kelseyfmeyer's version from 2015-04-16 18:48

alkylating agents

Question Answer
what is the MOA of all alkylating agents?formation of a carbonium ion--> instantaneous reaction with amine, hydroxyl or sulfhydryl groups(all part of DNA)--> causes intra and inter chain cross linking--> interferes with transcription and replication
what is the result/way alkylating agents are used as chemotheraputics?interferes with transcription and replication
what kinda ions do alkylating agents form?carbonium ion
what are the 5 major side effects of alkylating agents?(1) depress bone marrow (2) GIT disturbances (3) sterility in men!! (4) inc risk of leukemia/other malignancies (5) strong cross-resistance (basic (ALKyline) bitches will suck the manly virility out of you till it's just STERILITY. Shes so CANCEROUS that anyone around here is affected)
if alkylating agents have strong cross resistance, what does this mean?means if resistant to one specific alkylating agent, resistant to the other ones too.
what are the 5 groups of alkylating agents?(1) nitrogen mustards (2) (alkyl sulfonate) (3) triazenes (4) nitrosoureas (5) platinum coordination complexes
what are the 3(4 in table but only 3 gone over) nitrogen mustard drugs?(1) cyclophosphamide (2) melphalan (3) chlorambucil ( (4) ifosfamide ) ( MEL CYCLING THROUGH CHLORINE AND MUSTARD GAS)
((what is the alkyl sulfonate drug?busulfan)) (ALKYLine BUS, beep beep!)
what is the triazine drug?dacarbazine (TRI not to eat CARBs)
what is the nitrosoureas drug?lomustine (CCNU) ( you loMUST do nitros or you loMUST treat your roundcellbrain tumors or you liver loMUST perish)
what are the platinum coordination complexes drugs?cisplatin and carboplatin (covered earlier!)
which nitrogen mustard is a prodrug? HOW is it metabolized?cyclophosphamide, CYP450 metabolism
cyclophosphamide belongs to which group? What should you know about its metabolism? How is it administered? Side effects?(nitrogen mustard) INACTIVE PRODRUG UNTIL METABOLIZED BY CYP450!! Admin oral or IV. side effects include Alopecia, sterile hemorrhagic cystitis (the cycling isnt active till the wheels touch the ground (liver). but if you cycle till your hair falls out, you are prolly bleeding from your bladder)
which drug has the side effects of alopecia and sterile hemorrhagic cystitis(in bladder)? How does the SHC happen? How can you prevent the sterile hemorrhagic cystitis?cyclophosphamide (nitrogen mustard) is the drug which causes these side effects. The SHC happens bc cyclo. is a prodrug that MUST be metabolized (CYP450) and one of the resulting metabolites is acrolein, which reacts with sulphydryl groups in the bladder. you can prevent the sterile hemorrhagic cystitis by giving the animal N-acetylcystein, because this is a sulphydryl donor (if you CYCLE you're an ACRO-lete and you prolly have sulfury farts)
melphalan--> which group of alkylating agents does this belong to? admin? side effects?nitrogen mustard group. Oral admin (IV possible), side effects are persistent BM depression; nausea and vomiting (Mel likes to TALK (oral) )
chlorambucil--> which group of alkylating agents does this belong to? admin? noteworthy attributes?nitrogen mustard group. Oral admin. slowest working alkylating agent - lowest chance of toxicity (CHLORine gas and MUSTARD gas. drinking a little chlorine wont hurt you, what are you, slow?)
which alkylating agent has the lowest tox, and why?chlorambucil, and it has the lowest tox bc it is the slowest working
lomustine--> which group of alkylating agents does this belong to? admin? what should you know about its metabolism? How widely used is it?nitrosourea alkylating agent, ORAL admin, metabolized into active metabolites in the LIVER, but there is limited info on it in vet med. (loMUST inhale the NITRO through your MOUTH, but loMUST be careful of your LIVER)
lomustine--> for what cancers do you use this drug? what are the side effects?(nitrosureas) used in relapse canine lymphoma, brain tumours, epitheliotropic cutaneous lymphoma, mast cell tumours. Major side effect is that it causes hepatotoxicity in dogs (makes sense, since it's metabolized into active metabolites IN the liver) (lymphomas and mast cell tumors are both discrete cell, and then BRAIN CRAP, so, you loMUST treat these fast! but you loMUST watch your liver!)
dacarbazine--> what group does this drug go under? what should you know about its metabolism? what cancer is it used to treat? What can you combine it with?it is a "non classical alkylating agent" (in chart it's a triazene) and it is metabolised into active metabolites in the liver. it is used in refractory lymphoma combined with doxorubicin(cytotoxic agent) (TRI not to eat CARBs, if you do, be ACTIVE to METABOLIZE, so you can run with your dog (a DOXie). This regiment might get rid of your REFRACTORY fat...or lymphomas)

