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Question 1

Alemtuzumab

Answer 1

Recombinant humanised monoclonal antibody
Anti-CD52
CD52 is found on most B cells, T cells, monocytes, macrophages and some granulocytes
Rx: CLL, multiple sclerosis
Caution: may cause transient and severe hypotension caution with IHD

May cause hypotension, infusion related reactions, profound lymphopenia, pancytopenia

Question 2

Bevacizumab

Answer 2

Recombinant humanised
binds to VEGF inhibiting angiogenesis
Risk of heart failure
Hypertension, impaired wound healing, thromboembolic events,

Question 3

Blinatumomab

Answer 3

Recombinant, bispecific mAb
Binds to CD19 (B cells ) and CD3 (T cells)
Forms link that results in activation of T cells and the elimination of CD-19 positive B cells
Indicated: B cell ALL
Cytokine release syndrome, neurological toxicity, infection

Question 4

Brentuximab vedotin

Answer 4

Conjugte - toxic payload: chimeric antibody (CD30) + monomethyl auristatin E (MMAE) a microtubule poison > cell cycle arrest and apoptosis
Containdicated with bleomycin
Renal avoid: <30mL/min
Hepatic avoid: Child B and C
Peripheral neuropathy, infusion related, PML, pneumonitis

Question 5

Cetuximab

Answer 5

Recombinant chimeric 
Binds to EGFR 
inhibits proliferation, 
Skin reactions: acne, rash,
infusion reaction, VTE, mucositis,

Question 6

EGFR inhibitors

Answer 6

Cetuximab
Panitumumab
Afatinib
Erlotinib
Gefitinib

Question 7

EGFR inhibitor skin reactions

Answer 7

Papulopustular rash
Face and upper body
Occurrence/severity may be associated with response to treatment
Rx doxycycline prophylaxis and steroids
Other skin signs: itch, dry skin, fissures, paronychia, nail disorders, abnormal hair growth

Question 8

Ipilimumab

Answer 8

Human monoclonal Ab

CTLA-4 (cytotoxic T lymphocyte-associated antigen 4

Question 9

CYP450 inducers

Answer 9

SCRAP GPS
St. John's Wort
Carbamazipine
Rifampicin
Alcohol (chronic)
Phenytoin
Griseofulvin
Phenobarbital
Sulphonylureas

Question 10

CYP450 inhibitors

Answer 10

SICKFACES.COM GQ
Sodium valproate
Isoniazid
Cimetidine
Ketoconazole
Fluconazole
Alcohol (acute)/amiodarone
Chloramphenicol
Erythromycin
Sulphonamides
Ciprofloxicin
Omeprazole
Metronidazole
Grapefruit juice
Quinidine

Question 11

Omalizumab

Answer 11

Recombinant humanised
Monoclonal antibody against IgE
Reduces the immune systems response to allergen exposure
Rx: asthma, chronic spontaneous urticaria
Thrombocytopenia, ? association with Churg-Strass syndrome
SE: injection site reactions, bleeding, headache, MSS pain, anaphylaxis , serum sickness-like reaction

Question 12

Anti-CD20 antibodies

Answer 12

Rituximab
Ofatumumab
Obinutuzumab

Question 13

Basilixumab

Answer 13

Chimeric monoclonal antibody against IL-2
Blocks IL-2 inhibiting T-lymphocyte proliferation
Rx: prevention of acute renal transplant rejection (also liver and lung)
Caution if previous Rx with basilixumab, may increase risk of hypersensitivity; ?increase in surgical wound complications
SE: hypersensitivity, cytokine release syndrome

Question 14

Crizotinib

Answer 14

Tyrosine kinase inhibitor
Inhibits anaplastic lymphoma kinase (ALK) and hepatocyte growth factor (HGFR, c-Met)
Rx: anaplastic lymphoma (AKL +); non-small cell lung cancer (ALK+)

Question 15

Afatinib

Answer 15

TKI
EGFR
HER2, HER4

Question 16

Axitinib

Answer 16

VEGF 1-3

Question 17

Dasatinib

Answer 17

BCR-ABL
Src family
c-KIT
PDGFR
ephrin receptor

Question 18

Erlotinib

Answer 18

EGFR

Question 19

Gefitinib

Answer 19

EGFR

Question 20

Ibrutinib

Answer 20

Bruton’s tyrosine kinase (BTK)

