antimetabolites

Question 1

name some

Answer 1

FU, capecitabine
mercaptopurine
MTX

Question 2

MHRA/CHM advice: IV FU, capecitabine - what do you need to test for

Answer 2

DPD testing recommended before initiation to identify patients at increased risk of severe and fatal toxicity
CI in complete DPD deficiency
partial DPD deficiency, a reduced starting dose is recommended

Question 3

IV FU - Patients should be monitored for toxicity, particularly during

Answer 3

the first cycle of treatment or after a dose increase; severe toxicity can occur even in those with negative test results for DPD deficiency.

Question 4

CI for FU

Answer 4

Bone marrow depression (after treatment with radiotherapy or other antineoplastic agents);

Complete or near complete absence of DHD activity (increased risk of severe, life-threatening, or fatal toxicity)

Question 5

Common SE of DU

Answer 5

mucositis (suck on ice chips during short infusions)
alopecia
neutropenia, thrombocytpenia
skin reactions
n/v
stomatitis

Question 6

FU , monitoring With intra-arterial use or intravenous use

Answer 6

regularly monitor cardiac function

Question 7

mercaptopurine + allopurinol

Answer 7

Manufacturer advises reduce dose to one-quarter of the usual dose with concurrent use of allopurinol.

Allopurinol potentially increases the risk of haematological toxicity when given with Mercaptopurine.

Question 8

FU - interactiosn are to do wiht (4)

Answer 8

increases AC effect of coumarins
increased risk hepatotoxicity (e.g. azoles, heparin, tetracyclines etc)
increased risk myelosuppresion
live vaccines - risk of generalised infections, possibly life threatening

Question 9

mercaptopurine CI
When used for non-cancer indications

Answer 9

absent TPMP activity

Question 10

what is TPMT

Answer 10

The enzyme TPMT metabolises thiopurine drugs (azathioprine, mercaptopurine, tioguanine); the risk of myelosuppression is increased in patients with reduced activity of the enzyme, particularly for the few individuals in whom TPMT activity is undetectable. Those with reduced TPMT activity may be treated under specialist supervision.

Question 11

mercaptopurine + febuxostat

Answer 11

Febuxostat is predicted to increase the exposure to Mercaptopurine. Manufacturer advises avoid.

Question 12

mercaptopruine + trimethoprim

Answer 12

Trimethoprim might increase the risk of haematological toxicity when given with Mercaptopurine in renal transplant patients. Manufacturer makes no recommendation.

Question 13

MOA Methotrexate

Answer 13

Methotrexate inhibits the enzyme dihydrofolate reductase, essential for the synthesis of purines and pyrimidines.

Question 14

MTX contraception and conception

Answer 14

Manufacturer advises effective contraception during and for at least 6 months after treatment in men and women.

Question 15

MTX pre treatment screening

Answer 15

Exclude pregnancy before treatment.

Patients should have full blood count and renal and liver function tests before starting treatment.

Question 16

Folinic acid following methotrexate administration helps to prevent methotrexate-induced ….

Answer 16

mucostitis and myelsuppression

Question 17

…… should be provided to patients on once-weekly dosing for MTX

Answer 17

patient alert card

Question 18

pt on MTX need to report (3)

Answer 18

any feature of blood disorders (e.g. sore throat, bruising, and mouth ulcers)

liver toxicity (e.g. nausea, vomiting, abdominal discomfort and dark urine)

respiratory effects (e.g. shortness of breath).

Question 19

pt on MTX need to avoid

Answer 19

Patients and their carers should be advised to avoid exposure to UV light (including intense sunlight, sunlamps, and sunbeds)—see Important safety information.

Patients should be advised to avoid self-medication with over-the-counter aspirin or ibuprofen.

Question 20

pt on MTX develops ulcerative stomatitis. What to do?

Answer 20

Withdraw treatment if ulcerative stomatitis develops—may be first sign of gastro-intestinal toxicity.

Question 21

folic acid is given with MTX to reduce SE. what SE does it reduce

Answer 21

Folic acid decreases mucosal and gastrointestinal side-effects of methotrexate and may prevent hepatotoxicity; there is no evidence of a reduction in haematological side-effects.

Question 22

MTX

Manufacturer advises withdraw treatment if these two develops—may be first sign of gastro-intestinal toxicity.

Answer 22

stomatitis or diarrhoea

Question 23

MTX and pulmonary toxicity

Answer 23

Pulmonary toxicity may be a special problem in rheumatoid arthritis. Manufacturer advises patients to seek medical attention if dyspnoea, cough or fever develops; monitor for symptoms at each visit—discontinue if pneumonitis suspected.

Question 24

MTX and photosensitiy reactions

Answer 24

Psoriasis lesions may be aggravated by UV radiation—skin ulceration has been reported.

Radiation recall reaction has been reported in both radiation- and sun-damaged skin.

Photosensitivity reactions, including phototoxicity, are known side-effects of methotrexate that may occur with low- and high-dose treatment. These reactions are distinct from radiation recall reactions, and can appear as severe sunburn (e.g. rashes with papules or blistering, and sometimes swelling); rarely, photosensitivity reactions have contributed to deaths from secondary infections.

Question 25

MTX - increased risk of toxicity with these abx

Answer 25

all penicillins
ciproflox
all sulfadiaxoles

Question 26

increased risk of MTX toxicity with

Answer 26

pencillins
cipfloxacin
sulphur abx
NSAIDs
PPIs
Aspiirn
Coxibs