Pharm 2 - Cancer 1

roxydelmar's version from 2015-04-30 00:35

Intro+Tumorigenesis+complications of chemotherapy+combination therapy

Question Answer
what is cancer?Cancer is an uncontrollable multiplication (from abnormal regulation of cell division and tissue growth) & spread of abnormal forms of the body’s own cells
what is a major complication with anti-cancer meds?Host cell toxicity with cancer mediation
what are the interventions for cancer (between two big choices)Medical vs. surgical intervention
what are two genetic/epigenic(relating to or arising from nongenetic influences on gene expression) causes of cancer formation?(1) inactivation of tumour suppressor genes (2) activation of oncogenes (mutation of normal genes)
uncontrolled proliferation is caused by what three things? (not gene stuff)(1) growth factors and/or their receptors (we can try to antagonize these) (2) intracellular signalling pathways(tumors inhibit apoptosis) (3) telomerase expression
How are vessels affected by tumors? And what we sthing we can do about this?Tumors can cause angiogenesis (since it needs O2 and energy to grow), but we can slow down or inhibit this angiogensis with NSAIDS
what are the 5 characteristics of cancer cells?(1) uncontrolled proliferation and/or escape from normal regulation of cell division and tissue growth (resistance to apoptosis (NSAIDs) - telomerase expression) (2) dedifferentiation and loss of function (3) angiogenesis (4) invasiveness (5) metastasis
what are the 4 categories of complications of chemotherapy?(1) extravasation of the drug (2) anaphylactic reactions (3) toxic side effects (4) acute tumour lysis syndrome
A type-1 acute hypersensitivity reaction to chemotherapy can happen from what two drugs?doxorubicin or L-asparaginase (DOXies are ALLERGIC to ASPARAGUS)
explain the differences of location of hypersensitivity reactions (remember which drugs usually cause hypersensitivity rxns) in dogs vs cats(doxorubicin or L-asparaginase) dog is usually cutaneous and GIT. The cat is usually respiratory. (dogs always get skin problems! and also of course the bigger animal barfs. and cats not breathing? think of the resp video of the cat with asthma, say, because of allergies bc this is hypersensitivityies)
What are the two main toxic side effects (which systems) of chemotherapy, and why is this?Chemotheraputics usually target rapidly dividing cells--> where in the body are there usually rapidly dividing cells? GIT AND BONE MARROW!!
describe what happens in bone marrow toxicityUsually develop leukopenia since the half life of a leukocyte is usually just a few hours (chemo attacks rapidly dividing cells), whereas anemia is a fairly rare symptom because the t1/2 of a RBC is ~120d
describe what happens in gastrointestinal toxicityDirect stimulation (of the CTZ?) will cause anorexia and vomiting. Also diarrhea can be caused by some specific drugs (doxorubicin, methotrexate, vincristine). There are also breed susceptibilities (Scottish shepherd, Bobtail, West Highland White Terrier)
what are the chemo drugs which are know to cause diarrhea?doxorubicin, methotrexate, vincristine (If Christ's doxy takes meth, he's gonna shit everywhere)
what are the breeds most suseptible to GIT toxicities?Scottish shepherd, Bobtail, West Highland White Terrier (BOB had a SCOTch in the WEST HIGHLANDS and it made his stomach upset)
What situation would cause there to be a much higher risk of toxicities with chemotheraputics? Which drugs are the primary exacerbaters of this problem?if the animal (dog?) has a mutation in the MDR1 transporter (IT IS A P-GLYCOPROTEIN). The transporter isn't there/doesn't work, so drug stays in system longer and causes MORE bone marrow and GIT toxicities than usual.The drugs which usually are transported by the MDR1 transporter (And thus exacerbate the prob) are doxorubicin, vincristine, and vinblastin
mutations in the MDR1 P-glycoprotein transporter mean the animal will have more toxicities associated with what three drugs?doxorubicin, vincristine, and vinblastin (MD(as in doctor) R has a DOXi named VINVIN)
acute tumor lysis syndrome--> what causes this? what has a higher risk of making this happen? what happens (clinpath wise)? Clinical signs?Happens if there is RAPID tumor lysis. It is esp. seen in malignant lymphoma(makes sense, since it's in a major highway in the body) after chemo/radiotherapy. It leads to high uric acid conc, hyperphosphatemia, hypocalcemia, hyperkalemia, and metabolic acidosis (stuff from inside cells released, products of cell destruction)... Clinical signs include mental depression, vomiting, diarrhea and hyperventilation
what are two reasons you'd want to use combinations of chemotheraputics, as opposed to a single one?(1) increasing cytotoxicity without necessarily increasing general toxicity (attack tumor in diff ways, so don't need super high dose of any one thing) (2) decreases the possibility of the development of resistance to individual agents
how often do you dose chemotheraputics, and why?given in 2-3 week intervals to permit the bone marrow to regenerate
would you want to break up chemotheraputics into small doses, or give in a few big doses?same dose of an agent is more effective when given in 1 or 2 large doses, in contrast to giving a bunch of smaller doses (bigger is better, in this case)


