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Cancer > Cancer part 2 - Cytotoxic CT > Flashcards

Cancer part 2 - Cytotoxic CT Flashcards

1
Q

Describe the Log Kill hypothesis

A

It is when the chemotherapy kills off 99% of the cancer cell every round

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2
Q

What are the physical barriers of cytotoxic chemotherapy

A

No blood supply to supply drug to the middle of a solid mass tumour due to necrosis

Pressure impacts the movement of drugs into tumour (High tumour interstitial pressure )

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3
Q

Adverse effects of Cytotoxic chemotherapy

A

Nausea
Damage to the GIT
>Causes mouth ulcers
Damage to the the Haemopoietic system
>Myelosuppression (Bone marrow damage)

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4
Q

How can the Mucositis be treated

A

Local anaesthetics in the from of sweets

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5
Q

What can myelosuppression cause

A

Increased viral and fungal infections

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6
Q

How can myelosuppression be avoided

A

Chaning the treatment

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7
Q

How can myelosuppression be avoided

A

Treatment
>Change the timing of the dose
>Through Transfusion of Platelets,
>CSF
Prevention
>Avoid exposure to infection
>Patients do better at home
>Avoid infected people/crowds
>Watch kitchen hygiene

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8
Q

How long does it take for hair loss to occur

A

within 1-2 weeks

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9
Q

What side effect of CT agents normally affect men

A

Gonadal damage: Pt’s become sterile

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10
Q

List some drug specific side effect and the drugs that cause the S/E

A

Cisplatin: Renal toxicity

Ifosfamide and cyclophosphate: Haemorrhagic cystitis

Doxorubicin: Cardiotoxicity

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11
Q

How does drug resistance occur with Anti-cancer drugs

A

> Improved proficiency in DNA repair

> Decreased drug activity

> Increased drug inactivity

> Increased efflux of drug

> Alternative biochemical pathway

> Alteration in target enzymes

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12
Q

What factors need to be considered before starting chemotherapy

A

Patient age- older
Health status
Geographical variation
If it is write for the patient

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13
Q

What percentage of people die within a month of starting chemo and what does that indicate`

A

8.4% lung cancer, 2.4% breast cancer

Indicates that Chemo was the likely cause of their death

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14
Q

What scales are used to assess pt’s performace status

A

Zubrod scale (0-4)

Karnofsky scale (100-10)

Who score (0-1)

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15
Q

What are the two types of cell cycle drugs

A

Cell cycle specific
Cell cycle non-specific

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16
Q

Properties of cell cycle specific drugs

A

Kills cells most effective at a stage in the cycle

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17
Q

Properties of cell cycle non-specific drugs

A

Can kill cell at any stage
It is dose dependant

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18
Q

Which class of drugs affect the specific cell cyle stages (Cell specific drugs)

A

G1:
>Hormonal drugs
>Antineoplastic enzymes
S:
>Topoisomerase-1 inhibitors
>Antimetabolites
G2:
>Epipodophyllotoxin derivatives
>Bleomycin
M:
>Taxanes
>Vinca Alkaloids

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19
Q

List some Antineoplastic enzymes (G1)

A

Asparaginase
Pegaspargase

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20
Q

List some Topisomerase-1 inhibitors (S)

A

Topotecan
Irinotecan

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21
Q

List some Subclasses of Antimetabolites (s)

A

Folate analogues

Purine Analogues

Pyrimidine Analogues

Miscellaneous class: Hydroxyurea

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22
Q

Name some folate analogues

A

Methotrexate

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23
Q

Name some purine analogues

A

Cladribine

Fludarabine

Gemcitabine

Mercaptopurine

Pentostatin

Thioguanine

24
Q

Name some Pyrimidine Analogues

A

Capecitabine

Cytarabine

Gemcitabine

Floxuridine

Fluorouracil

25
Q

Name some Epipodophyllotoxin derivatives (S)

A

Etoposide

Teniposide

26
Q

Name some Taxanes (M/G2)

A

Docetaxel

Paclitaxel

27
Q

Name some Vinca Alkaloids (M)

A

Vinblastine

Vincristine

Vinorelbine

28
Q

Name some Cell cycle Non-specific classes

A

Alkylating agents

Antitumour antibiotics

Miscellaneous

29
Q

List some Alkylating agents

A

Busulfan

Chlorambucil

Cyclophosphamide

Ifosfamide

Mechlorethamine

Melphalan

30
Q

Name some Anti-tumour Antibiotics

A

Dactinomycin

Daunorubicin

Doxorubicin

Idarubicin

Mitomycin

Mitoxantrone

31
Q

Name some Miscellaneous non-cell cycle specific drugs

A

Carboplatin

Carmustine

Cisplatin

Dacarbazine

Hexamethyl-melamine

Hydroxyurea

Lomustine

procarbazine

32
Q

How are chemotherapy usually administered

A

They are given as a combination that do not have over lapping mechanisms or toxicities.

