10 - anti-cancer drugs

Anti cancer drugs : kill or modify growth of cells.

Classification: ( many mcqs are based on this classification)

A] Drugs acting directly acting on cells : CYTOTOXIC DRUGS :

1. Alkylating agents :

Meclorethamine (mustine HCL)

Nitrogen Mustards :-- Cyclophosphamide
Ifosfamide
Chlorambucil
Melphalan

Ethylenimine :-- Thio – TEPA
Alkylsulphonate :-- Busalphan
Nitrosoureas :-- Carmustine (BCNU)
Lomustine (CCNU)
Triazine :-- Dacarbazine(DTIC)


2.ANTIMETABOLITES:
Folate antagonists :-- Methotrexate
Purine antagonists :-- 6-Mercaptopurine
6-Thioguanine
Azathioprine
Pyrimidine antagonists :-- 5-fluorouracil
Cytarabine (cytosine arabinoside)

3.VINCA ALKALOIDS :-- Vincristine ; vinblastine

4. TAXANES ;-- Paclitaxel ; Docetaxel

5. EPIPODOPHYLLOTOXIN :-- Etopodoside

6. CAMPTOTHECIN ANALOGUES :-- Topotecan
irinotecan


7. ANTIBIOTICS :-- Actinomycin D( Dactinomycin ) ; Doxorubicin;
Daunorubicin (rubidomycin) ; Mitoxantrone; Bleomycins ;
Mitomycin-C ; Mithramycin(plicamycin)


8.MISC :: Hydroxyurea ; Procarbazine ; L-Asparginase ; Cisplatin ; Carboplatin.


B]Drugs altering hormonal melieu:
1. Glucocorticoids- Prednisolone, others.
2. Estrogens -- Fosfestrol, Ethinylestradiol
3. Antiestrogens – Tamoxifen
4. Antiandrogen – Flutamide
5. 5- alpha- reductase- inhibitor --- finasteride.
6. GNRH analogues – Naferelin, Goserelin.
7. Progestins – hydroxyprogesterone acetate.



Individual drugs:

Alkylating agents as a class form, in the body, reactive intermediates that covalently modify bases in DNA leading to cross-linkages of strands or cause breaks in them – which are intrinsically unable to complete cell division.

· NITROGEN MUSTURDS decompose rapidly in aqu soln to giv bifunctional carbonium ions. Given only by I.V. route. Potent vesicant.. therefore infiltration to b treated symptomatic by infiltration of affected site with—1/6 M Thiosulphate. Used in dilute soln in cutaneous lymphomas.

· CYCLOPHOSPHAMIDE is a prodrug. Activated by liver to aldophosphamide.
**** Chloramhenicol retards metab of cyclophosphamide.

· MESNA used to prevent cystitis due to cyclo and ifosfomide. It is –SH compd it binds and inactivates vasicotoxic metabolites of both these drugs.

· Chlorambucil active against lymphoid tisse. Thus DOC for CLL, Hodgkins.

· Melphalan DOC multiple myeloma.

· Busulphan DOC for CML. Profound myelosupression , alopecia, pulm tox. Relative lymphocyte sparing.

· Nitrosoureas : Cross blood brain barrier. Streptozotocin is unique with glucose lik structure n has specific tox for islet cells of pancreas.—for whose tumor types it is indicated.

· Procarbazine- metab in liver. – causes disulfiram lik reactions to ethanol.

· Thiotepa can b used intrathecally for neoplastic meningitis.
ANTIMETABOLITES

· Folate antagonist- Mtx – inhibits dihydrofolate reductase- blocks conversion of DHFA to THFA- an essential coenzyme for 1carbon transfer rxns in de novo purine synthesis.

· Folinic acid inhibits action of Mtx. And reverses its toxicity.

· Purine antagonists- mercaptopurine and azathioprine are metab by xanthine oxidase thus inhibited by ALLOPURINOL. Reduce dose of hese by ½ to ¼ th if given with allopurinol.

· 5 – fluorouracil kills in S-phase. Very useful for many solid tumors.

· Cytarabine- is phosphorylated in body to corresponding nucleotide n inhibits DNA synth. Triphosphate cytarabine is inhibitor of DNA POLYMERASE.*** imp***
VINCA ALKALOIDS

· MITOTIC INHIBITORS : bind to “tubulin” n prevent its polymerization.. Chromosomes fail to move apart during mitosis—METAPHASE ARREST OCCURS.
TAXANES

· Opposite action to vinca. Enhance polymerization of “tubulin” leads to stabilization- inhibition of normal dynamic reorganization of microtubules that is vital for interphase.
CAMPTOTHECIN ANALOGUES

· Irinotecan is a prodrug. Cholinergic effects are produced in some patients cos it inhibits AchE
ANTIBIOTICS

· Daunorubicin, Doxorubicin(adriamycin) –Cause breaks in DNA by activating topoisomerase II and generate quinone lik free radicals(this meyb the cause for cardiotoxicity). CARDIOTOXICITY is a unique adverse effect to the group.

· Bleomycin—very low myelosuppression.

MISC

· L-Asparginase- only enzyme used as anti neoplastic drug.

· Cisplatin—effective in testicular tumors. Highly nephrotoxic