2 - Cytotoxic Agents Flashcards Preview

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Flashcards in 2 - Cytotoxic Agents Deck (85):
1

Cytotoxic agents can be categorised into anti metabolites and alkylating agents

True

2

The general risks associated with cytotoxic agents are carcinogenesis, teratogenesis, and myelosuppression and an increased potential for infection

True

3

Cytotoxic agents modulate the behaviour of cells through inhibition of growth and development

True

4

Anti metabolites are cell cycle specific and mimic the DNA nucleotides, and are most active during the S phase when DNA is being synthesised

True (S "synthesis" phase)
G1 = preparing the cell for DNA reproduction
S = DNA synthesis
G2 = interphase for preparation for division
M = "mitosis" cell division
G0 (some cells) = resting phase awaiting to re-enter cell cycle

5

The anti metabolites are methotrexate, azathioprine, mycophenolate, topical 5-fluorouracil, thioguanine and hydroxyurea

True

6

Cyclophosamide, chlorambucil and melphalan are alkylating agents

True

7

Alkylating agents are independant of the cell cycle

True (exert effect by direct damage to DNA through physiochemical interactions I.e. Alkylation, cross-linking, carbamylation which are cell cycle independent)

8

Patients using cytotoxic agents should be given general instructions on bleeding risks

True (thrombocytopenia from myelosuppression)

9

Thioguanine is an antimetabolite from the thioguanine family with a mechanism of action similar to Azathioprine

True

10

Thioguanine is a not a first line agent in psoriasis

True (third line agent in psoriasis)

11

Thioguanine is metabolised by the liver and converted to 6-thioguanilyic acid, which is then further converted to di- and triphosphates

True

12

Thioguanine and hydroxyurea are both renally excreted

True (similar to methotrexate)

13

Thioguanine has an unpredictable absorption pattern

True

14

Thioguanine is metabolised by thiopurine methyltransferase (TPMT) and not by xanthine oxidase

True (contrary to Azathioprine which is degraded by both enzyme pathways, Thioguanine is metabolised by TPMT only and so TPMT is more important in its detoxification)

15

Thioguanine may be administered concurrently with allopurinol (xanthine oxidase inhibitor) without the need for dose reduction

True (xanthine oxidase is not involved in the metabolism of Thioguanine)

16

Aminosalicylates use should be minimised or avoided in patients on Thioguanine

True (aminosalicylates may inhibit TPMT activity which is involved in metabolism of Thioguanine)

17

Thioguanine is a prodrug that yields nucleoside analogs which is then converted to nucleotides and incorporated into cellular DNA during the S phase of the cell cycle

True (This produces cytotoxic effects via apoptosis of activated T lymphocytes and decreased T lymphocyte counts in skin lesions)

18

Myelosuppression and GI side effects are the most common adverse effects in Thioguanine use

True

19

Thrombocytopenia is an early indicator of myelosuppression in patients using Thioguanine

True

20

Thioguanine does not usually need to be discontinued due to GI side effects

True (GI adverse effects are usually tolerated without drug discontinuance)

21

Thioguanine is less hepatotoxic than methotrexate (another antimetabolite agent)

True (Unlike Methotrexate, Thioguanine is not considered particularly hepatotoxic though there have been rare cases of hepatic veno-occlusive disease)

22

TPMT levels should be considered before starting Thioguanine

True (TPMT levels may guide selection of an adequate starting dose and improves Thioguanine dosing)

23

Hydroxyurea is a third line agent for psoriasis

True

24

Hydroxyurea is well absorbed though the metabolism is incompletely understood

True

25

Patient with renal impairment are more susceptible to hydroxyurea toxicity

True (80% of the drug is excreted through the kidneys)

26

Hydroxyurea impairs DNA synthesis through inhibition of ribonucleotide diphosphate reductase which reduces nucleotides to deoxynucleotides and limits the supply of DNA bases available for synthesis, resulting in strand breakage and cell death

True

27

Hydroxyurea prevents cells from repairing damage due to UV or ionising radiation

True

28

Hydroxyurea is most effective in cells with a high proliferative index, preferentially concentrated within leukocytes

