Antikanker

Linda P. Suherman
 Antibiotika

– Bleomisin
– Daktinomisin
– Daunorubisin
– Idarubisin
– Plikamisin
 ANTIBIOTIK
1. DAKTINOMISIN
MK : berinterkalasi dengan pasangan basa DNA
guanin-sitosin  kompleks daktinomisin-DNA 
mengganggu polimerase RNA bergantung DNA
Penggunaan terapi : kombinasi dalam pembedahan
dan vinkristin, sarkoma jaringan
Farkin : diberikan secara IV, terkonsentrasi di hati,
tidak masuk ke cairan serebrospinal, eksresi
sebagaian melalui empedu dan sisa melalui urin.
2. DOKSORUBISIN DAN DAUNORUBISIN
MK :
- Interkalasi dalam DNA pada pasangan basa yang
berdekatan  sintesis DNA dan RNA terhambat.
- Terikat pada membran sel  proses transport yang
menyatu pada aktivitas fosfatidilinositil terganggu.
- Pembetukan radikal oksigen melalui peroksidasi lipid
dgn cara sitokrom P-450 reduktase mengkatalisis
reduksi antrasiklin menjadi radikal bebas semikuinon.
Zat ini akan mereduksi molekul O2 menjadi anion
superoksida dan hidrogen peroksida
• Farkin : diberikan IV karena dapat merusak
GIT, tidak masuk SSP, terikat dalam protein
plasma, diekskresi terbesar di empedu.
3. BLEOMISIN
MK : bleomisin merupakan campuran copper
chelating glycopeptide  interkalasi dengan DNA
 kompleks DNA-bleomisin-Fe(II)  mengalami
oksidasi  kompleks DNA-bleomisin-Fe(III) 
bereaksi dengan O2  anion superoksida 
merusak ikatan fosfodiester DNA  sel mati.
Farkin : diberikan secara SC,IM,IV. Terkonsentrasi
dihati, obat diekskresikan utuh melalui urin.
 ADR of Antineoplastic Drugs in Humans
Tissue Undesirable Effects
Bone marrow Leukopenia and resulting infections
Immunosuppression
Thrombocytopenia

Anemia
GI tract Oral or intestinal ulceration
Diarrhea
Hair follicles Alopecia
Gonads Menstrual irregularities, including premature
menarche; impaired spermatogenesis

Wounds Impaired healing

Fetus Teratogenesis (especially during first trimester)
Chemotherapeutic agents are much more toxic to
tissues that have a high growth fraction than to tissues
that have a low growth fraction.
• Proliferating cells are
especially sensitive to
chemotherapy because
cytotoxic drugs usually
act by disrupting DNA
synthesis or mitosis,
cellular activities that
only proliferating cells
carry out.
• Unfortunately, toxicity
to the anticancer
agents is to any rapidly
dividing cells. (e.g.
bone marrow, hair
follicles, sperm forming
cells).
 Distinctive Toxicities of Some Anticancer Drugs
Toxicity Drug(s)
Renal Cisplatin,* methotrexate

Hepatic 6-MP, busulfan, cyclophosphamide

Pulmonary Bleomycin,* busulfan, procarbazine

Cardiac Doxorubicin, daunorubicin

Neurologic Vincristine,* cisplatin, paclitaxel

Immunosuppressive Cyclophosphamide, cytarabine,

dactinomycin, methotrexate
Other Cyclophosphamide (hemorrhagic
cystitis); procarbazine (leukemia);
asparaginase* (pancreatitis)
*Less Bone marrow suppression – “marrow sparing”
 Prevention or Management of Drug
Induced toxicities
• The toxicities of some anticancer drugs can be
well anticipated and hence be prevented by
giving proper medications
• E.g. mesna is given to prevent hemorrhagic
cystitis by cyclophosphamide
• Dexrazoxane, is used to reduce the risk of
anthracycline-induced cardiomyopathy
 TERIMA KASIH

SELAMAT BELAJAR :D