1 - METHOTREXATE Flashcards Preview

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Flashcards in 1 - METHOTREXATE Deck (97):
1

Methotrexate is a chemotherapeutic agent

True (cytotoxic and teratogenic)

2

Methotrexate is an immunosuppressive agent

True

3

MTX is often used with TNF-alpha antagonists

True (FDA approved in patients with arthritis)

4

Methotrexate is a potential competitive antagonist and inhibitor of dihydrofolate reductase

True

5

Methotrexate is structurally similar to folic acid

True

6

Folic acid is the natural substrate for the enzyme dihydropteroate synthetase and dihydrofolate reductase

True

7

Methotrexate can be administered orally

True

8

Methotrexate can be administered intravenously

True

9

Methotrexate can be administered intramuscularly

True

10

Methotrexate can be administered subcutaneously

True

11

Methotrexate is rapidly absorbed through the GI tract

True

12

Peak plasma levels of orally administered Methotrexate are reached more slowly than intravenous or subcutaneous/intramuscular route

True

13

The oral route of Methotrexate provides more reliable blood levels than parenteral administration even though the absorption of oral methotrexate may be incomplete and variable with doses > 15mg

True

14

Concurrent food intake, particularly milk-based meals may reduce bioavailability in children

True (though bioavailability in adults is not affected by concurrent food ingestion)

15

The bioavailability of methotrexate in adults is not affected by concurrent food ingestion

True

16

The absorption of methotrexate may be reduced by non-absorbable antibiotics such as neomycin

True

17

Methotrexate does not penetrate the blood brain barrier well

True (the reason why intrathecal methotrexate is needed in some chemotherapy regimens)

18

The level of plasma Methotrexate once absorbed, has a triphasic reduction

True

19

The first phase of the triphasic reduction of plasma methotrexate occurs rapidly over 0.75 hours and reflects distribution of the drug throughout the body

True

20

The second phase of the triphasic reduction of plasma methotrexate occurs over 2-4 hours and reflects renal excretion

True

21

The third phase of the triphasic reduction of plasma methotrexate occurs between 10 and 27 hours and reflects the terminal half life and slow release of methotrexate primarily bound to dihydrofolate reductase from the tissues

True

22

Methotrexate is a weak organic acid and is excreted through the kidneys

True

23

Methotrexate is a weak organic acid predominately excreted through the kidneys; MTX glomerular filtration and active tubular secretion are susceptible to drug interactions with other weak acids I.e. Salicylates, probenecid, and sulfonamides

True

24

Approx 50% of methotrexate is bound to plasma proteins and 50% is the unbound free fraction/active portion of the drug

True

25

The beneficial effects and potential for toxicity is increased when the unbound free fraction of methotrexate is increased by certain drugs I.e. Salicylates, sulfonamides, probenecid

True

26

Methotrexate is metabolised intracellularly in all cells that it is actively transported into, including the liver

True

27

Methotrexate is metabolised intracellularly to polyglutamated forms/metabolites which are potent inhibitors of dihydrofolate reductase and play a key role in methotrexate toxicity

True

28

The polyglutamated metabolites of intracellular methotrexate metabolism contributes toward methotrexate toxicity

True (the metabolites are also dihydrofolate reductase inhibitors)

29

Methotrexate has a greater affinity to dihydrofolate reductase than the enzyme's natural substrate folic acid

True

30

Folic acid (natural substrate of dihydrofolate reductase) is converted to tetrahydrofolate by dihydrofolate reductase

True

31

Tetrahydrofolate is converted to DNA by thymidylate synthetase

True

32

Methotrexate competitively and irreversibly binds to dihydrofolate reductase with a greater affinity than folic acid

True (prevents conversion of dihydrofolate to tetrahydrofolate)

33

Methotrexate prevents the conversion of dihydrofolate to tetrahydrofolate by competitively and irreversibly binding to dihydrofolate reductase

True

34

Methotrexate also competitively and partially reversibly inhibits thymidylate synthetase within 24 hours of methotrexate administration to prevent thymidine and purine nucleotide synthesis to take place from tetrahydrofolate

True (affects DNA synthesis)

35

The overall effect of methotrexate is inhibition of DNA synthesis/cell division which takes place during the S phase of the cell cycle

True

36

The competitive and irreversible inhibition of dihydrofolate reductase by methotrexate can be bypassed by Leucovorin (folinic acid)

True (thus folinic rescue may reverse the acute haematologic toxicity secondary to methotrexate)

37

Leucovorin (folinic acid) may reverse the acute haematologic toxicity secondary to methotrexate

True

38

Methotrexate acts via an immunosuppressive mechanism by affecting the proliferation of lymphocytes

True

39

Methotrexate affects the proliferation of lymphocytes

True

40

Methotrexate blocks migration of activated T cells

True

41

The anti-inflammatory effects of methotrexate are predominately mediated by adenosine

True

42

There is decrease methotrexate efficacy with concomitant folic acid

True (folic acid is no longer routinely recommended unless adverse effects arise I.e. GI upset or haematologic toxicity

43

The use of folic acid as a method of inhibiting Methotrexate induced GI adverse effects and pancytopenia is controversial

