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House Pharmacology > Cancer Chemotherapy > Flashcards

Cancer Chemotherapy Flashcards

1
Q

Cancer is a disease characterized by (controlled or uncontrolled?) and spread of (normal or abnormal?) forms of the body’s own cells

A

uncontrolled

multiplication

abnormal

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2
Q

Cancer is one of the major causes of death in the developed nations

T/F

A

T

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3
Q

One in ________ people will be diagnosed with cancer during their lifetime

A

three

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4
Q

Cancer is also responsible for approximately ______ of all deaths in the UK

A

1⁄4

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5
Q

_____ and _____ cancer comprises the largest category, closely followed by _____ and _______ cancer

A

lung and bowel

breast and prostate

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6
Q

Malignant tumours are distinguished by their capacity for __________ , their __________ and their ability to __________

A

de-differentiation

invasiveness

metastasise

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7
Q

There are three main approaches to treating established cancer:
 __________
 __________
 __________

A

 Surgical excision
 Irradiation
 Chemotherapy

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8
Q

Cancer cells manifest to varying degrees. Four characteristics distinguish them from normal cells:

¤ Uncontrolled ____________
¤ ____________
¤ ____________
¤ ____________

A

¤ Uncontrolled proliferation
¤ Differentiation
¤ Invasiveness
¤ Metastasis

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9
Q

Genesis of a Cancer cell

A normal cell turns into a cancer cell because of one or more ______ in its DNA, which can be ______ or __________

A

mutation

acquired or inherited

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10
Q

Genesis of a Cancer cell

The activation of __________ to __________.

A

proto-oncogenes to oncogenes.

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11
Q

Proto-oncogenes, which are genes that normally control ________, ________ and ________ may be converted to ________ that induce ________ change by ________ or ________ action

A

cell division

apoptosis ; differentiation

oncogenes; malignant

viral ; carcinogenic action

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12
Q

Genesis of a Cancer cell

The inactivation of __________ genes: Normal cells contain genes that can _______ malignant change- termed __________ genes (__________)

A

tumour suppressor genes

suppress ; tumour suppressor genes

antioncogenes

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13
Q

Loss of function of tumour suppressor genes can be the critical event in carcinogenesis

T/F

A

T

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14
Q

A major difficulty in treating cancer is that tumour growth is usually __________ before cancer is diagnosed

A

far advanced

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15
Q

Doubling time of tumour cells varies from ________ (___________) to ________ (______) to ______ (__________ cancer)

A

24 hours (Burkitt’s lymphoma)

2 weeks (leukaemia)

3 months (mammary cancer)

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16
Q

____ doublings will be required to produce a cell mass of ___ cm (containing ___ cells)

A

30

2

10^9

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17
Q

The cells of a solid tumour can be considered as belonging to three compartments:

  1. Compartment A: Consists of ________ cells, possibly being ___________________________
  2. Compartment B consists of _____\ cells (___ phase), which ______________________
  3. Compartment C consists of cells that are ________________ but which contribute to the ______________
A

dividing cells; continuously in cell cycle

resting cells ; Go phase ; not dividing, are potentially able to do so

no longer able to divide; tumour volume

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18
Q

Only the ____% of cells in compartment A are susceptible to cytotoxic drugs, the cells in compartment C do __________ while the cells in compartment B make ______________

A

5

not constitute a problem

cancer chemotherapy difficult

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19
Q

Cytotoxic drugs affect only the _______ of cancer cells but no inhibitory effect on _______,_______, or _________

A

cell division

invasiveness, differentiation or metastasis

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20
Q

Cytotoxic drugs may have the following adverse effects

__________ toxicity (______suppression) Impaired ___________
Loss of _____ (_____)
Damage of __________ epithelium (Mucositis)

A

Bone marrow (myelosuppression)

wound healing

hair (alopecia)

gastrointestinal

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21
Q

Cytotoxic drugs may have the following adverse effects

Depression of ______ in children
________
_____________
They can be ________ (_______ Malignancies)

A

growth

Sterility

Teratogenicity

carcinogenic ; Secondary

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22
Q

Special Characteristics of Cancer Cells

A. Uncontrolled Proliferation
Changes that lead to the uncontrolled proliferation of tumour cells are:

Inactivation of _________ genes Transformation of ________ into ________

A

tumour suppressor genes

proto-oncogenes into oncogenes

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23
Q

Special Characteristics of Cancer Cells

A. Uncontrolled Proliferation

Uncontrolled proliferation can also occur as a result of changes in several cellular systems