Cytotoxic antibiotics AND L-asparaginase

Question Answer
how do cytotoxic antibiotics produce their effects?mainly through direct interaction with DNA
what should you NEVER use cytotoxic antibiotics with?do not use together with radiotherapy (toxicity) (bad talk about ABX on the RADIO)
doxorubicin and the anthracyclines (and mitoxantrone)--> how do these work? What is mitoxantrone, exactly?inhibits DNA (topoisomerase II) and RNA synthesis. Mitoxantrone is substitute for doxorubicine, because doxorubicine has a high risk of cardiotox and mito. doesnt. (DoX and mitoX both have x's, so, can substitute each other. all cytotox Abx (hince -cin, -cycline) and thus interfere with DNA/RNA synth)
dactinomycin--> how does this work?intercalates in DNA interfering with RNA polymerase and with action of topoisomerase II (Dac made of Tin is just interfereing with the Riverbank of the TOP river)
bleomycin--> how does this work?fragmentation of DNA also acts on non-dividing cells (remember -mycin is Abx, so, know its a cytotox. abx, in this case it a-BLEO-ates everything, incld healthy cells)
mitomycin--> what should you know about this?activated to give an alkylating metabolite! (remember: mito was a basic cis boy, but we bonded anyway)
(basic) MOA of of L-asparaginase?deaminate(s? d?) asparagine, inhibits protein synthesis
(steps) MOA of L-asparaginase?catalyses hydrolysis of l-asparagine to l-aspartic acid and ammonia--> depletion of extracellular stores of l-asparagine leads to inhibition of protein synthesis
what is the limitation of using L-asparaginase as a chemotheraputic agent?it only works in tumors which LACK l-asparagine synthetase (bc if they have this enzyme, they can make their own asparagine, so you can't deplete it)
what are the side effects of L-asparaginase?hypersensitivity reactions and pancreatitis (allergic to asparagus and why would you give it to your dog anyway, will proly cause pancreatitis)

Plant derivatives

Question Answer
what is the MOA of vinca alkaloids?drugs bind to tubulin and inhibit its polymerisation into microtubules-->prevent spindle formation in dividing cells - arrest at the metaphase
how safe are vinca alkaloids?relatively safe
what are the side effects of vinca alkaloids?mild myelosuppression - paraesthesia (sensory changes) - muscle weakness (relatively safe drugs) (hanging out with vin is interesting-- I feel weak and i feel paraesthesia, and he looks kinda suppressed)
where do vinca alkaloids come from (which plant)? what are the three active substances?come from Madagaskar periwinkle. vincristine, vinblastine, vinorelbine
what is the MOA of taxanes?they stabilize the microtubules in the polymerised state (so no cell division occurs)
what are the two taxanes? how do you admin them?paclitaxel (iv) docetaxel (po) (PAC your blood full of PAC, and then eat a DOCE to get your mind off your TAXing day)
where do taxanes come from? (plant)the taxus sp. from the BARK OF THE YEW TREE
what are the side effects of the taxanes?serious bone marrow depression and cumulative neurotoxicity. paclitaxel (pacman is very sensitive) may cause hypersensitivity (pacman is sensitive) DO NOT USE IN HORSES, VERY TOXIC!! (LOTS OF TAXES ON HORSES. expensive animals. Also TAXING on the BONES AND BRAINS. (but you dont need brains to bone, har har)
which plant derivative do you not use in horses?dont use the taxanes (paclitaxel and docetaxel) in horses

tyrosine kinase inhibitors-- and monoclonal antibodies-- and selective inhibitors of nuclear transport