True

44

Salicylates increase methotrexate levels and toxicity due to decreased renal excretion and displacement from plasma proteins

True

45

NSAIDS increase methotrexate levels and toxicity due to decreased renal excretion and displacement from plasma proteins

True

46

Sulfonamides increase methotrexate levels and toxicity due to decreased renal excretion, displacement from plasma proteins and inhibition of dihydropteroate synthetase (converts folic acid to dihydrofolate)

True

47

Probenecid increase methotrexate levels and toxicity due to increased intracellular accumulation and decreased renal excretion

True

48

Dipyridamole increase methotrexate levels and toxicity due to increased intracellular accumulation

True

49

Chloramphenicol increase methotrexate levels and toxicity due to displacement from plasma proteins

True

50

Phenothiazines increase methotrexate levels and toxicity due to displacement from plasma proteins

True

51

Phenytoin increase methotrexate levels and toxicity due to displacement from plasma proteins

True

52

Tetracyclines increase methotrexate levels and toxicity due to displacement from plasma proteins

True

53

Trimethoprim inhibits dihydrofolate reductase (coverts dihydrofolate to tetrahydrofolate) in the folate pathway resulting in increased haematologic toxicity

True (methotrexate and trimethoprim are competitive inhibitors of dihydrofolate reductase)

54

Folic acid is also converted to dihydrofolate by dihydropteroate synthetase

True (and folic acid can be converted to tetrahydrofolate by dihydrofolate reductase)

55

Dapsone and sulfonamides inhibit dihydropteroate synthetase (coverts folic acid to dihydrofolate) and thus can amplify the inhibition of dihydrofolate reductase by methotrexate due to less dihydrofolate being available to the enzyme, resulting in increased haematologic toxicity

True

56

Therapeutic doses of folic acid competes with methotrexate for dihydrofolate reductase to decrease the adverse effects of methotrexate by increasing tetrahydrofolate production

True

57

Systemic retinoids may synergistically increase hepatotoxicity if given concomitantly with methotrexate due to the liver being the common target organ for toxicity in both drugs

True

58

Alcohol may synergistically increase hepatotoxicity if given concomitantly with methotrexate due to the liver being the common target organ for toxicity in both drugs

True

59

Trimethoprim and sulphamethoxazole in combination markedly increase the risk of haematologic toxicity when used with methotrexate due to a more complete inhibition of 2 step folate pathway

True (trimethoprim inhibits dihydrofolate reductase, and sulphamethoxazole being a sulfonamide inhibits dihydropteroate synthetase)

60

Methotrexate is absolutely contraindicated in pregnancy

True (category X)

61

Methotrexate may cause hepatotoxicity in the form of liver fibrosis

True (procollagen type III peptide non-invasive test)
L - Liver toxicity
I - Infections
M - Marrow suppression/Malignancy
I - Idiopathic pulmonary fibrosis
T - Teratogenecity
G - GI effects
P - Phototoxicity
S - Sunburn recall

62

Methotrexate may cause infections

True
L - Liver toxicity
I - Infections
M - Marrow suppression/Malignancy
I - Idiopathic pulmonary fibrosis
T - Teratogenecity
G - GI effects
P - Phototoxicity
S - Sunburn recall

63

Methotrexate may cause idiosyncratic acute pneumonitis and pulmonary fibrosis with small doses of methotrexate

True (CXR only if patient develops symptoms suggesting penumonitis)
L - Liver toxicity
I - Infections
M - Marrow suppression/Malignancy
I - Idiopathic pulmonary fibrosis
T - Teratogenecity
G - GI effects
P - Phototoxicity
S - Sunburn recall

64

Methotrexate may cause pancytopenia

True (risk significantly reduced by folic acid supplementation, consider supplementation regardless of whether patient is experiencing GI side effects)
L - Liver toxicity
I - Infections
M - Marrow suppression/Malignancy
I - Idiopathic pulmonary fibrosis
T - Teratogenecity
G - GI effects
P - Phototoxicity
S - Sunburn recall

65

Poor renal function may precipitate haematologic toxicity associated with methotrexate

True (due to increased free methotrexate in plasma) - avoid combining trimethoprim/sulphamethoxazole and NSAIDS with methotrexate and consider folic acid supplementation regardless of whether the patient is experiencing GI side effects

66

Folic acid supplementation is usually given to improve the GI side effects associated with methotrexate

True

67

Regardless of whether GI side effects are present, consider folic acid supplementation to reduce the risk of pancytopenia associated with methotrexate

True

68

Should significant myelosuppression develop from methotrexate, Leucovorin (folinic acid) can be given promptly to treat this

True

69

Patients who inadvertently take methotrexate daily are at a greater risk for pancytopenia

True

70

A high MCV without anaemia is common in dermatologic dosage levels of methotrexate

True (not a cause for concern)

71

Lymphoma has been reported in patients with psoriasis on methotrexate

True (although EBV has been found within these lymphomas and demonstrated regression of the lymphoma with cessation of methotrexate, there is no statistical evidence that methotrexate increases the risk of developing a subsequent malignancy in psoriasis patients)
L - Liver toxicity
I - Infections
M - Marrow suppression/Malignancy
I - Idiopathic pulmonary fibrosis
T - Teratogenecity
G - GI effects
P - Phototoxicity
S - Sunburn recall