1)Growth factors- ______ and ______ pathways

2) Cell cycle transducers e.g .______, _________ kinase of cyclin dependent ________

3)________ machinery that normally disposes of abnormal cells

4) ___________ expression

5) Local blood vessels- tumour directed _________

A

receptors and signalling

cyclins, cyclin dependent; inhibitors

Apoptotic; Telomerase

angiogenesis

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24
Q

Special Characteristics of Cancer Cells

Uncontrolled proliferation:

Apoptosis: Programmed cell death and genetic mutations in the ________ genes.

__________ is a hallmark of cancer.

Inactivation of _________ factors or activation of _________ factors

A

anti-apoptotic

Resistance to apoptosis

anti-apoptotic

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25
Q

Special Characteristics of Cancer Cells

Uncontrolled proliferation:

Telomerase expression: Telomere are specialized structures that _____________________________, ______ them from _________,___________, and __________ with other chromosomes

A

cap the ends of chromosomes

protecting

degradation, re-arrangement and fusion

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26
Q

Special Characteristics of Cancer Cells

Uncontrolled proliferation:

  • control of tumour related blood vessels: this factor influences ________ due to development of _____________
A

total tumour mass

its own blood supply

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27
Q

Special Characteristics of Cancer Cells

B. Differentiation and loss of function

Division of undifferentiated stem cells giving rise to _____ cells which also differentiate to become ______ cells

A

daughter

mature cells

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28
Q

Special Characteristics of Cancer Cells

B. Differentiation and loss of function

Example: fibroblasts secrete and organize ____________

A

extracellular matrix

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29
Q

Special Characteristics of Cancer Cells

B. Differentiation and loss of function

Poorly differentiated cancers multiply (slower or faster?) and carry (better or worse?) prognosis than well differentiated
cancers

A

Faster

Worse

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30
Q

Special Characteristics of Cancer Cells

C. Invasiveness
Ability of cancer cells to ______________

A

move around the system

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31
Q

Special Characteristics of Cancer Cells

C. Invasiveness

Cancer cells secrete ________ that break down the ___________, enabling them to move around

A

metalloproteinases

extra cellular matrix

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32
Q

Special Characteristics of Cancer Cells

D. Metastases
Formation of ________ tumours by cells that are released from the initial or primary tumour and reach other sites through ______________

A

secondary tumours

blood vessels

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33
Q

_________ are the principal cause of mortality and morbidity in most cancers and constitute major problems in cancer therapy

A

Metastases

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34
Q

Metastases of mammary cancer are often found in ______,________ and ______

A

lungs, bones and brain

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35
Q

Classification of cancer drugs

A

_______ agents
Anti______
_____ products
__________ and ________
Miscellaneous

A

Alkylating agents
Antimetabolites
Natural products
Hormones and antagonists
Miscellaneous

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36
Q

Classification of drugs

A

Alkylating agents: ________,________,______,________,__________ , methylhydrazine derivatives, alkyl sulfonate, nitroso ureas, triazenes, platinium co-ordination complexes

A

Cyclophosphamide, chlorambucil, nitrogen mustard, ethylene imines, methylmelamines

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37
Q

Classification of drugs

A

Antimetabolites: _______ analogues ( ————- ), ________ analogues (______________ ), _______ analogue (________) and related metabolites

A

Folic acid; methotrexate

pyrimidine; 5 fluorouracil

purine; mercaptopurine

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38
Q

Classification of drugs

A

Natural products: ________ alkaloids (_______,_______), _______,____________,__________

A

Vinca alkaloids

vinblastine, vincristine

taxanes, camptothecins, antibiotics

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39
Q

Classification of drugs

A

Hormones and antagonists:________,_________,________, _______

A

Estrogens, progestins, androgens, adrenocorticosteroids

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40
Q

Classification of drugs

A

Miscellaneous:__________
inhibitors, -__________ modifiers

A

Protein tyrosine kinase

biological response

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41
Q

Classification of drugs
B

Action on particular phases on the cell
cycle

  1. Phase-specific agents e.g. _____ alkaloids act in __________;

cytarabine, hydroxycarbamide,
fluorouracil, methotrexate and
mercaptopurine act in _____-phase

