >el80/e, 05@ @a :@8 la=a ?8n9nana >a 5 e /a6l 8n9. (/el8na >/el6naa 8 n<l ::a 5le, a n>6>8aln a9/en na/5l/e >@6a /; al l/e6 ne >/el8/8. %a</ an;9 ne:a/8 8na na ne@a6ne ::e ;0?aa :6a9/e. N6/ an;9 e e <e a l/e: 0a n9/aln l/een/e :an/e. Ne e <e 0a l/een/e a8ne :an/e, a a<<:8, 0a a0na, 6ena ?en/a0na :a ane:e 8na, proklorperazin e < a: 0a 68 n>a9/8. Fenotijazini a /el8/8 0a la=an/e 6<5eCa  a e>a6prometazin.

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TOK%I$NO%T Re6e<05ln ne8<l= 8n9 *  >0 6n ealn 8n9 8 5ne0/a, <@>n  0e  ana@n05n: <:/en: :8a<n; 5laalna n /e e=a a ;ale<>l:  en/e, :@8 e </e= l/een/e: >?en;>6na >ne0/a * /e n><: n; na e<:. Pa naa/e 05@ a:ne<@n; a88  8a:en8. A8n:n 8n9 * e e<?e a</; a9/enaa. Tle@ađa a >8@<n: el na/la5/e. Kl0an  an l/e6 :a/8 n/e a8n:ne 8ne.  e e :8a<ne 5la>e, 8n9 ln a<n88;a 8a, na9/a, 8<na: 8 e > <>a0na  l<<:a0na. O6 8n9 8  > an; an;a al ne  > 0na  a<e :8a<n; a<na  <9l; an>ee  ?en/a0na. K> a</;, 6a. Kl0an  0n ađe< 5l<n  :ea5l 8n9 *  8 ;e<<lane:/a, @ne:a/a, n><: a:enn. O6 neCel/en 8n9 8 :an?ea9/a 5la>e D 2 a:n /e n;5< en e5n >Ce /a5e@en 8na>e5l/an/e, ;e<@le:/a. O6 8n9 :@8 5 e5n an 8 <8>n. A<n ne:a/8 naa6 en><n l :ea5l 8na. Ne8<len :al@n 8na * a9/en / 8 e5n /el/6 na ealne 8ne an;a :@8 <:. %:: 8 :=na <@>n, an<len, >a0ea:  a@ne >a:na.

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%e>a9/a * /e e=a > ?en/a0nal<<:a0n ne@ al; an;a 6a/ 8na /e ne8@>an > l/8> / ne:a/8 ;08. Fl8?ena0n  ;ale<>l :a/8 na/:an/ 8na e>a9/e, a a< n6/; l/e6a. Ra0ne n * <>a0n 80<8/e e0e < 6: >0a:a =e8/e <an8 <6>l/6  >6> > ?aaln; 6en<8lan 80<8/8 <>8Cen/e ZT ne<6ala, = :Ce >6e > a<:/a. Kl0an 80<8/e > 1-2 a9/enaa a@0a:a n68l0/e. Kl<<:a0n 80<8/e >e0e 8 n/e: n: e@:en8. P0a0naa<>n  :e0<>a0na 5n n/e :<nn. 'en0/a >5< >@6aa0ea::  ?enn:. .ITI& I D0%7I .I&'K!I "# /IP.#0$I P0'1'Q#& L/ /e 8n6 8 l/een/8 :anne ?a0e 5laea. Fa<:anea * l/ e a<5<58  el:nana ea 5 e 8an6la 8n6a  @80a. Kn9ee. De;>:a, neen: an 8aln: l/e6:a N%AID, n;5<:a an@en0n-n6e<08 n; /el6an/a * n/e 8 8n >e?n/el6an/e <8@; @lana * ??a>ln0l-4,!-5??aaPIP2, a  :e  :an/: IP 3  DAG. O6 ><8@ @lan9 8 6aCn 8 ne8<al/e < 0a l/een/e 5lae<8@ l/e6 8 valproične kiseline i karbamazepina 8 /e>na 8n6. Tea0en 8 /el6a. lanzapin i kvetiapin 8 :ne<8@ l/e6 e <e >5n /e: n<le 5le. [:nee 5la
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Tn * neCel/en 8n9 l/a 8 a9/a, aa/a, a?a0/a. %:an/8/e ?8n9/8 =n/ae, al ;<>0a: /e </e>a. Re6e<05ln ne?<@en >/a5ee e e >@ađa < e0a:a. E>e: /e ea n8/a6a, ane?<:ne e<89/eane > l/ea, le890a /e 86/e <8na. P<5le: >?<:@en0e n/e </e=en, 80:an/e l/a /e: <8>ne :C>a 6ea6a <0 <an; an:al/a. Kn9/en/a. O%TALI LIJEKOVI A LIJE$ENJE BIPOLARNOG POREMEAJA Manna ?a0a 5laa9/8. !alproična kiselina :a an:ann 8na /e>na l/8,  8n6a /e > a9/ena / ne >@6ae
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3*.POGLAVLJE ) ANTIDEPRESIVI Vel >e@ena >ee9n@ l 8a9/@ 80<a, :an?ea e n a 5n: >@ađa/:a l /ea 8Ca. L/e6 / e <e 0a 6el >e/el6an/a na a:n :0@a, @6 nea l/e6 / 5l/=a6a/8 ::e 6el@ >e/el6an/e !-'T  NA 8 (N%-8. $n/en9e /e ne >8<8 68 e</8 8H:<aln a0al :an/en/e n9eeen >a 5 e 6> ln 8na 6ena an>en/e, 5aan 8n6 an>e/ele nee > ?a<:al=; 8naa. T(A e >5< a<5<589/e. Pn: >ne6n e >0ana. D<8@ lan6 6e @<8e citalopram9 escitalopram9 fluvoksamin9 paroksetin i sertralin ne 6a8@ >/el8/8e a6ne :ea5le. 'ETERO(IKLI$KI * 6 l/e6 :a/8 n  n 8 0n:e, n/;6 l8C6 /e /a ne6n. I$*I/IT0I 1$#1I$KID#"' * 1#Ifenelzin9 tranilcipromin 8 <88a:n. T/el6a al /el8/e1 /e>an ne@ al. Ia >/el8/8 /a >8@, <:/en/8/8 e 1 >ne6n. In;5< 1++

8 en0:a /ee/el6an/e NA l !-'T. N, ne?a0>n  n >/el8/8 a ana@n na !-'T 2A 6> > :an/ena 5</a Q e/el6an/a na na: <8@ 6e0n :/e. I:a/8 :n:alan n;5/el6an/e 5a ne8<e6enla?an l >8len. %NRI e T(A /e< ne 5ln  n 5lee/el6an/a 58<na /e ne0na. MAOI * 6ea6a/8 a:ne 8 :0@8 >/el8/8 na n/;6 :ea5l0a: na C6an: 0a6<=e9:a, = 6ea6a n9ea e 6e08le /el6an/e. FARMAKOLOKI U$INAK Bla>a n6ne ;6> > e<?ea9/a * /e e 8na <9l;  ne; ;ee<9l; l/e6a, @6 :<a0ana  ana@na !-'T2 na  na *tablica30-2, n/ e e <8/8 8 6<;8 e>a9/e  : < a6an/8. MAOI, %%RI,  58<n 80<8/8 :8la9/8 (N%-a. 1+1

Bla>a :8a<n; en. A<n8 lne neCel/ene 8ne ne ne?a0>n, a:an, :a<ln. Ka<>6a8laee  a>el/6:@8e a<:/e. Venla?an < 0n. Kn68l0/e * < 0 :a<ln  %%RI. KLINI$KA UPOTREBA Vel >ea9/a an>e@6<8 na n>6>8alne l/e6e. 5@ la >n=l/6; n8/a6a  @80an > n6/; l/e6a ne a08/e 8n6 a <9l l/e6. Ka alea9/8, </:. %ele@ln, < n: >0a:a n;5 e 0a >ee<:aln ?lae< / Ce 6e >0e  5ln8 l/een/a. %%RI, %NRI,  n6/ ;ee<9l 6ea6a/8 <0 a:85/6a > >/e9e  a>le9enaa. Oala lna 8a/a ane, ?5/e, en88len, 6enla?an e <e 0a ne8<an8 5l  ?5<:/al@/8 >8len 0a 5ln8 >/a5e8 ne8<a/8. Kl: a9/enaa a a/a, 9/alne ?5/e, PT%P, 58l:/e, ?<n@ 6a6an/8 > 8=en/a. TOK%I$NO%T I INTERAK(IJE LIJEKOVA T(A * neCel/en 8n9 T(A e :@8 na:@ 8na. T 8 a9/a, 8:<, nea> n?80/a :a::eHa;a<>/a, 80ne::a/e e5l/an/e. P0eel</, ne8<:88lael/6, e=e a<:/e. `3 K-:a, n68l0/e, a<>n. Inee>ana >e<8@: >ea0ena  >a. Tađe< 80<8/8 5/el6an/a @6ane>na 5l
1+2

0a6<=ee. R/eđe :@8 nee  ln>na. %%RI TOK%I$NO%T * ?l8en  ><8@ %%RI :@8 80<6a :8nn8, @la65l/8, an0n, 80ne:?8n9/8. Ne<60a e :Ce /aa :al: en: >0a:a l 80 >>an8 8a0ena. Kn68l0/e 8 l/e>9a @<:n@ 08Cen/e ZT < 0<: 8e0an/a /e a6> > 6eane a6n ><8@; l/e6a 8 T(A  6ae<:e<: /e <6 an 0a ne<: 8@<Ca6a C6, a :: 8:=na <@>n, :ln8, ;e<e<:/a, a<>6a8la<: MAOI, T(A, >e<:en, MDMAe9a. a l/een/e e <e ann68l06, n 80<8/e >e5l/an/e  e>a9/8. A:an, :a<ln, :<a0an  n 80<8/8 a8n:ne 8ne. A:an /e  5la< >a:n; <:. NeCel/en 8n9 58<na 8 an0n, 80ne:0a:a n68l0/e. A:an  :a<ln < 0n. Venla?an 80<8/e 6=en/e <6n@ laa 6n  >0,  :8lne >0e 6enla?ana. Venla?an  ne?a0>n 8 n;5< 9<: P4!+ 0en0:a. Pn /aa6a 8na a<5a:a0ena, l0ana, ana, T(A. Ne?a0>n  >8len </e 80<8/8 ;ean. MAOI TOK%I$NO%T * neCel/en 8n9 9naln; MAOI 8 ;e<en0/an>@> > a9/enaa / 80:a/8 MAOI  ;8n n>0n a %%RI <::.

1+3

31.POGLAVLJE ) OPIOIDNI ANALGETI&I I ANTAGONISTI O>n anal@e9 8l/88/8 <<>ne /ae  e:nee alal>e 0 :aa, ?a<:al= lne nee :le8le en>@en: e>:a. Na 5a0 n/;6@ >/el6an/a a >n: n e> l5đen 0 C6an; 0a6<=eaa :>8ln  <:aa /e @en: >n: n anal@e9  <>n l/e6 e >/el/en 8 nel >@<8a, na 5a0 n/;6@ en/, la5 a@n. Pa<9/aln a@n 8 > / 6<=e :an/e anal@e0/e ne@ :n l/e6 e la?9an, 5l<8@ <589/a * 6ena l/e6a e >5< a<58n 8 5l9 a >@đen: l5ađan/e: :na. O> e =< >58e n6<đena>. Mea5l0a: * a nel 0n:, > e :ea5l0a, </e el:na9/e 8 585na8 :/el8/e ne8<ea9/. Kodein9 oksikodon9 i +idrokodon e :ea5l0ena,  :Ce 5 80< @6<8 /e< e e:ela;><:n e :ea5l00a:a. a6n  l/e8,  1-2 aa?enanl > "-& a588n 8 5l9 / <8Ca/8 anal@e0/8 24 aa  >8Ce. Pl8C6 >a e 6ea6a 8 a9/enaa a 5le:a /en ?enanla e :ea5l0
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ME'ANIAM DJELOVANJA Re9e< - Mn@ 8n9 >n; anal@ea 8 5/a=n/en @ene e>e 8 (N%-8  e<?en n  na ne8<n:a 8 n/e: :0@8  <>8l/en/ :C>n / :>8ln na n  0na> n/e. A6a9/a b-en a c-a6n 8na a6a9/a dn e> * >n @en: e>:a. O6 e>, / 8l/88/8 en>/e e a8:8lne n: ana@n:a. En>n :>8ln  <:a585e, C6an: le88 9</e6a. In :e;an0: * >n anal@e9 n;5/el: n; /el: @en; >n; e>a, / n>a a: n;5na enla 9la08. Na na/ n; /el6an/e  8 na/:n/ >8n l/e6 0a la=an/e 5l. On 8/e8 na e:9naln  en05n. Kodein9 +idrokodon i oksikodon 8 a<9/aln a@n  :a/8 8:/e8n 8 :5na9/ a an: an8aln: l/e6:aN%AID.

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%e>a9/a  e8?</a * 6 8n9 e >@ađa/8 na :an/: >0a:a ne@ a9/a /e 05</6a a al: >eC6l/a6a/8 >?<ne 8ne > >n; l/e6a. P< 6=: >0a:a, :@8 80<6a 0a:8en/e 8:a, e/el6an/e >a 8 <>8Cen/ :C>n >6> > n;59/e @6 8n; a@na, >ean/a e :Ce 6>/e < n<:aln: >0a:a. P6ean P(O 2 80<8/e 9elaa9/8, 6ean/e <6n@ <a  6ean nn anal@e9 8 9 a9/enaa a 0l/e>a:a @la6e. %80a:a nC: ne@ 0a anal@e0/8. M8nna  6<8/a 8 :C>an: >e5l8,  /aan /e @5an/e:. Ga<nenaln 8na * na9/a naa/e 05@ :an/en/a e<ale, = /e 6/e<6an ne 0n:a :ee<>n 80<8/8 n8C8/e <>. M0a * n<9/a 8le /e aa : :ee<>na5ln: ana@n: naln:  a<n:. Ra0n * >n anal@e9, @6 :@6< na >ne anal@ee e /a6l/8/e > a9/enaa a n8?9/en9/: na>585e  ; 6; a8n; ?a<:al=; 8naa : :0e  na9/e. Me;an0a: >ne len8 len; a@na, al n/e 8na, = :@88/e <a9/8 >a @>/e /e anal@e0/a @6< na <nn8 ea 80:an/a l/e6a naa/e 1+"

anen9/ n><: / 8l/88/e 98a e ana@n <:/en a9/en8 / /e ?0 6an  >:a. KLINI$KA UPOTREBA Anal@e0/a * l/een/e alne 8:/e e=e 5l /e 6aCna n>a9/a. Ia e en < 8an /e 58aln  80a/8 a8Cena anal@e0/a, a :an/en/e: =en; 8naa, :Ce e  e>8e<:aln: 5l8,  @8 72 aa. a n/8 5l  <nn8 5l, n/e /a a@n e <:/en/8/8  8 :5na9/ a a0e n/e@ 80<8/8 ;al89na9/e, n?80/e, 8058đen/e, 6ean/e l :an/en/e 6elne 0/en9e, na@:8, n68l0/e, :8, >ean/a. L/een/e >/ae: * :na:@ 8na  :</8 8na :aCe. Anee0/a * > e <e a e <la anee0/e. Vela >0a namorfin9 fentanil /e 0naa/na :nena anee0/e 0a e:a * metadon>8@ >/el8/8 > e < 0a n<l8 ::a 8e0an/a  a <@n @8a,  a :an/8/e ::e. /uprenorfin :a /= >8Ce >/el6an/e  nea> e < 0a ::e 8e0an/a. U <@8Cen >/el6an/e :ea>na 5l /el8/8; >a;e<n, :n; anal@ea:8nna, na9/a, >ean/a 8 6>l/6 <>8Cea n/;6; ?a<:al=; 8naa. P0en/ /e >@6006na (N% >ea6n:-;n9:a, anee9:a, an;9:a, <9l: an>ea:ee<>n a n;5<:a :na:n>a0e 6ea6a <0 ;e<n a e 80:a a ele6n: n;5<:a 6<:. 1+7

#7$IT-#$T#7$IT .I&'K!I Anal@e0/a * /e la5/a ne@ > 8n@ a@na:en8. Re9e< * nal58?n  ena09n 8 a@n c-a/8 a9/en:a / nae <e 8ne a@ne b-8@ >/el8/e /e< e naCn 6eCe 0a b 0e/el6an/e nalna. Naln /e 8l/8en 8 ?<:8le 6; l/e6a >a 5 e 6n9 5e; <=en/a ;. Una * e 80<8/8 e>a9/8 < anal@e: >0a:a. V<@la69a, 0n/en/e, :8nna, an0n, ;al89na9/e, nne :e 8n; a@na, al e ne :Ce  8n; a@na,  :n:alna /e </ela0na len; <8@; 8naa < >0a:a ana@n0:a 8naa a@na. O6 l/e6 :a/8 6el a?ne na R-a9/a /e n<la a8n@ >n@ 0a/8 n8@ l8C6,  < e 0a 5la na e<?e<:a.

