CANCER CHEMOTHERAPY

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In tumour there are three kinds if cells.

Compartment A includes rapidly dividing cells.

Compartment B incldues cells that remain in G0 Phase i.e they will not divide but can divide.

Compartment C includes the cells that cannot divide.

The cells in the compartment B causes a main problem as they are not much effected by cytotoxic drugs, but they can enter into compartment A.

And almost all the drugs act on the cell division but on the other characteristics of cancer cell like invasiveness and metastasis.

The other toxic effects generally associated with anticancer drugs are alopecia, sterility, teratogenecity etc.

Now coming to the drugs used

The drugs comes under 3 categories

1) 1)

Cytotoxic drugs which includes alkylating agents, antimetabolites, cytotoxic antibodies
and plant derivatives.

2) 2)

Hormones

3) 3)

Miscellaneous agents

CYTOTOXIC DRUGS

Alkylating Agents:

These are largely used in cancer treatment. These are the agents that can form covalent bond with the DNA. These agents will become carbonium ion which reacts with electron donating groups like amine, hydroxyl and sulphahydryl groups.

The nitrogen at the 7th position in case of guanine is the principle targhet for these agents and nitrogens at the 1st and 3rd position in adenine and nitrogen at 3rd position in case of sytosine can also react.

If there are two functional groups, it results in the crosslinking, within and in between the chains.

These drugs action is present predominant in the S phase.

Coming to their side effects they cause disturbances in GIT, and it will lower the bone marrow functioning. And if the drug is used continuously for long times, it causes sterility.

Nitrogen mustards:

When Cl- is released from these compounds it results in the intramolecular cyclization, which eventually formed carbonium ion. This ion can react with nitrogen present at the 7th position in guanine.

Nitrosoureas
are soluble in the lipids. This criteria makes them able to pass through the blood brain barrier. Hence it is used for treating brain and meanings tumours.

Bisulfan
acts particularly for bone marrow

Platinum compoundsinclude cisplastina and carboplastin. Cisplastin consists of platinum at the centre surrounded by ammonia on two sides and chlorine atoms on the other two sides. When the chlorine atom is removed, it forms ion. This ion will react first with water. After water, it will react with DNA.

Antimetabolites

It includes foliate antagonists, purine analogues and pyrimidine analogues.

Folate antagonists:

Lets us know the importance of foliates. These are the substances that contain a preridine ring, PABA and glutamic acid. And these are needed for the production of thymidylate and purine nucleotides. The main folate antagonist is methotrexate.

MOA is by its action mainly on the production of thymidylate.

FH4 is the form that acts as conenzyme.

The conversion os done in presence of the enzyme dihydrofolate reductase.

These folate antagonists has more binding capacity than FH2 and it even form one more bond than FH2.

Route of administration:Oral, IM, IV.

Drawbacks: less soluble in lipids, so cannot pass readily through blod brain barrier.

Pyrimidine analogues:

It includes fluouracil, cytarabine and other drugs.

Flurouracil acts by changing into fluodeoxyuridine monophosphate. This has capability to stop the synthesis of thymidylate by combining with the enzyme thymidylate synthase.

Cytarabine gets phosphorylated to cytosine arabinoside triphosphate. This will stop the functioning of DNA polymerase.

Purine analogues:

It includes fludarabine, pentostatin etc.

Fludarabine: It will get converted to its triphosphate and will stop the synthesis of DNA.

Pentostatin: It stops the functioning of adenosine deaminase.

Cytotoxic Antibiotics

These are the drugs show their effect by acting on the DNA directly.

It includes following drugs.

Anthracycline: They include doxorubicin,idarubicin and daunorubicin etc.

Doxarubicin hinder the DNA and RNA synthesis. The action on DNA is achieved by its action on topoisomerase II.

Other drugs include dactionomycin, bleomycin, mitomycin, procarbazine.

Plant Derivatives:

Vinca alkaloids:
These are derived from the plant Madagaskar periwinkle.

MOA: It will stop the cell division at metaphase.

Taxanes:
It includes Paclitaxel and Docetaxel.

Source is yew tree.

They hinder mitosis.

Etoposide:Obtained from Mandrake root.

Campothecins:It includes irinotecan and topotecan.

Obtained from Campotheca acuminate tree.

It attaches and hinders topoisomerase I.

HORMONES

Drug

Used
for

Prednisolone

Dexamethasone

Leukemia

Megestrol

Norehisterone

Medroxyprogesterone

Endometraial
Neoplasm and

renal
tumours

Hormone Antagonists

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Drug

Type
of cancer in which it is used

Tamoxifen

Hormone
dependent breast cancer

Flutamide

Bicaltamide

Prostate
cancer

MISCELLANEOUS AGENTS:

Those drugs which cannot be included in the above are included in this category. They include:

1) Procarbazine

2) Crisantaspase

3) Amsacrine

4) Hydroxycarbamide

5)

Monoclonal antibodies like rituximab and alemtuzumab.

Reference:


Rang and Dales Pharmacology by Rang, Dale, ritter, moore, churchill livingstone publishers, 6th edition, page no 721 to 731


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Siva Mavuduru's picture
Author: Siva Mavuduru

Comments

Gangadhar Hari's picture

Good work Ganesh, keep it up. I have a small advise for you in interest for your betterment. Try to maintain uniformity with regard to every category you describe. I have noticed that there are no uses for some category of drugs, and some are lacking the explanation of MOA and others examples. Try to focus on the following things uniformly whenever you present classification of drugs MOA(Mechanism of Action) Therapeutic Uses Examples These are the main things on which you have to always concentrate. Arranging the information with you into the above relevant headings will give your readers a better clarity, and keeps it simple and apt. All the best..
Siva Mavuduru's picture

Hi Gangadhar Sir I am very much thankful for your suggestion. From the very next blog onwards i will concentrate on the topics which you said. Keep suggestion me sir so that i can present much better.
Vishnu Murthy Vummaneni's picture

" Camptothecins and Fluoro quinalones acts in the same way". Justify.

Vishnu Murthy Vummaneni

Siva Mavuduru's picture

Camptothecins They gets attached and stops the action of topoisomerase I used as anticancer agent Fluoroquonolones They act on the topoisomerase II. used as anti bacterial agents Topoisomerases are used to reduce the stress in the supercoiled DNA Topoisomerase cuts one strand of the DNA Topoisomerase cuts both the strans of the DNA