A

vinca ; mitosis

S

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42
Q

Classification of drugs
B

Action on particular phases on the cell
cycle

_______-_______ agents

_______ _______ agent

_______ _______ agents

A

Phase-specific agents

Cycle specific agent

Cycle non-specific agents

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43
Q

Classification of drugs
B

Action on particular phases on the cell
cycle

Cycle specific agents- act at ____ stages of the cell cycle but _________________

 e.g. _______ agents; _______,________,_______

A

all

do not have much effect on cells out of cycle

alkylating

Dactinomycin; Doxorubicin; Cisplatin

44
Q

Classification of drugs
B

Action on particular phases on the cell
cycle

Cycle non-specific agents: these act on cells _______________________

 e.g. _______ and ________

A

whether in cycle or not

bleomycin and nitroso ureas

45
Q

Phase non-specific drugs

_______ drugs
____________
_______ antibiotics
_______
___________
___________

A

Alkylating drugs
Nitrosoureas
Antitumor antibiotics
Cisplatin
Decarbazine
Procarbazine

46
Q

ALKYLATING AGENTS

Forms __________ bonds with cell substituents

Cause excision of __________ and __________

A

Covalent

guanine and chain breakage

47
Q

Alkylating agents

Principal effect occurs during ________ and the resulting ______ triggers ______

Alkylating agents contain chemical groups that can form ____________ with particular _______ substances in the cell

A

DNA synthesis ; damage

apoptosis; covalent bonds

nucleophilic

48
Q

Alkylating Agents

Alkyl agents form carbon atom with _____ reactive and unstable electrons and thus reacts with ______,______, or ______ group

They interfere with both _______ and _______ which is the critical effect of anticancer alkylating agents

A

six

amine, hydroxyl or sulfhydryl group

transcription and replication

49
Q

Alkylating Agents

The main impact is seen during ________ (____- phase) when some zones of the DNA are (paired or unpaired?) and more susceptible to ————-

This results in a block at _____ and subsequent _________

A

replication (S- phase)

unpaired ; alkylation

G2 ; apoptotic cell death

50
Q

Alkylating Agents

All alkylating agents depress ________ function and cause _____ disturbances

Other effects are depression of _______ (men), increased risk of ___________ leukaemia and other malignancies

A

bone marrow function; GIT disturbances

gametogenesis (men)

acute non-lymphocytic

51
Q

Alkylating Agents

  1. Nitrogen Mustards

Related to???

It is inactive until metabolized in the liver by P450 ____________________

Have pronounced effect on _______

Can also be used as _________ given by oral, i.m and i.v routes

A

mustard gas

mixed function oxidases

lymphocytes

immunosuppressants

52
Q

Most commonly used alkylating agent is??

A

Cyclophosphamide

53
Q

Side effects of cyclophosphamide are: _________ depression, vomiting, nausea, haemorrhagic ______

A

bone marrow

cystitis

54
Q

Other examples of nitrogen mustards are:

__________
_________
___________
__________\

A

Chlorambucil

Ifosfamide

Melphalam
Estramustine

55
Q

Estramustine- combination of _______(_______) and _________.

This has both ______ and _______ action.

Used in _______ cancer

A

chlormethine (mustine) and oestrogen

cytotoxic and hormonal

prostate

56
Q

Alkylating Agents: Nitrosoureas

Lipid (soluble or insoluble ?) and (can or can not ?) cross the blood brain barrier

Used against tumours of the ______ and _______

Have pronounced depressive effect on _______

Examples are _______ and _______

A

soluble; can

brain and meninges

bone marrow

lomustine and carmustine

57
Q

Alkylating Agents: Busulfan

Has _______ effect on bone marrow

Depressed formation of _____ and _______ in low dosage and _______ in higher dosage

Used in chronic granulocytic leukemia

A

selective

granulocytes and platelets

red blood cells

58
Q

PLATINUM COMPOUNDS

Cisplatin: _____ soluble surrounded by __________ atoms and ________ groups.

