chemotherapy cancer.pptx

8/17/2019 CHEMOTHERAPY CANCER.pptx

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CHEMOTHERAPY CANCER

Oleh :Dimas P.NugrahaBagian farmakologi F !R


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Chemo"hera#$ is "he use of %rugs "o


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• Tumor &ells &an 'e &lassi(e% as proliferatingcells and non-proliferating cells.

• The ra"io of #rolifera"ing &ells in "he )hole

"umor "issue is &alle% gro)"h fra&"ion *+F,.• The fas"er "he "umor &ells #rolifera"e- "he

'igger "he +F is an% "he higher "hesensi"ii"$ of "umor "o a %rug is.

• +enerall$- in the early stage, the GF of atumor is bigger and the eect of a drug onthe tumor is better.


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Base% on "he DNA &hanges in &ells- #rolifera"ing &$&le of"umor &ells &an 'e %ii%e% in"o / #hases

• Pre-synthetic phase *+a# 0 #hase or +0 #hase,.&ells &hie1$ make #re#ara"ions for "he s$n"hesis ofDNA.

• Synthetic phase *2 #hase,. &ells are s$n"hesi3ing"heir DNA.

• Post-synthetic phase *+a# 4 #hase or +4 #hase,.DNA %u#li&a"ion has 'een (nishe% an% "he$ are

e5uall$ %ii%e% "o "he ")o of fu"ure su'6&ells.• Mitosis phase *M Phase,. ea&h &ell is %ii%e% in"o ")o

su'&ells. 2ome of "hese ne) &ells en"er "he ne)#rolifera"ing &$&le- "he o"hers 'e&ome non6#rolifera"ing &ells.


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• Non6#rolifera"ing &ells in&lu%e G phase cells• *res"ing6#hase &ells,-

• + 7 #hase &ells hae #rolifera"ion a'ili"$

'u" %o no" %ii%e "em#orall$.• 8hen #rolifera"ing &ells are su9ere% hea$

&asual"ies- + #hase &ells )ill ge" in"o#rolifera"ing &$&le an% 'e&ome "he reasons

of "umor re&urren&e.• +7 #hase &ells are usuall$ not sensitive to

antineoplasticdrugs, which is the importantobstacle "o "umor &hemo"hera#$.


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Mechanisms of Antineoplastic Drugs

Mos" an"ineo#las"i&%rugs a&" on "he#rolifera"ing &$&le of &ell

( 1) destruction of DNA or inhibitionof DNA duplication

e.g. alk$la"ingagen"s- mi"om$&inC

*2) inhibition of nucleic acid (DNAand NA) synthesis

e.g. 61uoroura&il- ;6mer&a#"o#urine-me"ho"re


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( !) "nterfering #ith the transcription toinhibit NA synthesis

e.g. %a&"inom$&in- %auorui&in- an%

%o


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&lassi'cation of Antineoplastic Drugs

On "he 'asis of an"ineo#las"i& a&"ion on "he #haseof #rolifera"ion &$&le- %rugs are &lassi(e% as

• cell cycle non-specifc agents *#hasenons#e&i(& agen"s- CCN2A, *e.g. alk$la"ingagen"s,

6 A&" in all #rolifera"ing #hases- een "he +

6 e9e&"s are s"ronger.

• cell cycle specifc agents (phase specifcagents, CC2A,. *e.g. An"ime"a'oli"es-in&aalkaloi%s,

6 =us" a&" on s#e&i(& #hases of "he &ell &$&le

6 e9e&"s are &om#ara"iel$ )eaker.


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On "he 'asis of sour&e an% a&"ionme&hanisms- "he %rugs are also&lassi(e% as:

• alk$la"ing agen"s-

• an"ime"a'oli"es-

•

na"ural #ro%u&"s-• hormones an% an"agonis"s

• mis&ellaneous agen"s.


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• Alk$la"ingagen"s a&" ia a rea&"ie alk$l*RCH 4 >CH 6 4 ?, grou# "ha" rea&"s "oform &oalen" 'on%s )i"h nu&lei& a&i%s.

• There follo)s ei"her &ross6linking of "he")o s"ran%s of DNA- #reen"ingre#li&a"ion- or DNA 'reakage.

6 All alk$la"ingagen"s are #has#hase

nons#e&i(&

6 kill ra#i%l$ #rolifera"ing &ells- also killnon#rolifera"ing &ells.