1+&

32.POGLAVLJE ) OPOJNE DROGE P> 0l<@a e 5n >8=en@ l/ea l 9na 88=en@ l/ea, ađe< e ><@a:a al /e an 0a <na. P<:a<@a /e /ea/ 0a>6l/6a 05@ 8naa 8 (N%-8. %a</ 0a na06a a: 6n=8, a ;l=a 6n a: a>9/:na6:. Da:na e</a 6n * >a:n 8 :e0l:5: 8a68 @e, al a:ne<@na :8la9/8 >6> > al=@ ;a na=an/e ane :8l06n  nen<lna ne8<e:/a a<@a, n e >a ><@e /e 0a06a/8 na/6e8 6n 8l/88/8 /aa6an/e 8naa >a:na 8 (N%-8. 'D#TI!$I-*IP$TICI %e>a6n-;n9 8 >@6<@a. O6a @<8a 8l/88/e, etanol9 barbiturate9 benzodiazepine. Ben0>a0en e e <8/8 0a an0n, al :a/8 8:/e/el8/8 5a<58a6n-;n9 nCa6a/8 n;59/e, :an/8/8 an0n, 6aa6n;-;na 8l/88/8 /aa6an/e 8naa GABA-e, 6 l/e6 ađe< /aa6a/8 >a:ne<@ne 8e6e. L/e6 8 (N% >en; anal@ea, an;a, :a<;8ane... A8n 0e6a8la8Cen/ :C>n. Kn<la 0=n@ 8a  6enla9/8 <8. Fl8:a0enl e :Ce < 0a 5a0ena. Flunitrazepam(0o+Upnol), /e /a 5<0->/el8/8 5en0>a0en a /a: 8n: a:ne0/e, < e 0a l6an/e na /8. a/e>n a al;ln: e: klor-+idrat ili gama+idroksimaslačna kiselina(7*/) n C<68 ne5n: na < <6 l6an/a. G'B /e :ea5l GABA-e, 6eCe e 0a GABA A a e < a ><@a 0a 0ae 80<8/e e8?</8, /aan8 en0<8 e<9e9/8  a:ne0/8. Ue0an/e * 6n naa/e nan nn8a6n;-;na 0na6  :: 8e0an/a 8 na//a a l/e6:a / :a/8 l8C6  24 aaeanl, e5a<5al. Ia 6n :Ce naa a 6: e>a6n:-;n9:a. Na/6aCn/ 0na6 8e0an/a >la0e > el</, ;al89na9/e. Kn68l0/e n8 ee al :@8 8@<0 C6. L/een/e 8e0an/a 8l/88/e <:/en8 >8@->/el8/8e@ e>a6n@-;na>a0ea:, l<>a0e> 0a 8<:a a8n@ 8e0an/a, a n>a la@an :an/en/e >0e. Kln>n l <<nall :@8 5 < 0a :an/en/e <: e@ađa > a <nne <:/ene e>a6n;1+)

;na. U0 >>aa n<:aln; ::a 8e0an/a, 6a/ n><: 8l/88/eH:<=a6l/en/e, an; anal@ea 8 b,c  d /el6an/e >n;59/e >a:ne<@n; 8e6a 8 (N%-8. Oen 0l8n9:a meperidin i fentanil. Una n <na /e nale <@a0:n@ /ea/a a e>a9/:. In:na /e 6e0ana 5<0: /a6: le9/e. Oa 80<8/e la5/ 8na, a </: naan: le0:a >6> > e0a > 6na >6> > anen9/@ n><:a / /e an, 8e0an/e > >a /e </e ?aaln0a e>a6n;;na. L/een/e 8l/88/e 0a:/en8 ne>8=en@ l/ea a ?a<:al= /e>na: l/e::ea>n,  n>a e :an/8/e >0a. B88@ >/el8/8 >l8C6 ]4+a e ađe< < 0a :an/en/e ::a 8e0an/a  a 0a:/ena e:a. P<:/ena nalna > 5e /a < naCne >eal n/e 0 :a/ /e 8 6ne  >:a 0a;/e6a/8 e5n8 n<l8 ::a 8e0an/a. %TIMULAN%I K#F'I$ I $IKTI$ Una * a?en8 :a  nn8 9@a9ne 8ne. P8=en/e 9@a8;ana /e 6e0an a 6el: <0: a<>6a8la8Ce 6</e:e, ne>a6n <6en 8 0na6  :: anen9/e. Ue0an/e * a nan ne 8ne 8=en/a e < 0a n: 58=en < 0a 
11+

Tn * a8na n > 0 :ale >/e9e / 5 /el nn8 @8:8 l ?lae<. #1F'T#1I$I Una * a:?ea:n n;5a:na, n/el6an/e. U0<8/8 /ea/ e8?</e  a:80>an/a / <>ne 5<0: 6> > ;n@ an/a>el80/e  a ;0?0/a, ;e<e<:/a, ;e< n68l0/e. Ne:a e5n@ <8l/ea, a  a<:/a e n68l0/a. K<nna 0l8 :C>an: <6a<: aea 8 n>9en; a:?ea:n8 :a ;al89n@ena 6/6a. T 8 2,!->:e-4:ela:?ea:nDOM, :elen->a:?ea:n MDA  metilendioksimetamfetamin(1D1#W VVecstasUVV). MDMA :a ele6n/ 8na ne@ a:?ea:n na e<nn: <@a la=a6a :8na9/8  e /ea/ n:n. Re@8la0<:a3+.@la6l/e,  n68l0/e. %n><: 8e0an/a /e a8l/en: >eana > <nn; 6na. KK#I$ Kan, /e ađe< n;5< a:na, n. O6n9 @a e <e 8 5l8 l5>ne 5a0e9an/e  :enalna 58>n 8 /el6an/a  0a 8 n6n8 80 a<:/a, n68l0/a l en /e 05@ 5la>e n6n@ 8na n<n n68l0/a:a. D>an, /a 6a0n<6n 8na >6> > e=; ;e<en06n; e0>a, /e a  :C>an: 8>a<:. Ne / <8l/e. lne /e 6e0ana a 6ean: ?ealn: :<5>e:  :<ale:.

111

Ue0an/e * anen9/ n><: /e lan a:?ea:n:a. Jaa >e<@e. In>9e :a/ /e 8 6ne  an8l a:?ea:n:a :a/8 <0 0a e al; ><@a, ne:a/8 >/el6an/e na >a:ne<@ne ne8<ne 8 (N%-8. P(P /e 6/e<6an na/an/ ;al89n@en. P;ne 5a e 6> > ne>@60a0en>a0ea:, l<@e *  8 dietilamid lizerginske kiseline(.D)9 meskalin i psilocibin. 'al89n@en 8na e /a6l/8/e  a la:n:  ><8@: an:8a<n: l/e6:a. N/e>na > 6; :le8le ne:a 8na na >a:ne<@ne 8e6e 8 (N%-8,  0an:l/6, ne 80<8/8 6n, al ea 86> > a;?la/e. U0<8/8 05la6an/e 5la  5/a, e<9@>  ann naa>a/l= <. MARI'UANA Ma<;8anan na06 0a ;a6ne 6a< e ana5n>a tetra+idrocanabinola(T*C), ana5>la(BD,  ana5nla(BN. 'a== /e >/el:n <=en :ae</al / /e 6=e enan. Kana5n> * en>@en ana5n> 8 (N%-8,  8 anadamid i ?-ara+inodil glicerol, / e l5ađa/8 na  >/el8/8 a n @lan9 / n;5a:na. Re9e< 6; 6a< 8 9l/ e@0@en; ana5n>a 8 :a<;8an. Una * (N% 8n9 8l/88/8 /ea/ na8=en;@;, e8?</a, >n;59/a, nen<llaa9/a  6ea6a e 8l. I 80<8/e 9<6ene n/86e. Bla@ 8e0an/e e /a6l/8/e > <nn; <na :a<;8ane. Oan <=en/a :a<;8ane /e n: 80:an/e: e>a6n;;na  eanla. Pen9/aln en;
112

IN'ALANTI Anee9 * >8=n >8l, l<?<:  >elee<. O6e 6a< 8 ane /e< 8/e8 na <8đ6an/e  80<8/8 @85a 6/e. In;ala9/a @ >8=n@ >8la5e0 a 80<8/e @8=en/e  :<. Ee< /e /a 0aal/6. In>8</e aala * aala  =< 8n, n>8</a aala, >/e9a  a>le9en e 0ln8  e<?e
113

33.POGLAVLJE ) LIJEKOVI A LIJE#ENJE ANEMIJA I %EMATOPOENI #IMBENI&I RASTA K<6ne an9e @ n?ea, 9e. Na/e= 80< >e?9/en9/e e<<9aane:/a /e ne>aa Cel/e0a, 6a:na B12 l ?lne elne, / 8 ne;>n 0a n<:aln 6a>aa 6a< /a ne>a/e. Alee?9/en9/e ><8@; <6n; an9a /e <:/ena n/8 e?e: ne0e n<n0n@ ?a/ela Cel8>9a 8 /e: /e e<8@; <6n; an9a * >e?9/en9/a /a9/e l e:ee?9/en9/: e<<9a, ne8<?la, <:59a. Ne > 6; ?a@6 /e 6e0an 0a transferin<en na  feritin<en ; Cena 05@ @85a <6 /e: :en<8a9/e, 6e@ee</ana9a l ;6l/n@ 8na Cel/e0a. D/e9a  <8>ne Cene :a/8 6ee n@ Cel/e0a. *slika33-1 P= ne / 8n6 :e;an0a: 0a 0l86an/e Cel/e0a, 8la9/e a<9/e 8 9</e6:a. A<9/a * Cel/e0 0 ;66alenne :eale DMT1. #el/e0 8 nenaln: an9a:a e a >a0e. 114

T<8@; <@ana. El:na9/a * :n:alna lna Cel/e0a e @85 0n/en/e:  ln:, 05@ e?l/a9/e an9a Ce  nenaln; :80n; an9a. Klna 8e<enne ane:/e 05@ :an/a Cel/e0a /e  /e>na n>a9/a 0a <:/en8 Cel/e0a. Man/a Cel/e0a e :Ce >/a@n9>a: Cel/e0a 8 ; a /e0@<: Cel/e0 ;><>a <8Cen =ee9 >/e9e /a l8a/n /8 a5lee Cel/e0a. a6n  >0 Cel/e0a, 0a, :a  :<. K<nna n, 0naa a ;e:<:a0a, =e8/e <@ane / n<:aln ; 5a na nal/e>n: a5n<:aln a<9/e Cel/e0a  n; / <:a/8 ee :a;  a/ e > >0e  a5n<:aln ele<la,  an a ?ln: eln: ?a< 8 </en8 8na a /e>n: 8@l/:, = /e ne;>n 0a ne08 DNA. Ne:@8n ne0e DNA 8/ee na 6e an9e, al = e e<<9 <06>e nean, :an/a 6. B12 :Ce 80<6a ne8<l=a =een/a, = /e e a: 5ae</e, 6a/ 6a:n ne :@8 <06> 6=eann <@an0:. A<5e a</ealne an9e 8 Cel8>98. U la0: e /e 6aa 5a :a 0al;8 0a ! @>na. D6a 11!

>8na 5la 6. B12, cijanokobalamin i +idroksokobalamin :a/8 ln8 ?a<:ane8, al n/ :a >8C l8C6 8 9<8la9/. Fa<:a>na:a * 6. B12 /e een9/alan 8 >6/e e:>laa>TMP*slika33-3 <?laa lna e<?laa /e :an/ena  8n/a e<<9a. P<:/ena ?lne elne a9/en:a a :an/: 6. B12 :aCe 6ea ln8 e<?laa  a<9/aln l 8 8n 6a 5la 6. B12 * 9/an5ala:n  ;><5ala:n :a/8 /e>na 8na. In>a9/a 0a 6e l/e6e /e e9a. P= :an/a 6. B12 n/e 86/e 05@ ne>6l/ne a<9/e, 8 : l8a/e6:a >a/e e aan 5l 6. B12 ne:a 0naa/n8 n. F.$# KI'.I$# Ka 6. B12, ?lna elna /e an, :an/a ?lne elne /e: <8>ne 6ea6a <0 >e?ea ne8na:a * ?lna elna e <?la >/el6an/e: >;><?la8a0e. Ja 6aCan 8 <?lae  >;><?lae /e >TMP 9l8, /ele 8 /a /el/6e na :an/a ?lne elne, 05@ @a an?lan l/e6 8 <n 0a l/een/e na6n l/e >>a: ?lne elne 8 ;n 6ean /e <0 >e?e>aa ?lne elne ne. %8le:en ?lne elne e?9 05@ :an/a 6. B12. na, :an/a 6.B12 :
11"

*'1#TP'"$I 3I1/'$ICI 0#T# I>en?9?een 8n 0a l/een/e a9/enaa a :an/: <6n; an9a. '0IT0P'TI$ E<<en e <06> 8 585@6n/8 e<<9a  n/;6 l5ađan/e 0 =ane 6n < 0a ane:/8 80<6an8 585 /e 8n6 > ><8@; 5la ane:/e5le =ane a e:ea  12@>L, 6ean /e <0 <:50e  a<>6a8la8C l8C6. 1etoksi polietilenglikol epoetin beta(C'0#) /e >8@ >/el8/8 5l / e <:/en/8/e 1-2 8a :/een. Na/e=e :la9/e eL /e< n9e 6e 8 6e0ane a 6ean: <0: :<  a<>6a8lan/8  ?8n9/8 ne8<?la. GM-(%F ađe< :8ln/8 :/el>ne  :e@aa<9ne ln/e an9a. G-(%F,  8 :an// :/e< GM-(%F :5l0a:a; nan a8l@ne a :Ce 80<6a 5l 8 :a. GM-(%F 80<8/e 6=e neCel/en; 8naa, 8 6<89e, 5l6e 8 0@l56:a, =een/e alae:. Ale<@/e 8C l8C6 ne@ G-(%F.

117

1'7#K#0ICIT$I 3I1/'$ICI 0#T# prelvekinnena  6ea6a 5</ e<?e8 <:59en/e nan e:e a6; a9/enaa, :an/8/e  >6/e /e e>a /e 8 6e0ane 6alenn 0a ;8:an F( ?6a e>a F 2 8 6e0ana >8l?>n: 6e0a:a  6a9a: <:59enn: 8<8<: / ne >@6
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34.POGLAVLJE ) LIJEKOVI A LIJE#ENJE POREMEAJA KOAGULA&IJE L/e6 0a l/een/e 0@<8=a6an/a  <6aa/8 8 >6/e 6ele @<8eH 1l/e6 0a :an/en/e @<8=an/a  aan/e 8@<8=aa / 8 6e <8n 8 a9/en8 05@ <0a <6Clne l80/e  2 l/e6 0a /aan/e @<8=an/a > a9/enaa / :a/8 :an/a @<8=an/a. P<6a @<8a, l/e6 <6 @<8=an/a 8l/88/e /e>ne > na/<=en/; l/e6a. L/e6 <6 @<8=an/a e <e 0a l/een/e  a  ><8@e a8ne <na<:e, ?5<la9/8 a</a, ;e:n :C>an 8>a<, >85e 6ene <:50e. U / @<8 l/e6a, ana@8lan  ?5<nl l/e6 8 8n6 8 l/een/8 6en;  a<e</; <:50a, > l/e6 <6 a@n /e6ne0e<6a 8:a<na 6an l:e<. Velna :le8la 6a< 1!+++ > 2++++. 'ea<n /e /a el  :a 5 e 05/e@a <0 ;e:a:a 6e0an a n8Ce >/el6an/e ne@ ne?0e e :@8 <:/en6a / e nala0 8 ne?n: >ne6n. Me;an0a:  8na * ne?@en antitrombin IIIATIII n@ l/e>a. 'ea<n * ATIII :le e 6eCe  <8@; ?a/el8/e na 6e 6aa<n8, a  ne?aa<n8-ATIII @8/el8/8 na <:5n. aPTT e ne80>an :/e< ana@8lann 8na LM  ?n>aa<n8a  /e en9/aln <5le:, @6 < 0aa/en/8 585 /e@ /e la /e ana@8la9/a 85 6en; <:50a, l8ne e:5l/e, a8n@ n?a<a :a<>a. 'ea<n e < 8 :5na9/ a ?5<nl: l/e6:a 0a
a6l/an/a ena. Ne <la0 lan9enane. LM  ?n>aa<n8 :a/8 ln8 ln8 <:/en8. Tn * 6ean <6aan: 8>a<:. Protamin sulfat :Ce :an/ <0 an@ <6a/el6an/e ?n>aa<n8a. Ne?89 1-4 a9/enaa / <06>e an/ela. LM  ?n>aa<n8 8 :an/e 6/e<6an 80<6a :8nn 6e0an8 <:59en/8. K<nn <=en/e ne?/el6an/e > >85e 6ene <:50e /e /e>na LM, a <:/ena ne 0a;/e6a <8n na>0<. I"0#!$I I$*I/IT0I T01/I$# VeC8 e 0a a6n :/e <:5na  n;5<8@: l/e6:a na <e0e 0@l5a l/ena l 8a. D/el6naa LM. %ln <6a<a5an8 :a 0naa/ne n na> 6a<8@ 8:a<n ana@8lan 8 :ale, ll85lne :le8le /e e la a<556 en0:a. Me;an0a: >/el6an/a  8na * 6a<8@ 8:a<n ne?a9/: ?a6l/n/ ln 89<nn 5l. Va 6a:na K 8 89n. Tn * <6a ;e<a@8la5ln a ne<0: Ce. T /e 05@ :an/a <ena (, 12+

en>@en@ ana@8lana 6n@  6.K, / :a e?ee   <6a9ne. P= 6a 6ele 6aCn. L/e6 / n>89an/ >0. In;5< 9<: P4!+a:>a<n, %%RI, 9:e>n :an/8/8 lan/ >0. Genea 6a</a5ln 9<:a P4!+  VKOR 8/ee na >@6< na 6a@en ?5<nl en0: / n/8 la0:na  nan <6a8l/: >/el6an/e:. Tenekteplaza /e  :88C: l8C6:. T0'PTKI$#"# * e 80:a 0 5ae</; 8l8@en: la0:n@en: la0:n@en 8 6: :le8 <la0 n?<:a9/8 <:/en8  a e 5 -PA, ealn: 86/e:al/een/e 8 <8 " a 6 l/e6 :@8 5<0 an: 8>a<: /e 6e0ana a 5l/: an <6anaa /e :@8n /a6e > 6; ?5<nla. MC>an <6an/8 an/ela, 05@ /; @85 ?8n9naln l 80<6a e=8 ale<@/8 a 6e 6<la an/ela. P= 8 ;8:an <en, na 8n6.

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I$*I/IT0I #70'7#CI&' T01/CIT# A@n <9e8 @<8=an/a *slika34-1  e5n /e 6aCna 0a 8@<8=e / e 6a@en: :e>/a<:aH <:5an, a>en0n->??aADP, <:5n  ?5<n. T6a< /e 6ea6a/8 8n8a<ann8 n9en, <a9ln, a>en0n n;5<8@ neen an-8aln l/e6N%AID, n;5< @l<en II5IIIa , ana@n ADP @n,  n;5< ??>ee<>a:l, 9la0l. Me;an0a: >/el6an/a * aspirin  al N%AID n;5/el:n 8n6. P= <:59 ne 6a/el8/e nel >ana > e ne 6/el8/8 <6 a@<8@; 6a< 0a @l<en II5IIIa @66a nana >/el6an/a. On <>8C8/8 n;59/8 <:59a eee9AMP, 9GMP-6a0>la<. Tađe< n;5en0na 8 en>elne an9e  e<<9e  a 6ea6a/8 n9een0na 8 la0:. A>en0n >/el8/e en0n; A 2 5a /e 8 :ale /e>an l 6=e n?a<a :a<>a  0a :an/en/e <0a 0a <6 n?a<. O6a/ l/e e < 0a an@ 8>a<8@; <:5@en; /a6a. In;5< @l<en@ II5IIIa <:enea5lna an@na, n?a< :a<>a 5e0 Z 6ala. Kl>@n e 8n6 8 an@ 8>a a9/enaa / ne >ne a<n. Kl>@a:l e >5>aa 6aaan@ 8>aa9/e. 122

Tn * a<n  ><8@ N%AID 80<8/8 @a<nenalne  (N% 8ne3".@la6l/e. %6 n;5< a@<8@; l/e6a <6 0@<8=a6an/a. VaCne n 5lan e </e < /e< 80<8/e <l/e6 > 2+, <6a ! a9/enaa, e=8 ne8<en/8 > 1,  /a </e <:58 <:59enn8 8<8<8TTP. Kl>@<>a:la  9la0la 8 @la65l/e  ala9/e. (la0l /e n9 a9/enaa a n@e6n: 0aa/en/e: <9a. !IT#1I$ K Man/a 6a:na K, 6a:n l/6 8 :a:a, /e na/e= > a</; 5a a a5n<:aln:a a<9/e :a  n6<đena>, / 8 <0na 8na 0a <6a <:a/8 n/e9/8 ?na>na l/e <đena. Vele >0e 6a:na K 1 e <e 0a n=en/e ana@8lann@ 8na 
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3+.POGLAVLJE ) LIJEKOVI A LIJE#ENJE DISLIPIDEMIJA Ae<le<0a /e 6>e 80< :< 8 0aa>n: 6/e8. L/e6 8 6: @la6l/8 a<, an@na, e<?ean 8>a<  :an/8/8 :<n > a9/enaa a 6/e a<>6a8lae:/:. Ia 8 6 l/e6 8@la6n: @8/el8/8 8  ae<le<0e. U ne: 5el/:a, ;e<<@l9e<>e:/a /e 6e0ana a ae<le<0:. (l:<ne:/a, /a6a 9l:<na 8 e<8:8 /e: a, /e na /a6a 6e0ana a e: /a6: a8n@ ann 0:eđ8 8na :a, e 8 /e<, <=n/e 8 e<?e@ađa/8 8 6el: 5</8 @ene; an/a, 8 :8a9/e 8 al<en:a, n/;6: e. %e8n>an: 6/e8, :n@: en><n: an/:a, 5le:a /e/en ?a< / <>ne 6=en: a6l/a/8 <68 :e>8 n<le  :@8 5 >6l/ne 0a :an/en/e n9eCe <@l9e<>e  l<ene 6e:/: 5 @a a5< l/ea e 5a0a. L/e6 / 8 na/6=e 8n6 8 nCa6an/8 LDL le8a0e, :le, e0e:5,  na9n. De<6a ?5<ne elne@e:?5<0l  na9n 8 na/8n6/ 8 nCa6an/8 <@l9e<>a  n9e<:el@l8a<l en0:a A'MG-(A 8 :e6alna a 'MG-(A 8a0:. %an 8 <88 al n;5< 'MG-(A 8a0eatorvastatin9 rosuvastatin 8 >:a; a6n.

