Anticancer Drugs Flashcards
(111 cards)
1
Q
Cancer that causes the most deaths in both sexes
A
Lung cancer
2
Q
Overall trend of cancer death rates in recent years
A
Decreasing
3
Q
Most common cancer treatments
A
Surgery, radiation, chemo
4
Q
Goal of anticancer drugs
A
To destroy all cancer cells
5
Q
3 main functions of anticancer drugs
A
Act on DNA, inhibit chromatin function, act on hormone receptors
6
Q
Carcinoma
A
Cancer of epithelial cells
7
Q
Sarcoma
A
Cancer of muscle, bone, cartilage, fat, connective tissue
8
Q
Leukemia
A
Blood cancers that originate in bone marrow and result in underdeveloped blood cells
9
Q
Lymphoma
A
Group of cancers in lymphocytes
10
Q
Blastoff
A
Cancer in precursor cells
11
Q
Cancer cell stages
A
Initiation, promotion, progression
12
Q
Tumour progression depends on
A
Mutation/epigenetic alteration rate, selective advantage, proliferation rate, invasiveness
13
Q
Critical cancer genes
A
DNA repair genes, genes maintaining chromosome integrity, oncogenes, tumour suppressor genes
14
Q
3 outcomes of a diseased cell
A
Apoptosis, senescence, cancer
15
Q
Oncogene
A
Normally increases mitosis; can become constitutively active
16
Q
Tumour suppressor genes
A
Normally suppress mitosis; can lose function
17
Q
Angiogenesis
A
Tumours secrete growth factors to induce blood vessel growth
18
Q
Metastasis
A
Detachment from parent tumour → enter blood vessel → proliferate in new environment
19
Q
When chemotherapy is used
A
In addition to radiation or surgery, to cure, in palliative care
20
Q
What cells anticancer drugs are most effective against
A
Rapidly dividing cells
21
Q
Cell cycle checkpoints
A
G1, g2, metaphase
22
Q
G1 checkpoints
A
Checks for nutrients, growth factors, and DNA damage to make sure all is ready to synthesize
23
Q
G2 checkpoint
A
Checks for cell size and DNA replication
24
Q
Metaphase checkpoint
A
Checks for chromosome spindle attachment
25
When drugs are most toxic in the cell cycle
S Phase, some also M
26
Growth fraction
The percent of dividing cells that are sensitive to chemotherapy
27
What phase of the cell cycle most drugs are ineffective in
G0
28
Debulking
Shrinking tumour, which stimulates proliferation
29
Early metastases
Have a high growth fraction
30
Use of several chemo cycles
Synchronizes cells
31
Log kill
Amount of cells that are killed in each treatment due to first order kinetics
32
Therapeutic index of anticancer drugs
Very narrow
33
Factors that influence patient survival
Nature of the cancer, pharmacology, patient
34
Causes of failure of anticancer drugs
Lack of specificity and resistance
35
Major sites of toxicity of anticancer drugs
Bone marrow, gi tract, hair follicle, reproductive tract, 2° carcinogenicity
36
Resistance to anticancer drugs
Natural, acquired, or multi drug resistance
37
Treatment regimen of chemo
Usually given in combination, as frequently and as close to maximal effective dose as possible
38
Dosage is based on
Body surface area, pharmacokinetics, interactions, impacts on systems
39
Considerations for chemotherapy
Long-term gain versus risk, successful treatment versus qualify of life
40
Cyclophosphamide mechanism of action
Transfers an alkyl group to N7 or O6 of guanine to one or two DNA strands, resulting in monoalkylated or crosslinked strands
41
Cells most sensitive to cyclophosphamide
Proliferating cells
42
Most commonly used alkylating agent
Cyclophosphamide
43
Cyclophosphamide routes of admin
Oral or IV
44
Fates of aldophosphamide
To the cytotoxic phosphoramide mustard that binds the DNA, or to acrolein - toxic metabolite
45
Glutathione-s-transferase
Inactivates aldophosphamide products to nontoxic
46
Adverse effects of cyclophosphamide
Gi distress, bone marrow suppression, immunosuppression, alopecia, hemorrhagic cystitis, sterility, menopause, cancer * is less toxic than other agents due to ALDH tho*
47
Resistance to cyclophosphamide
Increased ALDH or GST, increased DNA repair (mgmt)
48
Cisplatin mechanism
Covalently binds N7 and O6 on guanine via a metal, but can also binds cytosine and adenine
49
Admin of cisplatin
IV
50
Adverse effects of cisplatin
Bone marrow suppression, anemia, severe nausea and vomiting, nephrotoxicity, electrolyte imbalance, neurotoxicity
51
Cisplatin resistance
Increased metabolism by GST or increased efflux, less access into cell, increased DNA repair
52
Bleomycin mechanism
Forms a complex with DNA and iron that gets oxidized to form free radicals → DNA strand breakage
53
Bleomycin admin
IV, IM, SC
54
Resistance to bleomycin
Increased DNA repair, increased efflux, increased antioxidants, increased bleomycin hydrolase
55
Adverse effects of bleomycin
Pulmonary fibrosis, hypersensitivity, gi distress, alopecia
56
CMF
Cyclophosphamide, methotrexate fluorouracil
57
Antimetabolites
Methotrexate and 5-fluorouracil
58
Methotrexate mechanism
Is structurally similar to folate so it binds dihydrofolate reductase and prevents the synthesis of purines and pyridines, metabolites also stay in alls to further inhibit synthesis
59
Routes of admin for methotrexate
IV, IM, SC, IT
60
Resistance to methotrexate