33
Q

Properties of Alkylating agent

A

> Most effective during the proliferating stages (G1 and S)
Toxic to any rapidly diving cells
Used in combo
Used for solid and lymphatic tumour
They are Mutagenic and carcinogenic leading to secondary malignancy

34
Q

what is the general mechanism of Alkylating agents

A

Binds covalently to nucleophilic groups on the nucleotides and prevents DNA replication

35
Q

Which specific locations do alkylating groups bind

A

N7 and O6 of guanine
N1 and N3 of adenine
N3 of cytosine

36
Q

Which binding location is most critical for cytotxic action

A

Guanine N7

37
Q

What are some ways that Alkylating agents can cause DNA damage?

A

> Inter-strand cross-linking of DNA strands - stops strand separation
Intra-strand cross-linking
Base ring cleavage - strand cleavage
De-purination - strand cleavage
Tautomeric mutation - G pairs with T, GC to AT in daughter cells
Ineffective repair - frameshift mutation

38
Q

What is nitrogen Mustard and how does it cause cancers

A

Bischloroethylamines (SCH2CH2Cl) developed from nitrogen or sulphurs used in chemical warfare

Lead to tumours (due to damaged DNA from remaining SCH2CH2- group)

39
Q

What are the mechanism of Alkylating agents (Nitrogen mustards)

A

Chlorine disaggregates

Undergo intramolecular cyclisation forming an unstable ethylene immonium cation

Tertiary amine is transformed into quaternary ammonium cmpd

Ring opens out to form reactive carbonium ion which performs the alkylation

Carbonium ion is unstable reacts with an electron donor (The DNA)

40
Q

What does changing the R group on the nitrogen mustards do

A

Changes the activity and specificity

41
Q

What are some general side effects of Alkylating agents

A

> Extravasation damage
N&V
Mucositis
Myelosuppression
Alopecia
Depressed Gametogenic
Increased risk of non-lymphocytic leukaemia
Drug handling/Waste handling

42
Q

What is the name of the most potent Nitrogen mustard

A

Mechlorethamine

43
Q

Why is mechlorethamine not used as often anymore

A

Very instable

Little drug excreted

lots of Extravasation accident at the injection site

44
Q

What are the most commonly used Alkylating Drugs

A

Cyclophosphamide

ifosfamide

45
Q

How is Cyclophosphamide aministered

A

Orally

46
Q

How is ifosfamide Administered

A
47
Q

How are both Cyclophosphamide and ifosfamide activated

A

By the enzyme in the liver- hepatic p450

48
Q

What causes the resistance of Cyclophosphamide and ifosfamide

A

Increased DNA repair

Increased production of thiols

49
Q

What conditions are Cyclophosphamide and ifosfamide used for

A

Burkitt’s lymphoma and other lymphomas
ALL (acute lymphoblastic leukaemia)
Breast cancer

50
Q

what are the standard side effects for cytotoxic chemotherapy

A

> N/V/D
Alopecia
Myelosuppression
Haemorrhagic cystitis - fibrosis of bladder - due to acrolein
Amenoohoea/sterility
Secondary malignancies

51
Q

Name some other Alkylating drugs

A

Chlorambucil

Melphalan

52
Q

What are the properties of Chlorambucil

A

Carrier molecule delays activation of the drugs for better distribution

Oral admin for lymphocytic leukemias

53
Q

Properties of mephalan

A

Has Phenlyalanine as a carrier
>Targets melanomas

Administered orally for myelomas and ovarian cancer

54
Q

Name tow other nitrogen mustards

A

Uramutine

Oestramustine

55
Q

What is a pharmacological sanctuary

A

When metastasis occurs where a drug can not get to.
>The Brain due to BBB

56
Q

What is a nitrosourea

A

A drug made from the slight alteration of nitrogen mustards

57
Q

what is the function of nitrosourea

A

To have more access to the pharmacological sanctuary

Cancer (18 decks)

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