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In;59/a ne0e lee<la 8 /e< <>n :al: 8>/el8 nCa6an/a 88n@ lee<la 8 e<8:8, 8n 6e 8na <0la0 0 >@689/8 8 6< aaa LDL  VLDL. In;5< 'MG-(A 8a0e :a/8 >a e <e 8 :5na9/ a al: l/e6:a 0a nCen/e lee<la. O6 l/e6 e 5n <e /e< 8 8n6  >5< e le<a n08/8 <0 > <na@ađa/a, :<n > ;e:ne <ane 5le,  n08/8 <0 > ;e:n@ :C>an@ 8>a al; n;5e  68/8 'DL > a9/enaa > /; /e a 6ea > 2!+:@>L. Fl86aan :a :al :an/8 8n6 ne@ al l/e6 8 6/ @<8. Tn * 8:/e 1+ a9/enaa 8 </e;, e /a6l/8/e 5l 8 :=:a  :l0a. In;5< 'MG-(A 8a0e e :ea5l056 l/e6 l ; ;ean  :a/e. 5@ >a0a  en. !'"I!#3I ;%3$I* KI'.I$#  1.' Me;an0a:  8na * n<:aln, e 8 9</e6:a  e. K> ne; a9/ena a 5el/: ;e<lee<le:/:, :le 6ea6a/8 <@l9e<>e  VLDL. Klna 8 a9/ena a ;e<lee<le:/:. %:an/8/8 6<5eC > a9/ena a lea0:  na8l/an/e C8n; l, e 0a <6an/e >@al:. Tn * neCel/en 8n9 8 na>8, na9/a,  ne8@>an =l/8n6 8. A<9/a 6a:na6.K, ?la  l/e6aa0>n >8
I$*I/IT0I C0I&'!$' #P0PCI&' T'0.# Me;an0a:  8na * 'zetimib /e <l/e / e n6e<8/e @a<nenaln 8n lee<la  ?e<la5l/n e<l / n<:aln 8la0e 8 eelne an9e, al e >:a; 6a e :5n8a0e, /= /e 8n6/. Klna 85< le<a e :5n8a0e, :Ce 6ea <0 ;ean. Kn9ea 8 e<8:8 e 6ea6a/8 05@ ?5/el6an/a, na9n n08/e LDL lee<l, <@l9e<>e,  VLDL,  e 6ea6a 'DL lee<l. U /e<, na9n :an/8/e ne08 VLDL,  n>a 80<n n08/e n9ea 8 la0:. %@a, :an/en /e 6a/el6an/e l<en la0e 8 alaeln: an9a:a  a 6ea6a le 8 e<8:8  6ea6a 'DL na9n /e ln =< <an 8 l/een/8 ;e<lee<le:/e, ;e<<@l9e<>e:/e  n; n9e<8@: N%AID n08/e ne0e 9<6enla, = na: @6< >a /e 6e0an a l5ađan/e: <a@lan>na. Tleana. M8nna 6na  >0  nela@>a 8 a5>:en8 8 ee. %6<5eC  ><8@e /a6e na C e nea> /a6l/8/8. U:/e e=a ;ean e nea> /a6l/8/e. Te= =een/e /e8l/en: 8=an/e:. 'e<8<9e:/a e /a6l/8/e > 2+ a9/enaa,  :Ce > > /el6an/e an;e<en06a.

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D'0I!#TI FI/0I3$' KI'.I$'(FI/0#TI) Me;an0a:  8na * ?5 0a /e0@a. Ineelne an9e ala:a. U  /e<, ?5a9/8 :an; elna, = :an/8/e ln8 <@l9e<>a  :an/8/e ne08 VLDL. Tađe< /aa6a/8 ee:/e. P= 6 l/e6 :a/8 <:an 8na na nCen/e LDL,  8 ne; a @a 6ea6a/8, n e :5nla0 > nCen/a le89a  ;e:a<a,  6 l/e6 /aa6a/8 >/el6an/e ana@8lana. P/ 6ean <0 lee<l; C8n; a:ena9a 6 l/e6 e : a9/enaa a lel/a0: 8 ana:ne0. Ka>a e <e 8 :5na9/ a n;5<:a 8a0e, ?5e:/: e l/ee <6 a <:/en: 6l/n a e l/e6 :>a. K:5na9/a l/e6a /e a 5 e 6a< :a:aln 8na nCa6an/a a :n:aln: n=8,  >a 5 e >5 Cel/en 8na na n, > ><8@e a6l/a/8 e9?ne 0a06e. P= :le :ea/8 a<9/8 ne; n;58a0e8a0e a ?5 :a/e.

127

3!.POGLAVLJE ) NESTEROIDNI PROTUUPALNI LIJEKOVI,  ANTIREUMATI&I KOJI MODIFIRAJU BOLEST, NEOPIOIDNI ANALGETI&I I LIJEKOVI A LIJE#ENJE ULOGA Uala /e :lean >@6< na 0l/e>8 an9e /a e <:a@ađa 8 6a8la<0@6<. Me>/a< 8ale 8lan/a/8 80< 0l/e>e  e ann >e5<, 8 <a 80< =een/a n/e 8ln/en, <nn8 5l  =een/e 6a a 8 n: a<<8. Nee<>n <88aln l/e6  a  an?e /e 9l/an na 8al8, > l/een/e <nn@ @;a /e ?8<8@; N%AID. *tablica36-1 %a</ neele6n N%AIDibuprofen9 indometacin :@8 6a<8Cn >/el6an/a. Ibuprofen i naproksen :a/8 8:/ea 5 e :an/la @a<nenalna n 6e0ana a (OY n;59/:, a a86ala e?an. NaCal, lna een9/8 a<>6a8la@ađa/a. Me;an0a: >/el6an/a * 9l@ena0a /e en0: / n6e<n8 eln8 8 en>e<>ne na, 6aCne :e>/a6/e 0?<:eH (OY-1  (OY-2. (OY-1 e nala0 8 ne8aln: an9a:a, > (OY-2 /e 8 a6<8@: 8aln: an9a:a. A<n  neele6n N%AID n;5na  <:5ana. %:an/en /e l5ađan/e <a@lan>na 8l/8en; 8 ;:ea8 ?8n9/8  8aln >@6<. (OY-2 ele6n n;5< :a/8 :an/e 8 na na <a@lan>ne 8l/8ene 8 ;:ea8 ?8n9/8, @6 na ne 8 GI /el6an/a a<na  ><8@; N%AID /e a >a aspirinal ne n/e@6 a6n :ea5l, al9la a9el n;59/a ><8@: N%AID /e 8Ce >/el6an/e a n;5< a@a9/8. Una * >e<6a ane elne 8 6aCn :e>/a< 8ale n;5< 9l@ena0e :an/8/8 8al8, a ne:a/8 8na na =een/e 6a l :8nl=e na 8 (N%-8 /a /e :8l5< 0na. 12&

%:an/ena /e a6a9/a e<?en/e <a@lan>na 8 =een: 68 >>an, 9ene. In;5< 9l@ena0e ađe< 8/e8 na ;:ean8 ?8n9/8 <a@lan>na. Na/6aCn/e, :an/8/8 <a@lan>n:a6an8 90a=8 8 GI 0aH n  /e 8n6 8 :an/en/8 a@n/  :a an e < 0a <88aln 8na. A<n e >5< a<5<l0a < :al: >0a:a, a l8C6: 3-! a. P< 6: >0a:a<88aln:, l8C6 /e 1! a  el:na9/a /e n8l@ a. I0l86an/e /e 5< a<5 a</; N%AID. $aproksen i piroksikam :a/8 /a >8@ l8C6, a e :@8 </eđe <:/en/6a. O6 N%AID e <e 0a l/een/e la5e > 8:/e :8elene 8ale a 8 a<<8  @;8. Tađe< e <e 0a l/een/e <8@; an/a, >:en88 a<e<08 > </e<đene >/e9e. Ke<la e < 0a e:n8 anal@e0/8, ne 0a <88aln 8na,  /e>n /e N%AID >8an 0a a a9/enaa a 5el/: a>en:a0n: l0:. D8@e5el@ 9</e6a. Tn A<n * 6ena neCel/en; 8naa > <88aln; >0a a<na /e =een/e Cel8>9a. K<nna <:/ena :Ce 9a, <6a8C8/e 6</e:e <6aa /e ne0a <a@lan>na n;50a:a a<na, 5a a ;e</el/6=8 na a<n6e0an a l:a 8 n8 :Ce >C6/e a:8 05@ n/e le8<ena. O6a/ 5l ;e</el/6 na a<n l/88/e <=en/e 5l /e@ N%AID. P< 6=: >0a:a a<na, :@8 e /a6 08/an/e 8 8=:a, 6<@la69a, ;e<6enla9/a, 0a:a, 80<8/e :ea5l8 a9>08, >e;><:a5<0a >e@eneen9/a /e nCa ne@ a > a<na. P/ <0 585 a9/enaa a /e: 5le 585
72 aa /e< /e <0 @a<nenaln@  5858Ce: <=en/8. P<:/eene 8 05l/ne ;e:al=e :ea9n:. %ELEKTIVNI (OY-2 IN'IBITORI * 9ele5, :a 8 la :an/ <0 @a<nenaln@ =een/a, 8 8l8a Cel8>9a  <6a<n ;:a: 585 <:50e a<e</a /e 05@ 6ee@ n;59/@ 8na na 6aeln@ <a9lnaPGI2 ne@ na 6alaa9/8  n;5 TYA 2 :a 5n 5e0/el8/e <88aln. Una * :a anal@e  ann/e: 0a. na <an /e a 0a:/ena a<n8, @6 > >/e9e a 6<8n: n?e9/:  n; / :a/8 nele5< a<5  a6n :ea5l N-a9el--5en06nn / /e an 0a /e<8  5850a:a, a0 a9/enaa a e=: =een/e: /ea9/8 8 9ne ne<:e>/a@ađa a ne>a/8 8. B<0a <:/ena a9el9na, >n<ln; @<8a, :Ce a C6. L/8> / 6n n08:ne6n :a/8 6e <0 > ;ean n>89?9/el8/8 anana > " :/ee9 >a 5 8na 5 6>l/6. K<e<> e :a/el6an/a</ > N%AID, 5 DMARD. Ia, <e<> 8 8@ a9/enaa a e=: 5le=8, / ne <8@e l/e6e. 13+

Me;an0a: >/el6an/a  8na * :e;an0a: >/el6an/a 6ene DMARD 8 l/een/8 n@ a<<a n/e 8 8n 0na. (n l/e6:e/el8/8  6; l/e6a e <e 0a l/een/e n/; @>na, /el6an/e TNF-8:< ne<0al:8:a5a,  :a/8 8na na n a<<, e n;5< ne<ln, :e e <:/en/8/8 0e DMARD, @6 :e<a/8 a9/en:a a 8:/en: a<<: 8 8=a/8 >a e n= <@ 6; l/e6a e <e 0a ><8@e ne 5le 8 l88a, a<<a 8 %/@<:8,  /86enln@ n@ a<<a. Tn * 6 DMARD 80<8/8 e=e l ?aalne n. O5a6e0n /e na>06a8lan LIJEKOVI A LIJE$ENJE GI'TAULOGA G; /e 6e0an 6=en: n9ea/ 8l/88/e 8al8 0@l56a a/aa l;9n:, N%AID, @l8<>:a*slika36-5 2 /aan/e 0l86an/a :, 8l?na0eal8<nl  ?e5e8a.

131

PROTUUPALNI LIJEKOVI A LIJE$ENJE GI'TA Me;an0a: >/el6an/a * N%AID 8 n>:ea9na 8 8n6 8 n;59/ 8ale a8n@ 8/el8/8 na  n;59/e ?a@90e <ala. Kl;9n, ele6n n;5< 6an; ala. Un9 * N%AID  @l8<>n0n :an/8/8 ne08 8aln; :e>/an/8 :<858la, l;9n /e @enean 0a n<:aln8 ann8 >58, <8@e <9ee. Fa<:anea  lna <:/ena * N%AID  @l8<> e a/e, 0e 80<8/8 @a<nenalne :en/e, @6 <l/e6. Man/e >0e l;9na e <e 0a a/a @;a > a9/enaa a ana:ne0: :8ll; a8n; naa>a/a. Kl;9n /e  <an 8 n<l a8ne :e>e:ea9n, ne @l8<>  l;9n e <:/en/8/8 8n 8 aa  l;9na. Tn * N%AID :@8 80<6a =een/e 585:ea9n :Ce 80<6a :an/en/e =ane a :Ce 80<6a <:/ene na=an/a  8:an/ n<l8 @l80e. P= l;9n :Ce an =e /e<8  5850a e :  n<l0, 8l?n0a:a, 6 l/e6 e :@8 na/e9a a : 6ea n9e0an/e n9ee. Tn * :@8 0a06a naa>a/ a8n@ @;a e: e:ea9na. P= 8 8l?na:>, 8<08<9 :@8 0a06a ale<@/e a.

132

IN'IBITORI K%ANTIN-OK%IDAE Me;an0a: * 6aa0e, en0:a / n6e<a0e alann /e aln n;5< en0:a. N6/ l/e ?e58a /e ne8<n n;5< ann->a0e / /e ele6n/ > al8<nla, / n;5na. Una * n;59/a ann->a0e 6ea6a n9ea0e e <:/en/8/8 na nan a8n@ naa>a/a,  <:/en/8/8 e 8 :5na9/ a l;9n: l N%AID 0a 05/e@a6an/e a8n; naa>a/a. Al8<nl e < a >>aa 0a e:e?8n9/8 =ane a0 0a el:na9/8. Fe58a :Ce 80<6a =een/e /e
133

3$.POGLAVLJE ) %ORMONI %IPOTALAMUSA I %IPOFIE '<:n / e <06>e 8 ;ala:88  ;?0 8 @la6n  0<n; <ne7n0* n/a ;?0aH;<:n 8n/e ;?0e 8 9en<n: 8a68.*slika37-1 %6 ;<:n n/e ;?0e 8 > n<l: ;<:na ;ala:8a,  6 : <lana, 8/8 8ne n/8 ;<:na 8 e<?en/e ;?0eT%', L', F%', A(T'  n/;6 n<l: ;<:na 0 e<?en/e ;?0e <8Ca 6=e :/ea 0a ?a<:al= 8na. *01$ 0#T#(7*) I 1'K#'01I$ G' * ;<:n /en6a  a>le9en9/e  6aCan /e a  8@l/;>/e9e  >/e9e a @ene: 5le:a 6e0an; a n: <:, Nnan6 n><:, Pe<-l/e6 n><:. T >/e9e /a ne na8/8 05@ <nn@ 585/e9e a nea>e6an: 5. Na/n<6e<0n/a 8 >/e9e a >a n: /e9e, <nna <:/ena ;<:na 6> > > :an/a ;<:na a9/enaa / 8 <=l <:. '<:n  <@el na C6n/a:a >a0al >a anal0 G'  IGF-1 n@:. Re:5nann @6eđ ;<:n n/e :l/ea. O>/e9a. NeCel/en 8n9 8 e<?ee:, 5l 8 :=:a  0@l56:a. R/e, 80<8/e n
1ekasermin * :ala @<8a >/e9e a @6a/e9 a :an/: IGF-1. Na/6aCn/a n /e ;@le:/a, /a e :Ce en: ;?0e / 0l88/8 ;<:ne /e9e  a>le9enaa. P > 14 a:nelna, n;58@->/el8/8 ne anal0 :aana, e <e 0a l/een/e a<:e@al/e, a<9n>a, @a<n:a, @l8an:a  al; en><n; 8: e <:/en/8/e 858an 2-4 8a >ne6n, > >8@>/el8/8   lan e <:/en/8/8 nna. O /e <an  8 a8n/ n<l <6an/aa. On 80<8/8 0naa/ne @a<nenalne :en/e, C8ne a:en9e,  a5n<:aln <ane <6>l/6. #gonisti dopaminski+ D? receptora * a bromokriptin /e :n@ 8n6/ 8 n;59/ 0l86an/a <lana ne@ ;<:na al/e 8 e8. Ia, 6ele >0e a@na D 2 6a :/ea 0a 6e0an/e na 8 >:e<06a G' 8@>/el8/8 l/e / /e 5an 6e0a >6a G' 89:e<0a9/8  F%'  L' 0a/e>n @ene08 8  /a/n9:a. U :8=a L' /e :8lan <>89/e an><@ena 8 e:a. Gna><n  n/;6 anal0 e <e 8 :5na9/ 0a :8la9/8 e<:a@ene0e 8 nel>n; :8=a Cena /e ne >@6a89/e 68la9/e /e 6e :l9a 5 @8a 5 6/e 05l/ne :la9/e * 6=e<8e <8>ne  n><: ;e<:8la9/e /a/na, / /e a89/e 68la9/e :a/8 3 n6na @en; @na><na a GnR' a@n:a l ana@n:a. 13!

D<8@, ne6n: n/e9/a:a <n/e, 0a <n. L/een/e :8=e nel>n 05@ ;@na>0:a 0a;/e6a 6=e:/een8 <:/en8 :/e=a6ne l/e6a a a6n=8 L'  F%'. D8an /e 6el 5</ <<na,  6 e <:/en/8/8 a<n e a/e > F%'  L', / 8 <=en 0 8<na :ena80aln; Cena/e <06>e 6ele lne F%'  L', 05@ >n;59/e 6a<na 8 ;?0 /a /e a e<>@ene0e 8 /a/n9:a. F%'  anal0 * >8na 8 < 5la F%'. %rofolitropin /e <==en 0 8<na Cena 8 :ena80. D6a ee:. L'  anal0 * +umani korionski gonadotropin(+C7), <en 0 el/9e / >ne, :a < >enn8 <88<8 L'  na=a 8na eae> / :8l<na a>a e 8l a@n GnR' a6n. D<8@ >8@>/el8/8 GnR' a@n 8 @e :8=a0<na @en; @na><na > Cena /e <la0e n>89/8 68la9/e, l > Cena a @nel=: :e<0a, le:: 8e<8a, > >/e9e a <6n: Cena, nn8a/e 6<8ne, 0n/en/e, @la65l/8. D8@<na <:/ena e 05/e@a6a 05@ <0a @85a =ane :ae  e<0e. K> :8=aa/ 6<8ne, 0n/en/e, @ne:a/a, :an/en l5>, :an/en ;e:a<, :an/ena @8a /8. K> :8=a/e9e a ana :Ce > > e@0a<9e5a9/e an/a. #ntagonisti 7n0* * ganireliks i cetroreliks 8 ana@n GnR' / e <e 0a 6</e:e n>89/e 68la9/e 8:/e a@na GnR' >a 5 e :an/la <06>n/a en>@en; @na><na. #bareliks i degareliks 8 ana@n GnR' / e <e 0a l/een/e 80na6al@ a@na GnR', al n ne 80<8/8 6ean/e 8: l/een/a <: ;e<:8la9/e /a/na a>a e <e 0a n>89/8 68la9/e. 13"

#$T#7$ITI P0.#KTI$#(#7$ITI DP#1I$KI* D? 0'C'PT0#) P<lan, ;<:n n/e ;?0e Cena  :8=a<: nel>n  @alaen:a / l8e <lan. Da:n /e ?0l= n;5< l5ađan/a <lana. A>en: / l8e <lan 5n 0a>a:n. U ;e<<lane:/, bromokriptin  ><8@ n. Ka /e  </e :en8, 6ele >0e a@na >a:na e <e 0a l/een/e a<:e@al/e. *01$I T0#;$&'7 0';$&# *IPFI"' ksitocin * /e e> / e ne089/8 l /aan/e <>a. #tosiban /e ana@n /el8/e en; anala na aaln/ :e:586@ ?a a9/enaa a ;?0n: >a5ee n>8:  8 a9/enaa a 5la@: ;e:?l/: A, l 6n lle56: 5le. Va0 < 0a l/een/e <6an/aa  >6e<8la lna. Nel ana@na e 8 an/:a 05@ 6=en@ 6a0
137

