anti-cancer drugs one star

methotrexate*

this drug is a folic acid look-alike
Pulmonary and liver toxicities GIT( mucositis)

Inhibit DHFR after polyglutamation

rescue: Leucovorin

antidote: Folinic Acid makes nml cells not use Methotrexate

5-Fluorouracil (5-FU)

pyramidine base, antimetabolite
given with folinic Acid to stablize

metastatic carcinomas of breast, GIT (colon), esophagus. Carcinoma of the ovary, bladder, prostate, pancreas.

inhib thymidylate syn...no DNA syn

CYCLOPHOSPHAMIDE

alkylating agent(CCNS)

Chronic lymphatic leukemia Solid tumors EG cancer of the breast( see CMF) Non Hodgkin’s lymphoma( see combo CHOP) Ovarian carcinomas

transcription and translation
**permanent amenorrhea and azoospermia** **leukemogenic**
Cardiotoxic in high dose strategies Renal and bladder toxicity

secret too much ADH, but given with water

ACROLIEN - metabolite
Mesna - antidote (conjugates metablite)

antidote demeclocycline (Blocks ADH)

Doxorubicin

CCNS
Solid tumors of the breast, endometrium, testes and lung(

Intercalates with DNA and binds the helical groove,
blocks TOPOisomerase 2
- free radical formation

resistance via MDR pump out

antidote: Dimethylsulphoxide (prevent free radicals), serious CARDICPROBLEMS

antidote Dexrazoxane : iron chealter for Heart damage

bleomycin

free radicals...via iron

Pulmonary toxicity( dry cough) Pulmonary fibrosis.

Vincristine

natural - neurotoxic , antimitotic

natural product
reversible myelotoxic

stop SPINDLE PROCESSES - TUBULIN

vinblastine

natural product
reversible myelotoxic

stop SPINDLE PROCESSES - TUBULIN - M phase

Paclitaxel

ovarian cancers, prevent DISSAMBELY mitotic tubules

adverse : perferial neuropathy

tamoxifen

anti-estrogen, blocks receptor binding

anastrazole

estrogen synthesis by inhibiting the aromatase enzyme which converts androstene dione to estradiol.

It is used to treat primary breast cancer and prophylactically to suppress the development of metastatic foci---

Asparaginase

enzymes (others)
hydrolyses asparagine to aspartic acid and ammonia, thus depriving the cancer cell of the aminoacid asparagine

hypersent - COMA,

herceptin (trastuzumab)

monoclonal antibodies

specific breast cancers

binds with high affinity and specificity to the extracellular domain of the HER2 receptor thus inhibiting growth of the tumor.

heart failure...

cisplatin

Platinum coordination complex

This then reacts with DNA, forming intra and inter strand links, leading to breaks and miscoding, causing inhibition of replication and transcription

nephrotoxicity & nerotox

Amifostine:antidote
Generates active thiol metabolites, which scavenge free radicals