chemotherapy drugs Flashcards
name the 4 classes of chemotherapy drugs
cytotoxic drugs
- alkylating agents
- antimetabolites
- cyctotoxic antibiotics
- plant derivatives
hormones
monoclonal antibodies
protein kinase inhibitors
name the 4 types of drug within the cytotoxic drugs class
- alkylating agents
- antimetabolities
- cytotoxic antibodies
- plant derivative
name the 4 types of alkylating agent
- nitrogen mustards
- nitrosoureas
- platinium compounds
- other
what is the mechanism of action of all alkylating agents?
targets cell in phase S (DNA synthesis)
forms covalent bonds with DNA (cross linking) to prevent uncoiling thus inhibiting replication
name a common nitrogen mustard
cyclophosphamide
cyclophosphamide is a prodrug, where is it activated and to what?
liver ⇒phosphoramide mustard & acrolein
name some other nitrogen mustards
- methlorethamine
- melphalon
- chlorambucil
- bendamustine
- estramustine⇒prostate cancer
name 2 nitrosoureas
- carmustine (BUNU)→IV
- lomustine (CCNU)→oral
which alkylating agent is highly lipophilic and can cross the blood brain barrier?
nitrosoureas
with cancers do nitrosoureas treat?
CNS tumours
name three platinium compounds used as chemotherapy drugs
- cisplatin
- carboplatin
- oxaliplatin
what is the specific mechanism of action of cisplantin?
binds to RNA►DNA►protein
binds to purine bases (ie. G, A, U)
resistance may develop with cisplatin, why?
DNA repair by DNA polymerase
which cancer is cisplatin used to treat?
testicular/ovarian - low levels of repair enzymes (ie. more sensitive to drug)
how is cisplantin administered?
slow IV injection/infusion
what are the side effects of cisplantin?
- v.nephrotoxic (hydration required)
- N&V
- tinnitus
- peripheral neuropathy
- hyperuricaemia
- anaphlaxis
what is carboplatin derived from?
cisplantin
what are the pros and cons of carboplantin over cistoplatin?
pros - less side effects /outpatient admin
cons- more myelotoxic (more effects on bone marrow)
which cancer is oxaliplatin used to treat
colorectal cancer
name 3 other alkylating agents
- busulfan
- procarbazine
- trabectedin
which cancer is busulfan used to treat?
selective for bone marrow→leukaemia treatment
which cancer is procarbazine used to treat?
Hodgkin’s disease (can cause hypersensitivity and inhibit MAO)
which cancer is trabectedin used to treat?
soft tissue sarcoma / advanced ovarian (hepatotoxic)
name the 3 types of antimetabolites
- folate antagonists
- pyrimide analogue
- purine analogue
what is the mechanism of action fo folate antagonists?
inhibits dihydrofolate reductase (rate limiting step in folate synthesis)
why is folate a useful target for chemotherapy drugs?
folate is essential for DNA synthesis/ cell devision
does metotrexate cross the blood brain barrier?
no
if metotrexate is given in high does what should also be given?
folinic acid (folate derivative) to resue normal cells
name 4 pyrimidine analogues
- flurouracil
- capecitabine
- cytarabine
- gemcitabine
what is the mechanism of action of pyrimidine analogues?
completes with cytosine and thymine bases which make up RNA & DNA→inhibits DNA synthesis
name 4 purine analogues
- mercaptopurine
- tioguanine
- pentostatin
- fludarabine
what is the mechanism of action of purine analogues?
compete with adenine and guanine - inhibit purine metabolism
which 2 purine analogues aremainly used to treat leukaemia?
- mercaptopurine
- tioguanine
name 4 cytotoxic antibiotics
- doxourubicin
- bleomycin
- dactinomycin
- mitomycin
what is the mechanism of action of doxorubicin?
binds to DNA→inhibits DNA & RNA synthesis
inhibits topoisomerase II (helps swivel DNA when seperating)
doxorubincin can cause local necrosis, how?
given IV, extravasation (tissuing) at injection site can cause necrosis
what are the side effects of doxorubicin?
cardiac arrythmias
heart failure (high dose)
what is the mechanism of action of bleomycin?
degrades pre-formed DNA
active against non-dividing cells (G0 )
what are the side effects of bleomycin?
little myelosupression
pulmonary fibrosis
mucocutaneous reactions
hyperpyrexia
name 3 vinca alkaloids
- vincristine
- vinblastine
- vindesine
name 3 types of plant derived cytotoxic chemotherapy agents
- vinca alkaloid
- taxanes
- etoposide
what is the mechanism of action of vinca alkaloids?
prevent polymerisation of tublin→microtubles→prevents spindle formation in chromosomes
which phase of mitosis do vinca alkaloids target?
