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Year 4 Oncology > Therapeutics > Flashcards

Therapeutics Flashcards

1
Q

Risk factors of N&V secondary to chemotherapy?

A
  • anxiety
  • age less than 50 years old
  • concurrent use of opioids
  • the type of chemotherapy used
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2
Q

Which anti-emetics may be used to treat N&V in chemotherapy?

A

For patients at low-risk of symptoms then drugs such as metoclopramide may be used first-line.

For high-risk patients then 5HT3 receptor antagonists such as ondansetron are often effective, especially if combined with dexamethasone

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3
Q

What is cyclophosphamide and how does it work?

A

An alkylating agent used in the management of cancer and autoimmune conditions.

It works by causing cross-linking of DNA

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4
Q

Cyclophosphamide adverse affects

A

haemorrhagic cystitis

myelosuppression

transitional cell carcinoma

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5
Q

How can the incidence of haemorrhagic cystitis in cyclophosphamide use be reduced?

A

Use of hydration and mesna

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6
Q

What is mesna and why is it used?

A

2-mercaptoethane sulfonate Na

a metabolite of cyclophosphamide called acrolein is toxic to urothelium
- mesna binds to and inactivates acrolein helping to prevent haemorrhagic cystitis

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7
Q

Cytotoxic agents: antibiotic examples?

A

Bleomycin

Anthracyclines (e.g doxorubicin)

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8
Q

What is the action of bleomycin?

A

Degrades preformed DNA

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9
Q

What is the action of anthracyclines e.g. doxorubicin?

A

Stabilizes DNA-topoisomerase II complex inhibits DNA & RNA synthesis

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10
Q

Cytotoxic agents: major adverse affect of bleomycin?

A

Lung fibrosis

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11
Q

Cytotoxic agents: major adverse affect of anthracyclines e.g. doxorubicin?

A

Cardiomyopathy

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12
Q

Cytotoxic agents: antimetabolite examples

A

Methotrexate

Fluorouracil (5-FU)

6-mercaptopurine

Cytarabine

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13
Q

Methotrexate mechanism of action?

A

Inhibits dihydrofolate reductase and thymidylate synthesis

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14
Q

Fluorouracil (5-FU) mechanism of action?

A

Pyrimidine analogue inducing cell cycle arrest and apoptosis by blocking thymidylate synthase (works during S phase)

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15
Q

6-mercaptopurine mechanism of action?

A

Purine analogue that is activated by HGPRTase, decreasing purine synthesis

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16
Q

Cytarabine mechanism of action?

A

Pyrimidine antagonist. Interferes with DNA synthesis specifically at the S-phase of the cell cycle and inhibits DNA polymerase

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17
Q

Cytarabine major adverse affects?

A

Myelosuppression

Ataxia

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18
Q

6-mercaptopurine major adverse affect?

A

Myelosuppression

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19
Q

Fluorouracil (5-FU) major adverse affects?

A

Myelosuppression, mucositis, dermatitis

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20
Q

Methotrexate major adverse affects?

A

Myelosuppression, mucositis, liver fibrosis, lung fibrosis

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21
Q

Examples of cytotoxic agents that act on microtubules

A

Vincristine, vinblastine

Docetaxel

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22
Q

Docetaxel major adverse affect?

A

Neutropenia

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23
Q

Docetaxel mechanism of action?

A

Prevents microtubule depolymerisation & disassembly, decreasing free tubulin

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24
Q

Vincristine, vinblastine mechanism of action?

A

Inhibits formation of microtubules

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25
Q

Vincristine major adverse affects?

A

Peripheral neuropathy (reversible) , paralytic ileus

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26
Q

Vinblastine major adverse affect?

A

Myelosupression

27
Q

Example of cytotoxic agent which inhibits topoisomerase?

A

Irinotecan

28
Q

Irinotecan mechanism of action?

A

Inhibits topoisomerase I which prevents relaxation of supercoiled DNA

29
Q

Major adverse affect of irinotecan?

A

Myelosupression

30
Q

Cisplatin - mechanism of action

A

Causes cross-linking in DNA

31
Q

Hydroxyurea (hydroxycarbamide) mechanism of action?

A

Inhibits ribonucleotide reductase, decreasing DNA synthesis

32
Q

Major adverse affects of cisplatin?

A

Ototoxicity
Peripheral neuropathy
Hypomagnesaemia

33
Q

Hydroxyurea (hydroxycarbamide)

A

Myelosuppression

34
Q

Hydroxyurea (hydroxycarbamide) and cisplatin are examples of what?

A

Cytotoxic drugs

35
Q

What are immune checkpoint inhibitors?

A

Immunotherapy (alternative to cytotoxic chemotherapy)

. In contrast to therapies such as chemotherapy and tumour-targeted drugs that directly affect the growth and proliferation of tumour cells, these targeted treatments harness the body’s natural anti-cancer immune response. They boost its ability to attack and destroy the cancer cells.

Some cancer cells make high levels of proteins that turn T-cells off, reducing their desrtuction. Checkpoint inhibitors block this process and reactivate and increase the body’s own T-cell population, enhancing the immune systems own ability to recognise and fight cancer cells.

36
Q

Where are the proteins CTLA-4 and PD-1 are found?

A

T-cells

37
Q

Where are the PD-L1 proteins found?

A

On cancer cells

38
Q

Types of checkpoint inhibitors?