Question 21

Imatinib

Answer 21

bcr-abl, c-KIT, PDGFR

Question 22

Nilotinib

Answer 22

bcr-abl, c-KIT, ephrin receptor, PDGFR

Question 23

Tofacitinib

Answer 23

JAK1, JAK2, JAK3

Question 24

Sunitinib

Answer 24

VEGFR 1-3
PDGFR
c-KIT
FLT-3

Question 25

Sorafenib

Answer 25

``` VEGFR 2-3 PDGFR c-kit FLT-3 also Raf kinase ```

Question 26

Pertuzumab

Answer 26

Recombinant humanised Monoclonal antibody against HER2 Prevents HER2 paring with other members of the HER family, arrests cell growth and induces apoptosis Activates immune response that lyses tumour cells Rx: HER2 positive breast cancer Caution: risk of cardiac failure/LV dysfunction caution if underlying heart disease, or other cardiotoxic agents SE: infusion related reactions, LV dysfunction, diarrhoea, oral mucositis, headache, neutropenia, rash, itch

Question 27

Secukinumab

Answer 27

Recombinant human monoclonal antibody IL-17 Inhibits the activity of IL-17 which is involved in inflammatory and immune responses Rx: psoriatic arthritis, ankylosing spondylitis Caution with IBD, may cause new cases or exacerbate SE: menstrual disorders, infection, hypersensitivity reactions, neutropenia May develop anti-drug antibodies

Question 28

Abiraterone

Answer 28

Inhibits CYP17 Results in reduction of androgen synthesis in testicular, adrenal and prostate tumour tissue Rx: prostate cancer May cause mineralocorticoid excess - give with supplemental prednisolone Caution if CVD, heart failure Contraindicated in severe liver impairment SE: fluid retention, hypokalaemia, hypertension, UTI, fracture, hot flushes

Question 29

Methotrexate

Answer 29

Folic acid antagonist Inhibits DNA synthesis and cell replication by competitively inhibiting the conversion of folic acid to folinic acid Rx: cancer, psoriasis, RA, Crohn's Caution: immunosuppressive, GI ulcers, third spacing, hepatic and renal Teratogenic Toxicity: myelosuppression, pulmonary, hepatic

Question 30

Cyclosporine

Answer 30

Calcineurin inhibitor Forms complex with cyclophilin which blocks the action of calcineurin in activated T cells. Prevents production of IL-2 and other cytokines Rx: transplant rejection, nephrotic syndrome, RA, psoriasis Caution: uncontrolled hypertension, renal impairment, immunosuppressive SE: "get more" gingival hyperplasia, hypertension, hypercholesterolaemia, hyperkalaemia, hyperglycaemia, raised bilirubin + aminotransferases BUT hypomagnesaemia Reversible posterior leucoencephalopathy syndrome Level C0 and C2, calculate AUC

Question 31

Leflunomide

Answer 31

Inhibits pyramiding synthesis in leucocytes and other rapidly dividing cells by inhibiting activity of dihydro-orotate dehydrogenase Rx: RA, psoriatic arthritis Contraindicated: lymphoproliferative disease in last 5 years, myelodysplasia Infection (TB, HBV), ILD Hepatotoxic: avoid if ALT+AST >2 ULN Teratogenic SE: abdominal pain, cholelithiasis, ILD, hypersensitivity, peripheral neuropathy Washout-cholestyramine

Question 32

Sulfasalazine

Answer 32

MOA is unclear Exerts local anti-inflammatory action on bowel wall Rx: UC, Crohn's (better for distal disease) Caution: G6PD deficiency, asthma Renal <20mL/min, hepatic clearance Safe in pregnancy, give folic acid supplement. SE: haemolytic, oligospermia, vomiting, yellow-orange discolouration of fluids, pancreatitis, interstitial nephritis.

Question 33

Ustekinumab

Answer 33

Recombinant human monoclonal antibody Inhibits activity of cytokines, IL-12 and IL-23, which are involved in inflammatory and immune response Rx: chronic psoriasis, psoriatic arthritis if unresponsive to TNFa Caution: malignancy of history of malignancy, infection (TB, HBV) May exacerbate psoriasis or psoriatic arthritis SE: pustular psoriasis, exfoliative dermatitis, hypersensitivity, injection site reaction

Question 34

Apremilast

Answer 34

Inhibits phosphodiesterase 4 Reduces proportion of pro-inflammatory cytokines (e.g. TNFa, IL-17, IL 23 and increasing anti-inflammatory cytokines (e.g. IL -10) Rx: chronic psoriasis, psoriatic arthritis Caution: depression Renal: <30mL/min Avoid pregnant SE: GI (esp. diarrhoea), depression, rebound psoriasis, weight loss

Question 35

Cyclophosphamide

Answer 35

Alkylating agent Immunosuppressive properties are considered due to cytotoxic effect on lymphocytes Interfere with cellular replication by forming cross-linkages between DNA strands Rx: autoimmune disease, cancer, vasculitis Caution: myelosuppression, haemorrhaging cystitis, cardiotoxicity Teratogenic SE: alopecia, hyperpigmentation heart failure, pulmonary fibrosis, hyponatraemia + seizures

Question 36

Mycophenolate

Answer 36

Mofetil and sodium are both converted to mycophenolic acid Selectively suppressed lymphocyte proliferation and antibody formation by inhibiting unisons monophosphate dehydrogenase Depletion of guanosine nucleotides results More lymphocyte selective than azathioprine Rx: prevent transplant rejection, autoimmune disease Caution: GI ulceration (increased risk bleeding), reduced absorption of MMF with low gastric acid (e.g. PPI use), use sodium in this context Renal: Teratogenic SE: myelosuppression, oesophagitis, gastritis, colitis, infection, aplastic anaemia, pure red cell aplasia, photosensitivity