Question Answer
what are the 5 groups of chemotheraputic agents?cytotoxic drugs, hormones, monoclonal antibodies, protein kinase inhibitors, and misc
what are the 4 groups of cytotoxic drugs?(1) alkylating drugs (2) antimetabolites (3) cytotoxic antibodies (4) plant derivatives
alkylating drugs are under what category of chemotheraputic drugs? How do they work?CYTOTOXIC drugs. They form covalent bonds with DNA, hence impede replication
antimetabolites are under what category of chemotheraputic drugs? How do they work?CYTOTOXIC drugs. They block or subvert one or more metabolic pathways involved in DNA synthesis
how do cytotoxic antibiotics work as chemotheraputic drugs?They are substances of microbial origin that block mammalian cell division
plant derivatives can be used as chemotheraputic drugs how? (what category of drugs do they fall under?)(CYTOTOXIC drugs) some plant derivatives specifically affect microtubule function and hence formation of mitotic spindle (MICRO-FLORA. get it?)
hormone chemotheraputics--> which hormone specifically is useful? explain how it workssteroids are the most important - drugs that suppress hormone secretion and antagonise hormone action
when do you use monoclonal Abs as chemotheraputic agents?useful when fighting a SPECIFIC type of cancer
protein kinase inhibitors--> how do they work/why are they used as chemotheraputic agents/ what makes these nice?inhibition of tyrosine kinases that transduce(pass on) growth signals in rapidly dividing cells (and it is restricted to only rapidly diving cells) (so stop the tyrosine kinase that is making growth signals happen in ONLY rapidly dividing cells)
[chart] which drug inhibits dihydrofolate reduction, block DTMP and purine synthesis?methotrexate (it is an antimetabolite of folate!) (It doesn't matter if you take your FOLATE when you're preg, if you're taking METH too, then your babies DNA is going to be screwed up)
[chart] which drug blocks topoisomerase function?doxorubicin (DOXies biting TOPs because theyre spinning around)
[chart] which drugs block activity of receptors?tyrosine kinase inhibitors, antibodies
[chart] which drug inhibits DTMP synthesis?5-fluorouracil (Five with a FLU is a DirtyTrampMostlyPolluting) (ALSO SHOuLD SAY BLOCKS THYMDALATE SYNTHASE, BC ISANTIMETABOLITE)
[chart] which drugs form adducts ( DNA adduct is a piece of DNA covalently bonded to a chemical) with DNA?alkylating agents, mitomycin, cisplatin (MITO was a ALKAline CIS boy, but we BONDED anyway)
[chart] which drug deaminates asparagine/-->inhibits protein synthesis?l-asparaginase
[chart] which drugs inhibit function of microtubules?paclitaxel, docetaxel, vinca alkaloids (MICROscopic PACman named VINcent wont pay his "DOCE millones") (these are all the plant derivatives)

BCG+cisplatin and caboplatin

Question Answer
what does BCG stand for? (what is it?)live whole cell Bacille Calmetter-Guerin (It's actually a vx!)
How does the BCG work (why would we use it?)believed to stimulate the immune system to recognise specific antigens of tumour cells
what does BCG enhance?enhances tumor cell destruction
Which cancers is BCG usually used to tx?usually used to tx squamous cell carcinomas and sarcoids (things youd see on a horses face like in that pic!)
how many doses of BCG do you usually give?repeated injections until complete regression
what are the side effects of BCG? How can you try to avoid this side effects?local and systemic anaphylaxis (pre-treatment with glucocorticoids to try to overcome anaphylaxis) (vaccine allergies? or just allergic to french names? put some sugar on it, baby)
what is the MOA of cisplatin and caboplatin?analogous to alkylating drugs (form covalent bonds with DNA, hence impede replication). So the drug enters the cell--> The Cl- (of the drug) disassociates, which forms a reactive complex--> the reactive complex causes intrastrand crosslinking of DNA--> causes local denaturation of DNA
what are the side effects of cisplatin and caboplatin?NEPHROTOXIC, nausea and vomiting (platinum kidneys aren't good for you!)
what is a benefit of using cisplatin and caboplatin?It has low meylotoxicity which means the bone marrow is preserved/spared (having platinum kidneys is bad, but your bones (marrow) will BE as strong as platinum)
what is oxaliplatin?a safer version of cisplatin and caboplatin used in human med (not yet avail for animals)

Antimetabolites (An antimetabolite is a chemical that inhibits the use of a metabolite, which is another chemical that is part of normal metabolism)

Question Answer
what are the three antimetabolite drugs mentioned?methotrexate, 5-fluorouracil, cytosine arabinose
methotrexate is an antimetabolite/acts as an antagonist for what?folate antagonist
folate antagonist?methotrexate
what are folates necessary for?essential in synthesis of purine nucleotides & thymidylate, which are necessary for DNA synthesis & cell division
So, what is the effect of methotrexate on cancerous cells (once you know what it is an antimetabolite for, and what the thing it's antagonizing does)inhibit DNA synth and cell division
HOW does methotrexate get into the cells? (what is the solubility of methotrexate? How does this affect it's ability to get into the cell?)methotrexate has a LOW lipid solubility, however, that doesn't really affect it much because it is taken up into the cell via the folate transport system
The metabolites of methotrexate stay in the cell for how long?weeks! (you'll feel like crap after taking meth for weeks)
what are the side effects of methotrexate?bone marrow depression and GIT irritation
Major side effect/contraindication of 5-fluorouracil?FATAL NEUTROTOXICITY IN CATS!!
which drug causes a fatal neurotoxicity in cats?5-fluorouracil (Five kills cats. Because he is neurotically hungry)
how does 5-fluorouracil work?interference with DNA synthesis: inhibition of thymidylate synthase (he had 'synthesis' but I'm pretty sure that's wrong. Either way, inhibits making nuc acids to make DNA) (just like how flucytosine also messes with DNA) (5's thighs)
cytosine arabinose has what properties?short elimination half-life and crosses BBB (ARABic horses live for a short time because they have no BBB)

Recent badges