A

Blockade of CTLA-4 (cytotoxic T lymphocyte-associated protein 4): Ipilimumab

Blockade of PD-1 (programmed cell death protein 1): Nivolumab (Opdivo) and pembrolizumab (Keytruda)

Blockade of PD-L1: Atezolizumab, Avelumab, Durvalumab

39
Q

What is pilimumab (Yervoy) and what is it used to treat?

A

A checkpoint inhibitor that blocks CTLA-4 (cytotoxic T lymphocyte-associated protein 4)

Advanced melanoma

40
Q

What are Nivolumab (Opdivo) and pembrolizumab (Keytruda) and what do they treat?

A

Checkpoint inhbitors that block PD-1
(programmed cell death protein 1)

These are treatments for melanoma, Hodgkin’s lymphoma, non-small cell lung cancer and urological cancers.

41
Q

What are Atezolizumab, Avelumab and Durvalumab and what do they treat?

A

Checkpoint inhibitors that block PD-L1 and is used to treat lung cancer and urothelial cancer. I

42
Q

Administration of checkpoint inhibitors?

A

All CTLA-4 inhibitors and PD-1/PD-L1 inhibitors currently available are monoclonal antibodies (laboratory-produced molecules engineered to serve as substitute antibodies that each bind to a specific protein). They are all administered by injection/intravenous infusion. Mostly, they are given as a single-agent treatment but sometimes, they can be combined with chemotherapy or each other. For example, ipilimumab and nivolumab can be used in combination.

43
Q

What side effects might checkpoint inhibitors cause and why?

A

This mechanism of action of these drugs can result in side effects termed ‘Immune-related adverse events’ that are inflammatory and autoimmune in nature. This is because all immune cells are boosted by these drugs, not just the ones that target cancer. The over-active T-cells can produce side effects such as:

  • Dry, itchy skin and rashes (most commonly)
  • Nausea and vomiting
  • Decreased appetite
  • Diarrhoea
  • Tiredness and fatigue
  • Shortness of breath and a dry cough.
44
Q

Checkpoint inhibitors: management and monitoring

A

Management of such side effects reflects the inflammatory nature, often involving corticosteroids.

It is important to monitor liver, kidney and thyroid function as these drugs can affect these organs.

45
Q

Radiotherapy is an important form of therapy for cancer and accounts for 50% of all treatment regimens.

There are many side effects of radiotherapy and they are best characterised into early and late onset side effects.

EXAMPLES OF EARLY SIDE EFFECTS

A

Tiredness/Fatigue

Skin erythema

Alopecia

Mucositis (diarrhoea, dysuria)

46
Q

Radiotherapy is an important form of therapy for cancer and accounts for 50% of all treatment regimens.

There are many side effects of radiotherapy and they are best characterised into early and late onset side effects.

EXAMPLES OF LATE SIDE EFFECTS

A

Skin pigmentation changes
Pulmonary fibrosis
Infertility

47
Q

What type of chemotherapy agent are doxorubicin and daunorubicin examples of?

A

Anthracyclines

48
Q

Examples of anthracyclines

A

doxorubicin
daunorubicin

49
Q

Important classical side effect of Anthracyclines (doxorubicin, daunorubicin)?

A

Cardiomyopathy

50
Q

Important classical side effect of anti-HER-2 monoclonal antibodies (e.g. Herceptin) cause cardiomyopathy?

A

Cardiomyopathy

51
Q

What is Herceptin and example of?

A

anti-HER-2 monoclonal antibody

52
Q

Examples of platinum agents?

A

Cisplatin
Carboplatin

53
Q

What are cisplatin and carboplatin examples of?

A

Platinum agents

54
Q

Important classical side effects of platinum agents (cisplatin, carboplatin)?

A

cause peripheral neuropathy and sensorineural hearing loss

+Cisplatin has a risk of ototoxicity and nephrotoxicity

55
Q

Important classical urinary system side effects of cyclophosphamides?

A

Haemorrhagic cystitis

TCC of the bladder

56
Q

What does gynaecological side effect is related to tamoxifen use?

A

Endometrial cancer

57
Q

Important resp side effect of belomycin

A

Lung fibrosis

58
Q

Important neurological side effect of cytarabine?

A

Ataxia

59
Q

What is Cetuximab and what is it used for?

A

Cetuximab is an example of a monoclonal antibody

Used in treating squamous cell carcinomas of the head and neck and to treat bowel cancer.

It targets epidermal growth factor receptor, blocking the activation of this receptor and inhibiting the growth and metastasis of the tumour.

60
Q

What is adjuvant chemotherapy?

A

Adjuvant chemotherapy refers to chemotherapy that people receive after another cancer treatment, such as surgery

61
Q

What is neoadjuvant therapy?

A

Neoadjuvant therapy includes treatmentsTrusted Source that doctors use as an initial step to shrink tumors and kill any cancer cells that have spread. After that, they will start the primary treatment.

62
Q

What type of cancer is cyclophosphamide commonly used to treat?

A

Glialblastoma

63
Q

Classes of chemotherapy

A

Alkylating agents

Taxanes

Vinka alkaloids

Platinum complexes

Platinum complexes

Antimetabolites

Anthracyclines

Antitumour antibiotics

Topoisomerase inhibitors

64
Q

Neutropenic sepsis: questions to ask

A

Date of last chemo

Which agent

Any lines?

Drug and allergies

Year 4 Oncology (15 decks)

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