It’s action is analogous to ________

A

Water

two chlorine atoms

two ammonia group

Alkylating agents

59
Q

Platinum compounds: Cisplatin

When it enters the cell, ____ dissociates leaving a __________ that reacts with ——- and then interacts with _____

This causes _______ of DNA

A

Cl-

reactive complex

water; DNA

denaturation

60
Q

Platinum compounds : cisplatin

Cisplatin is used in _____________ tumours

A

ovary and testes

61
Q

PLATINUM COMPOUNDS: Cisplatin

Given by I.V route or by infusion

It is highly ____toxic. Strict regime of ______ and ____- should be instituted

Nausea, vomiting, tinnitus, _____ loss, peripheral _______, hyper_______ and _______- reactions may occur

A

nephro

hydration and diuresis

hearing; neuropathies; uricaemia

anaphylactic

62
Q

Platinum Compounds: Carboplatin

Derivative of _______

Has (more or less?) nephrotoxic, neurotoxic, ototoxic, nauseating and vomiting effects than cisplatin

A

cisplatin

Less

63
Q

Platinum Compounds: Oxaliplatin

Platinum containing compound with ________

A

restricted application

64
Q

Platinum Compound: Dacarbazine

Activated in the liver and the resulting compound is subsequently cleared in the target cell to release an alkylating derivative

Unwanted effects include ______toxicity, severe nausea and vomiting

A

myelo

65
Q

Dacarbazine is a Prodrug

T/F

A

T

66
Q

Platinum Compounds: Temozolomide

related compound with a ______ usage (malignant ———-)

A

restricted

glioma

67
Q

Platinum compounds

_____platin
____platin
____platin
_________
__________

A

Cisplatin
Carboplatin
Oxaliplatin
Dacarbazine
Temozolomide

68
Q

ANTIMETABOLITES: Folate Antagonists

Methotrexate

Folates are essential for synthesis of _________ and ____ which are essential for _________ and cell division

Folate antagonists interfere with ——— synthesis

A

purine nucleotides and thymidylate

DNA synthesis

thymidylate

69
Q

Folate antagonists

Pharmacokinetics:
Given orally and also I.M, I.V or intrathecally

(Low or High?) lipid solubility thus poorly cross BBB

Metabolized into _________ derivatives
which are retained in the cell for ______ or _____

A

Low

polyglutamate

weeks or months

70
Q

Antimetabolites: Pyrimidine analogues

Fluorouracil

Analogue of ———-

Interferes with ________ synthesis

Converted to ________

Inhibits dna, rna, or protein synthesis

Given parenterally

A

uracil

2’- deoxythymidylate (DTMP)

fluorodeoxyuridine monophosphate (FDUMP)

71
Q

Antimetabolites

_______
_________
__________
_____________
________________

A

Raltitrexed

Pemetrexed

Capecitabine

Cytarabine

Gemcitabine

72
Q

Antimetabolites

Raltitrexed: Inhibits ____________

Pemetrexed: Inhibits _______________

Capecitabine: Metabolized to ______

Cytarabine:
Analogue of naturally occurring _______

A

thymidylate synthetase

thymidylate transferase

fluorouracil

2’- deoxycytidine

73
Q

Cytarabine:

Undergoes ______ reaction to give _____________________

A

phosphorylation

cytosine arabinoside triphosphate

74
Q

Gemcitabine

New analogue of __________

Given in combination with other drugs such as ________

A

cytarabine

cisplatin

75
Q

Antimetabolites: Purine analogues

Main examples are_________,__________,__________,__________ and _________

A

fludarabine, pentostatin, cladribine, mercaptopurine and tioguanine

76
Q

Antimetabolites: Purine analogues

Action interferes with critical pathways in purine metabolism and can have significant effects on cell proliferation

_______,________, and _______ are used mainly in the treatment of ______

A

Cladribine, mercaptopurine and tioguanine

leukemia

77
Q

CYTOTOXIC ANTIBIOTICS

Act through ___________________

Anthracyclines
Examples:
_____,________,_________,________,_________ and __________