Question Answer
(basic) MOA of tyrosine kinase inhibitors?Block activity or receptors
(steps) MOA of tyrosine kinase inhibitors?in cell, block downstream signaling of growth promoters/Growth promot. proteins. act on intacellular producton of these things. Or block receptors (STUDY GUIDE SAYS: Inhibit angiogenesis or cause dysregulation of cell growth: inhibit downstream signaling)
what are the three tyrosine kinase inhibitors he mentions?imatinib, toceranib, masitinib (ALL END IN NIB)
(group?) what is imatinib used to tx? in who?(tyrosine kinase inhibitors) mast cell tumors and sarcomas in dogs and cats (IM an equal opportunity lover of both cats and dogs-- I MAST SARcome to their adorable)
(group?) what is toceranib used to tx? in who?(tyrosine kinase inhibitors) mast cell tumors, sarcomas, carcinomas, melanoma, myeloma in dogs (toc-o dog made of mast cells and sarcoma/carcinoma, melanoma/myeloma)
(group?) what is masitinib used to tx? in who?(tyrosine kinase inhibitors) mast cell tumors in dogs (HAS MAST IN NAME- TX MAST CELL. END IN NIB- IS TYROSINE KINASE INHIBITOR)
MOA of monoclonal Abs?Block specific receptors, so you need to make sure these receptors are expressed in the tumor you are trying to target in order for an effect
cetuximab is used to tx?ErbB-1 expressing tumors (C #1)
trastuzumab is used to treat?ErbB-2 expressing tumors (T comes after C, so T #2)
bevacizumab is used to treat?VEGFR (receptor) in mastocytoma cells (put VEG in your BEVer if you dont have a MAST)
lifehack on remembering the tyrosine kinase inhibitors, and the monoclonal Abs?all the monoclonal Abs end in MAB (M.onoclonal A.nti B.ody) and all the tyrosine kinase inhibitors end in "nib" which are some of the letters in inhibit
what is exportin-1 (XPO-1)? how does it relate to "selective inhibitors of nuclear transport"?exportin-1 is a protein that transports growth regulator proteins and tumor suppressor genes out of the nucleus and promotes apoptosis. exportin-1 is upregulated in many cancers. (SO WE WANT TO InHIBIT IT)((so if you inhibit the transporter, more growth regulators and tumor suppressors and apoptosis encouragers accumulate and then tumor cells are more likely to be regulated/suppressed/apoptosis-ed)
what are the two drugs that are selective inhibitors of nuclear transport?selinexor and verdinexor (NEXOR SELECTS-OR)

steroid hormones and antagonists

Question Answer
what are the things glucocorticoids do?direct destruction of tumour cells, reduce tumour size, and help in management of secondary complications
what are the side effects of glucocorticoids?they induce PgP expression (PgP transports drugs out of cells) which means they might induce multi-drug resistance (resistance isn't futile- it's sweet)
anti-androgens--> what is the drug? when are these useful? when are these NOT useful?delmadinone. useful in perianal gland tumours as replacement for castration. NOT useful in prostatic carcinomas though (turn that dude into a madin (maiden) because that's better than tumors around your anus)
delmadinone is a what?anti-androgen
anti-estrogens--> what is the drug? when/how is this used?tamoxifen--> selectively inhibits estrogen receptors. dog and cat mammary carcinomas have decreased numbers of estrogen receptors (esterogen AND prosta stuff for mammary. TAM was not super femme, but she was amazing and would punch your breasts right off)
tamoxifen is a what?anti-estrogen which selectively inhibits estrogen receptors
anti-prostagens might be used for what?might be useful in some mammary tumours (prostaglandins and boobs and stuff)


Question Answer
what are the 2 basic types of resistance?primary or acquired (adaptation or mutation)
decreased accumulation of cytotoxic drugs is done by tumors how?increased expression of drug transport proteins on the cell surface
what are the drugs which have resistance gained on them by inc expression of drug export proteins on the cell surface?doxorubucin - vinblastine - dactinomycin (vin the doxie blasted off the tin dac because he was exported from the house)
which drug has resistance to be because of a decrease in the amount of drug uptake by the cell?methotrexate
resistance may be gained by insufficient activation of the drug--> what is a situation and a drug where this happens?failing metabolic activation with fluorouracil
increased utilisation of alternative metabolic pathways happens the gain resistance to what drugs?antimetabolites
rapid repair of drug induced lesions is how tumors gain resistance to what drugs?alkylating agents
altered activity of the target (in this case, of topoisomerase II) is how tumors gain resistance to what drug?doxorubucin

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