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• amples* Mechlorethamine 6 "he (rs" %rug use% in "he "rea"men" of

&an&er

6 A" #resen"- i" is mainl$ use% for Ho%gkin@s%isease an% non6Ho%gkin@s l$m#homas.

• amples* &yclophosphamide

6 Mos" )i%el$ use% in &lini&al "hera#$ for

"rea"men" of &an&er a" #resen". 6 " has no an"ineo#las"i&a&"ion ou"si%e

"he 'o%$ an% mus" 'e a&"ia"e%in "he lier


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• An"ime"a'oli"es are analogues of normalme"a'oli"es an% a&" '$ &om#e"i"ion-re#la&ing "he na"ural me"a'oli"e an% "hen

su'er"ing &ellular #ro&esses.• E


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• ample* methotreate

6 Mimi&s foli& a&i%- )hi&h is nee%e%for s$n"hesis of DNA- RNA an% someamino a&i%s

6 " a&"s mainl$ on "he 2 #hase &ells.

6 has a serious m$elosu##ression


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• ample* +-Mercaptopurine

6 A s"ru&"ural analogue of h$#o


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• ample* %-,luorouracil (%-,) 6 a 1urorine6su's"i"u"e% analogue of ura&il

6 mus" 'e me"a'oli&all$ a&"ia"e% "o a

nu&leo"i%e- in "his &ase F%!MP.6 "hen i"s me"a'oli"e inhi'i"s "he s$n"he"aseof %eo


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Natural Products

• This grou# is %e"ermine% '$ "he sour&e of"he %rug

• The ma=or &lasses of na"ural #ro%u&"s in&lu%e

6 an"i'io"i&s 6 in&aalkaloi%s

6 'iologi& res#onse mo%i(ers

6 en3$mes

6 e#i#o%o#h$llo"o


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• Antibiotic antineoplasticagents

Damage DNA in &$&ling an% non&$&ling&ells

• E


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/inca(plant) al0aloids• in&ris"ine an% in'las"ine are alkaloi%s

%erie% from "he #eri)inkle #lan".

•

'in%ing "o "u'ulin- in"erfere )i"h "heassem'l$ of s#in%le #ro"eins %uring mi"osis

• A&" in M #hase "o inhi'i" mi"osis- 'lo&king#rolifera"ing &ells as "he$ en"er me"a#hase.

• Bo"h &an &ause 'one marro) su##ressionan% neuro"o


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• The gro)"h of some &an&ers ishormone %e#en%en". +ro)"h of su&h&an&ers &an 'e inhi'i"e% '$ surgi&al

remoal of hormone glan%s-in&reasingl$- ho)eer- a%minis"ra"ionof hormones or an"ihormonesis

#referre%


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amples*

• Adrenocorticalsteroids "o inhi'i""he gro)"h of &an&ers of l$m#hoi%"issue an% 'loo%.

• strogen antagonists * "amo


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Miscellaneous agents

amples* ydroyurea

• H$%ro


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• n or%er "o enhan&e &ura"ie e9e&"- "o %e&rease"he "o


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1 Select drugs according to theirphase speci'c characteristics

• The aim of "his rule is "o urge more +7 #hase &ells "o en"er "he#rolifera"ing &$&le so as "o in&rease"he amoun" of "umor &ells kille% '$

%rugs.

Principles of combinationtherapies


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• For high +F "umor su&h as a&u"e leukemia-#hase s#e&i(& %rugs are (rs"l$ use% "o kill 2 or M#hase &ells- an% "hen #hase non6s#ei&(& %rugsare use% "o kill "umor &ells in o"her #hases- an%

(nall$ "he a'oe ")o s"e#s are re#ea"e% on&eagain "o kill ne) &ell from + 7 #hase.

• For lo) +F "umor su&h as soli% "umors- #hasenon6s#e&i(& %rugs are (rs"l$ use% "o kill &ells of

all #hases- an% "hen #hase s#e&i(& %rugs areuse%- an% (nall$ "he a'oe s"e#s are re#ea"e% "okill "he ne) &ell from +7 #hases.


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4 &ombinations of antineoplasticdrugs#ith di3erent action mechanisms.

&an %es"ro$ "umor &ells from arious

'io&hemi&al links a" same "ime. &ombinations of antineoplasticdrugs

#ith other therapies

E


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$ &ombination of lo#-toic drugs#ith hightoic ones

%oes no" o'iousl$ in&rease "he "o


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. 2ele&" %rugs a&&or%ing "o


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4oi

Short-term toicity

• Common si%e rea&"ions usuall$a##ear earlier an% man$ of "hem o&&ur

in ra#i%#rolifera"ing "issues su&h asmarro)- gas"roin"es"inal "ra&"- an% hairfolli&le.

•

m$elosu##ression-• gas"roin"es"inal "ra&" s$m#"om

• alo#e&ia


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5ong-term toicity

• The long6"erm "o


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The cell cycle and the relationship oantitumor drug action to the cycle


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One of "he grea"es" &hallen

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