Flashcards in Anti cancer drugs Deck (53)
Target unique structure (or expressed element) or process associated with cancerous cell
What is the mechanism of alkylating agents?
Insert alkyl group into DNA structure; cross-link between adjacent bases, particularly guanine bases, as well as proteins; cause stress in molecules leading to strand breaks and apoptosis
Which stage of the cell cycle do alkylating agents target?
generally, cycle non-specific
What does a bifunctional alkylating agent do?
Causes intrastrand linking and cross-linking
Why are cytotoxic antibiotics used in cancer therapy?
Too toxic to use in infectious disease therapy; the cost vs benefit ratio is different in cancer
What is the mechanism of cytotoxic antibiotics?
Inhibit transcription and translation processes
What do antimetabolites do?
Substitute themselves in the DNA synthesis pathway, block DNA synthesis, make molecule non-functional
Which stage of the cell cycle to antimetabolites target?
What are the three pathways by which antimetabolites may block DNA synthesis?
Folate pathway, pyrimidine base synthesis, purine base synthesis
Which pathway does methotrexate target?
Folate pathway, similar shape to folic acid
What is the mechanism of mitotic poisons?
Inhibit microtubule function so that mitotic spindles don't form or inhibit topoisomerase
Which stage of the cell cycle to mitotic poisons target?
Examples of mitotic poisons?
vinca alkaloids (from periwinkle plant), taxanes (European yew tree), etiposide (mandrake)
What is the mechanism of SERM?
Selective oestrogen receptor modulator agonises some oestrogen receptors (for bone development and blood coagulation) and antagonises others (in breast tissue)
What is the mechanism of aromatase inhibitors?
Lower circulating oestrogen (aromatase is used by fat cells to convert precursor substances into oestrogen)
2 drug groups used to treat breast cancer?
SERM and aromatase inhibitors
2 drug groups used to treat prostate cancer?
antiandrogens and gonadotrophin-RH analogues
Mechanism of antiandrogens?
Prevent access to growth factor, stops growth of cancer
Mechanism of gonadotrophin-RH analogues
Gonadotrophin releasing hormone, released from hypothalamus to act on pituitary gland to stimulate LH and FSH; analogue is given repeatedly to change HP axis and cause a decrease in LH secretion
Drug group used to treat blood-borne cancers e.g. leukaemia, lymphoma
Mechanism of action of glucocorticoids
High doses lead to lysis of affected cells
Common adverse effects of glucocorticoids
Also target rapidly dividing normal cell populations:
alopecia (hair follicles)
skin blistering and necrosis
gastrointestinal sores (stomatitis) and mouth inflammation (mucositis)
nausea and vomiting
infertility (for duration of therapy)
bone marrow suppression (bone marrow cells have rapid turnover)
organ toxicity - may occur after therapy is finished
Examples of organ toxicity from glucocorticoids
heart: dysrhythmia and altered contractility, acute heart failure
Kidneys: renal failure
nervous system: paraesthesias (numbness, tingling, burning sensation as a result of altered axonal transport) microtubules affecting cell division and axonal transport
urinary bladder: haemorrhagic cystitis
What are 2 drug groups that address the adverse drug reactions (ADR) of glucocorticoids?
Colony stimulating factors
Examples of antiemetic drugs
- dopamine/serotonin/neurokinin receptor antagonists e.g. dopamine connecting medulla to vomiting centre
- metoclopramide (maxolon) = dopamine receptor antagonist, ondansetron = serotonin receptor antagonist, aprepitant (Emend) = substance P receptor antagonist
- glucocorticoids (dexamethasone)
Examples of CSFs
Colony stimulating factors
Mechanism for CSFs
stimulate white blood cell populations
What compound can be used to manage organ toxicity?
Mesna for alkylating agents (cyclophosphamide and ifosfamide)
Mechanism of Mesna?
Prevents formation of metabolite that causes hemorrhagic cystitis without affecting the metabolite that's causing the desired action