Immune System and Malignant Disease

Question 1

Azathioprine

Answer 1

-antimetabolite - breaks down into mercaptopurine which inhibits the repairment + making of DNA
-It is broken down by thiopurine methyltransferase (TMPT)
-> pre-screening TPMT lvls is advised underactive TMPT -> myelosupression

Question 2

Azathioprine s/e

Answer 2

-hypersensitivity - malaise, dizziness, D+V, fever, rash, hypotension, myalgia
-neutropenia + thrombocytopenia = report sore throat, bruising, bleeding
-nausea - more common at start but resolves
-teratogenic = avoid in pregn

Question 3

Azathioprine monitoring

Answer 3

• TPMT
  -regular LFT + FBC in severe liver/renal impairment
  -FBC weekly 1st 4WK*3MT

Question 4

Azathioprine interactions

Answer 4

• Azathioprine + allopurinol -> high risk of haematological toxicity - dec dose of azathioprine
  -Azathioprine + ACEi - high risk of anaemia/lucopenia - avoid concommitant use

Question 5

ciclosporin

Answer 5

calcineurin inhibitor - inhibits lymphokines suppresses cell-mediated response
-prescribe by brand

Question 6

ciclosporin s/e

Answer 6

-avoid in pregn + BF
-HYPER - gylcaemia, lipidaemia, tension, uricemia, kalaemia
-HYPO-mg
-renal/liver impairment
-givgival hyperplasia
-skin reactions
-hair changes
-eye inflammation + visual disturbances ( topical - eyes)

Question 7

aciclosporin interactions

Answer 7

-grapefruit + pomelo juice - inc ciclosporin exposure
-purple grape juice - lowers exposure
-pre-screening exclude malignancies before systemic use

Question 8

ciclosporin monitor

Answer 8

LFT
Mg+
K+
lipidis
CrCl
BP (trough)
avoid exposure to UV/sunlight
vision with topical use

Question 9

tacrolimus

Answer 9

calcineurin inhibitor inhibiting lymphokines - supresses cell-mediated response
-prescribe by brand

Question 10

tacrolimus S/E

Answer 10

-avoid in pregnancy + BF
-HYPO/HYPER - tension
-HYPER-glycaemia, uricemia, kalaemia
-renal/liver impairment
-skin reactions
-visual disturbances
-blood dyscaria
-cardiovascular disease (QT prolongation, cardiomyopathy in children)
-nervous system disorder - peripheral neuropathy

Question 11

tacrolimus interactions

Answer 11

-grapefruit + pomegranate + pomelo juice - inc exposure
-x use in hypersensitivity to macrolides

Question 12

tacrolimus monitoring

Answer 12

-BP
-ECG
-blood glucose
-LFT
-electrolytes
-CrCl
-skilled tasks
-avoid exposure to sunlight/UV

Question 13

mycophenolate mofetil

Answer 13

inhibits purine synthesis
-bone marrow supression = report infections/bruising/bleeding
-pure red cell aplasia = reduce dose or discontinue
-hypogammaglobulinaemia = measure immunoglobulin lvls in recurrent infection
-bronchiestasis = consider if persistent cough/SoB develops

Question 14

mycophenolate mofetil MHRA

Answer 14

-contraception advise
-tetrogenic
-women = 1 effective contraception during + 6wk after (2MT ideal)
-men = effective contraception during + 90DY after (+partners)

Question 15

multiple sclerosis

Answer 15

-chronic autoimmune disease demyelinating CNS
-can be relapsing, progressive or both
-active: 2 relapses in past 2yr despite tx with interferon beta

Question 16

multiple sclerosis managing symptoms

Answer 16

-spasticity; baclofen (dose slowly avoid major S/E - sedation + hypotonia), diazepam, tizanidine, dantrolene
-relapses; methylprednisolone
-oscillopsia (objects appear to vibrate); gabapentin
-mood alteration; amitriptylline
-fatigue; amantadine or fampride

Question 17

handling cytotoxic drugs

Answer 17

-chemotherapy of cancer - specialists in oncology
-reconstitued by trained professionals
-wear protective clothing
-use eye protection
-avoid by pregn staff/child bearing age
-use local procedure - spillage, safe disposal, syringes, containers, abosbent materials
-monitor staff exposure

Question 18

cytotoxic drug classes

Answer 18

-alkylating agents
-anthracyclines
-antimetabolites
-cytotoxic antibodies
-platinum compounds
-taxanes
-vinca alkaloids

