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Derm Pharm 2020 > 2 - Cytotoxic Agents > Flashcards

2 - Cytotoxic Agents Flashcards

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1
Q

Cytotoxic agents can be categorised into anti metabolites and alkylating agents

A

True

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2
Q

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

A

True

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3
Q

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

A

True

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4
Q

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

A

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

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5
Q

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

A

True

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6
Q

Cyclophosamide, chlorambucil and melphalan are alkylating agents

A

True

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7
Q

Alkylating agents are independant of the cell cycle

A

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

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8
Q

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

A

True (thrombocytopenia from myelosuppression)

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9
Q

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

A

True

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10
Q

Thioguanine is a not a first line agent in psoriasis

A

True (third line agent in psoriasis)

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11
Q

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

A

True

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12
Q

Thioguanine and hydroxyurea are both renally excreted

A

True (similar to methotrexate)

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13
Q

Thioguanine has an unpredictable absorption pattern

A

True

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14
Q

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

A

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)

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15
Q

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

A

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

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16
Q

Aminosalicylates use should be minimised or avoided in patients on Thioguanine

A

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

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17
Q

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

A

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

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18
Q

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

A

True

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19
Q

Thrombocytopenia is an early indicator of myelosuppression in patients using Thioguanine

A

True

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20
Q

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

A

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

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21
Q

Thioguanine is less hepatotoxic than methotrexate (another antimetabolite agent)

A

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

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22
Q

TPMT levels should be considered before starting Thioguanine

A

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

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23
Q

Hydroxyurea is a third line agent for psoriasis

A

True

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24
Q

Hydroxyurea is well absorbed though the metabolism is incompletely understood

A

True

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25
Q

Patient with renal impairment are more susceptible to hydroxyurea toxicity

A

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

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26
Q

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

A

True

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27
Q

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

A

True

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28
Q

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

A

True

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29
Q

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

A

True (relatively contraindicated in haematologic disorders)

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30
Q

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

A

True

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31
Q

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

A

True

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

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32
Q

Dyspepsia may occur with hydroxyurea

A

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

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33
Q

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

A

True

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34
Q

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

A

True

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35
Q

Hydroxyurea may cause leg ulcers

A

True

36
Q

Hydroxyurea may cause hyperpigmentation of the skin and nails

A

True

37
Q

Hydroxyurea may cause limited and reversible alopecia

A

True

38
Q

Hydroxyurea may cause photosensitivity and radiation recall

A

True

39
Q

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

A

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
Q

Hydroxyurea should not be administered with other myelosuppression agents

A

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

41
Q

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

A

True

42
Q

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

A

True

43
Q

Cyclophosphamide is metabolised by the CYP 450 system in the liver

A

True

44
Q

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

A

True

45
Q

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

A

True

46
Q

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

A

True

47
Q

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)

A

True

48
Q

Cyclophosphamide has a greater effect on B lymphocytes than T lymphocytes

A

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

49
Q

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

A

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

50
Q

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

A

True

51
Q

Cyclophosphamide is FDA approved for treatment of mycosis fungoides

A

True

52
Q

Cyclophosphamide can be used in the treatment of vasculitis

A

True

53
Q

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

A

True

54
Q

Cyclophosphamide is uncommonly used in the treatment of pemphigus

A

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

55
Q

Cyclophosphamide is contraindicated in patients with a history of bladder cancer

A

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

56
Q

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

A

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

57
Q

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

A

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

58
Q

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

A

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

59
Q

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

A

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

60
Q

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

A

True

61
Q

Mesna may be prescribed to patients on cyclophosphamide

A

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
Q

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

A

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

63
Q

There is a potential association between cyclophosphamide and SCC

A

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

64
Q

GI adverse effects affect 70-90% of cyclophosphamide users

A

True (this can be managed with ondansetron and dexamethasone)

65
Q

Anaemia associated with cyclophosphamide and chlorambucil use is usually reversible

A

True (also less common)

66
Q

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

A

True

67
Q

Thrombocytopenia usually occurs with higher doses of cyclophosphamide and chlorambucil

A

True

68
Q

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

A

True

69
Q

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

A

True

70
Q

Cyclophosphamide may cause hyperpigmentation of the skin and nails

A

True (just as in minocycline, hydroxychloroquine and hydroxyurea)

71
Q

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

A

True (also in chlorambucil)

72
Q

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

A

True

73
Q

Cyclophosphamide may cause azoospermia in men

A

True (testosterone may lessen this risk)

74
Q

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

A

True

75
Q

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

A

True

76
Q

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

A

True

77
Q

Chlorambucil has a slower onset of action than cyclophosphamide

A

True (and also less toxic)

78
Q

Unlike cyclophosphamide, metabolism of chlorambucil does not yield acrolein

A

True (and so chlorambucil does not cause haemorrhagic cystitis)

79
Q

In dermatology, Chlorambucil is used most consistently in necrobiotic xanthogranuloma

A

True

80
Q

Epilepsy and mood alterations are specific to chlorambucil

A

True (differs to cyclophosphamide)

81
Q

There is a risk of carcinogenesis from chlorambucil use

A

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

82
Q

Hepatotoxicity is an uncommon adverse effect of chlorambucil

A

True

83
Q

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

A

True

84
Q

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

A

True

85
Q

Cyclophosphamide and chlorambucil are teratogenic

A

True

Derm Pharm 2020 (47 decks)

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