Antineoplastic Drugs Flashcards by Wadhha Alajmi

Which normal cells are affected by antineoplastic drugs ?

Rapidly dividing normal cells such as:
• Bone marrow
• Gut epithelium
• Spermatogenic cells
• Lymphoid tissue
• Hair follicles
• Foetus

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Describe the therapeutic index of antineoplastic drugs.

Very narrow (low) and serious side effects occur at the therapeutic dose

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What are the common adverse effects of antineoplastic drugs?

• Severe vomiting
• Nausea
• Stomatitis
• Alopecia occurs from (light to severe) with most antineoplastic agents

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What toxicities are common to many antineoplastic drugs?

Myelosuppression & associated immunosuppression

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What toxicities are specific to certain drugs?

• Cardiotoxicity with doxorubicin
• Pulmonary fibrosis with bleomycin
• Hearing loss with cisplatin

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Which drug causes this specific toxicity?

Cardiotoxicity

Doxorubicin

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Which drug causes this specific toxicity?

Pulmonary fibrosis

Bleomycin

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Which drug causes this specific toxicity?

Hearing loss

Cisplatin

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What are the major targets of chemotherapy in cancer treatment?

• Growth promoting hormones
• Tumour blood supply
• DNA synthesis precursors
• DNA
• RNA
• Proteins
• Microtubule assembly for cell division and continued cancer cell growth

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Which class of drugs targets growth-promoting hormones in cancer treatment?

Anti-hormones

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Which class of drugs targets tumour blood supply in cancer treatment?

Angiogenesis inhibitors

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Which class of drugs targets DNA synthesis precursors in cancer treatment?

Antimetabolites

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Which class of drugs targets DNA in cancer treatment?

DNA alkylating agents
Topoisomerase inhibitors

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Which class of drugs targets proteins in cancer treatment?

Tyrosine kinase inhibitors
Monoclonal antibodies

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Which class of drugs targets microtubule assembly for cell division and continued cancer cell growth in cancer treatment?

Tubulin-binding drugs (e.g., vinca alkaloids, taxanes)

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What are the major classes of antineoplastic drugs?

I. Alkylating agents & related compounds
II. Cytotoxic antibiotics
III. Hormones and hormone antagonists
IV. Antimetabolites
V. Tubulin/microtubule binding agents
VI. Miscellaneous drugs (e.g., angiogenesis inhibitors, tyrosine kinase inhibitors, monoclonal antibodies)

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What are examples of alkylating agents and related compounds?

• Nitrogen mustards (carmustine)
• Platinum compounds (cisplatin)

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What do alkylating agents contain?

Alkylating agents contain chemical groups that can form covalent bonds with particular substances (DNA, RNA, protein) in the cell.

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True or false

Alkylating agents kill both rapidly proliferating and non-proliferating cells

True

As a result of alkylation of DNA, RNA, and essential proteins

(Read picture if you want to understand more)

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How do cytotoxic antibiotics exert their antineoplastic effects?

Cytotoxic antibiotics interact with DNA, preventing DNA replication and cell division.

What are the major classes of antineoplastic (cytotoxic) antibiotics?

Anthracyclins (doxorubicin)

Bleomycins (bleomycin)

What types of tumors might be hormone-dependent?

Tumors derived from hormone-sensitive tissues (e.g., breast, prostate)

How can the growth of hormone-dependent tumors be inhibited?

• Hormones with opposing actions

• Hormone antagonists (e.g., tamoxifen in breast cancer)

• Agents inhibiting the synthesis of relevant hormones

What is tamoxifen

Hormone antagonist

What is the advantage of endocrine therapy compared to cytotoxic agents?

Endocrine therapy generally has far fewer serious adverse effects

What are the major types of antimetabolites?

A. Folate antagonists (e.g., methotrexate) B. Pyrimidine analogues (e.g., 5-fluorouracil) C. Purine analogues (e.g., 6-mercaptopurine)

How do antimetabolites interfere with cellular function?

They are structurally related to normal cellular components (e.g., metabolites for DNA synthesis) and generally interfere with the availability of normal metabolites. As a result, antimetabolites inhibit the utilization of the natural metabolite, e.g., interfering with DNA synthesis.

What is methotrexate

Folate antagonist (antimetabolite)

What are the types of tubulin/microtubule binding agents (mitotic inhibitors) ?

A. Vinca alkaloids B. Taxanes

What is the mechanism of action of vinca alkaloids?

They act by binding tubulin and preventing its polymerization into microtubules → prevents spindle formation in cells at mitosis stage → cells are arrested at metaphase → Cells cannot complete chromosomal segregation and mitosis = CELL DIES !

What are examples of vinca alkaloids?

Vincristine and Vinblastine ( alkaloids found in periwinkle plant -Vinca rosea- )

True or false Vinca Alkaloids are used in combination with other drugs to treat many cancers.

True

What is the mechanism of action of taxanes?

Microtubules are stabilized by taxanes. Taxanes bind to microtubules and inhibit their depolymerization into tubulin. With the spindle still in place, the cell can’t divide into daughter cells.

What is an example of taxanes?

Paclitaxel

Where are taxanes extracted from ?

the yew trees.

What is Paclitaxel ?

Taxane (mitotic inhibitor)

What is the mechanism of action of angiogenesis inhibitors?

They are designed to stop tumors from developing a blood supply, a pre-requisite for tumor growth and metastasis.

Example of angiogenesis inhibitors

Avastin

What is the mechanism of action of tyrosine kinase inhibitors?

They inhibit phosphorylation of growth-promoting proteins.

Examples of tyrosine kinase inhibitors

Imatinib Gefitinib

What is the mechanism of action of monoclonal antibodies?

They neutralize the actions of growth factor receptor signaling that promote cancer growth e.g., HER2 in breast cancers.

Example of Monoclonal antibodies

Trastuzamab

Explain the Log Kill Hypothesis And what the solution is.

Cancer drugs kill a constant fraction of tumor cells - a proportion of cancer cells can survive a course of treatment by CHANCE without being specifically resistant - log kill varies with cell growth rate - short doubling times make cancer cells more susceptible to treatment - log kill progressively DECREASES in the LATE stages of tumor when cells stop cycling SOLUTION: combination therapy + repeated cycles of treatment

Cancer cell growth is best described by Gompertzian Kinetics. What does that state?

Slow linear growth at smallest and largest tumor sizes BUT exponential growth in between

True or false A tumor is usually far advanced before diagnosed

True

What is the principal of cancer chemotherapy?

To attain maximal therapeutic cytotoxic effects to cancer cells WHILE causing lowest toxicity to normal cells

______________ is a disorder characterized by loss of notmal cell control of proliferation and differentiation. It affects many organs/cell types (ex: breast, lung, brain, prostate etc)

Cancer

True or false If more than one drug is used in the treatment regimen, then this increases the chance of resistance to the chemotherapy regimen.

FALSE DECREASES

Anticancer drugs can be divided into 2 groups: What are they? Describe each .

1. Cell-cycle phase independent drugs - they kill cells anywhere in the cell cycle - As dose increases ↑, cell kill increases ↑ 2. Cell-cycle phase dependent drugs - they kill cells that are in certain phases of the cell cycle - As time (not dose) increases ↑, cell kill increases ↑