Traditional Chemotherapies Flashcards Preview

IMED2004 Human development and genetics > Traditional Chemotherapies > Flashcards

Flashcards in Traditional Chemotherapies Deck (50)
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1
Q

What kind of tissue do classical cancer drugs act on? What were they initially designed for?

A

Highly proliferative tissues (not necessarily cancer)

They were initially used to treat leukemia and lymphomas and were aimed to selectively kill tumour cells.

2
Q

What is cancer chemotherapy and radiotherapy?

A

Drugs used to treat cancer.

Using megavoltage linear accelerators to treat cancer

3
Q

How was chemotherapy discovered?

A

Mustard gas used in WW1 showed myelosuppression and lymphoid hypoplasia

WWII bombing of allied ships released mustard gas and survivors developed severe myelosuppression.

Nitrogen mustard was then developed to treat lymphoid malignancies.

Folic acid is low in megaloblastic anaemia and in ALL folate is high meaning using folate analogues was found to put ALL into remission.

4
Q

What is a neoadjuvant?

A

Chemical given before surgery to shrink tumour and make surgery less extensive.

5
Q

What is an adjuvant?

A

Given after surgery to destroy remaining cells and prevent recurrence

6
Q

What is induction chemotherapy?

A

Given to induce remission, commonly used in the context of leukaemia treatment.

7
Q

What is consolidation chemotherapy?

A

Given once remission is achieved

8
Q

What is definitive chemotherapy?

A

Curative chemotherapy used on an early stage tumour that is chemotherapy sensitive such as testicular cancer.

9
Q

What are the important general principles of chemotherapy?

A

Specificity of cancer drugs

Kinetics of tumour growth and detection

Drug efficacy and fixed proportional killing - Cure vs remission

Drug efficacy and tumour regrowth

Cell cycle and susceptibility to specific drugs

Drug resistance

10
Q

What are cancer drugs specific to? What are the side effects of chemotherapy then?

A

Highly proliferative tissue such as tumour cells (most importantly), GI tract epithelial cells, hair follicles, bone marrow / haematopoeitic cells.

Side effects are then related to these tissue:

GI toxicity

Hair loss (alopecia)

Myelosuppression - infection, anaemia, and bleeding.

11
Q

What are the phases of tumour growth?

A

There is a dormant phase where it grows very slowly initially.

Then there is a rapid progression phase (at this stage it is far advanced)

12
Q

How effective can chemotherapy drugs be?

A

Given dose of chemo kills a fixed proportion of tumour cells (<100%) rather than a fixed number. if there are more than 10^5 cells then chemotherapy drug has to kill >99.999% of cells in the cancer

13
Q

What can potentially change if a tumour is undetectable after initial chemotherapy induces remission?

A

Remaining cells are either killed by the immune system (Cure)

Can still be actively growing with minimal residual disease (reappears)

Can be dormant for many years before re-activation (eg breast cancer metastases in bone marrow)

14
Q

When in the cell cycle are cancers susceptible to cancer drugs?

A

When cells are in G0 they are resistant to most chemotherapeutic drugs. However, different drugs act on specific stages of the cell cycle (including G0)

However, when they are dividing they are more susceptible to drugs.

15
Q

How are chemotherapeutic drugs prescribed?

A

They are prescribed in combination with other chemotherapeutic drugs targetting different stages of the cell cycle.

16
Q

What are the cell cycle specificities of drugs?

A

Non-phase dependent drugs

Phase specific drugs

17
Q

What are the non-phase dependent drugs?

A

Alkylating agents

Anthracyclines

18
Q

What are the targets of traditional anticancer drugs?

A

DNA replication is crucial to growing tumour cells.

Traditional anticancer drugs interfere with DNA synthesis and/or function

By interfering with cell function, drugs induce apoptosis to cause cell death.

19
Q

How is DNA damaged by anticancer drugs?

A

Chemical damage to DNA -> DNA adducts and strand crosslinking

Impaired synthesis of DNA bases - pyrimidines and purines

Inhibition of transcription or translation

Disruption of cell division mechanics (eg microtubule function)

20
Q

What are alkylating agents?

A

Oldest class of chemotherapy drugs.

Alkylate (methyl/ethyl) guanine bases to form DNA adducts or cross linking of DNA strands. (Base excision repair of guanine adducts causing strand to break, cross linked DNA cannot be replicated or transcribed.

DNA damage/cell death is independent of cell cycle -> Alkylating agents kill cells in G0.

Effects of alkylating agents are dose dependent.

21
Q

What are the types of commonly used classical alkylating agents?

