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Unit 2 > Principles of Chemotherapy I > Flashcards

Principles of Chemotherapy I Flashcards

1
Q

Targets of Drugs (4)

A
  • receptors
  • enzymes
  • ion channels
  • transporters
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2
Q

Function of Chemotherapeutic drugs

A

kill or suppress the proliferation of target cells

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3
Q

Principle of selective toxicity

A

drugs should be toxic to the infectious organism or tumour but not healthy host cells

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4
Q

How do cancer cells differ from normal host cells? (5)

A
  • uncontrolled proliferation
  • de-differentiation
  • loss of function
  • invasion
  • metastasis
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5
Q

Target: Chemotherapeutic Drugs… (5)

A

1) target Proliferation
2) modify DNA structure
3) inhibit DNA synthesis
4) inhibit Mitosis
5) inhibit Inflammation

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6
Q

Most chemotherapeutic agents…

A

Target Proliferation

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7
Q

Drugs that modify DNA structure (4)

A
  • alkylating agents
  • platinum compounds
  • cytotoxic agents
  • topoisomerase inhibitors
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8
Q

Example of Alkylating agent

A

cycle-phosphamide

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9
Q

What are Alkylating agents activated by?

A

liver CYP450 mixed-function oxidases

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10
Q

What do Alkylating agents alkylate? (3)

A
  • DNA bases
  • particularly Guanine
  • at postion N7
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11
Q

What do Alkylating agents do? (4)

A
  • cause intra-strand or inner-strand cross linking
  • interfere with both replication and translation of DNA
  • disrupt DNA synthesis in S-phase
  • causes cell cycle arrest and apoptosis at G2 checkpoint
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12
Q

Example of a Platinum compound

A

Cisplastin

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13
Q

What do Platinum compounds do? (4)

A
  • form a reactive complex in cell which binds to N7 and O6 at guanine
  • cause intra-strand cross linking
  • disrupt DNA synthesis (S-phase)
  • cause cell cycle arrest and apoptosis (G2 checkpoint)
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14
Q

Examples of Cytotoxic compounds (3)

A
  • Bleomycin
  • Anthracyclins
  • Dactinomycins
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15
Q

What do Cytotoxic compounds bind to? (2)

A
  • DNA
  • chelate Fe2+
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16
Q

What do Cytotoxic compounds do? (5)

A
  • lead to local production of free radicals, that break DNA strands
  • intercalate between adjacent DNA bases
  • inhibit Topoisomerase II
  • prevent DNA replication and transcription
  • causing cell cycle arrest and apoptosis (G1/2 checkpoints)
17
Q

Examples of Topoisomerase inhibitors? (2)

A
  • Camptothecins
  • Epipdophyllotoxins
18
Q

Topoisomerase inhibitor:

Example of Camptothecin

A

Toptecan

19
Q

Topoisomerase inhibitor:

What do Camptothecins do? (3)

A
  • inhibit Topoisomerase I
  • stabilise nicked single strands and prevent re-sealing
  • causing cell cycle arrest and apoptosis (G2 checkpoint)
20
Q

Topoisomerase inhibitor:

Example of Epipdophyllotoxin

A

Etoposide

21
Q

Topoisomerase inhibitor:

What do Epipdophyllotoxins do? (3)

A
  • inhibit Topoisomerase II
  • prevent re-sealing of double strands
  • often combined with Bleomycin and Cisplastin if treating metastatic cancers
22
Q

Drugs that inhibit DNA synthesis

A

Antimetabolites

23
Q

DNA synthesis inhibitor:

Examples of Antimetabolites (3)

A
  • Methotrexate
  • 5-fluorouracil
  • 6-mercaptopurine
24
Q

DNA synthesis inhibitor:

What do Antimetabolites inhibit? (2)

A
  • inhibit nucleic acid base synthesis
  • DNA synthesis
25
Q

Antimetabolites:

What does Methotrexate inhibit? (3)

A
  • inhibits dihydrofolate reductase, preventing folate cycling
  • inhibits pyrimidine synthesis
  • inhibits purine synthesis
26
Q

Antimetabolites:

What does 5-fluorouracil inhibit? (2)

A
  • inhibits thymidylate synthetase
  • inhibits pyrimidine synthesis
27
Q

Antimetabolites:

What does 6-mercaptopurine inhibit?

A

inhibitor of IMP dehydrogenation/deamination

28
Q

Drugs that inhibit Mitosis (2)

A
  • Vinca Alkaloids
  • Taxanes
29
Q

Mitosis inhibitor:

Examples of Vinca Alkaloids (2)

A
  • Vincristines
  • Vinblastine
30
Q

Mitosis inhibitor:

What do Vinca Alkaloids do? (4)

A
  • inhibit polymerisation of microtubules
  • inhibit formation of mitotic spindle
  • mitosis arrested in Metaphase
  • cell cycle arrested in M-phase
31
Q

Mitosis inhibitor:

Example of Taxane

A

Paclitaxel

32
Q

Mitosis inhibitor:

What do Taxanes do?

A
  • stabilise polymerised microtubules
  • prevent release of chromosomes from spindle
33
Q

Drugs that inhibit Inflammation

A

Anti-inflammatory drugs

34
Q

Example of Anti-inflammatory drug

A

Dexamethasone

35
Q

Drugs that inhibit Inflammation:

What does Dexamethasone do? (5)

A
  • anti-inflammatory synthetic glucocorticoid
  • mimics action of cortisol (stress hormone)
  • increases expression of anti-inflammatory genes and suppresses expression of pro-inflammatory genes
  • prevents formation of hospitable environment/enhanced blood supply
  • reduces swelling around tumour
36
Q

Drugs beyond Chemotherapy

A

Depleting Growth Substrates

37
Q

Drugs beyond Chemotherapy:

A
38
Q

Drugs beyond Chemotherapy:

Example of Depleting Growth Substrates

A

L-asparaginase

39
Q

Drugs beyond Chemotherapy:

What does L-asparaginase do?

A
  • breaks down L-asparagine
  • L-asparagine is needed in environment for cancer

Unit 2 (7 decks)

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