True

29

Hydroxyurea is relatively contraindicated in patients with bone marrow suppression I.e. Leukopenia, thrombocytopenia, severe anaemia

True (relatively contraindicated in haematologic disorders)

30

Myelosuppression is the most common adverse effect with hydroxyurea use (anaemia > leukopenia > thrombocytopenia)

True

31

Mild megaloblastic changes on FBC are common among patients receiving hydroxyurea but is not a reason for discontinuance of the drug

True
N.B. Megaloblastic changes may also be seen with folate supplementation

32

Dyspepsia may occur with hydroxyurea

True (hydroxyurea can be taken with food, milk or antacids if this occurs)

33

Hydroxyurea is the most common cause of a drug-induced dermatomyositis-like eruption

True

34

Hydroxyurea may cause a lichenoid drug eruption and drug-induced lupus

True

35

Hydroxyurea may cause leg ulcers

True

36

Hydroxyurea may cause hyperpigmentation of the skin and nails

True

37

Hydroxyurea may cause limited and reversible alopecia

True

38

Hydroxyurea may cause photosensitivity and radiation recall

True

39

Hydroxyurea and its link to non-melanoma skin cancers is unclear

True (reported as an association but confounding factors exist and the degree of risk is unclear although close surveillance for non-melanoma skin cancers is indicated)

40

Hydroxyurea should not be administered with other myelosuppression agents

True (added bone marrow toxicity with concurrent use of other myelosuppressive agents)

41

Cyclophosphamide and chlorambucil are derivatives of nitrogen mustard which act independently of the cell cycle

True

42

In dermatology, Cyclophosphamide is primarily used in the treatment of immunobullous disorders and vasculitis

True

43

Cyclophosphamide is metabolised by the CYP 450 system in the liver

True

44

Chronic liver disease such as cirrhosis may prolong the plasma half life of cyclophosphamide due to decreased CYP 450 activity

True

45

Cyclophosphamide is a prodrug that is first converted in the liver to 4-hydroxycyclophosamide (an inactive metabolite) that exists in equilibrium with Aldophosamide which diffuses directly into cells but is not directly cytotoxic; Aldophosamide is then converted to the directly cytotoxic active metabolite phosphoramide mustard and acrolein

True

46

Acrolein, a by-product from the cleavage of Aldosphosphamide (yielding the toxic active metabolite phosphoramide mustard and acrolein) is highly reactive and enhances cellular damage by depleting glutathione stores

True

47

Aldophosamide (a molecule that exists in equilibrium with 4-hydroxycyclophosphamide, the first inactive metabolite of cyclophosphamide) may be converted by aldehyde dehydrogenase to a second inactive metabolite (carboxyphosphamide)

True

48

Cyclophosphamide has a greater effect on B lymphocytes than T lymphocytes

True (Unlike other immunosuppressive agents with mainly affect T lymphocytes)

49

Cyclophosphamide has a greater effect on suppressor T cells than helper T cells

True (unlike other immunosuppressive agents which inhibit cytokines produced by T helper cells)

50

Resistance to cyclophosphamide may occur due to decreased cellular penetration, increased competition from other nucleophilic substances, improved DNA repair or increased drug metabolism

True

51

Cyclophosphamide is FDA approved for treatment of mycosis fungoides

True

52

Cyclophosphamide can be used in the treatment of vasculitis

True

53

Cyclophosphamide is a useful agent in treating mucous membrane pemphigoid (cicatricial pemphigoid) particularly when there is involvement of the ocular mucosa

True

54

Cyclophosphamide is uncommonly used in the treatment of pemphigus

True (widespread availability of other less toxic medications I.e. Azathioprine and mycophenolate tempers the use of cyclophosphamide in immunobullous disease)

55

Cyclophosphamide is contraindicated in patients with a history of bladder cancer

True (genitourinary toxicity with haemorrhaging cystitis and bladder carcinoma is the single most widely recognised consequence of cyclophosphamide use)

56

Cyclophosphamide should be used with caution in patients with a history of lymphoproliferative disease

