Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

Pharm Block 2 > Cancer Pharmacology (part I) > Flashcards

Cancer Pharmacology (part I) Flashcards

(66 cards)

Start Studying
1
Q

What are alkylating agents?

A

Highly reactive organic molecules which “alkylate” DNA by
interacting with nucleophilic groups in the DNA molecule. This disrupts normal DNA causing induction of
apoptosis.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What part of the cell cycle do alkylating agents target?

A

Alkylating agents are phase non-specific. Cells must be cycling to be killed, but the drugs are active at any point in the cycle

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What type of response curve do alkylating agents have?

A

Alkylating agents have a linear response curve

- higher dose => more cells killed

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are common side effects of alkylating agents?

A
  • Nausea
  • Marrow suppression
  • Mutagenesis
  • Secondary carcinogenesis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is mechlorethamine (nitrogen mustard)?

A

Mechlorethamine was the first chemotherapeutic agent

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

How is nitrogen mustard administered?

A

Nitrogen mustard is usually given via IV infusion but also topical to treat T-cell neoplasms

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Why does mechlorethamine not require dose adjustment in renal or hepatic failure?

A

Mechlorethamine is rapidly regraded by NON-ENZYMATIC hydrolysis and therefore does not require dose adjustment in renal or hepatic failure

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What are the major side effects of mechlorethamine?

A
  • Nausea
  • Vomiting
  • Alopecia
  • Myelosuppression
  • Secondary cancers (especially leukemia, lymphoma, MDS)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is Cyclophosphamide?

A
  • A chemical derivative of mechlorethamine

- The most widely used of the alkylating agents – used in a variety of hematologic and solid tumors.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

How is cyclophosphamide administered?

A

May be given either IV (used for higher doses) or orally.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

How is cyclophosphamide activated and eliminated?

A
  • Must be activated by the hepatic p450 system.

- Eliminated by hepatic metabolism (75%) of kidneys (25%).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is a unique side effect of cyclophosphamide and how is it caused?

A
  • Hemorrhagic cystitis.
    • This is caused by the metabolite acrolein that is secreted in the urine.
    • This can be prevented by aggressive hydration or (more commonly) MESNA (2-mercaptoethane sulphonate) that binds and inactivates acrolein in the urine.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is cisplatin?

A

Cisplatin is a bifunctional alkylating agent that is a commonly used analogue

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

How does cisplatin work?

A

Cisplatin enters cells by passive diffusion then becomes ionized

  • It binds to DNA to form interstrand and intrastrand cross links
    • Cell cycle specific
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What types of cancers is cisplatin used in?

A
  • Lung
  • Breast
  • Ovarian
  • Head and Neck cancers
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What are the major side effects of cisplatin?

A
  • Renal insufficiency
  • Neuropathy
    • Both are reversible
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What is a “secondary” malignancy?

A
  • Secondary malignancy are a side effect of drugs used to treat a primary or initial cancer
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What is a common phenomena associated with secondary malignancy?

A
  • Polycythemia vera

- Leukemia is also a side effect

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Treatment of lymphoma leads to risk of what secondary condition?

A
  • Treatment of lymphoma with intense therapy has lead to approximately 10% of patients being at risk of secondary leukemia and breast cancer
    • Risk is greatly increased when alkylators and XRT are combined
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What are the most common secondary malignancies?

A
  • AML
  • MDS
    • These are usually highly resistant to any therapy
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

How does chemotherapy cause emesis?

A
  • Enterochromaffin cells release serotonin in response to emetic chemotherapy agents
    • When serotonin binds its receptor it acts on the vagus nerve leading to emesis/nausea
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What is Ondansetron (Zofran)?

A

Ondansetron is a selective serotonin receptor blocking agent that is though to block 5HT stimulation of the vagus nerve

  • It may also work by blocking CNS serotonin receptors
  • HELPS TO PREVENT VOMITING AND NAUSEA
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

How is Ondansetron administered?

A

Ondansetron is given IV or po about 1/2 hour before chemo

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What can Ondansetron be combined with for maximal benefit?