3'.POGLAVLJE ) TIROIDNI %ORMONI I ANTITIROIDNI LIJEKOVI n/aa 0l88/e >6a a ;<:naH a:nelne a />: tiroksin  T> i trijodtironon  T=  e>al9nn. T<n  </><nn :a/8 =< 8na na n; ;<:na * =n/aa 0l88/e >6a ;<:na / a>H<n  </><nn. J>> la0 0 ;> e a<5/e e n6e< :8 e<>a0e.*slika38-1 P<en <@l58ln l8C a e:el/ 0a ne08 ;<:na =n/ae. Oa9 <0na 8 <@l58ln8 e /><0nMIT l >/><0nDIT, <9e / e na06a <@an?a9/a />a. U <@l58ln8, >6/e :le8le DIT e :5n /e>na :le8la MIT  /e>na :le8la DIT 6aa l5ađa/8 0 =n/ae. Nan l5ađan/a 0 Cl/e0>e, 8 <6 e 8n />>a. T%' :8l>a  ne08  l5ađan/e ;<:na =n/ae. I:a  8na e@8=a. Va n9ee <8/el /e a6<: ;e</el6an/a T4  T3 * T3 /e  >ee 8a enn/ > T 4. P= e T 4 n6e<@6 n<l: T 3 e 6a > 6a  8 Na K ATPa0a, na,
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U$INAK TIROIDNI' 'ORMONA Una na 86n@ 8a6a  n<l8 :e;an0:a :a, 8@l/;>) /e 5n <6 05<. .iotironin(T=) /e 5/el8/8, al :a 6a8la8@0e 8 e8 e
ANTITIROIDNI LIJEKOVI TI#1IDI * Me:a0l  propiltiouracil 8 :al a:> / n;5a0e, n0a9/8 <0na  6e0an/e DIT  MIT. P<l8 ne n;5/el6an/a /e <, <le 3-4 /e>na 0a 8n 8na. M@8 e <:/en/6a  :la>; a9/enaa a :al: Cl/e0>a:a  8:/en: >ne6n. Ia, <l8n /e< eCe <la0 8 el/98  :a/n :l/e. Tn 8na 8l/88/e e  e=e ?8n9/a /e>a n;50a9/8 <0na  l5ađan/e ;<:na =n/ae 6e l ađe< :an/8/8 6eln8  6a8la<0a9/8 ;e<lane =n/ae. P= n;5/el6a 0a 2-7 >ana. Ia, 8na /e <la0an, =n/aa 5/eC 0 5la>e />>:a nan nel /e>ana >ne l e <e 0a n<l8 ne l8/e  <  al/e6 />>  0aena na kalijeva jodida. NeCel/en 8n9 8 , 6<89a, :ealn 8, 
I e a<5a >0a /a 5 =ela Cl/e0>8 ne 5 8@<0la ala 6a. a a  />>a, 8n6a >0a 131I :Ce 8 8n 0l/e n9e  >/l/e 5 @a 
13)

#$I$KI I$*I/IT0I * 8 tiocijanata(C$-)  perklorata(CI>-) 5l>a 8 =n/a8 >n@ 6>l/6  e<l/e  al; <an; a5n<:aln 05@ e=e >, :Ce 80<6a ;a 5l> > 5a /e :a/8 /e8 5le =n/ae :8ln>8laa<n: e l/e <>n: ;<:n:. 'e<:a, > 8alna 6e<0/a a <e<>:a.

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3(.POGLAVLJE ) %ORMONI KORE NADBUBRE"NE "LIJEDE I NJI%OVI  ANTAGONISTI K<e<> 8 en ;<:n / e <06>e 8 < na>585e. %a/e e > >6/e ?0l=e  ?a<:al=e @<8eH 1 @l8<>a, / :a/8 6aCan 8na na ne<:e>/a@6<,  8al8H 2 :ne, / /el6an/a * <e<> 8la0e 8 an98  6eC8 e 0a 9la0:ae -eGRE l 0a ele:en e9?an 0a :nee.*slika39-4 T6n e9?an >@6< na ee e :@8 05@ <86a - :8l<8/:al9e,  80<8/8 aa5l0a: <ena :=a. D>an, 6e n9ea 80<8/8 @85a l:?n@  6e06n@ 6a, :a, C. Kaa5l 8na na  :Ce 80<6a e<08. U >/e9e, n;5 n;5@ađa/8 >5a96an/e <@ana <  :a/8 >589/8  ?8n9/8 le89a. O6 l/e6 6ea6a/8 n9e/el8/8 89/e ne0e n;5 8 <0la e e. Gl8<> :a/8 8na na (N%. Ka>a e >a/8 8 6el: >0a:a, 6 l/e6 80<8/8 <:/ene na=an/a. Vele >0e ađe< :8l
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VA#NI GLUKOKORTIKOIDI K0TI". * na/6aCn/ <<>n @l8<> /e <0l ;><<0n. F0l= 0l886an/e e ana9<a>/an <a: 6<;8na9 /e /e: /8e(BG. P<:/en/en 5< a<5/el6an/e ne@ ne anal0.*tablica39-1 Ia e la5 >?8n> a9/enaa a 8:<: na>585e / 0l88/e <0l l ;?0n@ 8:<:. %INTETI$KI GLUKOKORTIKOIDI * :e;an0a: >/el6an/a 6; l/e6a /e /e>na <0l8. Vel 5</ ne; @l8<>a /e >8an 0a <:/en8 prednizon  n/e@6 a6n :ea5l, prednizolon, deksametazon. N/;6a 6/6a8 85 a <0l: 8 >8C l8C6  >/el6an/e, :an/en 8na n; 5a</e 8 <8@; an/a > /; /e 5a e 05/e@ne e:n 8na. /eklometazon i butesonid ene<=n; 8e6a, al :a/8 a 8đ8 8 <6, a 8 >a :an/en e:n 8n9  n. Klna <:/ena P585e * @l8<> a=a6a/8 C6 a9/en:a a <nn: n8?9/en9/: 585eA>>n6a 5le   a8ne n8?9/en9/e 6e0ane a =:, n?e9/:,  e <e 0a nee 6e n@enalne ;e<la0/e na>585e, 8 // A(T' :8la. U 6: 86/e:a, <:/ena naCn@ ne@ @l8<>a :an/8/e 0l86an/e A(T'  a :an/8/e ne08 a5n<:aln; e<>a. P@6a:a. Ne > ; 8 8alne l :8nne <<>ea:a, >5/an/e  a :al: 8n/e: 6e0an/a 0a <ene, e >a/e <8>n9a:a 8 8 >a 5 e 85<0al a /e: <nne <:/ene @a e :Ce /a5ee, <=en/e :=a, e<0a, e :n:0
lalna <:/enaae<l 0a a:8, e<8@ >an>a 5 e :an/la 80e nan 0an/a e@6585e > a9/enaa a >8@<n: e>ane >0e /e: e=e 5le l </e 6ele ee 5 08, >a 5 e 585e. 1I$'0#.K0TIKIDI #ldosteron * na/6aCn/ <<>n :ne, / e e<na /e e<n :a . Me;an0a: >/el6an/a /e /e>na @l8<>:a. Oal :ne * 8 deoksikortikosteron e<na,  fludrokortizon / :a 0naa/an 8na @l8<>a. 5@ >8@@ >/el6an/a, ?l8><<0n /e l/e 05585e a :an/: :nea. #$T#7$ITI K0TIKT'0ID# Ana@n e<na na n/e@6: 8N@) /e :e6n n;5< a  <:a. In;5< ne0e * nel l/e6a n;5a 8 na>585. Na/6aCn/ 8 ena0l, a:n@l8e:>,  :ea  < e 0a 6el 5</ an/a 8 /: /e :an/ena n9ea Cel/naa<9n: na>585e, ;<080a:, /e. #minoglutetimid 5la / 8 a6n a ;<:n. MCe e < 0a/e>n a ><8@: l/e6:a 0a l/een/e a<9n:a 585e / l8 e<>e. 1etirapon n;5/a@ne e6e ?8n9/e na>585e,  0a l/een/e <8>n9a a (8;n@6: n><::.

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4*.POGLAVLJE ) SPOLNI %ORMONI I NJI%OVI IN%IBITORI %ln ;<:n 8l/88/8 e<>e 0 /a/nae<@ene  @ea@ene  eaee<n. %6/el6an/a a nn:, ana@n 8 ><8@: 68. M/e=an a@n a 8n: e<@ena 068 e ele6n :>8la< e<@en; <@en,  n a ana5l: 8n:, 8 >8n 0a ln8 <:/en8. Ra0n6<na @<8a l/e6a a 8n: <6 an><@ena e <e 0a l/een/e <@en0:a > Cena. 'ORMONI JAJNIKA Ja/n9 8 <:a Cena /e: 86n@ 5l/a. T/e: n<:alne 6; >@ađa/aH ?l8l e 8 /a/n9:a   :lana en>:e</ :ae :8la9/: e<@ena  <@ee<na, 0l88/e e a > :en<8aln@ a,  9l8 e na6l/a. Me;an0a: >/el6an/a e<@ena  <@ee<na 8l/88/e 8la0a 8 an9e, 6eC8 e 0a a e :le ;<:n-/e :>8ll. 'stradiol :a :al8 8an 8 ne: 5l8 / :a 5l/8 5e<:aln: ?lae<:, 6a@naln: /el8/8 ee< ela / e n6e<l, :@8 5 <:/en/en n:/en8 e86n@ 8a6a. O>@6a /e: >/en6a  0a a?9a  'DL 8 <6, > :an/8/e n9e0:a > :la>; Cena, > Cena a :an/: e<@ena 05@ 0aa/en/a /a/na, 8 :ena80, l <8<= >:/ena e
8<@enaln:  ;<:naln; n/e6/9a a ;@na>0::, >0a e<@ena e : >a e ne >@> 8@; /8. Ka>a e < a ;<:na na>:/ena e:e</a 6a/ 8na e :Ce </e :5na9/: e<@ena a @ea@en:a. U :ena80aln; Cena e<@en :al 6ea6a <0 /e  a<>6a8la@ađa/an?a< :a<>a, :C>an 8>a<. Tn 6na  >0 /e :8nna, /el/6 >/, 6ean <0 :@e:/e  ;e<en0/e. Dietilstilbestrol, nee<>n e<@en /, /e 6e0an a nel>n, en: <8>n:, a>ena<9n:: 6a@ne 8 e< Cena /e 8 l/eene 6: l/e: /e: <8>ne >a 5 e </e nan 5aa/. O6aa6 8na :a a: >ell5e<l. 7'T#7'$I Progesteron /e na/6aCn/ @ea@en 8 l/8>. D8n 8 ne 5l9 0a ;<:n8 na>:/en8 e<@en: 8n8. %a</ l/e6.-norgestrel i noretindron :a/8 /a an><@en 8na ne@ n6/ @ea@ennorgestimat9 dezogestrel. Una * <@ee<n n>89:e</8  ne. Oal @ea@en ađe< a5l0:e</ al ne >n8. Gea@en ne 8/e8 0naa/n na <ene la0:e, al 8/e8 na :ea5l0a: 8@l/;>la@an/e :a. Vele >0e 8<::/en/ ea 5 </el a<9n: en>:e</a 80<6an e<@en:a. P<@ee<n e < 0a : Cena:a /e :a/8 e=a a 0aee:  /e :a/8 :al 0a 8 an/e e<@ena 8  /a/n9:a,  >8@ 6</e:e 68@->/el8/8e n/e9/e, e<:aln ?lae<, 6a@naln <en, n8ne 8 14!

>6/e 6<e </ele na :n?a0ne 5lenanna >0a 5a <0a /e>n@ l 5a a/aa e :/en/a /e: 9l8a. Paln nn8 a e <:/en 8 <8 72 aa nan ne0a=en@ ln@ >na. '<:n e <:/en/8/8 a ane:e9:a. 1ifepriston, ana@n <@ee<n;  @l8<>n; /el6an/a * :5n/el6an/a, 8l/88/8 n;59/8 68la9/e<:ae,  /a/6>e  en>:e</ = :an/8/e =an8 l>n/e  :lana9/e. L/e6 / a>/el8/8 <8@; :e;an0a:a. Me;an0a: aln; na e <:/ene </e L' 6ala, n ;5e, /a/6>e  en>:e</. Oale lne <:/en/e  6l/n 8n9 * :5n :la>; Cena a <:a0:: 0a :en:e<0e. K<n9e :5n:e</a, 5en@ne 5le >/e, 8alne 5 le 0>/el9e,  :an/en8 n9>en9/8 ene <8>ne, ane:/e 05@ :an/a Cel/e0a  n@ a<<a. TOK%I$NO%T * /a6n n 6ne  >0 /e :an/ena a e <e :5n0a:a. T<:5e:5l/a * na/6aCn/ n 8na :5n/el6an/e: e<@ena na 0@<8=a6an/e <6. P/ >8:en@ađa/an?a< :a<>a, :C>an 8>a<, <:50a >85; 6ena, l8na e:5l/a 8 a</; Cena, 8=a9a, Cena a /e: <5le::a l 8 5el/,  Cena a @ene:  <8>ne. Ra >/e * 6 l/e6 ne 8/e8 na <0 /e, al 0e :5n/, @la65l/a, /aana @:ena9/a Ce,  >e<@ena :@8 80<6a >e5l/an/e, ane  ;<080a:. Ve >0e e<@ena 8 aln: n
I$*I/IT0I I #$T#7$ITI 'T07'$# I P07'T'0$# %ELEKTIVNI MODULATORI E%TROGEN%KI' RE(EPTORA * %ERM 8 :/e=an a@n e<@ena / :a/8 8na a@na e<@ena 8 ne: 6:a, a 8 ne: 6:a >/el8/8 a a<9/aln a@n l ana@n. Tamoksifen * /e %ERM / /e 8n6 8 l/een/8 a<9n:a >/e / >@6a >/el8/e a antagonist  0a @en: e<@en:a. P<?laa <:/ena a:?ena :an/8/e n9>en9/8 /e > Cena a 6: <0:. Ka agonist >/el8/e na :e</a, /aa6a ;e<la0/8 en>:e</a  6ea6a <0 a<9n:a en>:e</a. O6a/ l/e 80<8/e 6al8n@e8na ana@na  6ea6a <0 6ene <:50e8na a@na. Ta:?en :a /a 8na a@na na   a a9/e  n. 0aloksifen * e < 0a :e</. NeCel/en 8n9 8 6al8n08na ana@na  6ean <0 6ene <:50e8na a@na. Klomifen * nee<>n / a 6n ele6n: 8n:. In>89 Cena 5e0 68la9/e /e Cele 0a<8>n. %ele6n 5l/el8/e a ana@n 8 6: 6:a. K< e 0a l/een/e /e > Cena /e 8 n /e6letrozol 8 nee<>n :e6n n;5< a<:aa0e, en0:a n/ /e. Danazol * n;5<@ena, a. K< e 0a l/een/e en>:e<0e  ?5<9ne 5le >/e. ANALOI I ANTAGONI%TI GnR' Ka /e an 8 37.@la6l/8, nn8<na  a n;5 ".:/ee9 0a l/een/e en>:e<0e. L/een/e >8Ce > ".:/ee9 :Ce :an/ @88 /8 > 
ANTIGE%TAGENI 1ifepriston /e , ana@n <@ee<na  @l8<>a 3).@la6l/e. Na/6aCn/a <:/ena /e 0a  ne> 4) >ana nan 0a>n/e :en<8a9/e. K:5na9/a :?e<na  <a@lan>n E anal@a misoprostola 8n6 a <8>n8  7 /e>ana nan 0a>n/e :en<8a9/e. Na/e=a :la9/a /e ne8n a5<8. NeCel/en 8n9, <:a/el9. R/e, a9/en >C6e an8 n?e9/8  e8. #$D07'$I Testosteron  <>n an><@en e <06>e 8 e:a, na>585,  8 :al/ :/e< 8 /a/n9:a. Tee<n e ne0e;><ean><e<na. U la0:, ee<n /e 6en: 6e0an 0a @l58ln / 6eCe lne ;<:ne%'BG. '<:n e n6e<8@>/el8/8 ee< n/e9/: l e<:aln: ?lae<:. D8n 8  <@en 8 ne0a 5 e /aa ana5ln 8na 5e0 :an/ena an><@en@ >/el6an/aoksandrolon, 8 < la5<@en 8na. Ia, a06an ana5ln e<> :a/8 8n an><@en 8na a e <:/en/8/8 > l/8>. Me;an0a: >/el6an/a * a  al e<>n ;<:n, an><@en 8la0e 8 an98  6eC8 e 0a 9la0:ae 8l  >@6laa a:n/en/e Ce, 6ean/e :=ne :ae. Nan 85e<ea, ee<n >an  l5>. Tađe< >/el8/e na an9e >laa  80<8/e ela6. Na/6aCn/ 8na an><@en; ;<:na, /e ana5l 8na / 8l/88/e 6ean/e :=ne :ae,  6ean/e <06>n/e e<<9a. %:an/en /e 0l86an/e 88=a a/e 06na. Tađe< :aCe ><@ena /e na>:/ena e0:a. An><@en e <e 0a :8la9/8 <06>n/e e<<9a 8 >e5l/an/a > a9/enaa n><:: <=en/aAID% a9/en. Ana5l 8na <a= <e <80an 0a 6ean/e :=ne :ae  na@e. Tn * <=en/e an><@ena > Cena 80<8/e 6<l0a9/8;<080a:, 6ean/e l<a, >85 @la  ne <8>n9a a Cen: ?e8:, e@0@en an><@en :@8 80<6a 6<l0a9/8 een, 14&

0e > :8=an a <@ena 8 e<@ene. U 5a la, 6e >0e ana5l; e<>a :@8 80<6a lea8 C898, 6=en/e /e ;ea9el8la<@ena /e 6aCan 5l e/el8/8 na <@en@ 8a. *slika40-6 In;5< n l/e6 8 nee<>n :e6n ana@n an><@en; @en; an><@ena > a9/enaa a a<9n:: <ae. pironolakton, <6en6en e < a >8 al9/1!.@la6l/e, ađe< n;5<@ene Cena. In;5< !-8a0e * ee<n e n6e<;><ee<n :8 !8a0e. Nea 6a, @6 an9e <ae  ?l8l e, 0a6e  >;><ee<n8 0a an><@en8 :8la9/8. O6a/ en0: n;50a:a 0a an/a e > :8=an, @85a l5>a. Dutasterid /e n6/ n;5< !-8a0e, a 8n >8C: l8C6:. ANALOI I ANTAGONI%TI GnR' %8<na, @6 L', :an/8/e 6a8@>/el8/8: l/e6:a 8 le8<l>a l ln; a@na GnR'. O6 anal0 e <e 0a l/een/e a<9n:a <ae. T/e: <6@ /e>na e>a/e e ana@n an><@en@  >a 5 e </el 6ean/e 8:ana, 6aa na :n:8:. Ana@n GnR'a5ae@a6al@ Cena a ;<080:: 05@ 8na an><@ena. E<@en 8 n/el8/e 8 /e< 0a 6ean/e 6an@ an><@ena 8 <6 / 80<8/e ;<080a:. In;5< ne0e e<>a * ketokonazol, an:, n;5a 8 na>585  @na>a:a. L/e e < 0a :an/en/e <06>n/e e<>a 8 na>585 > :eaa0a @6ae.