72

The subject of folic acid compromising efficacy of methotrexate remains contradictory due to mixed reports

True

73

Nausea and anorexia are common adverse reactions to methotrexate

True
L - Liver toxicity
I - Infections
M - Marrow suppression/Malignancy
I - Idiopathic pulmonary fibrosis
T - Teratogenecity
G - GI effects
P - Phototoxicity
S - Sunburn recall

74

Diarrhoea, vomiting and ulcerative stomatitis are less frequent adverse effects of methotrexate

True
L - Liver toxicity
I - Infections
M - Marrow suppression/Malignancy
I - Idiopathic pulmonary fibrosis
T - Teratogenecity
G - GI effects
P - Phototoxicity
S - Sunburn recall

75

Methotrexate should be ceased if diarrhoea and ulcerative stomatitis is observed

True
L - Liver toxicity
I - Infections
M - Marrow suppression/Malignancy
I - Idiopathic pulmonary fibrosis
T - Teratogenecity
G - GI effects
P - Phototoxicity
S - Sunburn recall

76

Men on methotrexate should be counselled with regard to possible reversible oligospermia

True

77

Men on methotrexate should avoid impregnating a woman

True (although a recent study did not reveal any congenital malformations or spontaneous abortions associated with these men)

78

In dermatological doses, methotrexate is not likely to cause renal toxicity

True (encountered in the higher doses used in chemotherapy secondary to precipitation of methotrexate in renal tubules)
L - Liver toxicity
I - Infections
M - Marrow suppression/Malignancy
I - Idiopathic pulmonary fibrosis
T - Teratogenecity
G - GI effects
P - Phototoxicity
S - Sunburn recall

79

Methotrexate is phototoxic

True (may cause phototoxicity and sunburn recall)
L - Liver toxicity
I - Infections
M - Marrow suppression/Malignancy
I - Idiopathic pulmonary fibrosis
T - Teratogenecity
G - GI effects
P - Phototoxicity
S - Sunburn recall

80

Methotrexate may cause sunburn recall

True
L - Liver toxicity
I - Infections
M - Marrow suppression/Malignancy
I - Idiopathic pulmonary fibrosis
T - Teratogenecity
G - GI effects
P - Phototoxicity
S - Sunburn recall

81

Deaths due to methotrexate induced cirrhosis have occurred in patients with psoriasis

True
L - Liver toxicity
I - Infections
M - Marrow suppression/Malignancy
I - Idiopathic pulmonary fibrosis
T - Teratogenecity
G - GI effects
P - Phototoxicity
S - Sunburn recall

82

Patients with diabetes or obesity are presumed to be at greater risk for liver toxicity

True (increased incidence of non-alcoholic steatohepatitis in this group) - avoid prescribing methotrexate

83

Patients with history of exposure to hepatotoxins I.e. Alcohol or IV drugs are presumed to be at greater risk for liver toxicity

True (avoid prescribing methotrexate)

84

Avoid prescribing methotrexate in patients with personal or family history of liver disease

True (higher risk of hepatoxicity)

85

Patients with abnormal baseline LFTs or hepatitis serology are presumed to be at greater risk for liver toxicity

True (avoid prescribing methotrexate)

86

The need for repeated liver biopsies is based on the total dose of methotrexate - generally after every 1.5g total dose

True

87

Patients with grade I (normal vs mild fatty infiltration) or II (moderate to severe fatty infiltration) liver histology findings may continue methotrexate

True

88

Patients with grade IIIa (mild fibrosis) liver histology findings may continue methotrexate but should have a repeat liver biopsy in 6 months

True

89

Patients with grade IIIb (moderate to severe liver fibrosis) or IV (cirrhosis) liver histology findings need to stop methotrexate

True (also needs careful follow up of liver biopsies)

90

If the WBC count is <3500/mm3, discontinue or reduce the dose of methotrexate

True (methotrexate may be restarted at a lower dose if the lab abnormality has resolved after 2-3 weeks)

91

If the platelet count is <100,000 /mm3, discontinue or reduce the dose of methotrexate

True (methotrexate may be restarted at a lower dose if the lab abnormality has resolved after 2-3 weeks)

92

If the liver transaminases increase over twice the upper normal value, discontinue or reduce the dose of methotrexate

True (methotrexate may be restarted at a lower dose if the lab abnormality has resolved after 2-3 weeks)

93

Methotrexate is usually given as a single weekly dose

True

94

Methotrexate may be given in 3 divided doses over a 24 hour period each week I.e. Day 1 8am and 8pm followed by Day 2 8am

True (equally effective with similar toxicity to the once weekly dose)

95

Intramuscular methotrexate may be considered in patients non-compliant to the oral dose or patients who develop nausea from the oral dose

True

96

A methotrexate test dose of 5-10mg is generally given followed by a FBC and LFTs 6-7 days later

True

97

Patients receiving IM or IV methotrexate are able to tolerate higher doses due to more rapid renal clearance

True