M phase (cell division)
name 2 taxanes
- paclitaxel
- docetaxel
what is the mechanism of action of taxanes?
similar to vinca alkaloids - affects spindle formation
which cancers do taxanes treat?
advanced breast
paxlitaxal (& carboplatin) - ovarian
which cancers does etoposide treat
testicular cancer/ lymphomas
what must be monitored when giving etoposide?
BP - drops rapidly during infusion
name the 6 types of hormone used in chemotherapy treatment
- oestrogens
- progesterones
- GnRH analogues
- somatostain analogues
- Hormone antagonists
- glucocorticoids
when are hormones used to treat cancer?
in hormone sensitive tissue (eg. breast, prostate, ovaries)
name 2 oestrogens used in chemotherapy
- ethinloesteadiol
- diethylstilbestrol
what is the mechanism of action of oestrogens?
anatagonists androgen -dependant prostate cancer (palliative)
what are the side effects of oestrogens?
nausea
fluid retention
thrombosis
impotence & gynaecomastia (men)
what are oestrogens also used for?
stimulating resting mammary cells to proliferate (need dividing cells to target with drugs)
name 3 progestogens
- megestrol
- medroxyprogesterone
- norethisterone
what are progesterones use to treat?
endometrial cancer
name 4 GnRH analogues
- goserelin
- buserelin
- leuprorelin
- triptorelin
what is the mechansim of action of GnRH analogues?
inhibits GnRH release→ reduces LH/FSH→testosterone
what are GnRh analogues used to treat?
prostate
advanced breast cancer (premenopausal)
name 2 somatostatin analogues
- octreotide
- lanrectide
what is the mechanism of action of somatostatins?
inhibits cell proliferation / hormone (CCK/gastrin) secretion
what are somatostatin analogues used to treat?
hormone secreting GI tract tumours
name 7 hormone antagonists
- tamoxifen
- fluvestrant
- letrozole
- exemastine
- flutamide
- cyproterone
- bicalutamide
what are the mechanisms of action of tamoxifen and fluvestrant
competative antangonist at oestrogen receptors→inhibit transcription of oestrogen responsive genes
what are tamoxifen and fluvestrant used to treat?
breast cancer
what are the side effect of tamoxifen and fluevestrant?
menopausal effects
risk of endometrial cancer
increased risk blood clots
what is the mechanism of action of letrozole and exemastine?
aromatase inhibitor→blocks conversion of androgens to oestrogens
what is the mechanism of action of flutamide, cyproterone and bicalutamide?
androgen antagonists
what do flutamide, cyproterone and bicalutamide treat?
prostate cancer
name 2 glucocorticoids used in chemotherapy
- prednisolone
- dexamethasone
what are the mechanisms of action of glucocorticiods in relation to chemotherapy?
inhibits lymphcyte proliferation
which cancers are glucocorticoids used to treat?
lymphomas/ leukaemias - supportive/palliative therapy
name 4 monoclonal antibodies used in chemotherapy
- rituximab
- trastuzamab
- ofatumumab
- bevaizumab
how do monoclonal anitbodies help to treat cancer?
acts with specific target protein expresssed on cancer cells→activates immune system→lysis of cancer cells
what is the mechanism of action of rituximab?
binds to CD20 protein expressed on certain lymphoma cells→lysis of B-lymphocytes
what are the side effects of rituximab?
hypotension
chills
fever
hypersensitivity
what is the mechanism of action of trastuzamab (herciptin)?
binds to HER2 (a GF receptor)→induces immune response & cell cycle inhibitors
HER2 is over expressed on 25% of breast cancers (aggressive form)
what are the side effects of trastuzamab?
tremor
flu symptoms
itchy eyes
BP changes
palpitations
what is the mechanism of action of bevaizumab?
neutralises VEGF→prevents angiogensis
what does bevaizumab treat?
colorectal cancer
what does ofatumumab treat?
resistant chronic lymphocytic leukaemia
name 3 protein kinase inhibitors
- imatinib
- dasatinib
- nilotinib
what is the mechanism of action of protein kinase inhibitors?
blocks tyrosine kinase involved in GF signalling pathways
what do protien kinase inhibitors treat?
chronic myeloid leukaemia (CML)
cytotoxic drugs are often given in combination, why?
- inrease cytotoxicity with increasing general toxicity
- reduce chance of resistance to drugs
what is the typical treatment regime in chemotherapy?
large doses every 2-3 weeks - allows bine marrow regen.
how can myelosuppression be treated?
stem cell transplant
- autologous - from patient
- allogenic - from donor
which drug is used to boost stem cell production?
lenograstim (recombinant GM-CSF)
