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Year 4 - Toxicology > 16 - Antineoplastic Agents > Flashcards

16 - Antineoplastic Agents Flashcards

1
Q

Describe the TNM system

A
  • T = tumour size (0-4)
  • N = lymph node involvement (0-3)
  • M = metastasis (0-1)
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2
Q

Describe the role of surgery for cancer

A
  • *Remission is usually used rather than cured
  • Useful for reducing tumour mass and curative if all cancerous cells are removed
  • Tissue removed examined by pathologist to ensure that a margin of healthy tissue was also removed
  • Surgery may be necessary for determining tumour size and extent of metastases in order to accomplish staging
  • May be useful as a palliative tx to relieve conditions such as spinal cord compression
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3
Q

What determines the dose of radiation?

A
  • Type of cancer
  • Proximity of sensitive tissue or organs
  • Constitution of pt
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4
Q

What are the goals of combination chemotherapy?

A
  • Synergy between some of the agents
  • Reduce possibility of resistance developing
  • Reduce dose-related adverse effects
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5
Q

What is the IT route? When is it used? When is it contraindicated?

A
  • Intrathecal route (injection into CSF) is used in order to get the agent across BBB
  • IT route absolutely CI for a number of antineoplastic drugs such as vinca alkaloids which will result in px death
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6
Q

Mechanism of alkylating agents

A
  • Inhibit DNA replication by causing cross-linking and abnormal base pairing of DNA strands
  • Can form a highly electrophilic immonium ion which can covalently bind to a nucleophilic compound like N-7 nitrogen of guanine
  • Resulting inter or intra-strand cross-linking makes the DNA non-functional
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7
Q

Why are alkylating agents toxic?

A

Able to react w/ any cell component containing nucleophilic groups such as hydroxyl, sulfhydryl, amino, or carbonyl

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8
Q

How can cancer cells become resistant to chemotherapy?

A
  • Increased ability to repair DNA lesions
  • Decreased permeability to agents
  • Increased production of glutathione which reacts w/ alkylating agents
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9
Q

Adverse effects of alkylating agents

A
  • Myelosuppression w/ granulocytopenia
  • Thrombocytopenia and anemia
  • N/V
  • Reversible hair loss
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10
Q

Mechanism of anti-metabolites

A
  • Structural analogues of naturally occurring substrates for biochemical reactions occurring in the body
  • Several act as false substitutions in the production of nucleic acids and stop replication process
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11
Q

Mechanism of antibiotics as chemotherapy

A
  • Intercalation

- Sliding between DNA base pairs and inhibiting DNA synthesis

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12
Q

Mechanism of vinca alkaloids

A

Prevent formation of mitotic spindle and stop cell division

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13
Q

Mechanism of platinum compounds? What are examples?

A
  • Act in a similar manner as the alkylating agents

- Group includes cisplatin and carboplatin

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14
Q

Which normal cells are more sensitive to anti-neoplastic drugs?

A

Those w/ higher turnover rates (ex: bone marrow, mucous membranes, hair follicles)

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15
Q

Common toxicities of anti-neoplastics?

A
  • Myelosuppression
  • Mucositis (mouth sores, diarrhea)
  • Alopecia
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16
Q

Onset of myelosuppression

A
  • Usually 7-10 days after tx

- Lowest cell counts seen 10-14 days after tx

17
Q

How long does it take for myelosuppression to return to normal?

A

Usually 2-3 weeks

18
Q

3 most common effects of myelosuppression

A
  • Neutropenia or reduction in # of neutrophil WBCs predisposes pt to infections
  • Thrombocytopenia or reduction in # of platelets can lead to bleeding
  • Anemia secondary to chemotherapy not as common due to long lifespan of erythrocytes (~120 days)
19
Q

How can neutrophil counts return to normal faster?

A
  • Administration of growth factors G-CSF (filgrastim)

- May prevent febrile neutropenia and allow therapy to continue at full doses

20
Q

What factors can increase risk of N/V from anti-neoplastics?

