immune system and malignant disease (medium)

Question 1

what the MOA of azathioprine and how is it broken down

Answer 1

antimetabolite which breakdown into mercaptopurine
this then inhibits repairmen’s and making of DNA

azathioprine is broken down by TPMT

Question 2

How is myelosuppression observed with azathioprine

Answer 2

need to prescreen TPMT levels

underactiveTPMPT means azathioprine toxicity/ myelosuppresion

Question 3

what are the side effects of azathioprine

Answer 3

hypersensitivity: fever, rash, hypotension, malaise, dizziness, myalgia = STOP
neutropenia and thrombocytopenia: sore throat, bruising, bleeding
nausea - common at start of treatment
teratogenic

Question 4

monitoring of azathioprine

Answer 4

TPMT
regular LFT and FBC in severe renal and liver impairment
FBC weekly for the first 4 weeks then at least every 3 months

Question 5

interactions of azathioprine and management

Answer 5

with allopurinol - increased risk of haematological toxicity - reduce dose of azathioprine

with ACE inhibitor - increased risk of anaemia and leukopenia - avoid use together

Question 6

MOA of cyclosporin and tacrolimus

Answer 6

calcineurin inhibitor which inhibits lymphokines and suppresses cell mediated response

Question 7

similarities and differences of cautions, side effects and monitoring or cyclosporin and tacrolimus

Answer 7

similarities:
- both must be brand specific
- both can cause hyperglycaemia, hyperuricaemia, hyperkalameia
- both cause renal/ liver impairment
- both cause skin reactions - rashes, toxic epidermal necrolysis
- both can cause visual disturbances and eye inflammation with topical use
- both should be avoided in pregnancy and breastfeeding
- both should avoid grapefruit juice and pomelo juice
- both avoid UV/ Sunlight
- avoid high potassium diet

differences:
- cyclosporin can cause hypomagesemia, hyperlipidaemia and hypertension unlike tacrolimus
- tacrolimus may cause hypo or hypertension
- tacrolimus can cause blood dyscrasia
- tacrolimus can cause CVD - arrhythmia, cardiomyopathy in children…
- tacrolimus can cause peripheral neuropathy/ nervous system disorders (headaches/ tremors…)
- ciclosporin can cause hair changes and hirsutism
- cyclosporin can cause gingival hyperplasia
- tacrolimus must also avoid pomegranate juice
- cyclosporin should avoid purple grape juice - decreases cyclosporin conc
- magnesium needs to be monitored with cyclosporin
- tacrolimus should not be used if hypersensitivity to macrolide

Question 8

monitoring parameters for tacrolimus and ciclosporin

Answer 8

LFT, blood pressure, CrCl, blood glucose, electrolytes

ECG also required for tacrolimus

Question 9

MOA for mycophenolate

Answer 9

inhibits purine synthesis

Question 10

side effects of mycophenolate

Answer 10

bone marrow suppression: infection, bleeding, bruising
pure red cell aplasia: reduce dose or discontinue
hypogammaglobulinaemia: measure immunoglobulin in recurrent infections
bronchiectasis: SOB/ cough could indicate this

Question 11

MHRA warning for mycophenolate

Answer 11

teratogenic

male: contraception needed during and 90 days after (for partner as well)
women: contraception needed during and 6 weeks after (2 methods preferred)

Question 12

what are the 3 types of MS

Answer 12

relapsing, progressive and both

Question 13

what is considered as active MS

Answer 13

2 relapses in the past 2 years despite treatment

Question 14

management of symptoms of MS

Answer 14

spasticity: baclofen, diazepam, tizanidine, dantrolene
relapse: methykprednisolone
oscillopsia (objects vibrate): gabapentin
mood alteration: amitriptyline
fatigue: amatadine or fampridine

Question 15

side effects and cautions of baclofen

Answer 15

can cause sedation and hypotonia (low muscle strength)

increase dose slowly to avoid major side effects

Question 16

what are alkylating agents and their main side effects

Answer 16

cyclophosphamide
ifosfamide
melphalan

SE: bone marrow suppression, male sterility, N/V with cyclophosphamide and urothelial toxicity with cyclophosphamide and ifosfamide

Question 17

what are the anthracyclines and their main SE

Answer 17

doxorubicin, daunorubicin, epirubicin, idarubicin

SE: sore mouth, bone marrow suppression, red urine, formulation NOT interchangeable, cardiotoxic SE, liposomal = less cardiotoxic

Question 18

antimetabolites and their SE

Answer 18

Flourouracil, methotrexate, cytarabine, mercaptopurine

SE: bone marrow suppression, myelosuppresion with methotrexate, mucositis (sore mouth) with fluorouracil and MTX

Question 19

cytotoxic antibiotics and their SE

Answer 19

bleomycin, mitomycin

SE:
bone marrow suppression (not bleomycin)
pulmonary toxicity/ fibrosis: SOB, coughing, wheezing

Question 20

taxanes and their main SE and monitoring

Answer 20

docetaxel, paclitaxel, carbazitaxel

SE: bone marrow suppression, hyperactivity - premeditate with corticosteroids and antihistamines

monitoring: cardiac output, symptoms pneumonitis and sepsis

Question 21

vinca alkaloids and their main SE and cautions

Answer 21

vinblastine, vincristine, vindesine

SE: bone marrow suppression (but not vincristine), mild N/V, bronchospasm, neurotoxicity, motor weakness, myalgia, neuropathy…

caution: GIVE BY IV NEVER GIVE BY INTRATHECAL

Question 22

platinum compounds and their main SE

Answer 22

carboplatin, cisplatin, oxaliplatin

SE: bone marrow suppression, high N/V with cisplatin

Question 23

which cytotoxic drug does NOT cause bone marrow suppression

Answer 23

vincristine and bleomycin

Question 24

which drugs cause mucositis and how to prevent this and the treatment

Answer 24

fluorouracil and MTX
anthracyclines (rubicins)

prevention: good oral hygiene and sucking on ice chips
treatment: saline mouthwash or use colonic acid if caused my MTX

Question 25

what causes tumour lysis syndrome:

Answer 25

more common in non-hodgkins, burkitts, lymphoblastic, acute myeloid leukaemia

hyperkalamia, hyperphosphotaemia, hypercalcemia, hyperuricaemia can cause it and result in renal damage and arrhythmia

Question 26

how to treat hyperuricaemia

Answer 26

allopurinol 24 hours before
OR
febuxostat - given 2 days before treatment

Question 27

how to manage bone marrow suppression

Answer 27

occurs 7-10 days after treatment
check blood count before treatment and reduce dose if haven’t recovered
avoid treatment during acute infection
if become ill after treatment - seek medical attention
neutropenic fever: give immediate broad spectrum antibiotics

Question 28

what is urothelial toxicity and what drugs can cause this and how to treat this

Answer 28

haemorrhage in urinary tract
common with cyclophosphamide and ifosfamide
treat with mesa

Question 29

cause and treatment of myelosuppression

Answer 29

cause: MTX
treatment: folonic acid

Question 30

what are highly ematogenic drugs

Answer 30

cisplatin, dacarbazine, high cyclophosphamide dose

Question 31

treatment of acute symptoms of N/V in low and high risk patients

Answer 31

low risk: dexamethasone + lorazepam

high risk: dexamethasone + ondansetron + aprepitant

Question 32

treatment of prevention of delayed symptoms (after 24 hours of treatment) if on moderate and high emetogenic drugs

Answer 32

moderately emetogenic drugs: dexamethasone + ondansetron

highly emetogenic drugs: dexamethasone + aprepitant

Question 33

prevention of anticipatory N/V

Answer 33

lorazepam