A

Nitrogen mustards; Cyclophosphamides, chlorambucil, and melphalan

Nitrosureas: Lomustine, Streptozotocin

Akylsulphonates: Busulphan

22
Q

What are the nonclassical alkylating agents called and what types are there?

A

Platinum-based drugs:

Produce DNA adducts and X-links like classical agents: Cisplatin, carboplatin, oxaliplatin

23
Q

What are the anti-metabolite drugs? What do they do?

A

Deprive cells of building blocks required for growth and division such as:

Folic acid antagonists (eg methotrexate)

DNA base analogues (pyrimidine, purine, and nucleoside analogues)

24
Q

What are the types of folic acid antagonists?

A

Analogues which block DHFR (Methotrexate)

Deplete cellular folates (blocks purine synthesis)

25
Q

What are the commonly used DNA base analogue drugs?

A

5-Fluorouracil (5FU), mercaptopurine, Gemcitabine

26
Q

What are mitotic inhibitors?

A

Interfere with mitotic spindle -> Target microtubules

27
Q

What are the types of mitotic inhibitors?

A

Vinca alkaloids (Bind tubulin and prevent MT and mitotic spindle formation)

Taxanes (Bind MTs to prevent disassembly at mitosis)

28
Q

What are the commonly used vinca alkaloids called?

A

Vincristine

Vinblastine

29
Q

What is the commonly used taxane called?

A

Paclitaxel

30
Q

What do anthracyclines do?

A

Intercalate between base pairs and inhibit topoisomaerase II.

Both mechanisms prevent DNA replication, and are cardiotoxic.

31
Q

What are anthracyclines?

A

Cytotoxic antibiotics that are derived from micro-organisms.

32
Q

What are the commonly used anthracyclines?

A

Doxorubicin

Daunorubicin

33
Q

What do bleomycins do?

A

They induce single and double stranded DNA breaks

34
Q

What are the classes of bleomycins?

A

Bleomycin A2 and B2 (both derived from streptomyces bacteria)

35
Q

What is the side effect of using anthracyclines?

A

Cardiotoxicity

36
Q

What is the side effect of using bleomycins?

A

Pulmonary fibrosis

37
Q

What are the classes of cytotoxic chemotherapy drugs?

A

Anthracyclines

Bleomycins

Topoisomerase inhibitors

38
Q

What hormones are used in cancer therapy?

A

Breast cancer:

Tamoxifen and other SERMs

Aromatase inhibitors

Prostate cancer:

Anti-androgens

Lymphoid cancers:

Corticosteroids

39
Q

What are the side effects of classical chemotherapy drugs?

A

GI - mouth ulcers (mucositis), nausea, vomiting (especially alkylating agents), and diarrhoea

Hair loss - severe with cyclophosphamide and platinum drugs

Myelosuppression - Infections (WBCs), anaemia and bruising (especially anti-metabolites and mitotic inhibitors

Can cause secondary malignancies (Myeloid neoplasms - MDS and AML)

40
Q

What is the side effect assocaited with cyclophosphamides?

A

Haemorrhagic cystitis (activated in the liver to phosphoramide mustard and acrolein)

41
Q

What is the side effect assocated with methotrexate?

A

Hepatic damage

42
Q

What is the side effect associated with 5-fluorouracil?

A

Skin pigmentation

43
Q

What is the side effect assocaited with paclitaxel and other mitotic inhibitors?

A

Neurotoxicity

44
Q

What are the side effects associated with cisplatin?

A

Neurotoxicity

Nephrotoxicity

Ototoxicity

45
Q

What is radiotherapy?

A

Use of linear accelerator to focus radiation on a cancer.

46
Q

What tumours is radiotherapy used for?

A

Many solid tumours such as hodgkins lymphoma and testicular tumours

47
Q

How does radiotherapy work?

A

Damages DNA causing apoptosis

Ionises water which forms free radicals

48
Q

What are the types of radiotherapy?

A

External beam (deep X-rays or electron superficial beams) (Megavoltage X-rays not the same as diagnostic X-rays)

Brachytherapy - sealed source

Systemic radioisotope therapy

49
Q

When is drug resistance seen usually?

A

Can be seen with first dose (Primary)

Acquired over course of treatment

Can develop simultaneously to multiple drugs

50
Q

What are the mechanisms of drug resistance?

A

Increased metabolic activation of drugs

Decreased activation of metabolism dependent drugs

Decreased accumulation of drug due to decreased uptake or increased efflux.

Increased DNA repair enzyme expression

Altered expression of target proteins.