Lecture 5 cancer chemotherapy Flashcards
General principles and challenges of cancer chemotherapy
-organ specific and
general principles and challenges of cancer chemotherapy
-toxicity is a huge issue, the drugs will target cells which are not specific to the cancer like hair loss. they drug will usually target the rapidly multiplying cells eg. GIT, bone marrow, other organs (liver, kidney and heart, so drugs will target certain organs like the ones listed)
-you can’t do chemotherapy when the a female is pregnant because there are growth hormones because the foetus is growing
- no ideal drug, its very hard to find the right drug
cytotoxicity follows 1st order pharmacokinetics (with each dose you only kill a certain amount and it the same every time therefore curing is very hard) drug combinations are more effective (because of combined different mechanics and different dose limiting toxicities)
If there are a lot of mitotic figures present in a tumour and you want to use a drug to kill the tumour what should this drug target in the cell cycle?
If there are a lot of mitotic figures present in a tumour and you want to use a drug to kill the tumour, you will target the mitotic part of the cell cycle.
When determining the dosage why do you surface area instead of body weight
for dosage you use surface area instead of body weight because of the surface area of an animal has a good correlation to the metabolic activity of the animal
List the different types of resistance
different types of resistance
Resistance be kinetic, biochemical or pharmacological
kinetic resistance; if most cells are in GO phase in the cell cycle are in large no., drug targeting S- phase in the cell cycle won’t be effective
pharmacological biochemical resistance maybe due to;
decrease drug uptake
increase drug efflux eg. due to MDR
target mutations are possible or increased repair
increased drug metabolism and elimination
List the different classifications of cancer chemotherapeutic agents
different classifications of cancer chemotherapeutic agents Alkylating agents; cyclophosphamide anti-metabolites mitotic inhibitors antibiotics; doxorubicin others
For Alkylating agents; cyclophosphamide list the MOA and what type of cancer its used for
Alkylating agents; cyclophosphamide MOA this drug will bind to specific residual on DNA it will stop transcription and stops the proliferation of tumour cells what is it used for soft tissue sarcomas carcinomas brain tumours mast cell tumours
For antimetabolites list the characteristics and when is this used
Antimetabolites (cytosine)
compete with cellular substitutes for viral metabolic processes
most of these agents are highly specific (s phase of cell cycle)
used for lymphomas
soft tissue sarcomas
other immune conditions
For mitotic inhibitors list the mechanism
and list the clinical applications
mitotic inhibitors (vincristine) mechanism; these agents bind alpha/ beta tubular dimers and stops polymerisation and the formation of cellular microtubules- essential contractile proteins of mitotic spindle and this leas to mitotic arrest, avoids binding to platelets and cell cycle phase specific drugs clinical applications acute lymphocytic leukaemia mast cell tumours soft tissue sarcomas
For antibiotics list characteristics,
mechanism
clinical application
Antibiotics (doxorubicin)
not cell cycle specific by maybe more active in S-phase
mechanism
-binding to DNA’ by interactions bw DNA base pairs perpendicular to the long axis of the double helix and fucks up DNA topoisomerase & DNA dependent RNA synthesis
-anthracyclines chalet divalent cations, metabolism of this compounds generates very reactive intermediates
clinical application
lymphomas
vaccine associated sarcomas
Describe 3 adverse effects that are associated with the clinical use of vincristine in veterinary patients
adverse effects of vincristine extensive nerve damage via intrathecal admin. myelosuppression and neutropenia GI toxicity tissue sloughing with extravasation
