Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
75 Cards in this Set
- Front
- Back
|
What is Gompertzian kinetics?
|
Tumors may outgrow their blood supply causing the cells to proliferate less, making them harder to kill
|
|
|
What is a one log kill?
|
90% of cells in the population are killed
|
|
|
What is a two log kill?
|
99% of the cells in a population are killed
|
|
|
If there are 10E12 cells in a population and a drug is used that kills 99% of the cells, how many will be left?
|
10E10 cells will remain because this would be a two log kill
|
|
|
The killing of cancer cells generally follows what kinetic pattern?
|
First-order kinetic pattern
|
|
|
What are some mechanisms that may allow a cell to become resistant to a particular chemotherapy?
|
gene amplification
increased production of P-glycoprotein-like efflux pumps |
|
|
What are the basic principles of combination chemotherapy?
|
1) each drug must be individually active against the tumor type
2) the mechanisms of interaction must produce an optimum effect 3) drugs have different toxic effects |
|
|
What is adjuvant chemotherapy?
|
Chemotherapy after surgery or radiation to improve the outcome by eliminating clinically unapparent tumor cells
|
|
|
What is neoadjuvant therapy?
|
Chemotherapy or radiation before surgery to shrink the tumor to make it more operable
|
|
|
What are the major divisions of alkylating agents?
|
1) bischloroethylamines
2) nitrosoureas 3) alkyl sulfonate 4) ethyleneimines |
|
|
Name the bischloroethylamines. Of what broad class do they belong?
|
Bischolorethylamines are alkylating agents
1) mechlorethamine 2) melphalan 3) cyclophosphamide 4) chlorambucil |
|
|
Name the nitrosoureas. Of what broad class do they belong?
|
They are alkylating agents
1) carmustine 2) lomustine 3) streptozocin |
|
|
What is the alkyl sulfonate and to what broad class does it belong?
|
Busulfan is an alkyating agent
|
|
|
What is the ethyleneimine and to what broad class does it belong?
|
Thio-TEPA is an alkylating agent
|
|
|
What is the mechanism of action of alkylating agents?
|
They are activated to chemically reactive metabolites (spontaneously or by enzymes) that bind to bases in DNA
|
|
|
What are some common adverse affects to alkylating agents?
|
Myelosuppression- can be delayed
GI upset - nausea and vomiting Reproductive effects - amenorrhea, decreased sperm production Carcinogenicity |
|
|
What are some possible mechanisms of resistance against alkylating agents?
|
1) repair of damaged DNA
2) decreased tumor uptake of drug 3) increased inactivation of drug |
|
|
What drugs commonly causes hemorrhagic cystitis and how can this be overcome? To what class do these drugs belong?
|
Cyclophosphamide and Ifosfamide are bischloroethylamines (alkylating agents) that can cause hemorrhagic cystitis
This can be overcome by increased hydration or with the administration of the drug mesna |
|
|
What bischoloroethylamine is commonly used as an effective immunosuppressant?
|
cyclophosphamide
|
|
|
What alkylating agents are used in the treatment of brain tumors because they cross the BBB?
|
The nitrosureas carmustine and lomustine
|
|
|
What are the non-classical alkylating agents?
|
1) procarbazine
2) dacarbazine |
|
|
What are the toxicities associated with procarbazine?
|
1) MOA inhibition - tyramine induced hypertension
2) disulfaram-like effects 3) myelosuppression |
|
|
What is the use of Dacarbazine?
|
Malignant melanoma
|
|
|
What is the mechanism of action of cisplatin?
|
It binds to DNA and inhibits DNA synthesis and function
|
|
|
What are the adverse side effects of cisplatin?
|
1) Nephrotoxicity - diminished by hydration and diuresis
2) HIGHLY EMETOGENIC 3) ototoxicity 4) myelosuppression |
|
|
When administering cisplatin, how would you help reduce the chance of nephrotoxicity?
|
Make sure the patient was well hydrated and give diuretics
|
|
|
What are the drugs that work as antimetabolites?
|
1) methotrexate
2) 6-mercaptopurine 3) 6-thioguanine 4) 5-FU 5) cytarabine 6) gemcitabine |
|
|
What is the mechanism of action of methotrexate?
|
It inhibits dihydrofolate reductase, preventing the formation of FH4 which is needed as a cofactor in the synthesis of thymidylate
Overall decrease in DNA, RNA , and protein synthesis Polyglutamates are formed which also contributes to toxicity |
|
|
What are the possible mechanisms of resistance against methotrexate?
|
increased synthesis of DHFR
mutated DHFR decreased cellular uptake increased efflux |
|
|
What are some of the toxicities associated with methotrexate use?
|
1) myelosuppression
2) GI mucositis 3) hepatic with long term use (macrovesicular fatty change) |
|
|
What are some of the non-cancer uses of methotrexate?
|
Rheumatoid arthritis
Psoriasis |
|
|
What is leucovorin and for what is it used?
|
This is a form of folic acid that is administered as an antidote for excessive doses of methotrexate
|
|
|
What is leucovorin rescue?
|
This is the use of leucovorin as part of a high-dose methotrexate therapy to "rescue" from some of the adverse effects of methotrexate
|
|
|
What is the mechanism of action of pemtrexed?
|
It inhibits thymidylate synthetase and is converted into polyglutamates
|
|
|
What is given to supplement patients taking pemetrexed?
|
B12 and folic acid; they reduce toxicity but do not interfere with efficacy
|
|
|
What drugs are purine and pyrimadine analogs and how do they work?
|
1) 6-mercaptopurine
2) 6-thioguanine 3) 5-FU 4) cytarabine 5) gemcitabine 6) fludarabine phosphate 7) cladribine They must be converted into active nucleotides and interfere with DNA synthesis/function |
|
|
How is 6-mercaptopurine metabolized and how can this be affected?