Non-proliferating cells, decreased cellular uptake, increased dihydrofolate reductase expression, decreased binding to dihydrofolate reductase
61
Adverse effects of methotrexate
Bone marrow suppression, gi distress, alopecia, liver damage, renal damage
62
Drug interactions with methotrexate
Aminoglycosides inhibit its absorption, NSAIDs, penicillins, cephalosporins, cisplatin, probenecid decrease its elimination
63
How 5-fluorouracil and methotrexate enters cells
Carrier- mediated transport
64
5-fluorouracil mechanism
Gets converted to ribose and deoxyribose nucleotide metabolites and incorporated into RNA and DNA to prevent elongation, also inhibits thymidine synthesis
65
Routes of admin of 5-fluorouracil
Iv or topically
66
Adverse effects of 5-fluorouracil
Bone marrow suppression, gi disturbances, alopecia, cardiotoxicity, skin irritation
67
Dosing concerns of 5-fluorouracil
Very narrow therapeutic index, under and overdosing are both concerning
68
Resistance of 5-fluorouracil
Decreased cell uptake, increased 5-fluorouracil metabolism, decreased conversion to nucleotide metabolites, increased thymidylate synthase activity, DNA repair
69
Topoisomerase inhibitors
Doxorubicin
70
Chromatin modulators
Doxorubicin, vincristine, paclitaxel
71
Doxorubicin mechanism
Binds and stabilizes topoisomerase II DNA complex to prevent re-ligation of DNA breaks; also generates free radicals
72
Topoisomerase ll
Hydrolyses double-stranded DNA during replication and transcription, and then re-ligates it
73
Routes of admin of doxorubicin
Iv
74
Adverse effects of doxorubicin
Cardiomyopathy/HF, bone marrow suppression, gi disturbances, alopecia, swelling of hands and feet
75
Resistance to doxorubicin
Increased efflux by p-glycoprotein, over-expression or mutation of topoisomerase lI
76
Microtubule inhibitors
Vincristine, paclitaxel
77
Vincristine mechanism
Inhibits tubulin polymerization
78
Paclitaxel mechanism
Inhibits tubulin depolymerization
79
Route of admin of vincristine
Iv
80
Affected cell cycle stage by vincristine
M
81
Resistance to vincristine
Altered tubulin structure, altered tubulin isotopes, increased efflux by p-glycoprotein
82
Adverse effects of vincristine
Peripheral neuropathy, nausea, vomiting, alopecia, constipation
83
Interactions of vincristine
Metabolized by CYP3A4, so it’s metabolism is accelerated by HIV meds and anticonvulsants, and slowed by azoles, other HIV meds, and grapefruit juice
84
Adverse effects of paclitaxel
Hypersensitivity, peripheral neuropathy, bone marrow suppression, alopecia, gi distress and anorexia
85
Interactions of paclitaxel
Same as vincristine
86
Resistance to paclitaxel
Same as vincristine
87
Uses for steroid hormones and antagonists
Cancers with steroid-hormone sensitive cells because steroids regulate genes for cell growth and proliferation
88
Prednisone action
Binds irreversibly to glucocorticoid receptors and induces apoptosis of leukemic and lymphoid cells
89
Resistance to prednisone
Absence or mutation of receptor
90
Adverse effects of prednisone
Immunosuppression, hypertension, hyperglycemia, pancreatitis, weakness, osteoporosis, mood changes
91
Tamoxifen mechanism
SERM, metabolized in liver by 3A4 and 2D6 and prevents estrogen-mediated expression and growth in breast tissue
92
Resistance to tamoxifen
Absence or mutation of receptor
93
Adverse effects of tamoxifen
Hot flashes, irregular periods, blood clots, reduced cognition, uterine cancer
94
Anastrazole mechanism
Inhibit aromatase, do not induce uterine cancer
95
Most immediate way to reduce cancer deaths
Prevention, screening, early detection
96
Multi drug resistance
An efflux pump that affects several drugs, such as p-glycoprotein
97
P-glycoprotein
Transmembrane atp-binding transporter that interferes w/ chemo agents
98
P-glycoprotein mechanism
Hydrolyses ATP and releases the phosphate to shift the position of the drug and cause excretion
99
_________ downregulates expression of p-glycoprotein
Estrogen
100
________ inhibits efflux of drugs by p-glycoprotein
Tamoxifen
101
__________ and __________ induce expression of p-glycoprotein
Cisplatin; doxorubicin
102
Piperine analogs
Helps overcome drug resistance
103
Hormone sensitive breast tumours
ER positive, progesterone receptor positive, hER-2 positive
104
Trastuzumab mechanism
Antibody that acts an antagonist at HER2
105
Bevacizumab mechanism
Antibody that acts as an antagonist at vascular endothelial growth factor receptor 2 to inhibit angiogenesis
106
Adverse effects of trastuzumab
Fever, ache, chills, nausea, diarrhea, cardiac dysfunction including congestive heart failure
107
Adverse effects of bevacizumab
Inhibition of blood vessel growth for maintenance and healing, hypertension, bleeding
108
Olaparib mechanism
Inhibits PARP, which down-regulates DNA repair mechanism
109
Adverse effects of olaparib
Bone marrow suppression, gi disturbances, anorexia, fatigue, muscle and joint pain
110
Atezolizumab mechanism
Antibody against programmed cell death-ligand 1, which allows t cells to kill the tumour alls
111
Adverse effects of atezolizumab
Nausea, anorexia, fatigue, UTI