14)

41.POGLAVLJE ) %ORMONI GUTERA#E I LIJEKOVI A LIJE#ENJE EERNE BOLESTI U en><n/ @8=e<n; an9a, Aal?a, @l8a@n, B5ea, n08ln  a:l>n e>, D>ela, :aan,  Fan. Bn08ln an9e 8 na/5</n/e. Na/e=a 5le @8=ea5ee :ell8, :an/a n08lna l n/e@6@ 8na. Da5ee e l/e a nel a6a8laen?96a 6aCna 5la >a5eea :ell8a. Da5ee a 1 5n n/e /e: >/en6a  5, n9>en9/a > >/e9e  a>le9enaa >6a 5la e 0naa/n /e8,   <6/e<8 @l80e 8 <6 l/e /ela,  n9ea5eea a 2 5n e :Ce n<l>a/8 n08ln 8 e. Una * n08ln :a 6aCan 8na na < 6a 6a 8 /el8. Ka>a e n08ln /el6an/a n08lna 8H Je=en8 @l808  @l@en 8 /e<. O6 8l/88/e 8:ean/e >>an; GLUT2 <8@; en0:a. In08ln ađe< :an/8/e aa5l0a: <ena. %elen := * n08ln :8l=en/e <@l9e<>a a6a9/: l<en la0e, 6ea6a 8n=en/e @l80e 
1!+

PRIPRAV(I INULINA L/8> n08ln e <06> 5ae</: 8l/ne >/el6an/a /e 6a< 5<0>/el8/8; > >8@>/el/8/8;.*slika 41-5 (l/ e/alne n9ea 5 e @a a/ 9l/. /rzodjeluju:i inzulin * < anal@a n08lnainzulin lispro9 inzulin aspart9 inzulin glulizin :a/8 5<0 ea >/el6an/a  /alne n9e:a; </e /ela  n08ln 8 05/a5ee ea9>0e. Kratkodjeluju:i inzulin * regularni inzulin e < nn/e@ l >8@@ >/el6an/a. P</e /el8/8; n08lna, < e 0a n<l8 /alne n9e@đen >/el6an/e  6<=n 8na. NP' n08ln e 5n :5n/el8/8: n08ln:a. Dugodjeluju:i inzulin * inzulin glargin i inzulin detemir 8 :>?9/el8/8 6=e > 2+ a, = :@8a6a n<l8 5a0alne n9eanne6n: n/e9/a:a  <8Ca/8 ?le5ln a9/en:a. P<@a6l/a 24 an8 5a0aln8 /e9a :lađa > 7 @>na 8 na//el/6 na =ene 8ne ;@le:/e. Na/e= 5l :8nl=e :la9/e /e 6a
1!1

0#.$I($'I$"%.I$KI) .I&'K!I "# .I&'3'$&' DI&#/'T'# D8ne 8 e< @<8e /a5eea a 2. T 8 n08ln e :e?<:n, a0l>n>n,  n;5< -@l80>a0a.*slika41-2 T< n6/a l/ea * , eena>, a@ln * 9l/a/8 en>@ene /el6an/a  8na * n08ln e@en@ n08lna 0a6aela<0 a9/enaa / ne:a/8 ?8n9naln; B an9a. Vena n08ln; ee<6aa 8l?nl8, l<<a:>, la0a:>. 0epaglinid, 0 skupine meglitidina,  nateglinid, derivat D-fenilalanina, 8 n08ln e/el6an/e  0a 8 <n 0a <:/en8 >:a; </e /ela, 0a n<l8 /alne n9e<8@e @ene,@l0> :@8 80<6a ;@le:/8, al /e <0 8n nC ne@ a n08ln:. %a</ >e<6a 8l?nl8, l<<a:> e eCn 6eC8 0a <ene e<8:a,  l/e6 / e 6eC8 0a e <ene :@8 /aa n/;6 8na ;@le:/e. Nea> 6 l/e6 80<8/8   ><8@e ale<@/e a9/enaa a >a5ee: a 2 / 8 6e /el6an/a  8na * 1etformin, :an/8/e /alne  naa=e n9e n;5/el6an/a 8 /e< 8l/88/e a6a9/8 en0:a <en-na0e /8 a6@en 6an/e n08lna  = ne 0a06a >e5l/an/e * 0a n>na * :e?<:n /e l/e <6@ 05 /a5ee: a 2. Klna a08/8 >a :e?<:n :an/8/e <0 > >/a5eea > a9/enaa 6@ <0a. Me?<:n e < 0a 6n > Cena a l9n: 5le /a/na  >e<6aa 8l?nl8 ne 80<8/8 ;@le:/8. Na/e= neCel/en 8na 8 @a<nenalne :en/e:8nna, <l/e6, :@8 80<6a laa9>08, @6 > a9/enaa a 5le:a /e
05@ /; / 09/a 0a 6n8 an/8  6a8l:nalna >?8n9/a. TI#".IDI$DI$I Me;an0a: >/el6an/a  8na * rosiglitazon i pioglitazon, 6ea6a/8 /el/6 6a na n08ln, a6a9/: a. P<:an>na /e 6ean/e 8na @l80e 8 :=e  :an 6. Tađe< n;5a  >la@an/e :a. %:an/8/8 naa=e  /aln n9e<8@: /a5eea. [R@la0n  a<>6a8laa e <:/en/8/8 a:, <0 ;@le:/e /e </e>a. M@8 80<6a e, = e 6> a 5la@a ane:/a  e>e:  :@8 6ea <0 <an@ 0aa/en/a. N6/ >a9 6e08/8 <@la0n a <0: n?a<a :a<>a. P<6 a0l>n>n <@la0n /e 68en 05@ ;ean. N6/ l/e6 ne a08/8 =een/e /e/el6an/a  8na * #karboza i miglitol 8 anal0 8@l/;>/el8/8 8 9</e6:a  n;5a08, /a a;a<>e, 8 :na;a<>e / e :@8 /alna n9en>n, n;5< -@l80>a0e :an/8/8 <0 >/a5eea a 2. Tn * <:a:an/e, <l/e6, a5>:nalna 5l 05@ 6eane ?e<:ena9/e nea<55/8 ;@le:/8, e<0:, ne a;a<0: /a 5 a<9/a 5la >@đena. P0#1.I$TID * /e n/ea5ln ne anal@ a:lna. P 8/e 0l86an/e @l8a@na, 89a,  8 (N%-8 :an/8/e ae. Nan 858ane <:/ene, 5<0 e a<5/el8/e. K< e 8 :5na9/ 0a n<l8 /alne n9e
1!3

'K'$#TID * @l8a@n8 lan le>-17.P-B /e lan nn; ;<:na, / e l5ađa/8 0 en><n; an9a eela 9/e6a 8 >@6<8 na ;6an @l80: 0 B an9a, 89a, n;58@>/el8/8 n/ea5ln anal@ GLP-1, e < 8 :5na9/ a :e?<:n: l >e<6a:a 8l?nl8/a5eea a 2. NeCel/en 8n9 8 @a<nenalne :en/e, @6 :8nna na e8 ea e :5ne<6a:a 8l?nl8e>l-e>a0e-4DPP-4, en0:a / /a5eea a 2 a :nene>n:a. Ka eena>, a@ln /aa6a l5ađan/e n08lna, n;59a, :a an=n; 8e6a. LIJE$ENJE DIABETE%A MELLITU%A TIP 1 * e/e8, a8@ >/el8/8e@ 5la 0a n<l8 5a0alne  /alne n9e 0a 5l/8 n<l8 /alne n9e>an aCl/68 0/ee. TIP 2 * = /e 6a 5le <@/ee. Pen l/een/e /e a n  ><8@:a l a n08ln: >a 5 e >5la = 5l/a n<la @le:/e  :n:06l/n 6a/el6an/e :e?<:n, a0l>n>n, l n;5< -@l80>a0e a n:a / 6ea6a/8 ln8 n08lnan08ln e/el8/8 l/e6>e<6a 8l?nl8n>n, eena>, a@ln, ?<:8la9/e n08lna n<l/alne n9e /el8/8 l/e6n;5< -@l80>a0e, , , 5<0 >/el8/8 n08ln n<l/aln8 n9e >/a5ea
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1!!

42.POGLAVLJE ) LIJEKOVI S U#IN&IMA NA %OMEOSTAU MINERALA KOSTI Kal9/  ??a, >6a @la6na ele:ena , 8 l/8n ne a: 0a :e;an8 na@8 elea al  0a n<:aln8 ?8n9/8 :n@; ><8@; an9a /ela. Pn ;<:nPT'  6a:n D 8 <:a al9nn, @l8<>  e<@en @a/el8/e n/8  6ean/e: a6n e5laa  elaa.*slika42-2! A6a9/a elaa n/e 0a 8 e5la:a, lana TNF 5el/ 9na / :8l?e0a:a;e<a0a:, ne 8na 6=en@ PT' /e 6eana 0e PT' :a/8 8na 6a/el6an/a teriparatida, teriparatida, n@ n0ae;><lee<la > 8/e9a/e: UV 0<6a:n D * al9?e>l  585;><6a: D * al9<l. %ne0a 8 585e e5la  ela. %ne0a al9<la 8 585n@ l 6=e /e9e  a>le9enaa, e:ala9/8 e:ala9/8 1!"

> >e<6a e <e 0a l/een/e an/a :an/a, <?/a, <nn 0aa/en/e 585<:. Tađe< e <e 8 :5na9/ a 8le:en:a al9/a, >a 5 e  a</; Cena  :8=a8n a >a/8 e 8 :l/ene <06>e  al8 ; a9/enaa a =een/e: 6aa<6a:n D 2dokserkalciferol dokserkalciferol <l/e / e 8 /e< n6e< 8 parikalcitol i kalcipotrien anal0 kalcipotrien anal0 al9<la. %6 la5/e 80<8/8 ;e<al9/e:/8  8 a9/enaa  a9/enaa a n<:aln: ?8n9/: 585e<al9?e<l  5a0n ;<:n, / e 6a l 5??na. Ia /e >8an ;8:an 5l, e=e e < al9nn la 05@ >8Ce@ l8C6a  /ae@ >/el6an/a. P<:/en/8/e e n/e9/: l na0aln: /el8/8  >
1!7

NE'ORMON%KE TVARI KOJE UTJE$U NA 'OMEO%TAU MINERALA KO%TI /IFF$#TI #lendronat9 ibandronat9 pamidronat9 risedronat i zoledronat 8 zoledronat  8 l??ane 6a< /e :an/8/8 /el6an/e: na <ale ;><aaa. I:a/8  ><8@e :lene 8ne, na 6a<na  0le><na 8 >8n 0a a8n  8 ne6ne >0ealen><na, <e><na, 5an><na, /e>ne >0ealen><na, <e><na, :/eene >0e5a><na, <:/eene >0e5a><na, @>=n/e >0e0le><na. P<:a0a 5??naa 8 <a9/a /e>n/aa  Cel8>9a. Da 5 e  :an/l, e  05/e@a6an/e 8a9/a /e :@88/8 0e 5??naa 0a l/een/e ;e<al9/e:/e 8 6e0ane a =een/e: 585. K< e 0a an@ a<9n:a. Tn 8 ;al9/e:/a  :8nna e a>na:na 5le /8. F.%0ID * F.%0ID * <la>ne n9ea 8 / 6> l 8 085n/ a :an/8/8 <0 >enaln@ a</ea. K<nna 0lCen ?l8<>8, @6 < 6: n9ea l /e n6a  /e>na naCna. A8na n ?l8<>a<5a6a <6a 0a =a6a a:a <n9/a, e a08 elaa  6ea6a n9e8/e 0a l/een/e ;e
UVOD * /a6a a6l/a aln 0a06 0a 80a/n>an; 6a< /e :@8 0a= > na6a9/e, 8e<6aa an5a,  na/an/a >a e 05/e@ne 0l
43.POGLAVLJE ) BETA-LAKTAMSKI I DRUGI ANTIBIOTI&I KOJI DJELUJU NA STANI#NU STIJENKU I MEMBRANU Pen9l  9e?al<n 8 @la6n an59 / n;5ne > na/8n6/; l/e6a / e na=< <e  >5< le<n6ena 0a :<<@an0:e. D8n /e 6=e > e>ee an5a / >/el8/8 a n;5< ne0e anne /ene, a n>6>8aln: e<: a6n  =<: e<6a "-a:nen9lane elne  a>6<e en9lna :a/8 e:/e 88ene / >6>e > /el6an/8, /el/6 na elne, en0:/ ;><l0  5>n. Fa<:anea * en9ln 6a<8n 0a n/e9/e. Pen9ln 8 la 3+ :n8a > 1 aa. Prokain i benzatin penicilin e penicilin e <:/en/8/8 n8@ l8C6 /e< e a6n l/e < l5ađa 8 <6. Vena en9lna <la0 5a</e<8 <6-:0a a: a 8 :enn@e 0a/el6an/a  a9/e /a 6eCe e>@lan lana9 > /e@ /e @<l0a 5ea-laa:@ <ena
laa:a08en9la08 /a /e @la6n :e;an0a: 5ae</e <8@ :e;an0a: @6 a?la  0a ne8:a  ene<a. K> ne; <>6a @<ne @<8e en9lna / :a/8 @a n: an59:a. Penicilin ! /e @<8a 8l/88/e meticilin<, al e </e < 05@ ne?<n, nafcilin i oksacilin0a0ll en9ln. P<:ae<:>-MR%E 8 a9/e lne a 0a en9ln G,  n?e9/e > enterokoka% listerie $onoctogenes% esc'eric'ia coli% protes $irabilis% 'ae$op'ils in(len&ae% $ora+ella catarr'alis, 80 /a68 a e <e 8 :5na9/ a n;5<:a en9la0ela68lana elna, n/;6 8na /e /aan. a l/een/e n?e9/a enterokoka i listeria, <e e 8 :5na9/ a a:n@l0>:a. PIP'0#CI.I$ I TIK#0CI.I$ * 6 l/e6 >/el8/8 <6 gra$-negativni' ro#ova% popt  pse#o$onasa% enterobakteri)e i neka# klebsiele. Vena e < a a:n@l0>:a <6 6a6; n?e9/a. I e e <e a n;5<:a en9la0e. Tn Ale<@/e * ale<@/e C6e ale<@/8 n/: en9lnaen9lna elna naa/8 <>8 / 8 an@ena >ee<:nana. M@8a /e 8<Cana 
Ga<nenalne :en/e * :e:5e<6a 7-a:n9e?al<8@e, l/e>8 86đen/a 8 ln8 <:/en8. Fa<:anea * >8n /e nel 9e?al<na 0a <8@e @ene 8 :enn@e 8al/ene. Me;an0a: >/el6an/a  en9lna, :an/e 8 /el/6 na en9la08 /8 <06>e a?l, al >a 5ae</a /e <8@; 5ealaa:a0a /e na6 6; <@an0a:a  <8<=a <?laa 8 >/el8/e <6 @ anareobni' bacteroi#es (ragiliscefotetan9 cefoksitin,  n?e9/e n8a, 8;a  >=n; 8e6a > .in(len&ae ili .catarr'alis cefamandol9 cefuroksim9 cefaklor. TREA GENERA(IJA LIJEKOVA * ae 5ea-laa:a08, :an/e 8 8n6 <6 /e6a ene<5ae</a /e <06>e 5ea-laa:a0e =<@ e
na/8n6/ 9e?al<n <6  pne$okoka / /e /el8/8 cefoperazon i ceftazidim, a <6 !.(ragilisceftizoksim. L/e6 8 6/ @<8 e <e a: 0a e=e n?e9/e. Ceftriaksonan/e@ 8;a, /e>na n/e9/a 9e?<ana /e 5n 8n6a a >ee >ana l/een/a a a:9ln:. $ETVRTA GENERA(IJA LIJEKOVA * Cefepim /e e gra$-negativne bakteri)e, 8 enterobakter% 'ae$op'ils% neisseria% i na penicilin re&istentnog pne$okoka. (e?e: :5n a > ana?la@ =a. O6e @ađa/8 a a9/en / 8 ale<@n na en9ln 8 6en l8a/e6a e :@8 8/e=n l/e a 9e?al<n:a. Ia, a9/en / 8 :al ana?lan = > en9lna, ne 5 e :/el l/e a 9e?al<n:a. Oal neCel/en 8n9 * 9e?al<n 80<8/8 5l na :/e8 n/e9/e  <:5?le5 nan na a e <:/en/8/8 0a/e>n. (e?al<n / a>l, 9e?e8l?e gra$negativni ro#ovi,klebsiella% pse#o$onas% serratia . L/e ne >/el8/e <6 @/el8/e ne<@ a a:n@l0>:a. P<:/en/8/e e n8Cen > 0aa/en/a 585<8@a/ > en9lna al a 5ea-laa:: <en: a n: /el/6=8 na 5ea-laa:a0e. I:a/8 =< :naa e <e 8 :5na9/ a a:n@l0>:a. Ka<5aene: e <:/en/8/8 ae;><e>a0: I 8 58
<:/en/8/e e 8 :5na9/ cilastatinom, / /e n;5< 6@ en0:a. (laan 6ea6a l8C6 :ene:a  n;5/el:na <Cna e;><e>a0:  </eđe 80<8/e n68l0/e. E<aene: :a >8@ l8C6, al /e :an/e 8n6 <6 ene<a  e8>:naa,  na :/e8 n:a >e @n, :na, e<n @l<en / e 6eCe 0a D-alann-D-alann 0a6<=ea na9enn@ e>@lan@ enae>a  n;58Cen/e e>@lan@ lan9a  :ea <Cn 6e0an/e. Re0en9/a 8 /e6:a ene<a6an:9n-  pne$okoka re&istentnog na penicilin. Van:9n /e 0a:/en l/e 0a l/een/e n?e9/a 80<6an; a clostri#i$ #i((icile. Teikoplanin, :a lne aa6l/a en9/aln 05l/an ln <5le: = a6 /e6 a08/8 a e <:/en/8/e a0e 8 5a6e0ne 0a a9/ene a =een: 585?80n 9<6enln><: 9<6en@ 6/ea 05@ 8=an/a ;a:na. FF1ICI$ * /e n;5< 9la0:a@ en0:a enl<86a-@lana. Re0en9/a na ??:9n naan/e /e n9ena >0a 6@ l/ea /e :al :an/e 1"3

8n6a ne@ e>a: >ana e0/el8/e ne<@ a 5ea-laa::a  nln:a 8 e9?n: n?e9/a:a. /#CIT0#CI$ * /e e>n an5 / :ea 0a>n/8 ?a08 ne0e anne /ene > gra$-po&itivni' bakteri)a. Ja /e ne?<an, a /e l:n/8 D-alanna 8 enae>n 5n lana9 e>@lana. 5@ en9/alne ne8<n a e<: a 6an:9n, al /e 8n6 na /e6e / 8 n 
1"4

44.POGLAVLJE ) KLORAMFENIKOL, TETRA&IKLINI, MAKROLIDI, KLINDAMI&IN, STREPTOGRAMINI I LINEOLID An59 8 6: @la6l/8 ele6n n;5 n@ 8 a69:a. Bae</a :a Y6 <5:, > a69 :a/8 &+% <5:. Ra0la /e 8 >/e>n9a:a <5:a, e:/: aa68  ?8n9naln: 4!.@la6l/e 8 <6 <6en n;5< ne0e <ena. P= 8 :al =< ea< 8n6  :ll e >a :a/8 :al8 n,  5ae</a /e 8 5le /el/6e na 6e l/e6e 8 ale a 6 l/e6 <e a: 0a >n an5, :a 80a ea< >/el6an/a al /e  >al/e 8n6 <6 nel 6aCn; a@ena. A0<:9n, la<<:9n  ln>a:9n, l8ne :a<l>, :a/8 e9?na 6/6a 8 85 a e<<:9n:. N6/ n;5< ne0e <ena, , el<:9n  @e9lnanal@ e/el8/8 na /e>n9 <5:a. Kla9/8 e>l-: 6e0an/a a:na9lne 8ne RNA na :RNA. Ta e e> ne :Ce , el<:9n  ln>a:9n, >/ele 6e0n :/e na !+% <::8,  a 5la9/8. Te/e>n98 <5:a  a n 0a 6en8 /el/6; 5ae</a. VeC8 e 0a !+% >/e>n98,  eC8 anal na <5:8 <0 / 0la0e n6 le>. D>an, n;56> > :an/en/a lne l5>ne RNA 8 an9. Lne0l> >/el8/e 5ae<a, 6eCe e 0a /e>n6en :/e na !+% <5:8, n;5: 6a/e>n98 <5:a 8 a69:a, a :Ce n;5</aln; <5:a, / a>
1"!

