Module 5.1.1 (Part 2 --> Targeted Antineoplastic Drugs) Flashcards
For SERMs (Selective oestrogen receptor modulators)
A) What are two types of drugs used?
B) What are they used for?
C) MOA?
D) AE?
A)
Tamoxifen or Toremifene
B)
- Breast cancer treatment
- Prophylactic if family history suggests risk
C)
- Competes with oestrogen for receptor (ER)
- Induces tertiary structure change
- stops TGF-b production
D)
- (similar to excess oestrogen) hot flushes, nausea, vomiting, fluid retention, vaginal discharge, irregular menstrual cycle
What additional adverse effects does tamoxifen have over toremifene?
Given orally, stays in body at low levels for one week
- Hypercalcaemia
- If tumour metastasised to bone; gives pain n
- Can cause endometrial cancer & eye cataracts
For aromatose inhibitors;
A) What is aromatose
B) MOA?
C) Examples of reversible and irreversible inhibitors
D) AE?
E) How is it excreted?
A)
Aromatase normally generates oestriol & oestradiol from precursors
B)
- These drugs inhibit the enzyme aromatase
C)
Reversible: Anastrozole (1) & Letrozole (2)
Irreversible: Exemestane
D)
Similar to tamoxifen but more bone issues (fracture and pain)
> Add Vit D to diet and Ca2+ due to bone mineral density loss
E)
- Excretion – Kidney as metabolites (liver generated)
For colaspase;
A) What is it used for?
B) MOA?
C) AE?
A)
Acute lymphoblastic leukaemia (ALL)
B)
- Decrease asparagine synthesis
- Drug is bacterial asparaginase
C)
anaphylactic shock, liver damage, prolonged clotting time due to decreased fibrinogen, increased hyperglycaemia, intracranial haemorrhage
IM, or IV infuse (2-4 h)
What are the main targets for tyrosine kinase inhibitors? What form are they given in?
- BCR-ABL1
- Platelet-derived growth factor receptor (PDGFR)
- Epidermal growth factor receptor (EGFR)
- Stem cell factor receptor (c-Kit)
- HER-2
- Vascular endothelial growth factor receptor (VEGFR) – sub types within this (1 to 3)
- FLT-3
Small molecule drugs – orally active
For TK inhibitors
A) What is gefitinib (iressa) used for? MOA?
B) what is imatinib (glivec) used for? MOA?
C) what is the MOA of lapatinib?
D) what is the MOA of sunitinib and pazopanib used for? AE?
E) What is the MOA of axitinib?
F) What is the MOA of SORAFENIB? What is it used for?
G) What is the MOA of DASATINIB? What is it used for? AE?
A)
- Blocks EGFR
> Arrest of cell cycle - decreased angiogenesis
> for metastatic non-small cell lung cancer
B)
- PDGFR inhibitor
- Also BCR-ABL, c-kit
- Induces apoptosis
> for CML (chronic myeloid leukemia)
Both CYP3A4 metabolised
C)
- HER-2 inhibitor –> HER-2 +ve in 30% of breast cancer
D)
- Vascular Endothelial growth factor receptor-TK (VEGFR-TK) blocker
- PDGFR, & c-kit & FLT-3 also
AE: Hypertension, NVD, haemorrhage, Yellow skin, hypothyroidism, colour loss in hair, impaired wound healing
E)
- VEGFR-TK only blocker
F)
- PDGFR, vascular endothelial (VEGFR) blocker –> these control angiogenesis
- c-Kit, FLT-3 & raf kinases blocker –> these control cell division
- For kidney, liver and thyroid cancers
G)
- PDGFR, BCR-ABL, c-kit, ephrin receptor, Src family blocker
- For CML & some ALL subgroups
AE: increased QT interval – arrhythmia, fluid retention, haemorrhage (CNS, GI, nose), pulmonary hypertension, myelosuppression
What are the adverse effects of Gefitinib and other EGFR inhibitors?
- Papulopustular rash – face/upper body, itch, abnormal hair growth, nail disorders, haemorrhage (nose), oral mucositis, increased AST, NVD
- Infrequent: but can be fatal –> Interstitial lung disease
What are the AE of Imatinib
Neutropenia, thrombocytopenia, fluid retention, muscle cramps, hypocalcaemia, maculopapular eruptions & photosensitivity – skin, GI bleeding, increased AST, increased CK, impaired growth of children
For antineoplastic antibodies
A) What is the MOA of Trastuzumab? How is it given? AE?
B) What is the MOA of Pertuzumab? What is it for? AE?
C) What is the MOA of Rituximab? What is it for? AE?
D) What is the MOA of Bevacizumab? What is it for? AE?
E) What is the MOA of cetuximab? What is it used for?
A)
- Humanised monoclonal to HER-2
- Weekly IV infusions (90min each) Or SC inject over 2-5 min
AE: Hypotension, fever, chills, cardiac dysfunction (tachycardia, palpitations), Heart failure, peripheral oedema, infection
B)
- For HER-2 +ve metastatic breast cancer
- Combination therapy – bind different parts of HER-2 —> can be used with trastuzumab or with docetaxel (non specfiic therapy)
AE: diarrhoea, hair loss, ê white blood cell count, nausea, fatigue, rash, and peripheral sensory neuropathy
C)
Anti CD20 monoclonal
- b-lymphocytes (B-cell non-Hodgkin’s lymphoma) + RA
- Rapid & sustained depletion of B cells after slow IV infuse
Increased risk of angina/arrhythmia
D)
Anti-VEGFR monoclonal
- Prevents angiogenesis (no new blood vessels)
AE: Hypertension, stomatitis, delayed wound healing, stroke, MI, angina, nosebleeds, neutropenia
E)
- Anti-EGFR monoclonal
- Squamous cell head and neck cancers, & EGFR +ve colorectal cancers
AE: Papulopustular rash (face – upper body), difficulty breathing, low blood pressure, desquamation – nail damage, fever, constipation, hypomagnesaemia, abnormal hair growth
What is iplimumab used for? What is the MOA? AE?
[for metastatic melanoma]
- CTLA4 blocking
- Enhances T-cell activity
AE: Life-threatening reactions – gut, liver, skin, thyroid, pituitary especially if existing autoimmune disorder present
What is Thalidomide/ Lenalidomide/ Pomalidomide used for? MOA? Adverse?
Anti-angiogenesis
Inhibit myeloma cell growth
- Multiple mechanisms: inhibit anti-apoptopic effect of NK-kB –> cell death occurs
- Disrupt cell interactions with adhesion molecules
- Decrease IL-6 release, Decrease TNFa production
- Increase T-cell mediated cytotoxicity
AE
- Peripheral sensory neuropathy, sedation, headache, constipation, thromboembolism, secondary cancer risk
