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DDT > DDT 9 Chemotherapy drugs > Flashcards

DDT 9 Chemotherapy drugs Flashcards

1
Q

fundamental techniques to treat cancer

A

surgery
radiation therapy
chemical based approach

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2
Q

purpose of chemotherapy

A

Cure a specific cancer
Reduce the size prior to surgery
Sensitize tumour to radiation therapy
Destroy small metastases after surgery

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3
Q

what is chemotherapy useful for?

A

useful for eliminating cancers that are relatively small in size.

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4
Q

why are chemotherapy not used for large cancers

A

large cancers are not perfused by blood and thus the inner part may not be accessible to chemotherapeutic agents.

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5
Q

limitation of chemotherapy

A

the lack of selectivity of the agents for normal versus malignant cells.

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6
Q

assumption in chemotherapy

A

tumour cells - high metabolism - divide much quicker than normal cells
will uptake more chemotherapy drugs

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7
Q

why are the side effects of chemotherapy, hair loss,depression of
immune system and nausea.

A

cells that are strongly affected by chemotherapy include
hair cells
bone marrow cells
cells lining the gastro-intestinal tract

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8
Q

mechanism of chemotherapy

A 
topoisomerase inhibitors
Alkylating agents
Antimetabolites 
Monoclonal antibodies
intercalating agents
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9
Q

topoisomerase function

A

helps DNA uncoiling for the process of DNA replication and protein synthesis

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10
Q

intercalating agents

A

can insert into double helix of DNA and distort structure

can inhibit the enzymes involved in replication and transcription processes

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11
Q

Anthracyclines

A

naturally occurring antibiotics isolated from bacteria

have anti-cancer properties - bind to DNA structure

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12
Q

doxorubicin is isolated from what

A

streptomyces peucetius in 1967

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13
Q

what type of cancer does doxorubicin target

A

broad range of solid tumours

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14
Q

how does doxorubicin act against cancer

A

binds into DNA and acts as a topoisomerase II poison
stabilises the complex formed between DNA and topoisomerase II
Excessive no. of stabilised DNA-enzyme complexes
triggers apoptosis.

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15
Q

how does doxorubicin bind to DNA?

A

bind to CG or GC base pair to form a buckle
distort DNA structure and prevent Van der Waals forces
stabilized by - H bonding and aromatic pi bonding

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16
Q

Dactinomycin is isolated from what

A

S. parvullus

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17
Q

what does dactinomycin contain

A

3 fused aromatic rings

Two identical pentapeptide side chains

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18
Q

what tumour does the dactinomycin target?

A

pediatric solid tumours

19
Q

where does dactinomycin bind to DNA and what holds the drug in place?

A

between GC base pairs
favours intercalation between 2 G bases on diff. strands
Held by aromatic pi stacking interactions between tricyclic ring and

20
Q

tubulin

A

strucutral protein - crucial to cell division

acts as building block for microtubules - polymerised and depolymerised in cell division

21
Q

how do drugs block the process of microtubules

A

Drugs can block this process by either binding to tubulin to prevent
polymerization or binding to the microtubules to prevent
depolymerisation

22
Q

why do anti cancer cells acting on tubulin effective in inhibiting cancerous cell division

A

cancer cells divide rapidly through mitosis and need microtubules for division

23
Q

where does vincristine bind to

A

bind to tubulin inhibiting assembly of microtubule

stops mitosis in metaphase and prevent cell replication

24
Q

what types of cancers does vincristine work for?

A

work w/ other drugs for non-Hodgkins lymphoma and childhood leukemia

25
Q

paclitaxel function

A

stabilise microtubules - interfere w/ normal breakdown of microtubules
blocks progression of mitosis - triggers apoptosis

26
Q

features of alkylating anti cancer agents

A

Drug contains highly electrophilic groups.
They form covalent bonds to nucleophilic groups in DNA (e.g. N-7 of guanine).
This prevent replication and transcription.
Useful anti-tumour agents.

27
Q

function fo alkylating anti cancer agents

A

Used as anticancer agents

Can cause interstrand and intrastrand crosslinking if two electrophilic groups are present

28
Q

toxic side effect of alkylating anti cancer agent

A

Toxic side effects due to non-selective alkylation

e.g. alkylation of proteins or alkylation of DNA in rapidly dividing non-cancerous cell

29
Q

what can alkylation of nucleic acid lead to?

A

Alkylation of nucleic acid bases can result in miscoding

30
Q

DNA alkylating agent

A

cause cross linking of intrastrand (within the same strand)

interstrand (between two strands in DNA)

31
Q

function of chlormethine - an alkylating agent

A

Causes intrastrand and interstrand crosslinking
Prevents cell replication
Monalkylation of guanine also possible

32
Q

when was chlormethine first used

A

Used medicinally first in 1942

33
Q

chlormethine is an example of what

A

nitrogen mustard

34
Q

reaction mechanism of hydroxide/ammonia w/ chloromethane

A

OH-/NH3 attack the nearest H in the chloromethane - forms methanol/ chloromethine and Cl-

35
Q

describe in detail the mechanism of the azridine ion from chlormethine to the DNA

A

chloromethine (Electron in N of chloromethine is drawn to partially positive charge in Cl and moves to C - electron from C moves to Cl) -> aziridine ion
nitrogen bind to corner of molecule
1st chemical mod.: N from DNA strand attaches to C end of Azridine ion
electron from N moves to C near other Cl and electron from C moves to Cl
N from other side of strand attacks the complex

36
Q

what is the purpose of anti-cancer drugs interfering with microtubule function

A

to prevent mitosis

37
Q

how do alkylating agents prevent anti-cancer cells from replicating

A

interfere with DNA base pairing, leading to strand breaks and stopping DNA replication

38
Q

Antimetabolites function as an anti-cancer drug

A

block the formation and use of nucleic acids essential for DNA replication

39
Q

Monoclonal antibodies function as an anti-cancer drug

A

recognition of over expressed antigens on cancer cell membrane

40
Q

what helps stabilise the dactinomycin bound to DNA

A

DNA bases

Stabilised by peptide hydrogen-bonding to nucleic acid bases of DNA

41
Q

how does dactinomycin act as an anti-cancer drug

A

→ interferes with Topoisomerase II,

→ inhibition of replication and transcription

42
Q

Name chemotherapy drugs that act on tubulin

A

vincristine

paclitaxel

43
Q

types of cancer paxlitaxel is used for

A 
ovarian
breast
lung bladder
prostate 
melanoma
oesophageal cancer

DDT (21 decks)

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