K.0#1F'$IK. Klna6n8  58/el6an/a  5n >/el8/e 5ae<a. Ne /e6 .in(len&ae% .$eningiti#i#% bacteroi#es 8 /a /el/6,  0a n/; /e 5ae<9>an. N/e 8n6 <6 la:>/a. Re0en9/a na la, naa/e 6a 5a /e 8 /el/6e na 5ea-laa:e. Nea> e < 0a rikeci)e  0a n?e9/e 80<6ane anae<5:a 8 bacteroi#es (ragilis. O5n e < aln. Tn Ga<nenalne :en/e * > 0>/a0a. K=ana 0  n<: 6@ >/eea * 6a/ 8na e /a6l/8/e > >/e9e  a6a8la, @6 0e l<:a?enla, /e 5 a</a >/e9a le<<589/8  6:a  <la0e lan9enaln8 5a</e<8. %6 e8C > al; e/el8/8 <6 gra$ po&itivni'% gra$-negativni'% rikeci)a% kla$i#i)a% $ikopla&$a i neki' proto&oa. Ia,
:e;an0:a 0a a6n 05a96an/e e:naa / :a/8 8:e 0a 05a96an/e :a 8 en: l/een/8 >:9lne ne8:n/e. %e8n>a/el6an/e AD' 8 585/el6an/a,  na 5ae</e /e 8 8an

a: 0a n 5la@e :8nne  <l/e6a, > e=@ ene<la. 5@ <:/ena 8 n<:aln/ ?l< :@8 e >/a0a??9le. K  085 * a e <:/en/8/8 /e: <8>ne :@8 >6e > >la0/e 9alne  =een/a 9n, /e 8a9/e 8 /:a ; /e /e9e 80<8/e >la0/8 9alne  >e?<:a9/8 <8ne 085e > 0e e <8>n9a  n; a /e: 5le /e > 0e, a a</: ee:el9ln, :@8 80<6a /aan8 /el/6 Ce na UV 6/el. Ve58la9ln  :n9ln 80<8/8  >0 6n8,
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1#K0.IDI Ma<l>n an59eritromicin9 azitromicin i klaritromicin 8 :a<9l lan <en a 6e0an: >e =ee<:a. O6 l/e6 :a/8 >5<8  e ><58n6en /e< n9eana, 6en: ne<:/en/en 8<n:. An5ae</a a6n * eritromicin /e 8n6 <6 ca$plobacter% kla$i#i)e% $ikopla&$e% legionele% gra$-po&itivni' koka% i neki' so)eva gra$-negativni' bakteri)a.

%ea< 8n6 azitromicina i klaritromicina 8 ln, al 8 8n6/ <6 kla$i#i)e% $ikobakteri)e i toksopla&$e. A0<:9n /e 8n6  <6 @ne > @>a/e :eln8 @<88 na 6e0n :/e na <5:8. K<Cna  6; :a<l>a. K> /e6a / <06>e :ela08, / a<9/alna <Cna , 8 ln>a:9na  
l/e /e 8n6  <6 gra$-po&itivni' kokaal ne <6 na en9ln /el6an/a, al /e 8n6/ <6 .in(len&ae% ora+ella catarr'alis% eisseria. 5@ 6@ >8@@ l8C6a, /e>na >0a a0<:9na /e 8n6a 0a l/een/e 8<@enaln; n?e9/a 80<6an; a C.trac'o$atis, a e6e<->ne6na >0a 0a l/een/e a$blantne pne$oni)e. Klaritromicin :a <  ea< >/el6an/a  lne <:/ene a e<<:9n. O6a/ l/e e < 0a <?la8  l/een/e <6 cobacteri$ avi$ co$ple+ ,  > /e a > >/e9e, al /e 6ean <0 > <8>n9a. E<<:9n n;5a, >@na  e?lna. %lne ne<8@a/a, a 8 ne
T'.IT01ICI$ Tel<:9n /e el> <88:a. O6a/ l/e :a  :e;an0a: >/el6an/a a e<<:9n  lan ea< 8n6. Ia, ne /e6 / 8 e, /el/6 8 na el<:9n /e< e /ae 6eCe 0a <5:e  la5 e 05a98/e 0 an9a. L/e e < 0a a$blantn pne$oni) a  0a n?e9/e 80<6ane 5ae</a:a /e 8 n: >ne6n  el:n8Cen/e ZT ne<6ala. I n;5< /e (P3A4 en0:a. K.I$D#1ICI$ Kln>a:9n n;5, a e:/ n8 ln. Me;an0a: /e>n9 <5:a  en0:ae na6a9/e. Ga:9n <0 6an/8 :e:5a:9na  :a<l>a. Nan <589/a /e >5a:9n <la0 :ea5l0a: 8 /e<, :ea5l  ne<:/en/en l/e e el:na:9na /e l/een/e e=; n?e9/a 80<6an; anae<5:a 8 !acteroi#es. Kln>a:9n /e < a 0a:/ena 0a gra$ po&itivne koke8n6 /e <6 06an5ln@ na :e9ln a<>a 8 a9/enaa a 5le:a <an; 0alaa / 8 ale<@n na en9ln. O6a/ l/e /e 8n6 <6 ne$ocstis )iroveci   < e 8 :5na9/ a <:ea:n: 0a l/een/e toksopla&$e 6e0ane a AID%-:. Tn ln>a:9na /e @a<nenalna <a9/a,  na C, ne8<en/a, =een/e /e??9lee8>:e:56a /el6an/e >8Ce ne@ l8C6 5a l/eaan5 8na. An5ae</a 8n6 /e <6  pne$okoka ko)i s re&istentni na penicilin% " i "% re&istentne .(aeci$ E.?ae9al /e n<0n <:. %a, 9l<na, >a0ea:a, nen8le0>n; n;5
1")

.I$'".ID P<6 > n6/e @<8e an5aoksazolidinoni, lne0l> /e 8n6 <6 gra$-po&itivni' koka,  n; / 8 e 6eCe na /e>n6en :/e na ?=  !+% >/e>n9e,  a na 6e0n :/e. D8an /e 8  :8n8<:<:: > a9/enaa / 8 <l n;5
17+

4+.POGLAVLJE ) AMINOGLIKOIDI An5ae</ >/el6an/e U l/een/8 5ae</; n?e9/a a an59:a, 9naln 8 08@ /e :@8e. Ia, n 66 8n6 ne; an5a, 8 a:n@l0>a, a e n9e MI(, a:n@l0> 85/a/8 :n@ 5/e /e n/;6a 8n6 n 66 6na  6 MI(,  ne6na  n9ea e >@ne MI(. A:n@l0> ađe< :a/8 an5 8na, aa6 >a n/;6 8na 85/an/a e naa6l/a nan = n9ene na n8l8. %8la>n :e, a:n@l0> 8 8n6/ a>a e <:/ene 8 /e>n/ 6el/ >0 ne@ nel :al; >0a. Tn a:n@l0>a 6  <n/ n9ene 6ele >0e. O6 n9e 8 5a0a 0a  /e>n>ne6n >0a, = /e 6=e 8n6  :an/e n ne@ 9naln >0 8 <88n: 6e0a:a. On 8 la589/8 <0 6a  ne <la0e <6-:0a 5a</e<8. Gl:e<8laa /e <<9naln la /e 2-3 aa. D0a e :a 5 e </ela na a8:8la9/a. P0e. a 9nalne 0ne6n, 6<=na n9en>ne6n: >0/el6an/a A:n@l0> 8 bakteriocidni n;5< ne0e <ena. N/;6a e<:ea5ln <0 ann8 :e:5a e :Ce /aa n;5<:a ne0e anne /ene, = /e 5a0a an5ae</@ ne<@0:a. Un8a< an9e, a:n@l0> e 6eC8 0a =6 >/e>n98 <5:a  :ea/8 ne08 <ena na 5aa na :RNA 3 n;5 ađe< =e8/8 l:aln8 <88<8, =
171

Me;an0: a, /e< ne :@8 < <0 :e:5e, @6 > @a. O6 en0: 8 e na6enla9/:, a9ela9/: l ??<la9/:. In>6>8aln a:n@l0> 8 an, n; a:n@l0>a leC 8 n/;6/ a6n <6 6a. 7entamicin9 tobramicin i amikacin 8 6aCn l/e6 0a l/een/e 05l/ne n?e9/e 80<6ane aerobni$ gra$-po&itivni$ bakteri)a$a%  popt .coli% nterobacter% /lebsiella% rotes% rovi#encia% se#o$onas i erratia. O6 a:n@l0> 8 8n6 <6 /e6a .in(len&ae% ora+ella catarr'alis i 'igella, a n8 l/e6 05 e <e 8 :5na9/ a 5ea-laa::a. Ka>a e <e a:, n8 86/e 8n6 8 l/een/8 n?e9/a 80<6an; @@ađa a>a e a:n@l0> <e 8 :5na9/ n;5<:a ne0e anne /ene. Na <:/e<, <e e 8 :5na9/ a en9ln:a 0a l/een/e e8>:naa, le</e  ene<a. treptomicin 8 :5na9/ a en9ln: /e 8n6 8 l/een/8 enterokoknog kar#itisa. O6a :5na9/a e < 0a l/een/e tberklo&e% kge i tlare$i)e, al a:n@l0> 8 5n 8n6 0a 6e n?e9/e. #mikacin e < a /e :95a9e<8: 85e<98l <8@ l/e6 ne >/el8/8. 5@ n neomicin i kanamicin e <e a: aln l 8an  0a aln8 <:/en8. $etilmicin e < 0a l/een/e 05l/n; n?e9/a 80<6an; 5ae</a:a /e 8 e. pektinomicin /e a:n9lln an5 <>an a:n@l0>:a. Je>na <:/ena :8 /e a 0a:/en l/e, <:/en/8/e e nna >0a 0a l/een/e gonore)e, > a9/ena / 8 ale<@n na 5ea-laa:ae. Ne / <Cna
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Tn On * l8=n l 6e58la:a  :Ce 5  6e58la8 8 n9n /e< /e <:/eena ?ealna n. Ne?<n * /e 8 5l8 a8ne 858la a</; a9/enaa  n; / 6a * a </e>a, a 80a:a a:n@l0>a  :Ce a9/enaa, a nan >e<:a > 5a /e <88/8 l/e:. Ne:9n na/e=e 80<8/e 6e neCel/ene 8ne.

173

4!.POGLAVLJE ) SULFONAMIDI, TRIMETOPRIM I KINOLONI %8l?na:>  <:e<: 8 an:ea5l / 8 ele6n n na :<<@an0:e /e< :ea/8 ne08 ?laa. %8l?na:> e  >al/e <e n>6>8aln, a /e a a <:e<:: 80<8/e e6en9/8 n;59/8 ne0e ? laa. Re08la /e ne<@n >/el6an/e <6 =<@ e/el6an/a, / 8l/88/e  ee a@ene. Re0en9/a e /a6la na a</e l/e6e 8 6/ @<8, n n6/ ?l8<nln :a/8 /= =< ea< >/el6an/a. #$T#7$ITI F.#T# Kla?a9/a  ?a<:anea Ana@n ?laa / e <e 0a l/een/e n?e9/a 8 8l?na:>, / n;58a0e >;><?lne elne. %.F$#1IDI * 8 la5e elne / 8 lne <88<589/a <0 6a, :ea5l0a: 8 /e<, 0l86an/e ne<:/en/en@ l/ea  a9ela >a 5 e :an/ <0 alCen/a. %8l?na:> e la?9/el8/8sulfizoksazol, n/e>/el8/8sulfametoksazol,  >8@>/el8/8sulfadoksin. %8l?na:> e 6eC8 0a <ene la0:e na :/e @>/e e 6eCe 5l<58n  ><8@ l/e6. T0I1'TP0I1 * 6a/ l/e /e <88/el6an/a %ULFONAMIDI * 8 5ae<a n;5< ne0e ?laa. Ka an:ea5l PABA, n 8 :e6n n;5< >;><e/el8/8 a 8a <0la0 0 n/en9e >a a69 ne <06>e ?lae ne@ ; :;><?la 8a0e / <?lne elne. Bae</a >;><?la 8a0a /e !++++ 8a /el/6/a na n;59/8 <:e<:: ne@ en0: a6a9a. KOMBINA(IJA TRIMETOPRIM-%ULFOMETOK%AOL * a>a e 6a >6a l/ea <e 8 :5na9/, an5ae</a ne<@/a /e e ne0e ?laa. O6a :5na9/a /e bakterioci#na <6 /el/6; 5ae</a. Re0en9/a 174

Re0en9/a na 8l?na:>e /e ea  :. Re08la /e :an/en/a 8n8a<anne a8:8la9/e l/ea, 6ean@ 6a;><ee. Klna ;><?la 8a0e /a :a :an/ a?ne 0a l/e. Klna <:/ena %.F$#1IDI * 8 8n6 <6 gra$-po&itivni' i gra$-negativni' organi&a$a% kla$i#i)a i nokar#i)a . %e9?n lan6 @<8e 8l?na:>a e <:/en/8/8 ><8/: <8a:a 0a >na6ne n?e9/e 8<na;><?la 8a0e l8 ?lna elna T0I1'TP0I1-%.F1'TK#".(TP1-1") * 6a :5na9/a l/e6a /e 8n6a  :8n8<:8na 0a a9/ene / n8 5n 80:a l/e a 'e<en06n * ale<@/e a  al; e:/ ln; l/e6a. E?l/a6n >e<:a, n>0n la<e<, %e6en-J;nn6 n><: e /a6l/8/8 </e. Ga<nenalne :en/e * :8nna, 6?8n9/a  /ea. 'e:an * a 8 6 8n9 </e, 8l?na:> :@8 80<6a @ 5a /e :a/8 :an/a @l80a-"-??a >e;><@ena0e. Ne?<n * 8l?na:> e :@8 0a> :@8 0a:/en 5l<85n na <en:a la0:e,  a 6ea <0 e n6<đena> a e <e 8 0a>n/e: <:/ee/8 <8>ne. 17!

Tn <:e<:a T<:e<: 80<8/e 6>6e neCel/ene 8ne a an?lan l/e, :e@al5lan8 ane:/8, le8en/8  @:a. AID% a9/en / <:a/8 TMP-%M :a/8 6e8 n9>en9/8 neCel/en; 8naa, 8 6<89e, a, le8en/e  <l/e6a. F.%0KI$.$I %8 la?9e<6a nal>ne elne, /e 8n6 <6 6ene a@ena / 80<8/8 8<na<8@a @ene;la ne8:nae. T/el6an/a, a /aan: 8n6 <6 anae<5a. Fa<:anea %6 ?l8<nln :a/8 >5<8  a l6alenn: n:a :@8 :ea a<9/8  ><586l/ne n9e:. %:an/en/e >0e /e /el: :ea5l0 & a. Me;an0a: >/el6an/a Fl8<nln :ea/8 ne08 5ae</e DNA, n;59/: 0:e @ @8la9/8. In;59/: 0:e6a/an/e /el/en/a an9e. Fl8<nln 8 5n bakterioci#ni  <6 /el/6; 5ae</a. Ka a:n@l0>, a08/8 an5 8na, @>/e /e ne > :n:alne n;5
17"

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K<l 8 e 0a n?e9/e a /e 6a</a5lna 05@ /a6e n/ >0 8 e <l a 0a:/ena 9e?<an8 l 9e?:8 8 @n:->ne6n  ne8<enn; a9/enaa. Tn Ga<nenalne :en/e 8 na/e= neCel/en 8na. Fl8<nln :@8 80<6a e na C, @la65l/8, 6<@la698, nean98, a5n<:alne /en  <88<8 e6e. P/a6l/8/8 e <8ne n?e9/e a (.al59an  /e98  <8>n9e /e< 80<8/8 =een/e ;<a69e 8 8C8/8 ZT ne<6al. T8Cen: ZT ne<6al:  n / <e ><8@e l/e6e / <>8C8/8 ZT ne<6al.

177

4$.POGLAVLJE ) LIJEKOVI KOJI DJELUJU PROTIV MIKOBAKTERIJA L/een/e n?e9/a 80<6an; a M95a9e<8: 85e<98l, M.le/el6an/a l/e6a 2 8@a 5 e n l 5ae<a, 6n  n9e@6a. I"$I#"ID Me;an0a: >/el6an/a * /e <88n8. Me;an0a: >/el6an/a /e  ele9/: 8 aG @en8 / >a08 /a /e 8l/8ena 8 a6a9/8 0na0>a. Na ele9/: n;A @ena / >8a08 a9ln@  /e 5ae<9>an 0a 5a9le / a6n e >5< a 5 >/el6a <6 8n8a<ann; :5ae</a. Mea5l0a: 8 /e< /e  5<0; a9ela <; a9ela e8<l/ana. Klna <:/ena * 0na0> /e na/6aCn/ l/e 0a l/een/e 85e<8l0e  :nena /e 8 :5na9/ a ><8@: l/e6:a. a l/een/e laenne 85e<8l0e, n9l8>n@ n e 9n6e<e<,  0a l/8>e / >la0e 8 na a a9/en:a / :a/8 a6n8 5le, 0na0> e <:/en/8/e a:. Tn  ne /e ;eaan  :Ce 80<6a a5n<:alne /e >/e9e. I0na0> :Ce n;5 a9/enaa a :an/: @l80a-"-??a >e;><@ena0e. R/e e /a6l/8/e n><: nal l888.

17&

0IF#1PICI$ Me;an0a: >/el6an/a * >e<6a <?a:9na, /e bakterioci#an <6 M.85e<98l. 6a/ l/e n;5a e <:/en8/e 5< a<5<58/el: e :ea5l0n l/e  :ea5l, / 8 na<8@: l/e6:a. Ia, :Ce e < a: 0a l/een/e laene 85e<8l0e > a9/ena nele, l a9/enaa / 8 5l 8 na8 a 5: /a :a a6n8 n?e9/8 80<6an8 /e: / /e . U lepri , <?a:9n <:/en/en  /e>n: :/een >@ađa /a68 an. R?a:9n e < a 6an:9n: 0a n?e9/e 80<6ane a MR%A ili penicilin re&istentne streptokok  pne$oniae. Oala <:/ena /e l/een/e kliconotva $enigokoka i sta(ilokoka . Tn  ne@6< <8/ela. P6 >6a 8a /e>n, 80<8/e n><: lan @<  ane:/8. R?a:9n naCn n>89na, e<5na?na  6ana /e 8n6 a an:5ae</ l/e, 5n e  a9/enaa a AID%-:. 'T#1/%T. Me;an0a: >/el6an/a * ea:58l n;55< <580e 8 l8a/8 =een/a 585<8@: l/e6:a. Tn * na/e= neCel/en 8n9 8 6n  >0,  8 =een/e 6>a, :an/en/e =<ne 6>a, l/ea 0a 9<6en8  0elen8 5/8,
PI0#"I$#1ID Me;an0a: >/el6an/a * n/e 0na a 5ae<a 8na 0a;/e6a :ea5l8 n6e<0/8 a a0: n9A @en 8 M.85e<98l. Re0en9/a e /a6l/8/e  e >5< a<5<58/el: :ea5l08Cen > =een/a /ea  al; l/e6a <6 85e<8l0e /e 6aCan ?a< 8/e;a  5 e n. T0'PT1ICI$ O6a/ a:n@l0> e a>a e=e < 05@ na:a 8 lne al: a:n@l0>:a. RE#IM LIJE$ENJA K:5na9/a 0na0>-<?a:9n /e: >e6e:/een@ l/een/a 0l/e )!-)& l8a/e6a 85e<8l0e 80<6ane /el/6: 80<n9:a. D>a6an/e: a l/een/e e , <?a:9n, , ea:58l l >an8 0a=8 8 l8a/8  l <?a:9n.

1&+

4'.POGLAVLJE ) LIJEKOVI PROTIV GLJIVI&A Gl/6ne n?e9/e e e= l/ee, @6 > :8n8<:8n /e a: nel l/e6a 0a l/een/e e:ne @l/6ne n?e9/e. A:?e<9n B  a0l?l8na0l, n6en 0a ann8 :e:5na >a0an 8  8n6 8 ne: 5le:a a :an/: <0: n; 8naa. Kla?a9/a  ?a<:anea * A:?e<9n B /e len :a<l> / /e lan nan8. A:?e<9n e la5 a<5na l>na 8en0/a, a l>n :le, l 8 l:aln: 5l8. L/e e ><58na. Mal > l/ea e 0l88/e 0e /e /al0/el6an/a * (ngici#no >/el6an/e a:?e<9na B /e 05@ 8na na <8n  <?ln:  l?ln: 6/6:aa:?a. VeCe e 0a e<@e<l, e<l /e>n6en 0a :e:5an > na/6aCn/; >8n; l/e6a 0a l/een/e e:ne @l/6ne n?e9/e,  e e < 0a ea l/een/a </e /el6an/a,  l/e /e 05n: <:/en: an;a:na, anna, l <e<>a. K8:8la6na n * a:?e<9n B :an/8/e 5<0n8 @l:e<8la08 a <=en/e: :a@ne0/a  al/a. 1&1

Ane:/a :Ce naa 05@ :an/en/a naa/ana e<<ena. Ia 60. %:an/en/e >0e:an/a n /e :@8a > ne; n?e9/a a>a e a:?e<9n B < a ?l890n:. L:aln 5l9 a:?e<9na B :a/8 :an/ ne?<n 8na, 6/e<6an 05@ :an/en@ 6e0an/a l/ea 0a an9e 585na, e:/ lan e:e<580a : a9/enaa a =een: 585/el6an/a * ?l890n e a8:8l/el6an/e: :e:5ea:na0: 8 !-FU, 0a: 8 !?l8<>e8<>nF>UMP  ?l8<8<>n-<??aFUTP, / n;5ea:na0e. Re0en9/a e /a6l/8/e 5<0 a e < a:,  8l/88/e :an/en8 a6n @l/6n; e<:ea0a  >ea:na0a. Ka>a e ?l890n <:/en/8/e a a:?e<9n: B, l <a0la 8 @ađa e ne<@n an?8n@aln 8na. Klna <:/ena * ea< /e 80a, lna <:/ena /e @8Cene 6e n9e98. Fl8na0l  6<na0l e 5l/e 8n 0a <58@689/el6an/a * a0l :ea/8 <8n :e:5/el8/8 na 14->e:ela9/ lane<la, = e aal0
@l/6n: 9<: P4!+ 0en0::. %a 6ean/e: 88@<n8 <?la8 :8n8<:/el6an/a,  80<6an/a 6=e neCel/en; 8naa > al; a0la, ena0l e </e < 0a e:ne n?e9/e. L/e /e >8an a: 0a na >0a e9an a a:?e<9n: B 0a l/een/e a6ne n?e9/e 80<6ane a (<9998 ne?<:an. Je>na /e a:?e<9n8 B 8 an>>e:/. IT0#K$#". * 6a/ l/e /e >e, (<9998  'la:a. U e0?a@ealn/ an>>/a08, l/e /e 8n6 <6 /e6a / 8 e<:a?0a, @6 oni'o$iko&a. !0IK$#". * :a /= =< ea< >/el6an/a ne@ >e:/8, 8n6 /e <6 /e6a AID% a9/enaa 0a l/een/e e0?a@a 80<6an@ an>>:. P#K$#". * :a na/=< ea< >/el6an/a > 6; <a0la, 8n6 /e <6 6ene Can#i#a i "spergillsa. Je>n /e a0l / /e 8n6 <6  $kor$iko&a i &igo$iko&a,  < e 0a <?la8 <6 @l/6n; n?e9/a /e: e:e ;ean, @6 > a9/enaa a /e: =een/e: /ea 585e  @na>a,  :Ce >6e > @ne:a/e, nen. Oal a0l 8 6=e ele6n n;5< @l/6n@ 9<:a P4!+. Ia </eđe 80<8/8 en><n8 >?8n9/8, al a0l :@8 80<6a nene <:/ene, 8 0 a:8en/a 6>a, > 3+ a9/enaa. Pana0l n;5
1&3

'*I$K#$DI$I Kapsofungin /e e;nan>/, <6 > 6e n6/e @<8e l/e6a <6 @l/69a. Oal e;an>n 8 anidulafungin i mikafungin. K<e e n<588C, > an>a?8n@na /e 24-4& a. Me;an0a: >/el6an/a * e;nan>n :a/8 /e>n6en  (ngici#no >/el6an/e, n n;5 a9/enaa / ne >@6a8la?8n@n e < 0a e0?a@ealn8  n6a06n8 an>>/a08. M?8n@n e < 0a :88an8 an>>/a08  0a <?la8 n?e9/a (an>>e, > a9/enaa / 8 Ce n9ena a 9l<n: :Ce 6ea /e<58/e e 6eCe 0a e/el6an/a * @<0e?8l6n :ea ?8n9/8 :<858la 8 #er$ato(iti$a   n;5e<:a? 8ne l/e 9e<:a?0e Ce  e, al /e 8 0a>n/e 6</e:e 0a:/en/en e<5na?n:  a0l:a. NeCel/en 8n9 8 @la65l/a, n?80/a, @a<nenalne <a9/e, ?en06n, <:/ene ?8n9/e /e
1&4

T'0/I$#FI$ Me;an0a: >/el6an/a * e<5na?n n;5a9/8 6alena. U0<8/e a8:8la9/8 ne n9e8an /e 0a 0na 8n6 a  nn80an /e>an, a >:< < /e>na. Pn 8l0n/a n69a. Taln 5l9 e <e 0a e<:a?0e. TOPIKALNI LIJEKOVI A LIJE$ENJE POVRIN%KI' GLJIVI$NI' INFEK(IJA Vel 5</ l/e6a e < aln 0a 6<=ne n?e9/e 80<6ane (.al59an  >e<:a?0e. $istatin /e len an5n @>a n?e9/e  < e 9/8 @a<nenaln; @l/69a > :8n8<:<8@.

1&!

4(.POGLAVLJE ) ANTIVIRUSNI LIJEKOVI Ka 5l@an 8n8a<ann a:ana. An6<8n l/e6 >/el8/8 na nel ?a0a 8 <ena,  8 0a>n// ?a0 an. %ele6na n an6<8n; l/e6a 6  6e/ /el/6  n;59/ 6<8n; en0:a ne@ na en0:e an9e >:ana. Na/6aCn/  8 l/een/8 6<8n; n?e9/a, @6 0a n<l8 'IV n?e9/a /e 86đen/e :5na9/e l/e6a. O6 e :an; na0a 8 6a< /e n;5/el6an/a * a9l6< /e anal@ @6an0na / /e 8n6 <6 'erpes si$ple+ virsa,-1%-2 i varicella-&oster virsa,:. O6a/ l/e e a66a nana. D/el8/e a :e6n 86> > e<:na9/e lan9a nan 8:ean/a 8 6<8n8 DNA. *slika49-3 Re0en9/a '%V-a 8l/88/e <:/ene na 6<8n: DNA l:en na0e, en0:a / /e 8l/8en 8 en8 ??<la9/8 a9l6ne6ne >0e. I0l86an/e 5850a e : a9/enaa a =een: 585 AID%  :8n:<:5< le< ael</, 
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7#$CIK.!I0 Me;an0a: >/el6an/a * @an9l6<, >e<6a @6an0na, e <??<ln-na0e 8 5< e ><58na l<8@; (MV n?e9/a > :8n:<:?8n9/a /ea e < a 0>68>n: l ><8@: :/el8ne n;5n a n;5<:a 'IV <ea0eIP. Va6na an6an/e: 5le. K> :n@; AID% a9/enaa, 'AART 8en9/8 <8n; n?e9/a. $%K.'"ID$I I$*I/IT0I 0'!'0"$' T0#$K0IPT#"'($0TI) a n6e<0/8 RNA 8 DNA, 6l/n a @8:ana 8 <??ae,  n>a :e6n n;5n; n8le>a na lan9a < @<8e na <en8 <50e, ne:@8e /e 6e0an/e l/e>ee@ n8le>a. Re0en9/a naa/e 5<0 a>a e NRTI <e a:, 5<8  12-24 aa. 'IV 6/e > < 6 ! a9/enaa e /a6l/8/e ?aalne. D<8@

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neCel/en :: 8 6<89a, @a<nenalne :en/e, Cn !+ a9/enaa. M@8e 6=ene 0e /e  a9/enaa a =een/e: 585n /e @8/ee. "ID!%DI$ * anal@ >e:>na, a6an /e <58a9/:  0l86an/a 5850e /e  a9/enaa a =een/e: 58568>na /e 86n a al: :8n86> > ane:/e  ne8<en/e, /e 0a;/e6a/8 5na <:/ena <5ene9>a, ?enna, :ea>na, ?l8na0la, 6al<ne elne l la:68>na :Ce 6 n9e68>na. R?a:9n 6ea6a l68>na. NRTI  laktatna acidoza * NRTI l/e6, a: l 8 :5na9/ a al: an08  e=8 ;ea:e@al/8 a ea0:. R0n ?a< 8 8Cen l/een/e a NRTI, /ee =een/e /e l/een/a a NRTI > a9/enaa a 6=en: n9e<8@a/e :/e na n l/e6 ne 0a;/e6a/8 ??<l0a9/8 >a 5 5l a6n  ne na/e8 e a n8le0>n: <??a:a. Ne:a <Cne n: >ne6n /e< :a >8@ l8C6 4+-!! a. Mana ;?8n9/a (N%-a,  na C 3+, 6eana n9en, @6 8 <6: <:/ee/8 /e< 8 aCene ?ealne a5n<:aln > C6n/a. I$*I/IT0I P0T'#"#(IP) O<@an0a9/a n?e6n; 'IV 6<na /e 6na > aa<a <ea0 'IV-1 <ea0 /a /e >0a/n
6=e<8; :8a9/a l @ena e@ <Cne /el/8/8 8 ne0n: >ne6n. Oa 5 e @> 12 a. L/e <>0e 0a06a/8 <>8Cen/e ZT ne<6ala. Ja /e n;5< C i C50e /e  a9/enaa a =een/e: /ea 8 la0:. L/e6 / 6ea6a/8 a6n C ann68l06, <?a:9n :an/8/8 n9en, e<<:9n 68/8 n9e<na5nla, ena0la, n0na, <?a:9na. Ne >0e <na60a. Una na :ea5l0a: 8@l/;>a * <:/ena IP 8 'AART 6> > a, 05@ n;59/e <ena / e, / :a/8 a6na :/ea lna 'IV <ea0a:a. O6a/ n><: 8l/88/e ;e<@le:/8  e:/8,  <:/en8 ><589/e :an@ 6a. M@8 e /a6 ><09e<6aln na8l/an/e :a, @ne:a/a, <: e /a6l/8/e > 3+-!+ a9/enaa, @>n8 >ana nan ea l/een/a. I$*I/IT0I %.#K# !I0%# % T#$IC% 1#0#!I0K * 'IV-1 n?e9/a n/e 6e0an/e: 6<8ne 6/n9e 8/8 an@ene 8 :a<?a@a  >en<n; an9a. Ve0an/e 5<8 >589/8 <0 6a. Vena l/ea&+ e 0l88/e l9:, :al > 8<n:. %80a :
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689na, 6eCe e 0a ne@:ana. L/e e :ea5l0a9/:  ne ne89a @>. Re0en9/a naa/e 05@ /e>ne :8a9/e, a e l/e :<8@: l/e6:a. NeCel/en 8n9 8 <l/e6, :8nna, :a@l9a, @la65l/a,  6=ene /el6an/a * 6 l/e6 8 n;5< ne8a0e /8 <06>e in(lenca " i !,  /el8/8 /el6an/a, 6 l/e6 a0a:a, al /e <6; ::a. A e 80:a <?la, ela:6< 0naa/n :an/8/e n9>en9/8 n?l8en9e. M@8 e /a6 @a<nenalne :en/e a ela:6<: 0ana:6< 80<8/e a=al/  /ea/ nela@>e 8 @89 a:an; a9/enaa.

1)+

.I&'K!I P0TI! *'P#TITI# L/e6 0a l/een/e n?e9/a 80<6an; ;ea: B'BV 8 spresivni , a ne l/e6. P<:a/el6an/a * IFN- /e 9n / >/el8/e :ana,  6ea6a a6n Jan8 na0a. O6 en0: ??<l:ana /a <<en <l0e 8 585n. Pe@ln: /e>n. Klna <:/ena - IFN- e < 0a kronični !  a: l :5na9/ a ><8@: l/e6:a. Ka>a e < 8 :5na9/ a <5a6<n:, na6an/e a8n@ '(V 8 <nn e :an/8/e. Pe@l an>a<>n@ 5la 8 '(V-8. Oale <:/ene IFN- 8 0a l/een/e /aposi)eva sarko$a% papilo$ato&e% i topikalno &a genitalne bra#avice. Inee:na9/8 ;e<e 0e a9/enaa a 89e (MV ;e>>n@ a?e< <:, ne8<en/a, <nna la5  :a/a, ale9/a, ?8n9/a =n/ae, n?80/a, e=a >ea9/e 8 a8:8ne 5le, ana:ne0a <an; a<:/a,  <8>na.

1)1

+*.POGLAVLJE ) ANTIMIKROBNA SREDSTVA 1'T0$ID#". Me;an0a: >/el6an/a * metronidazol i tinidazol 8 >e<6a :>a0la / 8 8n6 <6 <0a  5ae</a. O6 l/e6 <la0e 5a6a9/8 89/: n/;6e n< 8ne ?e<n: <8na 8 anae<5n: aa0l  n>a0l 8 8n6 <58na8 a 8 <6. Me<n>a0l e :Ce <:/en  n0a e : a9/enaa a =een/e: /ea0l :a >8C l8C6,  0a e :Ce <:/en /e>n: >ne6n. Klna <:/ena * a an5ae</ 6, :e<n>a0l :a na/6e8 8n6 <6 !acterioi#es i Clostri#i$. L/e /e 05:naln: n?e9/a:a  a9e8 :0@a. Tn>a0l :a lan 8na <6 anae<5n; 5ae</a. Me<n>a0l e <  <6 n?e9/a 80<6an; a ;ar#enella vaginalis  9a. Ka l/e <6 <0a, 5a l/ea 8 8n6a <6 tri'o$oni)a&e% giar#i)a&e% intestinalne a$ebi)a&e i )etrenog apscesa a$ebo$. Tn * neCel/en 8n9 8 @a<nenalna <a9/a, @la65l/a, a:n 5/en/e 8<na. TeC n 8n9 8 le8en/a, :a@l9a  aa/a. M@8 e /a6 <8ne @l/6ne n?e9/e. Inea0l: 8 >8l?ne, n <>8 Pe8>:na ?l89 a9/enaa  :e>9n@ 5l/a. Tn * laln 6<5eC  e9an/e 8 e. MCe 80<6a , e<e:  nan >e<:a.

1)2

+2.POGLAVLJE ) LIJEKOVI PROTIV PROTOOA METRONIDAOL I TINIDAOL Fa<:anea * :e<n>a0l  n>a0l 8 8n6 5< e ><58a0la /e "-& a, a n>a0la /e 12-14 a. El:na9/a /e /el6an/a - l/e6 <la0e 5a6a9/8 89/: n/;6e n< 8ne ?e<n: <8na 8 anae<5n: aa0l l n>a0l 8 l/e6 05<8@8 e:a. T8Ce a :e<n>a0l:. Me<n>a0l /e l/e 05a0l /e 8n6 <6 <@an0a:a / 8 a0l. Oale lne <:/ene :e<n>a0la 8 l/een/e giar#i)a&en>a0l /e /e>na 8n6,  n?e9/a 80<6an; a ;ar#nerella vaginalis i anaerobni' bakteri)a,!.(ragilis% C.#i((icile. Me<n>a0l e < 8 :5na9/ a ><8@: l/e6:a 0a l/een/e @a<nenaln; 8l8a 6e0an; a .plori . Tn * neCel/en 8n9 :e<n>a0la 8 @a<nenalna <a9/a a e 80:e a /el:, @la65l/a, aa0l :a lne neCel/ene 8ne, al e la=e le<ne  >/en/a.

+3.POGLAVLJE ) ANTI%ELMINTI&I #./'$D#". Me;an0a: >/el6an/a * >/el6an/e al5en>a0la /e a>n/ 5le  anl:0, a ovici#an 8na 8 aa<0, anl:0  <;8</a0. Klna <:/ena * al5en>a0l :a =< ea< >/el6an/a. P<:aa0l e <  0a 'i#ati#n bolest   8n6 /e <6 cisticerko&e. Tn * al5en>a0l :a :al neCel/en; 8naa 05@ ana. Ia, < >8C/ <:/en :@8 e /a6
1'/'$D#". Me;an0a: * :e5en>a0l >/el8/e ele6n: n;59/: ne0e :<858la  8na @l80e 8 ne:a>a. Klna <:/ena * <:a 1+ l/ea /e a<5 e 5<0 :ea5l0n 6ea6a. Tn * < nC: >0a:a 8 @a<nenalne <a9/e, al < 6: >0a:a 8 a@9n 05@ ea aa  9e>a = /e /el6an/a / 8l/88/e n?e9/e tre$ato#a$a i cesto#a$a. L/e /e 05a e < a niklosamidom, a a alea0l8 0a l/een/e 99e<0e. Fa<:anea * a9/a 0 9</e6a /e 5<0a,  l/e e :ea5l08e. Tn * e neCel/en 8n9 8 @la65l/a, :a@l9a, la5  </eđe @a<nenalna <a9/a, , 6<89a. Ne8<l= 8n9 :@8 e /a6 < l/een/8 ne8<99e<0e, 8 n:a :an/8/e <0 eC; 9/el8/e n;59/: >a9/e ??<la9/e l a6a9/: ATPa0e. Klna <:/ena * nl0a:> /e aleaenia saginata% svin)sko$ trakavico$,>.soli$ i ribl)o$ trakavico$,?ip'llobot'ri$. B<0 8n=a6a >
<6 cri)evni' $etil)a. Tn * neCel/en 8n9 8 5n 5la@, a 8l/88/8 @a<nenalne :en/e, @la65l/8, , 6<898. Ne > 6; 8naa 8 05@ a<9/e an@ena a/8; a
1)4

+4.POGLAVLJE ) LIJEKOVI A LIJE#ENJE LOUDNI% BOLESTI Ke:eal/e n<@anan > ?a<:al@/e. U /e>n8 <88, 8en9/8 0l/een/a > 5le, /a 5e0 e:e >/e9e, @n6 l:?:. U ><8@8 <88, ne 5l9 @6a8ne l/e6e. Dal/e, a @<8a, l/e6 <6 0l8>n; 5le 8 n/ > 6; al; l/e6a,  0a e n/;6a n : na >8n; l/e6a 8 9n na 6e an9e /e e >/ele, an9e<@ene  n<:alne. Kn9e >/el6an/a  lne <:/ene l/e6a <6 0l8>n; 5le. Ne > 6; l/e6a >/el8/8 specifično na pojedine faze staničnog ciklusa, a ><8@ bez specifičnosti djeluju i na stanice u fazi ciklusa i mirovanja a 8 an9e 8 ?a0 9l8a /el/6/e. L/e6 / >/el8/8 na ?a0e 9l8a, 8n6/ 8 8 e5n: ?a0a:a. *slika54-2 O5a a l/e6a 8 e5n 8n6 a>a 6ela <<9/a 8:<; an9a a /e ?/el8/8 a 8 :=/e: :>el8 le8e:/e. U 6: e:8, 8 /e: 6e an9e <la0e <0 ann 9l8, >ana >0a 85/a nann8 ?a 6elna 85/en; an9a ne 5le, /e 5n 0:eđ8 5</a 8:<; an9a  0l/een/a. *slika54-1 Mae:a :>el 8a08/8 >a 6ena l/8>; l>n; 8:<8@; ?an; 8:@6< na e:e al;><?la 8a0,  6eana ne0a 6@ en0:a 8 :e;an0: n; 5le * 6eana a6a9/a en0:a / na6n; 1)!