A

direct action on DNA

Doxorubicin, idarubicin, daunorubicin, epirubicin, aclarubicin and mitoxantrone

78
Q

CYTOTOXIC ANTIBIOTICS

Anthracyclines

Doxorubicin binds to ____ and inhibits ___________________________

Has a direct action on __________ (a DNA
gyrase

A

DNA

both DNA and RNA synthesis

topoisomerase II

79
Q

CYTOTOXIC ANTIBIOTICS

Anthracyclines

The activity is markedly increased in _______ cells

Doxorubicin is given by I.V infusion

Causes cumulative, dose-related ______ damage leading to _______ and _______

Action may be the result of generation of _______ _______

A

proliferating

cardiac damage; dysrhythmias

heart failure; free radicals

80
Q

CYTOTOXIC ANTIBIOTICS :Dactinomycin

Intercalates in the _______ of DNA between adjacent ___________ pairs, interfering with the movement of ____________ along the gene and thus preventing transcription

Has similar action as anthracyclines on __________

Has no ________toxic effect

Mainly used in the treatment of ______ cancers

A

minor groove

guanosine-cytosine ; RNA polymerase

topoisomerase II

cardiotoxic

pediatric cancers

81
Q

CYTOTOXIC ANTIBIOTICS: Bleomycins

Group of ___________ glycopeptide antibiotics that ____________________, causing chain ______ and release of ______ leading to generation of ______

Most effective in ____ phase of the cell cycle and mitosis but also active against _______ cells (___ phase)

Used to treat _____ cancer

A

metal-chelating

degrade preformed DNA

fragmentation ; free bases

superoxide; G2; non-dividing cells

Go phase; germ line cancer

82
Q

CYTOTOXIC ANTIBIOTICS: Mitomycin

Functions as a _________ alkylating agent

Binding preferentially at ____ of the ______ nucleus

_______ DNA and may also ______ DNA through the generation of _______

A

bifunctional ; O6

guanine nucleus; Cross-link

degrade DNA ; free radicals

83
Q

CYTOTOXIC ANTIBIOTICS: procarbazine

Inhibits DNA and RNA synthesis and interferes with mitosis at ____

Given orally

Mainly used in ______

Causes ______-like actions with alcohol

Exacerbates the effects of ________

A

interphase

Hodgkin’s disease

disulfiram; CNS depressants

84
Q

CYTOTOXIC ANTIBIOTICS: Hydroxycarbamide

Aka ____________

-A ______ analogue that inhibits ________, thus interfering with the conversion of _________ to ________

A

hydroxyurea

Urea; ribonucleotide reductase

ribonucleotides to deoxyribonucleotides

85
Q

PLANT DERIVATIVES: Vinca Alkaloids

Derived from ____________

Examples are _______,_______, and _______

Vinorelbine is a semi-synthetic vinca alkaloid with similar properties that is mainly used in ______ cancer

Only effective at _____ stage (mitosis)

A

Madagascar periwinkle

vincristine, vinblastine and vindesine

breast cancer

mitotic stage (mitosis)

86
Q

PLANT DERIVATIVES: Vinca Alkaloids

Binds to ______ and inhibits its _______ into ________, preventing _______ formation in ______ cells and causing arrest of __________

Inhibits other cellular activities that involve the ______ such as _______ and ________ as well as _________ in neurones

They are relatively (toxic or non-toxic?)

There could be (reversible or irreversible ?) alopecia

A

tubulin ; polymerization

microtubules ; spindle

dividing cells ;metaphase

microtubules ; phagocytosis

chemotaxis ; axonal transport

non-toxic; reversible alopecia

87
Q

PLANT DERIVATIVES: TAXANES

______ and ________ are derived from a naturally occurring compound found in the _____ of the ______ tree

Acts on ________, by ________ them
in the _________ stage achieving
similar effects as __________

Given by I.V infusion

A

Paclitaxel and docetaxel

bark; yew tree

microtubules; stabilizing

polymerase; vinca alkaloids

88
Q

PLANT DERIVATIVES: TAXANES

Used in the treatment of _______ cancer

_______ plus __________ are choice in the treatment of _______ cancer

A

breast cancer

Paclitaxel ; carboplasmin

ovarian

89
Q

PLANT DERIVATIVES : Etoposide

Derived from_________

Acts by inhibiting _______ function and _______ transport

Also have effect on _______ similar to that seen with _________

A

Mandrake root

mitochondrial ; nucleoside transport

topoisomerase II ; doxorubicin

90
Q

PLANT DERIVATIVES: Camptothecins

________ and. _______ isolated from the ____ of the tree __________________—

Binds to and inhibits _________

High levels occur _______

A

Irinotecan and topotecan

stem; Camptotheca acuminata

topoisomerase II

91
Q

Hormones

Tumors derived from hormone sensitive tissues may be ______________, an effect related to the presence of ——— receptors in the malignant cells