Question 19

alkylating agents

Answer 19

cyclophosphamide
fosfamide
mephalan

Question 20

anthracyclines

Answer 20

daunorubicin
doxonrubicin
epirubicin
idarubicin

Question 21

antimetabolites

Answer 21

cytarabine
fluorouracil
methotrexate
mercaptopurine

Question 22

cytotoxic antibodies

Answer 22

belomycin
mitromycin

Question 23

platinum compounds

Answer 23

carboplatin
cisplatin
oxaliplatin

Question 24

taxanes

Answer 24

cabazitaxel
docetaoxel
paditaxel

Question 25

vinca alkaloids

Answer 25

vinblatine
vincistine
vinderine

Question 26

cytotoxin s/e

Answer 26

-extravasation of IV drugs - severe local tissue necrosis due to leakage of cyotoxin
-oral mucositis
-tumor lysis syndrome
-hyperuricaemia
-bone marrow suppression
-alopecia (most common)
-thromboembolism (chemo inc risk)
-urothelial toxicity
-myelosuppression

Question 27

oral mucositis

Answer 27

-sore mouth assoc with fluorouracil, methotrexate, anthracyclines
-good oral hygiene + sucking ice chips = fluorouracil
-tx is less effective than preventing - tx with saline mouthwashes
-if caused by methotrexate use folinic acid (levofloinic)

Question 28

tumor lysis syndrome

Answer 28

-occurs due to rapid destruction of malignant cells
-high risk in non-hodgkins lymphoma, burkitts lymphoma, acute lymphblastic leukaemia + acute myeloid leukaemia
-high risk in pre-exisiting hyperuricaemia, dehydration + renal impairment
-causes HYPER- kalaemia, phosphataemia, calcaemia - renal damange + arrythmia

Question 29

hyperuricaemia

Answer 29

-more present in high grade lymphoma + leukaemia
-allopurinol start 24HR before tx tumors - hydrate pt
-alternative - feboxostat given 2DY before tx

Question 30

bone marrow suppression

Answer 30

-caused by all drugs other than vincristine + bleomycin
-occurs 7-10DY after admin
-check blood count before tx - reduce dose if bone marrow x recovered
-avoid tx during acute infections/seek medical
-neutropenic fever immediate broad spectrum antibodies

Question 31

urothelial toxicity

Answer 31

-causes haemorrhage in urinary tract
-common in cyclophosphamide + ifosfamide
-tx with mesna

Question 32

myelosuppression

Answer 32

-can be caused by methotrexate
-use folinic acid to tx toxicity

Question 33

Cytotoxin drugs + reproductive systems

Answer 33

–mostly teratotogenic - x pregn
-exclude pregn before tx
-contraception advise before tx
-women of child-bearing age = contraception before + after tx
-alkylating drug or procarbazines
->high risk of permanent male stetility
->consider sperm storage
->affects women less onset of premature menopause

Question 34

N+V

Answer 34

-symptoms can be acute, delayed or anticipatory
->delayed or anticipatory more difficult to control than acute
-more common in women, pt <50, anxiety, repeated exposure

Question 35

mild N+V

Answer 35

-fluorocuracil, exopuride, methotrexate, vinca alkaloids

Question 36

moderate N+V

Answer 36

-taxanes, doxorubicin, less cyclophsophamide doses, mitoxantrane + high methotrexate doses

Question 37

severe N+V

Answer 37

-cisplatin, dacarbazine, high cyclophosphamide doses

Question 38

prevention of N+V acute symptoms

Answer 38

-within 24hr of tx
-low risk pt = dexamethasone, lorazepam
-high risk pt = ondansetron, dexamethasone + aprepitant

Question 39

prevention of N+V delayed symptoms

Answer 39

-after 24hr tx
- moderate emtogenic drugs = dexa + ondan
-highly emetogenic drugs = dexa + aprepitant

Question 40

prevention of N+V anticipatory symptoms

Answer 40

-before tx
-lorazepam

Question 41

alkylating agents

Answer 41

-cyclophosphamide, ifofsamide ,melphalan
-urthoelial toxicity
-high risk of permanent male sterility

Question 42

anthracyclines

Answer 42

-daunorubicin, doxorubicin, epirubicin, idarubicin,
-rubi - red urine
-formulation x interchangable (conventional, liposomal, peggylated liposomal)
-cardiotoxic s/e
-liposomal - less cardiotoxicity but causes painful mascular skin eruptions - prevent by cooling hands/feet/ avoiding gloves + sicks

Question 43

antimetabolites

Answer 43

-cytarabine, fluorouracil, methotrexate, mercaptopurine
->mucositis + myelosupression

Question 44

cytotoxic antibodies

Answer 44

-blemoycin, mitomycin
-progressive pulmonary fibrosis
-pulmonary toxicity

Question 45

taxanes

Answer 45

-carbazitaxenes, docetaxes, paciltaxes
-hypersensitivity reactions - premediate with corticosteroids + antihistamines
-monitor cardiac output
-monitor for signs + symp of penumonitis + spesis

Question 46

vinca alkaloids

Answer 46

-vinblastine, vincristine, videsine
-IV admin only - intratheal = fatal
-bronchospasms
-neurotoxicity - neuropathy, motor weakness, myalgia