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Part 3 – PM3B COPY T > (PM3B) Chemotherapy > Flashcards

(PM3B) Chemotherapy Flashcards

1
Q

What is a benefit of combination chemotherapy?

A

Increased remission

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2
Q

What is a downside of combination chemotherapy?

A

Increased side effects

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3
Q

What are some potential chemotherapy targets?

A

(1) Nucleic acids
- DNA double helix
- DNA synthesis
- Amino acid synthesis

(2) Protein targets – enzymes/ receptors/ structural proteins
(3) Other biomacromolecules – cell surface feature (different on cancer cells to normal cells)

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4
Q

What do alkylating drugs do?

A

Damage DNA

Interfere with cell replication

e.g. procarbazine/ cyclophosphamide

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5
Q

Briefly, what are cytotoxic antibiotics?

A

Interact with proteins + DNA

e.g. doxorubicin

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6
Q

Briefly, what are antimetabolites?

A

Incorporated into new nuclear material

Combine irreversibly with vital cellular enzymes

Prevent normal cellular division

e.g. methotrexate/ 5-fluorouracil

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7
Q

Briefly, what are sex hormones and hormone antagonists?

A

Target biological hormone pathways

Interact with receptor binding sites

e.g. oestrogens/ progesterones

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8
Q

Briefly, what are drugs that affect the immune response?

A

Include antiproliferative immunosuppressants + immunomodulating drugs

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9
Q

Briefly, what are vinca alkaloids?

A

Target structural proteins

e.g. vinblastine/ vincristine

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10
Q

Give an example of a chemotherapy drug not classified.

A

Taxanes

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11
Q

What are alkylating agents?

A

Highly electrophilic compounds

React with nucleophiles (to form covalent bonds)
- Can react with any nucleophilic group

In DNA: purine bases

  • N1 + N3 of adenine
  • N3 of cytosine
  • N7 in guanine is MOST targeted

Include nitrogen mustards, cisplatin + analogues, mitomycin C

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12
Q

What is the mechanism of action of alkylating drugs?

A

(1) Drugs with 2 alkylating drugs can bind to guanine on each chain to cross-link the strands
(2) Disrupts replication/ transcription

Can also link 2 guanines on the same chain
- Prevents access by DNA enzymes required for DNA function

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13
Q

What is cyclophosphamide?

A

Alkylating drug

Prodrug - metabolised in the liver to active form

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14
Q

What is cisplatin?

A

Alkylating drug

Aggressive treatment

Called CISplatin due to two chlorine are on same side (not diagonal)

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15
Q

What happens to cisplatin in the body?

A

(1) Enters extracellular environment
(2) Diffuses inside the cell
(3) Chlorine concentration is low inside the cell
(4) Hydrolysis of chlorine (loss)
(5) Replaced with water
(6) Reacts (crosslinks) with DNA at N7 of guanine (nucleophile)

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16
Q

What does cisplatin that actually reacts with the DNA in the cell look like structurally? What processes has it undergone?

A

Two hydroxyl groups where the chlorine groups were previously

Undergone hydrolysis

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17
Q

How does cisplatin react with DNA?

A

N7 of guanine acts as a nucleophile

Cisplatin is nucleophile

Kinks DNA if binding 2 guanines on same side

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18
Q

What are cytotoxic antibiotics?

A

Intercalating agents

Contain a planar aromatic region

Get in between DNA base pairs to inhibit enzymes + distort its structure

e.g. anthracyclines – cardiotoxic side effects

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19
Q

How do cytotoxic antibiotics enter the DNA?

A

Via the major groove of the double helix

Intercalates using the tricyclic system

Charged amino group attaches to the sugar via an ionic bond to DNA backbone

20
Q

What is the purpose of intercalation of the DNA by cytotoxic antibiotics?

A

Inhibition of topoisomerase 2

Which is crucial for effective DNA replication + mitosis

21
Q

What is etoposide?

A

Targets topoisomerase 2

NOT via intercalation

Heterocyclic ring system, NOT aromatic

Binds to DNA + protein to keep ends apart – to inhibit re-ligation

22
Q

What are antimetabolites?

