1 Flashcards
Alemtuzumab
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
Bevacizumab
Recombinant humanised
binds to VEGF inhibiting angiogenesis
Risk of heart failure
Hypertension, impaired wound healing, thromboembolic events,
Blinatumomab
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
Brentuximab vedotin
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
Cetuximab
Recombinant chimeric Binds to EGFR inhibits proliferation, Skin reactions: acne, rash, infusion reaction, VTE, mucositis,
EGFR inhibitors
Cetuximab Panitumumab Afatinib Erlotinib Gefitinib
EGFR inhibitor skin reactions
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
Ipilimumab
Human monoclonal Ab
CTLA-4 (cytotoxic T lymphocyte-associated antigen 4
CYP450 inducers
SCRAP GPS St. John's Wort Carbamazipine Rifampicin Alcohol (chronic) Phenytoin Griseofulvin Phenobarbital Sulphonylureas
CYP450 inhibitors
SICKFACES.COM GQ Sodium valproate Isoniazid Cimetidine Ketoconazole Fluconazole Alcohol (acute)/amiodarone Chloramphenicol Erythromycin Sulphonamides Ciprofloxicin Omeprazole Metronidazole Grapefruit juice Quinidine
Omalizumab
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
Anti-CD20 antibodies
Rituximab
Ofatumumab
Obinutuzumab
Basilixumab
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
Crizotinib
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+)
Afatinib
TKI
EGFR
HER2, HER4
Axitinib
VEGF 1-3
Dasatinib
BCR-ABL Src family c-KIT PDGFR ephrin receptor
Erlotinib
EGFR
Gefitinib
EGFR
Ibrutinib
Bruton’s tyrosine kinase (BTK)
Imatinib
bcr-abl, c-KIT, PDGFR
Nilotinib
bcr-abl, c-KIT, ephrin receptor, PDGFR
Tofacitinib
JAK1, JAK2, JAK3
Sunitinib
VEGFR 1-3
PDGFR
c-KIT
FLT-3
Sorafenib
VEGFR 2-3 PDGFR c-kit FLT-3 also Raf kinase
Pertuzumab
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
Secukinumab
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
Abiraterone
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
Methotrexate
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
Cyclosporine
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
Leflunomide
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
Sulfasalazine
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.
Ustekinumab
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
Apremilast
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
Cyclophosphamide
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
Mycophenolate
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