A
  • Can be combined with steroids for maximal benefit
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
What is aprepitant?
Aprepitant, a nerokinin1 agonist that blocks substance P binding is a new antiemetic that can be combined with 5-HT inhibitors.
26
What are antimetabolite agents?
- Broadly antimetabolite agents inhibit the normal metabolic functions of cells - Most antimetabolite drugs are targeted to DNA or RNA synthesis - These agents commonly resemble normal metabolic intermediates
27
Which phase are antimetabolite agents specific for?
Most antimetabolites are specific for the S phase
28
How should antimetabolites be administered?
Antimetabolites should be given by continuous IV infusion or hyper fractionated IV bolus
29
Which cells are particularly sensitive to antimetabolites?
-- Rapidly cycling normal cells (bone marrow and gut epithelium) are often highly sensitive to these agents
30
What is methotrexate?
Methotrexate is a direct descendant of aminopterin | - this is a an analogue of folic acid and inhibits DHFR by competitive inhibition
31
How is methotrexate administered?
- Low dose => oral immuno-suppresion | - High dose => IV
32
What cancers are methotrexate commonly used for?
- Lymphoma - Braset cancer - Head and neck cancer - Lung cancer
33
How is methotrexate given to treat CNS cancers?
Methotrexate is give intrathecally to treat CNS cancers
34
What are common side effects of methotrexate?
- Marrow suppression - Gi toxicity (mucositis, diarrhea) - Renal failure
35
How is renal failure caused by methotrexate?
- Renal failure is caused by precipitation of the drug in the renal tubules - Decreased clearance of the drug will increase other side effects - Urine is alkalinized to prevent this
36
What is also give with methotrexate to prevent lethal side effects?
- Methotrexate is often given at lethal doses to achieve greater tumor cell kill - This must be followed by LEUCOVORIN rescue to prevent lethal side effects
37
How do tumors become resistant to methotrexate?
- Decreased transport - Gene amplification - Mutation of DHFR => so that it is no longer inhibited by Methotrexate but is able to utilize folic acid
38
For what diseases is methotrexate used for immunosuppresion?
Methotrexate is used in rheumatoid arthritis and lupus
39
What is 5 fluoroucil?
5 Fluoroucil works in the same metabolic pathway as methotrexate - It inhibits the enzyme thymidylate synthase by a suicide mechanism
40
For what cancers is 5 fluoroucil used?
- Breast | - GI malignancies
41
What are the common side effects of 5 fluoroucil?
Bone marrow and GI toxicities
42
What drug is used to potentiate the action of 5 Fluoroucil (5FU)?
Leucovorin
43
What is cytarbine?
Cytarbine is the clinically most used member of the nucleoside analogues - It is the analogue of cytidine with a sugar molecule arabinose
44
What is the mechanism of action of cytarbine?
- Cytarbine is taken int o the cell and metabolized just as the normal compound - Once converted to ara-CTP it binds to and competitively inhibits DNA polymerase alpha - This interferes with DNA replication - Some of the drug is incorporated into DNA where it acts to slow chain elongation and inhibits DNA ligation
45
At what phase does cytarbine work?
Cytarbine (ara-C) acts on the S phase
46
What is ara-c most commonly used for?
Cytarbine (ara-c) is most commonly used to treat acute myeloid leukemia (AML) - It is also used to treat lymphoma
47
How is ara-c administered?
Ara-c is give by continuous IV for seven days as par tot the AML induction chemotherapy along with Daunarubicin (7+3 regimen)
48
What are the side effects of cytarbine?
- Marrow aplasia - GI toxicity - Alopecia
49
What dangerous toxicity is associated with high dose ara-c?
HiDAC can cause acute severe cerebellar toxicity
50
How do topoisomerase inhibitors act?
- Topoisomerases are involved in the unwinding of the supercoiled DNA during DNA replication and mRNA synthesis - If topoisomeraseas are inhibited DNA damage results and induces apoptosis
51
What are two major members of anthracycline antibiotics?
- Doxorubicin | - Daunarubicin
52
How do anthracycline antibiotics work?
- Anthracycline antibiotics consist of a sugar molecule attached to a tetracycline backbone - The drug is able to intercalate into DNA - This inhibits DNA replication and mRNA synthesis - Also inhibits topoisomerase II
53
How do anthracycline antibiotics act on topoisomerase Ii?
- Anthracyclines stabilize a DNA-TopII intermediate and inhibit relegation of DNA ends - This results in DNA fragmentation and cell death
54
What are anthracyclines generally used for?
- Hematologic malignancies - Breast - Lung - GI and GU cancers
55
How are anthracyclines administered?
IV infusion
56
How are anthracyclines metabolized?
Hepatic metabolism | - Give decreased dose in liver failure
57
What are the major side effects of anthracyclines?
- GI - Marrow - Cardiac - Anthracyclines are vesicants (blister agents)
58
What are the cardiac effects of anthracyclines?
- Anthracyclines produce a cumulative dose dependent cardiomyopathy - Increased dose leads to increase risk of cardiomyopathy (esp 550mg/m^2) - The cardiomyopathy is reversible - Patients are subject tot congestive heart failure and arrhythmias
59
What are epidophyllotoxins?
- Epidophyllotoxins complex with topoisomerase II and cause DNA breaks
60
What dose limiting toxicity is associated with epidophyllotoxins?
- Neutropenia
61
What are the main drugs in the epidophyllotoxin class?
- PV-16 | - Etoposide
62
What is VP-16 used to treat?
- Testicular - Ovarian - Lung - Lymphoid cancers
63
What are topoisomerase I inhibitors?
- Topotecan/irinotecan are topoisomerase I inhibitors which inhibit the enzymes ability to relegate DNA during replication - This results in double strand breaks which are strong activators of DNA damage dependent apoptosis pathways -
64
What phase of the cell cycle do topoisomerase I inhibitors work?
S phase
65
What cancers are treated with topoisomerase I inhibitors?
- Lung - Ovarian - Colorectal
66
What is a lethal side effect of topoisomerase I inhibitors (topotecan/irinotecan)?
Diarrhea

Pharm Block 2 (15 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions