Cytostatika

- L k lb ndorovch onemocnn (rakovina = cancer) - tl m r!st tkn s vysoko "roli#eran rychlost a "roto$e se ndorov %vrhl tk& dl velmi rychle' cytostatika (i ne(vc "ostih ( - m!$o mt i )inky cytocidn * "or cha normlnho "r!bh mit+%y m!$e vyvolat "ro,ramovano smrt - a"o"t+% -./ "ostih %drav tkn s vysoko #rekvenc b nnho delen' nema( s"eci#ick (selektivn) )inek - 012 * inhibice obnovy e"itel 3 )"orn "r!(my (m!$e bt d!vodem "4er 5en lby) - )tl m kostn d4en' "o5ko%en sli%nic trvicho )stro(' vy"advn vlas! to limit (e dvkovn - 6 im nity ()bytek lym#ocyt!) -789: * vsledek nere, lovanho ttk&ovho r!st a tonomn "ovahy aty"ick str kt ry ;< =eni,n (ne%h bn) -"omal r!st' nein#iltr ( do or,n!' nemetast% (' "o odstrann nerecidiv ( (lokali%ovan - da( se chir r,icky odstranit)' na okol "!sob tlakem - "od mikrosko"em (e slo$en shodn s mate4skm takivem ( mali,nch ne) #ibr+m - % va%iva li"+m - % t kovho tkaniva oste+m - % kosti' s"o(ivov tkn my+m - %e sval aden+m * %e $l%natho e"itel >< ?ali,n (%ho bn) - rosto rychle' (e(ich b &ky se ne%astav ( na hranici or,n!' ale in#iltr ( do nich - (e(ich b &ky (so odtrans"ortovan cvami do odlehlch or,n! a vytv4 >@ metast%y (>@ ndor) 3 metast% ( - ,enerali%ovan - neda( se chir r,icky odstranit karcin+m - % e"itelovho tkaniva sark+m * % va%iva nebo (inho s"o(ivov takn - %vis i od vk (karcin+n %4dka "od ABlet' sark+m v cel "o" laci i dt) CD-1E -789:F/ na %klad ,enetick in#ormace kancero,enn vlivy = kancero,eny/ #y%ikln - %4en ioni%an' radioaktivn' GC' :20 chemick * dehet' "ara#n' barviva' a#latoHiny (v o4echch)

biolo,ick * vir sy (na"r< Ielicobacter "ylori)

J2781K DI9G=-LI9 =GMN-O/ ;< 1niciln #%e * obdob intrakc s kancero,enem >< Latentn #%e * "4emena tkn na ndorovo b &k A< ?ali,n #%e * trval vskyt mali,nch b nk - #aktory * ko 4en' v$iva' "ro#esionln eH"o%ice' sl nen %4en DM1PQ9C7-O DI9G=-LI9 -789:G/ kdy$ se %a%namen vic (ak >; dn/ a) krvcen % tlnch d tin b) b lky na "rso a (inde na tle c) %mny ve # nkci st4ev d) neho(c se rny na k!$i' v d tinch' a#ty e) nech R do (dla' t$ksti "4i hltn STO1-U J?:21/ nemoci kardiovask lrnho systm onkolo,ick onemocnn

CNJ2U ?N2KJ27D/ - sark+m konetin 3 do "lic S9J2GS ST1 2N:KS11/ ;) chir r,ick lba >) radiotera"ie A) chemotera"ie V) im notera"ie W) "od"!rn lba (K2=' krevn derivty' anodynaX)
- ,enov mani" lace * cesta S WA * kdy$ ho m 3 neb de rakovina

-dor indik (eme "4i "ot b nk ;BY na ; , * lba cytostatikama $ nen a$ tak )s"5n' om d4v dia,nostik (eme' tm (e le"5 lba< G nkterch nadorovch onemocnn (e mo$n vylen (na"4< le kemie' lym#om)' a sarkom! vt5ino (en %"omal (eme "ro,resi mali,nho "roces < karcinom!