an:ea5la. %:an/ena a8:8la9/e l/e6a * 6a/ 5l 89/a e:ene 5le  0a 80na6ale l>ne 8:89/a :Ce 0l/e :al 5</ a9/enaa / :a/8 80na6al8 :eaa8 5le l:?:, a8na :/elna le8e:/a, <a<9n:, 8 6en l8a/e6a 9l/ e6an/a 8:/86anna e:e/86anna e:en; 8:>aa 0a lalne <9e>8/a9/e. (l/ e :an/en/e <0a laln@ l e:n@ 6/el8/8 na ?a0e ann@ 9l8a  n; / n8 e9?n :Ce 5 9na 0a an9e /e e >/ele  ne /e :<8/8. O6 <n9 8 5n 8 >a5<8 <:/ea e a: < <6 >/el6an/a 3<Cna 6> > 8<Can@ 6e06an/a 5a0a, a5n<:aln@ a<6an/a, l:a DNA lan9a. Re0en9/a 8:<; an9a /e 
1)"

CIK.FF#1ID Fa<:anea * 0a a6a9/8 6@ l/ea a. 'e:a naa/e 05@ a<lena,  :Ce e ?8n9/8, l8n8 ?5<08, n8?9/en9/8 na>585e. TIT'P# * < e 0a karcino$ #o)ke% )a)nika% povrinski karcino$ $okra@nog $)e'ra . NeCel/en a8n 8n9 :8nna  6<58@en: 6a<:a  ana@n 8 ?lne elne :ena ?l8<8/el6an/a  ;><?la 8a0e. O6a/ 8na >6> > :an/en/a ne0e :>laa, 8<na, a:nelna,  a :ea :ea5l0a: n8len; elna  <ena. *slika33-3 %6ae<6aa /e 6aCan 0a 9n 8na :e;><?la 8a0e,  :an/en: 6a5<8 ><589/8 <0 6a, : 8 (N%. Me@6a
1)7

Klna <:/ena * 8n6 /e <6 koriokarcino$a% koriokarcino$a% aktne leke$i)e% non-o#gkinova li$(o$a% pri$arni' C li$(o$a , 6el@ 5</a l>n; 8:n a<<  en8 <8>n8. Tn * e neCel/en 8n9 8 86e > ;ean, l8ne ?5<0e. 5-F.%0%0#CI.(5-F%) Me;an0a: >/el6an/a * ?l8<a9l e 8 an9a:a n6e<e8<>n!:n??a !-F>UMP, / n;5la na08  >6> > 6> > :< an9e 05@ :an/a :na. U:ean/e F>UMP 8 DNA n;5 8:ean/e ><8@@ :ea5la !-?l8<8<>n-!<??aFUTP !-?l8<8<>n-!<??aFUTP 8 RNA :ea <9ee  ?8n9/8 RNA. Re0en9/a 8:<; an9a naa/e :an/en: a6a9/: !-FU, 6ean: a6n :>la na0e,  :an/en/e: /el/6 en0:a na l/e. Fa<:anea * a>a e <:/en n5< ><58<: =aa-al. K#P'CIT#/I$ Me;an0a: * ae9a5n e :ea5l0l/e /e / e >5< <: =aa-al. R/eđe > ?l8<8e9>na / e n6e<??ane  <??ane n8le>ne 5le. Ge:9a5n >??a n;5-8a08  a :an/8/e ln8 >e<5n8le0>n; <??aa 0a ne08 DNA. Ge:9an <??a e :Ce 8:en8 8 DNA  a 0a06a  lan9a. Fa<:anea * el:na9/a /e 
Klna <:/ena * 5 /e >56al@ a<9n:a @8=ea e < 0a l/een/e sitnostaničnog sitnostaničnog karcino$a pl@a% karcino$a $)e'ra% non-o#gkinova li$(o$a. Tn * > 7+ a9/enaa /a6l/8/e e :8na  608. #$TIT%10KI K'1T'0#P'%TICI P0I0D$7 PD0I&'T.# O6 l/e6 <<>n@ ></ela 8 speci(ični &a po)e#ine (a&e staničnog ciklsa. !I$K0ITI$ Me;an0a: * 6na alal> 5l:e<58@đen e :@8 /a6 e<?e<: nea>e6ane e8n/8 :<858la 8 :n:e ! a9/enaa. O>@đena n /e :/el8
1))

'TP"ID Me;an0a: * e0>, l8ne >e<6a >?lna, n>89 :a !+ 5@đen :/el8n<8; lana9a DNA. Fa<:anea * el:n@đen :/el8/el8/e 6a ane ale. Bl8 e 0l88/8 
Tn * a8n 80<8/e :8nn8  9<6en 8<n. O>@đen :/el8n /e a8na 8 5l8 a<:/e  0 * a<>:a/a a 0aa/en/e: <9a 05@ 6an; ala. MCe 0a06a e<e:  l/8=en/e na :/e8 e
0#"$I .I&'K!I "# .I&'3'$&' ".Q%D$I* T%10# I1#TI$I/ * I1#TI$I/ * /e n;5< <0nna0ne >:ene 59<-al5 n<ena  a </el: 0 <:59a PDGFR  :5en el;a <::a, gastrointestinalni' gastrointestinalni' stro$alni' t$ora . Tn a8n 8n9 8 :8nna  6@đen e, <l/e6, :al@/a, 0aa/en/e <9a. C'T%KI1#/ * C'T%KI1#/ * /e :nln <8/el <6 06ananne >:ene e<:aln :5en @6< na e:eee8@<n ne<9/a l8na 5le, 8:<, ;:a@ne0/e:/a. /'!#CI"%1#/ * /'!#CI"%1#/ * /e :nln <8/el /e e 6eCe 0a :5en ela VEGF  @đen 8 a<e</ <:5e:5l/ <:5e:5l/ >@ađa/, :la9/e 9/el/en/a
2+1

++.POGLAVLJE ) IMUNOFARMAKOLOGIJA IMUNOFARMAKOLOGIJA Ia /e :8nn 8a6 een9/alan 0a 0a=8 0 a=8 <6 a@ena, 8 ne: l8a/e6:a /e naCan >e<86an :e;an0a: / n 6=e 0la ne@ >5 55a96an/a n/e 6</e:e e a/8 <ene 8 :8nn: :e;an0:8. U ne: l8a/e6:a, a l/e6 /aa6a/8 :8nn >@6<. IMUNO%NI ME'ANIMI K<e 8lađen >/el6an/e :le:ea, ?a@9a, NK an9a, 8<đena :8n n/e 5a /e 8<đena :8n ne>6l/na, :5l0 a6a9/e T l:?9a anna :8n,  6a6<e l:?9a / 8/8 /el6e :8nn@ >@6en?9en?9?e 9n T l:?9 :a/8 (D&. An@en e /e :@8 nM'( >6<e I  II. A6a9/e T ' an9a /el6an/e  :8la9/; :8la9/; :le8la. %anna :8n * a66/e >6<e :n; T l:?9a, T '1  T'2. T'1 an9e <@an0@đene e na M'( 1 :le8la:a na 8:<: an9a:a l an9a:a n?989/el8/8 na lan nan. '8:8/8 ;8:a e l:?9 B 6eC8 0a an@en e 8 e>e 6e0ane 0a M'( II :le8le, / 8 na 6<=n l:?9a B. Ka>a e :lea, n 0l88/8 ne89?e@6< * 8l/88/e e?9/en9/8.

2+2

I1%$%P0'I!$' T!#0I P<:a <e<>a > an:ea5l; an8:<; l/e6a > l/e6a /e ele6n 9l/a/8 an9e :8nn@ 8a6a. K0TIKT'0IDI Me;an0a: >/el6an/a * @l8<> >/el8/8 na 6=e :/ea na an9  :a/8 8na na 8alne  :8nne <9ee 3).@la6l/e. Na 5e:// na, le8<ena, 9na  al; @naln; :le8la /e 8>/el8/8 8 :8nn: >@6<8. Na ann/  n;56<e T l:?9a. Ia @l8<> 0naa/n =e8/8 ann8 :8n,  ;8:9n: an/:a / 8 >l0 :a/8 neCel/ene :8nl=e a9/enaa / <la0e <0 585e, n;59/a /el6an/a * 6 :8n8n/8 9na /e: >@6@6< T an9a na 9ne, 5e0 8/e9a/a na <06>n/8 9na. %<l:8 n;5n/8 <8/ela. Klna <:/ena  ?a<:anea * <:/ena 6; :8n8n; <@ana. K<e e 8 n; <@ana  0a  <:ael/a al@enn; :an; an9a. O6 l/e6, @6 9l<n  a<l:8, e <e 0a nee a8:8nne 5le, 8 n@ a<<a, 86ea, </a0e, a:e  >a5eea a 1. %en6 8n 8  <l:8 /e 2+3

>8an a: 8@ l8C6. Na n/e@6 :ea5l0a: 8/e8 :n@ ><8@ l/e6. Tn * 9l<n  a<l:8 :a/8 lne ne 8ne. Na/e= neCel/en 8n9 8 >?8n9/a 585e:/8, lel/a08. %<l:8 e=e 80<8/e ;e<<@l9e<>e:/8, ;ean, <l/e6  :/el8e;><@ena08, en0: 8 >e n6 ne0 @6an0n <??aa GTP. O6 >/el6an/e 8/e a6a9/8 l:?9a B  T. L:?9 8 e5n /el/6 na n;5e n6 ne0e /e< :a/8 :an/a en0:a 0a ale0a:a 9l<na :an/8/e ne?<n 05@ 9l<na. Tn * 6a/ l/e 80<8/e @a<nenalne :en/e  :/el8a6n l/e, 0na  6: e89/e TNF-, 6ean/a 6a;e0/; :le8la, /aan/e anne :8n. Tal>:> e < 0a :8ll :/el:, <:al/e :e<a8<na, >/el8/e a an:ea5l !4.@la6l/e. D5< e a0a @a /el8/8 9n na a6n a<<. en 8n9 8 :/el80a:a Cn , 6<89a, :8nna  6
2+4

1$K.$K# P0T%TI&'.# Mnlna <8/ela MAB :a/8 n 6ele e9?n /e< e :@8 n: :le8l:. '8:an0a9/: :=/; :nln; <8/ela  ;8:ana <8/ela :a/8 :an/ <0 6a5a96an/a 0a:a,  ne8<;/a</e  /e>n98 IL-2 5a96an/a na n: > la9e5a. /aziliksimab /e :e<n I@G a >/el6an/e:  /e>na: >al08:a58. I$F.IKI1#/ * 6 ;8:an0;e0/; :le8la 8l/8en; 8 a6a9/8 le89a. %:an/8/e @6an@ a<<a. Tađe< /e 8n6 0a l/een/e 8l9e<0n@ la, anl0la  </an@ a<<a. M@8 e /a6 n?80/e n@ a<<a. /'!#CI"%1#/ * ;8:an0ela VEFG,  n;5
2+!

+'.POGLAVLJE ) #ESTI TOKSI#NI SINDROMI [TABLI(A!&-4, 5e0 >0a P#0#C'T#1. * 8 e8 <6an/a 5e0 ::a l a 5la@: @a<nenaln: :en/a:a, nan >6a >ana /a6l/8/e e =een/e /e0a:a /e e 0ln, /ea/ na>:  5la@an/a. P< 6e: >0a:a ne:<, 80ne:/a. P<>8Cena :=na ;ee;>n/e :l0  ;e<e<:/, /a 0a06a =een/e :0@a, a@8la/8  585<: e a/ > 9<6enla, ;e<e<:/e, 8;; l80n9a ne:a 0n/en/a, 0a:a@l/en 6>  9lle@/a, n?80/a  >el</, n8na a;a<>/a  :></a0a. T<0an/e :=a, a</; :8=a/el6an/e: e<?eea 6a0>laa9/a, nan 80ne:ena-<>8Cen/e ZR%, <>8Cen <6đen/e, a<:/e. L/een/e /e ::a, >a:n  nn. #PI0I$(#.ICIT#TI) * <6an/e >6> > >a6ne ??<la9/e  :ean/a n<:aln@ ann@ :ea5l0:a. P<6 0na <6an/a /e ;e<6enla9/a   :ea5la a9>0a,  6ean ann <9/e 05@ na8l/an/a laaa  0l86an/a 5a<5naa. M@8a /e 6=ena e:ee:, a<>6a8laa/e e na</e6 a<5na 0a 6ean/e alal0a9/e :a<>/a  ;en0/a, 68l0/e  5la>a <6đen/a. L/een/e /e a/e e <8<6 @l8a@n / >Ce n9e
2+"

/.K#T0I K#.CI&KI* K#$#.# * < 5la@: 0l/6 AV 6l/6, a al 8 @l8a@n, 6a00e n08lna 80 @l808. I$*I/IT0I K.I$'T'0#"' * <6an/e naa/e 05@ ne9>a. %:: :8la9/e :8a<n; 6e > ;e<en0/e, a;a<>/e l 5a<>/e, <0an/e :=a  ?a98la9/e /e >6>e > a=n; :=a, a@a9/a, 058n/en, n68l0/e. L/e e ena:na9/8, e <8<6e atropin i pralidoksim. CI&#$ID * e 6eCe  n;5a08, >6> > anne ;/e  laane :ea5le a9>0e. %:: 8 a;a, ne:<, a;a<>/a, n68l0/e, ;en0/a  :<. L/een/e /e 6a 5la nitrita (amil nitrit i natrijev nitrit) i natrij tiosulfat, / n>89a<>/e  AV 5la. 'T#$. I 'D#TI!$I-*IP$TICI * e8?an/a  <;an/a. L/een/e 0a0en:a e </e l/e ?l8:a0enl:, /e< :Ce 0a06a n68l0/e > 6na  5en0>a0en:a l > n; / 8 80el <9le an>ee08, :8  l/e8. L/e e n;59/: en0:a al;lne >e;><@ena0e :e6n: n;5<:a 8 fomepizola, :Ce e <  eanl al /8,  ;en0/8, ;al/e:/8  ;e<@le:/8, <ane a<:/e. L/e e 
2+7

!2.POGLAVLJE ) LIJEKOVI A LIJE#ENJE BOLESTI PROBAVNOG SUSTAVA Ga<nenaln <n8  e@0<n8 ?8n9/8. O6e ?8n9/e 8 9l/ nel 6aCn; 6<a l/e6a. Ne > 6; l/e6a 8 5eal/n 8/e ale l/e6e. .I&'K!I "# .I&'3'$&' P'PTI3$I* /.'TI Ul9e/ela @a<nenaln@ 9a  >8e>en8:a,  98 :an8la9/: 8a6a / n<l6 n*slika62-1, /e=8/8 0a=8 l80n9e,  8 l8a/8 en@ 8l8a, 8n=a6a/8 5ae</8 '.l<, /a /e <8na 8 8>en8:a. #$T#CIDI Ana9> 8 la5e 5a0e /e ne8a e <e 6 8 6el: >0a:a >a 5 6l ' Cel8>9a, ana9> :an/8/8 8 6a e@ 8l8a. Ana9> e  8 magnezijev +idroksid,  aluminijev +idroksid, / e la5 a<5<> :a /a laa6n 8na, > al8:n/e6 :a na9/ 8na. O6 l/e6 8 >8n a a:  8 :5na9/. Kalcijev karbonat i natrijev bikarbonat 8 la5e 5a0e, al e a<5, e :ea/8 a<9/8 l/e6ala5e 5a0e  elne, ee/e 5e0 8l8a  8 al/e <e, 6e 6=e ; 0a:/en/8/8 n;5< <ne 8:e / 8 8n6/  /e>na @8?8n>/e e n0 1+++ 8a. B<0 <la0e n6e<0/8 8 n an / @6
a9>/el6an/e /e  24 aa,   e< >0e >a 5 e @la 8na 8n6. In;5< <ne 8:e 8 8n6/ > ana@na ' 2 0a GERB  en 8l8, a  /e>na 8n6 0a >e/8 5e0 8l8a  <:a. NeCel/en 8n9 e </e /a6l/8/8   8 <l/e6, 5l 8 <58;8, @la65l/a. K<nn l/een/e a n;5<:a <ne 8:e :Ce a0 >a 6a/ l/e 6ea6a n9>en9/8 a<9n>n@ l a<9n:a lna. M@8 :an/ @n, ena0l. Pa9/en / 80:an/8 n;5<>a, :ala :le8la /e /e la5 l/6a  l:e<09a. O6a/ l:e< e 6eCe 0a =een 6  6a6a. NaCal, :ne6n. Pa 5 :a 0naa/ e:n 8na a /e n na. 1IP0T. * anal@ PGE1 <a@lan>n E, 6ea6a 0a=8 l80n9e  n;5 8l8a > nee<>n; <88aln; l/e6a N%AID al e ne < e /e< /e 0ne6n  e= e le<9n /e< 80<8/e n/el6an/a, 8 6a6:a en; 8l8a / n8 6e0an a N%AID. Ea9/a 6@ <@an0:a 0naa/n :an/8/e 8 6a 8l8a. ReC: 05 n;5 a9/enaa a ale<@/: na en9ln. .I&'K!I K&I TI1%.I0#&% 1TI.IT'T P0/#!$7 T0#KT# P<ne9 / :8l@đen 9a nan <8<=@ 0a;6aa. N/;6a 5n 0a 6ean/e laa na >n/e: e0?a@ealn: ?ne<8 n ; <n:a 0a nee a9/ene a GERB. U <=l, ln::e9 8 5eanela 8 e <l 0a GERB  @a<a8n :an/e n; l/e6a al/e < 0a ;al0en0/: >e5el@ 2+)

9</e6a. 7.@la6l/e U ene<: C6an: 8a68, >a:n /e n;5< ?8n9/e a e < <nn, :Ce 80<6a ::e a<nn0:a, ale ealne 8ne  ;e<<lane:/8. P= ne <la0 <6-:0a 5a</e<8, >:e<>n </eđe 80<8/e (N% 8ne. An5 eritromicin /e=8/e :le  ne; a9/enaa a @a<a e < 0a a8n <6ae l9e l85<9n;   >e<6a >a / :a/8 :a:alan 8na na <l/e6, a :n:alan na (N%. T 8 difenoksilat i loperamid, anal0 :ee<>na a  /a la5: anal@e: 8n:. D?enla /e ?<:8la 5 e :an/ <0 0l /e ?<:8ln ;><en l9e. M@8 80<6a na9/8  :ea/8 a<9/8 ><8@; l/e6a. .I&'K!I "# .I&'3'$&' I$D01# I0IT#/I.$7 K.$#(I/) IB% /e >a, <nn, 6:naln: :ean/a:a 5l, na>8, /a<9  laa6, :ale >0e <9l; an>e9l:na  la:na e < <6 a0a:a 0a la=an/e 5l a n/;6 8na n/e 8 8n >a0an. 21+

#losetron, naCn ana@n 5-*T= a l la5/ !-'T 3 ana@n / e <e a ane:e9 :a/8 8na na IB%. #$TI'1'TICI Mn@ l/e6 8 <n 8 89  ale ana@ne D 2 ?en;> >ea:ea0n 3).@la6l/e a@n ana5n>n@ <na5>l. Ana@n !-'T3 ane<na, @5/el6an/a n/e 8an6l/en, al :aa >/el8/e na  8aln; le8<ena,  :ean/e: 6a5< a<5e5el@ la5. F<:8la9/e !-A%A, 8 Pentasa9 #sacola9 .ialda >a6l/a/8 l/e 8 e5el@ 9</e6a. /alsalazid9 sulfasalazin i olsalazin a><8@8 !A%A :le8l8 l 8l?a<>n. O6a a0 <88 neCel/en; 8naa, 05@ e:ne a<9/e 8l?a<>na. O6 neCel/en 8n9 8 6n  >0H :8nna, @a<nenalne :en/e, @la65l/a, a<n e 5l/e le<, :8n8