Drugs Flashcards
Asatrazole, Letrozole, Vorozole?
Aromatase inhibitors
Who are aromatase inhibitors given to?
Postmenopausal women, ER positive, early stage breast cancer (following radiotherapy)
What is gemcitabine and when is it used?
Antimetabolite used in conjunction with cisplatin to overcome cisplatin resistant ovarian cancer. (Prevents DNA crosslink repair in cancer cells).
What is methotrexate?
An antifolate - binds to DHFR enzyme to inhibit the production of FH4 from FH2. No thymidine/ purine synthesis leads to cell death.
What is Pemetrexate?
CH2FH4 mimetic. Binds to TS enzyme to prevent the formation of FH2. No thymidine synthesis is toxic to cells.
What cancer has pemetrexate had a large success in treating?
Mesothelioma
What is Imatinib?
Small molecule that inhibits the tyrosine kinase domain of the BCR-ABL fusion protein (CML)
What is Rucaparib?
A PARP inhibitor. Single strand breaks persist because PARP function is inhibited. Subsequently, at replication the SSB becomes a DSB; In homologous recombination deficient cells (tumour cells) Mitotic catastrophe takes place as the DSB cannot be repaired.
What type of drugs are BCNU, CCNU and methyl-CCNU?
Chloroethylnitrosureas - alkylating agents which when metabolised form a chloroethyl adduct. If this adducts at O6 and not repaired, it leads to an interstrand crosslink and becomes cytotoxic to a cell.
What are chloambucil, melphalan and mechloroethamine
Nitrogen mustards - alkylating agents (on N7-guanine)
How do platinum drugs induce their cytotoxic effect in cancer cells?
Form a co-ordination complex that is able to produce mono and bifunctional adducts.
What is Doxorubicin>
An intercalating agent that binds DNA in the minor groove.
Which drug is melphalan used to treat?
Multiple myeloma
What is combrestatin?
A vascular disrupting agent - It binds tubulin at established tumour vessels. It blocks endothelial cell proliferation which leads to tumour necrosis (apart form the tumour rim as the vasculature surrounding the tumour is more normal)
What is Vendetanib?
A small molecule that inhibits the tyrosine kinase domain of VEGF2. It also inhibits EGFR and VEGF3
What is Avastin?
An antibody to VEGF
What was previously treated with Avastin and why did this stop?
Breast cancer - By inhibiting VEGF signalling PLCy signalling is stopped. This prevents the production of NO which is required for the maintenance of vasculare tone. So Avastin increases the likelyhood of thrombotic events.
What is asparaginase?
Antimetabolite that metabolises serum L-asparaginase into L-aspartic acid. This starves lymphoblasts of L-asparagine as they lack the intracellular machinery for L-asparagine production. Cellular proteins cannot be formed and the cells die.
How is Imatinib resistance tackled?
Increase the dose (especially if resistance has built due to BCR-ABL amplification)
OR
Switch to a different RTK inhibitor like dasatinib or nitolinib
What small molecule was produced to overcome the T790M mutant dependent acquired drug resistance for NSCLC?
Osimertinib
What is Cetuximab?
Antibody for EGFR (ErbB1)
What is Gefitinib>
Small molecule used to treat NSCLC - Resistance builds due to the T790M mutation and MET amplification
What is Piqray?
A p110 alpha inhibitor used in conjunction with hormonal therapy to treat ER positive breast cancers.
What are PI3K delta inhibitors used to treat?
B cell malignancies - lead to the accumulation of blasts in the circulation which can be targeted using CD20 binding immunotherapeutics.
What is Tamoxifen?
An ER inhibitor (specifically in breast tissue) -
Which breast cancer patients are offered tamoxifen?
Premenopausal women that are ER positive and at an early stage.
What is Goserelin?
An LHRH analogue
Which patients (breast and prostate) are offered Goserelin?
Prostate - first line treatment in advanced prostate cancer
Breast - Premenopausal women
What is fulversterant?
A selective oestrogen receptor degrader. Inhibits dimerisation and nuclear translocation of ER to the nucleus.
When is fulversterant used?
In ER positive breast cancer when tamoxifen and aromatase inhibitors no longer work or in metastatic cases. Also when patients have developed ESR1 mutations
What is Degarelix?
An LHRH antagonist
What is Bicalutamide?
A first generation antiandrogen - mutations in the ligand binding domain of androgen receptors cause it to become an agonist for the receptor.
What is Enzalutamide?
A second generation androgen receptor antagonist - Crosses the BBB and can cause seizures
What is Apalutamide?
A second generation antiandrogen that is less able to cross the BBB, reducing the likelyhood of seizures compared to enzalutamide.
What is Abiraterone?
A CYP17 inhibitor
What is Retuximab?
Chimeric antibody that targets CD20 on B-cells in lymphomas
What is herceptin?
A humanised antibody against ErbB2/HER2.
What is Ipilimumab?
A human antibody that inhibits PD-1 on T-cell receptors, preventing T-cell inactivation