=hem tera"ie se m!$e vyskytno t re%istence v!i "o $itm cytostatik < D7JK8U :KC19-7L-O 2N:KS1N/ ;< 2era"ii %ah(it co ne(d4v >< Sodvat kombinace cytostatik (na hranici toHicity) 3r!%n ?.' re%istence nev%ik tak asto A< 8odr$ovat s"vn dvkovn (nesni$ovat' m s bt na hranici toHicity) V< 2era"ii "4er 5ovat cyklicky W< C lb "okraovat i "4i doshn t remisie ("4echodn vymi%n t "4%nak! choroby) Z< S4i %trt citlivosti dt "4ednost alternativn kombinaci cytostatik "4ed %vy5ovnm dvky [< -elit cytostatikami lokali%ovan ndory \< na"odvat "acient!m s "okroilm stdiem * nevyliteln 3ne%hor5it krtk %bva(c %bytek $ivota 1-81EKCN K-21-N9SLKJ21CE]CI LL1C/ E rativn tera"ie/ lba Kd( vantn tera"ie/ na "od"or chir r,ickho len nebo radiotera"ie Saliativn tera"ie/ k "rodlo $en $ivota nebo ke %le"5en (eho kvality "4i onemocnn s in#a stn "ro,n+%o Cytostatick lba/ Edy$ se 6 "oet ndorovch b nk "od ;B\' "acient se ct l"e' "acient se "ova$ (e %a %dravho "4i 6 na ;BW ROZDLEN CYTOSTATIK PODLE MECHANISMU INKU: LL1CK S9PE9DGMOCO 8-K kovalentn va%bo na 8-K Klkyl (c ltky * CUEL9^9J^K?18 (le kemie' Iokinova ch<' karcin+m varlat) - ?./ alkylace b% 8-K 3 inhibice re"likace' transkri"ce (dlen) 3 %nehodnocen 8-K - "odobn )inek m i C1JSLK21-K

- -./ na %ea' "r!(em' %trta ch ti do (dla' vy"vn vlas!' nekr+%y v ledvinch a moovch cestch' )tl m myelo"oe%y v kostn d4eni * "okles "ot lym#ocyt!' ,ran locyt!' "o%d(i i 2:9 a N:U - 129^9J^K?18' CIL9:K?=GC1L' EK:?GJ21-' 2I192NSK volnnm reaktivn "latiny * C1JSLK21-K' EK:=9SLK21-K

- ?./ vytv4 m!stky me%i dvma molek lami 8-K nebo i ve vlkn - -./ centrln vyvolan %vracen (t$ko liteln b$nmi antiemetiky' %aveden W-I2Aanta,onisty 9-8K-JN2:9-G * %le"5en len -.)' "o5ko%en ledvin' sl ch interkalac ?./ ty"ick A-V lenn "lanrn systm se %ab d (e do "rova%c! 8-K a tm vyvol (e(ich %lomy L/ KE21-9?UCO- 8 = 8KE21-9?UCOKntracyklinov derivty * 8KG-9:G=1CO-' 89_9:G=1CO- (kardiotoHick )<)' NS1:G=1CO-' 18K:G=1CO- (mn kardiotoHick) inhibic to"oi%omer%y inhibitory to"oi%omer%y 11/ N"ido#ylotoHiny * N29S9D18' 2N-1S9D18 (der< "odo#ylotoHin *% ?andra,ory) ?./ nes"ov v "o5ko%en mitotickho v4etnka' ale v inhibici to"oi%omera%y 11' kter o"akovan "4er 5 (e ob vlkna dvo(5ro bovice * "4ekld (e "4es sebe a %ase s"o( (e inhibitory to"oi%omer%y 1/ 29S92NEK?./ inhibice to"oi%omer%y 1' kter 5t" (edno %e > vlken 8-K a "o "4emstn (e o"t s"o( (e L72EU 9CL1C`GMOCO JU-2LDG 8-K inhibice synt%y stavebnch (ednotek 8-K inhibice red kt%y kyseliny dihyrolistov (antimetabolity) * ?N292:N_72 ?./ #ale5n s bstrt "ro en%ym dihydro#oltred kt% * "odl na synt%e k< tetrahydrolistov' kter (e "ot4eb "ro tvorb " rnovch ltek a tymidin )' ?N292:N_72 m V--I> sk< msto V-9I k<listov' nava% (e se na red kt% k< dihydrolistov a tm inhib (e "roli#eraci b nk inhibice ribon kleotidov red kt%y * IU8:9_UEK:=K?18 (IU8:9_U?99C1-K)