Their growth can be inhibited by hormones with _______ actions, by hormone antagonists or by agents that inhibit the endogenous hormone synthesis

A

hormone dependent

steroid; opposing

92
Q

Hormones or their analogues that have _______ actions on target tissues can be used in the treatment of tumors of those tissues

A

inhibitory

93
Q

HORNONES: Glucocorticoids

e.g. __________ and __________

Have marked __________ effects on lymphocyte __________ and used in the treatment of __________ and __________

A

Prednislone and dexamethasone

inhibitory ; proliferation

leukemia and lymphomas

94
Q

HORNONES: Progestogens

e.g. give me 3 ________,________,________

Used in _______ neoplasms and in ______ tumors

A

Megestrol, norehisterone and medroxyprogesterone

endometrial; renal

95
Q

HORMONES: Oestrogens

Eg_____________ and ______________

Oestrogens are used clinically in the
________ treatement of androgen- dependent _______ tumours

Could also be treated with _________ hormone analogues

A

Diethylstilbesterol and ethinyloestradiol

palliative; prostatic

gonadotrophin-releasing

96
Q

HORMONE ANTAGONISTS
: Anti-oestrogense.g. ______

Effective in hormone-dependent ______ cancer and may have a role in preventing this cancer

It competes with _______ for the oestrogen receptors and inhibits the transcription of ________-

Tamoxifen has __________
effects

A

Tamoxifen

breast; endogenous oestrogens

oestrogen

cardio-protective

97
Q

HORMONE ANTAGONISTS
: Anti-oestrogens

Other examples are ______,______,_______,________,________ and _______

A

Toremifen,
fulvestrant, anastrozole, letrozole,
exemestane and aminoglutethimide

98
Q

HORMONE ANTAGONISTS: Anti-androgens

Eg _________,________, and ————

Used for ______ cancer

A

Flutamide, cyproterone and
bicalutamide

prostate

99
Q

RADIOACTIVE ISOTOPES

Radioactive iodine used in the treatment of ________ tumors

A

thyroid

100
Q

MISCELLANEOUS AGENTS

E.G. list 5

A

Crisantaspase, amsacrine, monoclonal antibodies, imatinib mesylate, biological response modifiers

101
Q

MISCELLANEOUS AGENTS
Monoclonal Antibodies

Immunoglobulins e.g. ______ and ______

A

rituximab and trastuzumab

102
Q

MISCELLANEOUS AGENTS

Alemtuzumab

Lyses ———-

Used in treatment of resistant ______________

A

B-lymphocytes

chronic
lymphocytic leukemia

103
Q

RESISTANCE TO ANTICANCER DRUGS

Decreased accumulation of cytotoxic drugs in cells. E.g. ________,________,______

decrease in the amount of drug taken up by the cell e.g. _________

Insufficient activation of the drug (e,g,
___________,_________, and ————)

A

doxorubicin, vinblastine and dactinomycin

methotrexate

mercaptopurine, fluorouracil and
cytarabine

104
Q

RESISTANCE TO ANTICANCER DRUGS

Increase in inactivation e.g. ______ and ———

Increased concentration of target enzymes e.g. _______

Decreased requirement for substrate e.g. __________

Increased utilization of alternative metabolic pathways e.g. _________

A

mercaptopurine and cytarabine

methotrexate

crisantaspase

antimetabolites

105
Q

RESISTANCE TO ANTICANCER DRUGS

Rapid repair of drug-induced lesions e.g. ________

Altered activity of target (modified topoisomerase II e.g. _______)

Mutation e.g. p53 gene and over expression of Bcl-2 gene family (________)

A

alkylating agents

doxorubicin

cytotoxic drugs

106
Q

MISCELLANEOUS AGENTS

Biological response modifiers

Agents that ___________ are biological response modifiers

E.g. _______,________ (recombinant interleukin 2) and _______ (form of vitamin A)

A

enhance the host’s response

Interferon α

aldesleukin

Tretinoin

House Pharmacology (50 decks)

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