A
  • Hx of motion or pregnancy-related nausea
  • Female
  • Fatigue
  • Age < 50 y/o
  • Lower performance status (general health)
21
Q

What are the 3 categories of chemotherapy-induced N/V

A
  • Acute
  • Anticipatory
  • Delayed
22
Q

Describe acute chemotherapy-induced N/V

A
  • Sx begin 1-2 h after administration
  • Peak after 4-6 h and then subside after 12-24 h
  • Due to stimulation of chemoreceptor trigger zone through serotonin release
  • Serotonin antagonists (ondansetron) helpful
  • Anti-emetic therapy must be individualized for each pt
23
Q

Describe anticipatory chemotherapy-induced N/V

A
  • Nausea triggered by stimuli associated w/ therapy (ex: smell or sight of hospital)
  • Managed w/ relaxation techniques, attention diversion, aromatherapy, and anxiolytics (ex: lorazepam)
  • Effective preventative strategy is ensuring good acute phase control
24
Q

Describe delayed chemotherapy-induced N/V

A
  • Begins at least 24 h after chemotherapy administration
  • May persist 2-5 days
  • Mechanism not understood but usually seen w/ highly emetogenic drugs like cisplatin
25
Q

Agents most likely to cause mucositis

A
  • 5-fluorouracil
  • Methotrexate
  • Doxorubicin
26
Q

How does mucositis present? How does it progress?

A
  • Usually starts w/ redness and burning around lips and mouth
  • Proceeds to ulcerations on buccal mucosa, lips, floor of mouth and tongue
27
Q

What is extravasation?

A

When IV drug inadvertently infused into tissue

28
Q

Drugs associated w/ alopecia

A
  • Cyclophosphamide
  • 5-fluorouracil
  • Doxorubicin
  • Vincristine
  • Bleomycin
  • Paclitaxel
29
Q

When does alopecia begin? When does hair begin to regrow?

A
  • Hair loss begins 7-10 days after tx initiation
  • Peaks after 1-2 months
  • Begins to regrow ~ 1 month after tx stopped
30
Q

What is pulmonary toxicity associated w/ anti- neoplastics? Which is the most likely drug cause?

A
  • Generally irreversible and may be fatal

- Best known is associated w/ bleomycin and about 4% incidence

31
Q

Other drugs associated w/ pulmonary toxicity

A
  • Cyclophosphamide
  • MTX
  • Cytarabine
  • Vinblastine
32
Q

Early sx of pulmonary toxicity?

A

SOB and dry cough

33
Q

What are some acute CV effects of anti-neoplastics?

A

Transient EKG abnormalities w/o clinical significance

34
Q

What is a chronic CV effect of anti-neoplastics? What drugs are associated w/ this?

A
  • Irreversible CHF
  • Anthracycline antibiotics (doxorubicin)
  • Due to this, recommended lifetime exposure to doxorubicin = 450-500 mg/m2
35
Q

Which anti-neoplastics are associated w/ neurotoxic AE?

A
  • Vinca alkaloids (w/ vincristine –> extent of neurotoxicity related to total cumulative dose)
  • Platinum compounds
36
Q

Examples of neurotoxic AE of anti-neoplastics?

A
  • Numbness of hands and feet
  • Gait disturbances
  • Severe motor weakness (in severe cases)
37
Q

Which anti-neoplastics are associated w/ nephrotoxicity?

A
  • Cisplatin (can be lessened by aggressively hydrating pt prior to tx and IV administration of mannitol)
  • MTX
  • Ifosfamide
38
Q

What is hemorrhagic cystitis? How can it be prevented?

A
  • Bladder toxicity seen after cyclophosphamide or ifosfamide
  • Acrolein = metabolite of both drugs that irritates mucosa
  • Aggressive hydration prior to tx and administration of mensa (drugs that binds acrolein)
39
Q

Which anti-neoplastics can cause infertility?

A
  • Cyclophosphamide
  • Chlorambucil
  • Melphalan
  • Mechlorethamine

Year 4 - Toxicology (22 decks)

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