A

Target enzymes

Structurally resemble the preexisting purines + pyrimidines

Mistaken by the cell for normal metabolites

Can become incorporated into the DNA – do not allow DNA function
- Can cause strand breaks/ premature chain termination

23
Q

Give an example of a dihydrofolate reductase inhibitor.

A

Methotrexate

24
Q

What is the mechanism of action of methotrexate (a dihydrofolate reductase inhibitor)?

A

Inhibit dihydrofolate reductase

Which is essential for folate metabolism

Slows DNA synthesis + proliferation

25
Q

What are some side effects of antimetabolites?

A

(1) Bone marrow suppression
(2) Mucositis
(3) Diarrhoea

26
Q

Why is folinic acid given with methotrexate for chemotherapy?

A

Overcomes metabolic block caused by methotrexate

Rescues patient from toxic effect of treatment

Is a tetrahydrofolate so provides an alternative source for the synthesis of nucleic acids

27
Q

When is methotrexate given in chemotherapy?

A

Often in combination

To treat neoplastic cancers

28
Q

Name a thymidylate synthetase inhibitor.

A

5-fluorouracil

29
Q

What is a thymidylate synthetase inhibitor?

A

Allow synthesis of thymidine to be terminated

Stops DNA synthesis

30
Q

Why is 5-fluorouracil considered a suicide substrate?

A

Inhibits thymidylate synthetase irreversibly

31
Q

When is 5-fluorouracil used in chemotherapy?

A

(1) Breast cancer
(2) Liver cancer
(3) Skin cancer

32
Q

What are some side effects of 5-fluorouracil?

A

(1) Neurotoxic side effects

(2) Cardiotoxic side effects

33
Q

What are antimetabolite DNA polymerase inhibitors?

A

Prevents DNA polymerase replicating DNA

Can lead to DNA chain termination

Incorporated into DNA strand

e.g. cytarabine

34
Q

What is cytarabine?

A

Antimetabolite

DNA polymerase inhibitor

35
Q

Give an example of an antimetabolite DNA polymerase inhibitor.

A

Cytarabine

36
Q

What are the vinca alkaloids?

A

Inhibit tubulin polymerisation in cell division

e.g. vincristine/ vinblastine/ vindesine

37
Q

How are vinca alkaloids sourced?

A

NOT synthesised

Found in plants – adjusted slightly

38
Q

What are taxanes?

A

Inhibit tubulin depolymerisation

39
Q

What is the mechanism of action of taxanes?

A

(1) Bind to ß subunit of tubulin
(2) Binding accelerates polymerisation + stabilises resultant microtubules
(3) Inhibits depolymerisation because of this
(4) Cell division cycle stopped at G2/M stage

40
Q

What is a kinase inhibitor?

A

Target enzymes (structural proteins) – switches off oncogenic signalling

(1) Prevents phosphorylation of signalling proteins
(2) Inactivates signalling proteins
(3) Stops cellular processes

41
Q

How can cells develop resistance to kinase inhibitors?

A

Mutation of key amino acids in kinase binding site

42
Q

What are hormone based therapies?

A

Used for hormone dependent cancers

Hormone antagonists can be used to block hormone action

e.g. tamoxifen

43
Q

Why are glucocorticoids used in chemotherapy?

A

Treatment of leukaemia + lymphoma

Target glucocorticoid receptor signalling

(1) Bind to glucocorticoid receptors
(2) Inhibits cytokine production
(3) Alters oncogene expression
(4) Induces cell cycle arrest + apoptosis

44
Q

What are monoclonal antibodies?

A

Cancer cells have individually specific antigens which have been over-expressed

Antibodies that recognise a distinct antigen

45
Q

What types of monoclonal antibody are there?

A

(1) Trigger immune response to attack cancer cells, e.g. rituximab
(2) Block signals related to cell division, e.g. trastuzumab
(3) Deliver drugs/ radiation to cancer cells, e.g. ibritumomab

Part 3 – PM3B COPY T (33 decks)

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