True (to be used with caution due to association of cyclophosphamide with non-Hodgkins B cell lymphoma and leukaemia)

57

Acrolein is the metabolite responsible for haemorrhagic cystitis, an adverse effect of cyclophosphamide

True (Mesna may be used as a scavenging thiol agent that binds acrolein in the bladder and reduce irritation)

58

Mesna (sodium 2-mercaptoethane sulfonate) may be used orally or intravenously as a protective measure against haemorrhagic cystitis from cyclophosphamide use, especially in high doses

True (though Mesna has also been associated with fixed drug eruption when used for this indication)

59

Bladder toxicity (haemorrhagic cystitis) is less frequent in patients on intravenous cyclophosphamide than oral form of the drug

True (perhaps due to the lower total dose used in the intravenous form as compared to oral form)

60

Increased fluid intake may prevent bladder toxicity (haemorrhagic cystitis) caused by cyclophosphamide

True

61

Mesna may be prescribed to patients on cyclophosphamide

True (co-administration of Mesna in dermatological doses of cyclophosphamide is not evidence based due to the lower doses prescribed in dermatological conditions, though Mesna can be considered for patients on prolonged courses of cyclophosphamide and/or high doses)

62

Continued monitoring of the urinary tract is indicated in all patients who have used cyclophosphamide

True (bladder cancer may arise decades after discontinuation of cyclophosphamide)

63

There is a potential association between cyclophosphamide and SCC

True (though much of this risk is found in transplant and oncology patients exposed to high doses for extended durations)

64

GI adverse effects affect 70-90% of cyclophosphamide users

True (this can be managed with ondansetron and dexamethasone)

65

Anaemia associated with cyclophosphamide and chlorambucil use is usually reversible

True (also less common)

66

Leukopenia is a dose-limiting common adverse effect from cyclophosphamide and chlorambucil

True

67

Thrombocytopenia usually occurs with higher doses of cyclophosphamide and chlorambucil

True

68

Pigmented band on the teeth is an irreversible adverse event from cyclophosphamide

True

69

Alopecia due to anagen effluvium is a reversible side effect of cyclophosphamide

True

70

Cyclophosphamide may cause hyperpigmentation of the skin and nails

True (just as in minocycline, hydroxychloroquine and hydroxyurea)

71

Amenorrhea may occur in 27-60% of women treated with cyclophosphamide

True (also in chlorambucil)

72

Premature ovarian failure from cyclophosphamide and chlorambucil may be prevented with luprolide acetate

True

73

Cyclophosphamide may cause azoospermia in men

True (testosterone may lessen this risk)

74

Urinalysis and cytological examination is indicated when the cumulative cyclophosphamide dose is > 50g

True

75

Evaluation for palpable lymphadenopathy and age appropriate cancer screening I.e. FOBT and Pap smear should be included in the follow up of patients on cyclophosphamide

True

76

Unlike cyclophosphamide (a prodrug), Chlorambucil is also metabolised in the liver but does not require activation in the liver (active drug)

True

77

Chlorambucil has a slower onset of action than cyclophosphamide

True (and also less toxic)

78

Unlike cyclophosphamide, metabolism of chlorambucil does not yield acrolein

True (and so chlorambucil does not cause haemorrhagic cystitis)

79

In dermatology, Chlorambucil is used most consistently in necrobiotic xanthogranuloma

True

80

Epilepsy and mood alterations are specific to chlorambucil

True (differs to cyclophosphamide)

81

There is a risk of carcinogenesis from chlorambucil use

True (as for cyclophosphamide, there is potential risk for leukaemia, non-Hodgkins lymphoma and SCC)

82

Hepatotoxicity is an uncommon adverse effect of chlorambucil

True

83

Drugs which may potentiate myelosuppressive, immunosuppressive and carcinogenic effects of cyclophosphamide and chlorambucil should be used with caution

True

84

There is possible decreased immunologic response with all vaccines and disseminated infection with live vaccines if used in Cyclophosphamide and chlorambucil patients

True

85

Cyclophosphamide and chlorambucil are teratogenic

True