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Clinical Pharmacology > Cancer Chemotherapy > Flashcards

Cancer Chemotherapy Flashcards

1
Q

What is the fractional cell kill hypothesis?

A
  • Repeated doses of chemotherapeutic given
  • Allows time for bone marrow cells to recover (recover more quickly) than tumour cells
  • Get an overall reduction in tumour cells
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2
Q

What cancers are highly sensitive to chemotherapy?

A
  • Lymphomas
  • Germ cell tumours
  • Small cell lung
  • Neuroblastoma
  • Wilm’s tumour
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3
Q

What cancers have modest sesnsitivity to chemotherapy?

A
  • Breast
  • Colorectal
  • Bladder
  • Ovary
  • Cervix
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4
Q

Which tumours have low sensitivity to chemotherapy?

A
  • Prostate
  • Renal Cell
  • Brain tumours
  • Endometrial
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5
Q

How do different chemotherapeutic agents target cancer cells?

A
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6
Q

Explain how alkylating agents work

A
  • Alkylating agent forms bond between 2 strands of DNA
  • Cannot replicate at replication fork- induces double strand break
  • Cell dies by apoptosis
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7
Q

How do Platinum compounds inhibit DNA replciation?

A
  • Form inter and intrasand adducts → inhibits DNA synthesis
  • Bulky adducts are difficult to repair
  • Cells die
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8
Q

Explain the mechanism of action of 5-Flurouracil as a chemotherapy agent

A
  • 5-FU inhibits thymidylate synthase
  • Thymidylate synthase needed for the synthesis of folic acid
  • Without folic acid- DNA and protein synthesis is reduced
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9
Q

Explain the mechanism of action of methotrexate

A
  • Methotrexate inhibits dihydrofolate reductase
  • Cannot form tetrahydrofolate so cannot form purines/ amino acids
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10
Q

Explain the mechanism of action of spindle poisons

A
  • Spindles essential to move sister chromatids apart to opposite poles during mitosis
  • Microtubule binding agents either:
    • inhibit polymerisation
    • stimulate polyermisate and prevent depolymerisation
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11
Q

Explain how Vinca alkaloids work

A
  • Soluble alpha and betal tubulin normally form microtubule polymers
  • Vinca alkaloid binds to the individual tubulins to prevent polymerisation
  • Microtubules cannot form and DNA cannot replicate
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12
Q

Give an example of a vinca alkaloid

A

Vincristine

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13
Q

Explain how taxanes work

A
  • Bind to the microtuble polymer and prevent its depolarisation
  • Mitosis fails
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14
Q

Give an example of a taxane

A

Paclitaxel

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15
Q

Give 3 examples of how cells can develop resistance mechanisms to alkylating agents

A
  1. Decreased entry or increased exit of agent
  2. Inactivation of agent in cell → glutathione can mop up active moeity neutralising agent
  3. Enhanced repiar of DNA lesions produced by alkylation
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16
Q

What factors influence predicted response to chemotherapeutic agents?

A
  • performance score
  • clinical staging
  • prognostic factors (biological factors)
  • molecular or cytogenetic markers
17
Q

What are the different types of IV pump for administering chemotherapy drugs?

A

PICC line- goes into large veins in the arm

Hickman line- direct to superior vena cava. Often better as repeated cycles of chemo can damage veins

18
Q

What are some of the side effects of chemotherapy?

A
19
Q

How can chemotherapy lead to acute renal failure

A
  • Rapid lysis of tumour releases lots of urate crystals → hyperuricaemia
  • Urate crystals precipitate in renal tubules
  • Unacceptable outcome today- pre-treatment given to prevent this
20
Q

What are the different patterns of vomiting in chemotherapy?

A
  • Acute phase- 4-12 hours
  • Delayed onset - 2-5 days later
  • Chronic phase - may last up to 14 days
21
Q

What local skin toxicity can occur from chemotherapy drugs?

A
  • Irritation and thrombophlebitis of veins
  • Extravasation (leakage of IV drugs to extravascular tissue surrounding injection site)
22
Q

What general skin toxicity can occur from chemotherapy drugs such as bleomycin?

A
  • Hyperkeratosis
  • Hyperpigmentation
  • Ulcerated pressure sores
23
Q

What is mucositis?

A
  • Damage to the epithelia of the GI tract
  • May be profound and involve with whole tract
  • Most commonly worst in the oropharynx, presents as:
    • sore mouth/ throat
    • diarrhoea
    • G.I bleed
24
Q

Which chemotherapy drugs are at high risk of causing cardio-myopathy?

A
  • Doxorubicin
  • High dose cyclophosphamide
25
Q

What lung toxicity can occur from chemotherapy?

A
  • Bleomycin (testicular tumour treatment) can cause pulmonary fibrosis
    • common in many drugs
26
Q

Why must chemotherapy drugs be prescribed by a specialist?

A
  • Narrow therapeutic index
  • Significant side effect profile
  • Dose needs altering for the individual patient
27
Q

What factors of chemotherapy drugs/ cancer patients cause abnormalities in drug absorption?

A
  • Nausea and vomiting
  • Compliance
  • Gut problems
28
Q

What factors of chemotherapy drugs/ cancer patients cause abnormalities in drug distribution?

A
  • Weight loss
  • Reduced body fat
  • Ascites → drugs accumulate in fluid causing toxicity over time
29
Q

What factors of chemotherapy drugs/ cancer patients cause abnormalities in drug elmination?

A
  • Liver and renal dysfunction
  • Other medications
30
Q

What factors of chemotherapy drugs/ cancer patients cause abnormalities in protein binding?

A
  • Low albumin (if nutrition is low)
  • Other drugs
31
Q

Give some important drug interactions of chemotherapy agents: Vincristine, capecitabine (oral 5FU), Methotrexate

A
  • Vincrinstine and intaconazole (antifungal) → leads to neuropathy
  • Capecitabine and warfarin
  • Methotrexate and penicillin and NSAIDs
  • Capecitabine and St John’s Wort, grapefruit juice
32
Q

What is neoadjuvant chemotherapy?

A

Given before surgery/ radiotherapy for the primary cancer

33
Q

What is adjuvant chemotherapy?

A

Given after surgery to excise the primary cancer, aiming to reduce relapse risk e.g. breast cancer

34
Q

What is palliative chemotherapy?

A

To treat current or anticipated symptoms without curative treatment

35
Q

What is primary chemotherapy?

A

1st line treatment for cancer… in many haematological cancers this is with curative intent

36
Q

What is salvage chemotherapy?

A

Chemotherapy for relapsed disease

Clinical Pharmacology (25 decks)

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