?./inhib (e "4emn ribon kleotid na deoHyribon kleotid %ab dovn #ale5nch stavebch (ednotek (antimetabolity) Kntimetabolity " rin / Z-?N:EKS29SG:1-' 2I190GK-1-' =G219SG:1?./ "rek r%ory' )inn se stano nav%nm na (deoHy-)rib+% a #os#orylac 3 stano se % nich normln n kleosidy' kter inter#er ( se synt%o 8-K a :-K KLL9SG:1-9L' KDK2I19S:1- (v%ik % n( Z- JI " rin)' ELK8:1=1(chloradenin a c kr) Kntimetabolity "yrimidin * CU2K:K=1-' ^LG9:9G:KCUL' 0N-C1=1-' KDKG:KCUL ?./ %sah do metablickho "roces ' kter m v%nam "4i synt%e n kleotid! a -E (ste(n ?. i antimetabolity " rin ) L72EU SFJ9=OCO 1-2N:KECO J ?1E:92G=GLU ?12921CELI9 CTN2L-EK E9LCI1C1- (antimitotick alkaloid % 9c)n ) * na ak tn %chvaty 8-U ?./ %astav (e mit+% v meta#%e' nen ov5em selektivn (nepouv se) Klkaloidy Cinca :osea/ C1-=LKJ21- (C1-EKLNGE9=LKJ21-)' C1-E:1J21a semisyntetick C1-8ND1-' C1-9:NL=1?./ inhibice mit+%y 1/ le kemie 2aHany/ SKEL12K_NL' 89CN2K_NL (2aH s brevi#olia * 2is tichomo4sk) ?./ inhibice de"olymeri%ace mikrot b l! L72EU SFJ9=OCO 8KLPO?1 ?NCI-1D?UL72EU 9CL1C`GMOCO :N0GLK-O S9CI98U C 9:0K-1D?G KJSK:K01-7DK * 5t" as"ara,in na as"att a amoniak' "latnn b nk' kter ne(so sch"ny samy synteti%ovat as"ara,in S9:^1?N: ?./ "!sob (ako #otosen%ibi%tor L72EU 9CL1C`GMOCO :N0GLK-O S9CCI98U 9:0K-1D?G I9:?9-U K STO=GD-L L72EU ndorovch

0esta,eny * ?N0NJ2:9L' ?N8:9_US:90NJ2N:9Nstro,eny - 81N2ULJ21L=NJ29L 0l kokortikoidy * S:N8-1D9-' IU8:9E9:21D9Knalo,y ,onadotro"inreleasin, I< * =GJN:NL1-' 2:US2N:NL1-

K-2K09-1J21 I9:?9-F K STO=GD-L L72EU Kntiestro,eny * 2K?9_1^NKntiandro,eny * ^LG2K?18

1?G-9J21?GLK-C1K - "otenc ( im nolo,icko od"ovd 1/ na stim laci im nity "4i mali,nch "rocesech 1nter#erony *1-^b>a' 1-^b>b' 1-^c;a' 1-^d;b 1nterle kny * 1L> (KL8NJLNGE1-) ?onoklonln "rotiltky * N8:NC9L9?K=' :12G_1?K=

I.

CYTOSTATIKA PRODNHO PVODU: Srotindorov K2= * Kntracyklny' 89_9:G=1CO-' 8KG-9:G=1CO-' 18K:G=1CO:ostlinn alkaloidy * C1-E:1J21-' C1-=LKJ218er< N"ido#ylotoHin 2aHany * SKEL12K_NL' 89CN2K_NL Nn%ymy EK?S292NC1-

II.

CYTOSTATIKA SYNTETICKHO PVODU: Klkyl (c ltky * CUEL9^9J^K?18' 129^9J^K?18' CIL9:K?=GC1L' EK:?GJ21-' 2I192NSK

Kntimetabolity * ?N292:N_72' ?N:EKS29SG:1-' ^LG9:9G:KCUL' ELK8:1=1S:9EK:=KD11n * C1JSLK21-K' EK:=9SLK21-K' KJSK:K01-7DK

CYTOPROTEKTIVA - 6 cytotoHick )inky nkterch cytostatik K?1^9J^1- * radiotera"ie

?NJ-K - 6 cytotoHick )inky 129^9J^K?18G