|
It is metabolized to 6-thiouric acid by xanthine oxidase and can also be S-methlyated by thiopurine-S-methyltransferase
Some patients have low TPMT activity and these patients have increased risk of toxicity Patients given Allopurinol to block xanthine oxidase must have their dose of 6-mercaptopurine decreased to avoid toxicity |
|
|
Describe the metabolism of 6-thioguanine
|
It is methylated by TMPT and deaminated to 6-thioxanthine which happens before the xanthine oxidase step, so these patients don't require a dose change when taking allopurinol
|
|
|
What is the mechanism of action of fludarabine phosphate?
|
It is a nucleotide that inhibits DNA synthesis and repair as well as inhibition of ribonucleotide reductase; it induces apoptosis
|
|
|
What is the mechanism of action of 5-FU?
|
It inhibits thymidylate synthase which decreases the production of TMP and DNA synthesis; it can also be incorporated into DNA and RNA
|
|
|
What are the platinum containing drugs?
|
cisplatin
carboplatin oxaliplatin |
|
|
What is the mechanism of gemcitabine?
|
Ribonucleotide reductase inhibition
incorporation into DNA inhibition of DNA synthesis and repair |
|
|
What drug causes mucositis and damage to the oral mucosa and mucosa of the GI tract?
|
Methotrexate
|
|
|
What is the form of tetrahydrofolate given in patients treated with excess methotrexate?
|
leucovorin
|
|
|
What drugs inhibit thymidylate synthetase?
|
5-FU and pemetrexed
|
|
|
What are the antibiotic anticancer drugs?
|
1) Dactinomycin (Actinomycin D)
2) Doxorubacin 3) Daunorubicin 4) Bleomycin 5) Mitomycin C |
|
|
What is the mechanism of action of dactinomycin?
|
It intercalates between base pairs of DNA and interferes with RNA synthesis
|
|
|
What are the mechanisms of action of doxorubicin and duanorubicin?
|
They intercalate between DNA bases and inhibit DNA and RNA synthesis; they also inhibit topoisomerase II and cause DNA strand breaks
|
|
|
What are the adverse reactions associated with doxorubicin?
|
1) Cardiotoxicity - cardiomyopathy and heart failure, also arrhythmia and myocarditis/peridcarditis
2) myelosuppression 3) nausea, stomatitis 4) hepatic dysfunction |
|
|
What is the mechanism of action of bleomycin?
|
It binds to DNA and causes strand breaks; it also generates free radicals
|
|
|
What are the major toxicities associated with bleomycin?
|
1) pumlonary fibrosis
2) skin manifestations such as erythema and tenderness 3) allergic reactions |
|
|
What drug can cause hemolytic uremic syndrome?
|
mitomycin C
|
|
|
Name the vinca alkaloids and their mechanism of action
|
The vinca alkaloids include vincristine and vinblastine
They are mitotic inhibitors by binding to the tubulin and inhibiting the polymerization to microtubules |
|
|
Which vinca alkaloid causes less myelosuppression? Which causes less neurotoxicity?
|
Vincristine causes less myelosuppression and vinblastine causes less neurotoxicity
|
|
|
What is the mechanism of action of paclitaxel?
|
It binds to microtubules and promotes the formation of microtubules, which leads to an inhibition of mitosis (opposite of vinca alkaloids); the mitotic spindle cannot break down during anaphase
|
|
|
What are the toxicities associated with paclitaxel?
|
hypersensitivity reactions
myelosuppression peripheral neuropathy arrhythmia |
|
|
What is the mechanism of action of etoposide?
|
It inhibits topoisomerase II and leads to DNA strand breaks
|
|
|
What is the mechanism of action of topotecan and irinotecan?
|
They inhibit topoisomerase I causing DNA damage
|
|
|
What enzyme is used to treat cancer and how does it work?
|
L-Asparaginase depletes asparagine in certain leukemic cells which cannot synthesize the amino acid, leading to decreased protein synthesis
|
|
|
What are the toxicities associated with L-asparaginase?
|
Allergic reactions, hepatotoxicity, clotting factor changes, neurotoxicity, pancreatitis, and hyperglycemia
|
|
|
What is the mechanism of action of imatinib?
|
It inhibits the Bcr-Abl tyrosine kinase expressed by CML cells by preventing the binding of ATP
|
|
|
What drug is used to treat CML?
|
imatinib
|
|
|
What is the mechanism of action of dasaitinib and nilotinib and when are they used?
|
They are used to treat imatinib resistant CML; they also inhibit the Bcr-Abl tyrosine kinase
|
|
|
Name the growth factor receptor inhibitors
|
1) cetuximab
2) panitumumab 3) Gefitinib 4) erlotinib 5) bevicizumab 6) sorafenib 7) sunitinib |
|
|
What is the mechanism of action of cetuximab and panitumumab?
|
They are monoclonal antibodies that bind to epidermal growth factor receptor and inhibit downstream receptor signaling
|
|
|
What are the adverse effects of cetuximab and panitumumab?
|
infusion reactions
acneifrom rash interstitial lung disease |
|
|
What is the mechanism of action of gefitinib and erlotinib?
|
They inhibit the tyrosine kinase domain of EDGF, leading to the inhibition of receptor signaling
|
|
|
What are the adverse effects of gefitinib and erlotinib?
|
diarrhea
acneiform rash interstitial lung disease |
|
|
What is the mechanism of action of bevicizumab?
|
It is a monoclonal antibody that binds to vascular endolethial growth factor
|
|
|
What is the mechanism of action of sorafenib and sunitinib?
|
They inhibit many tyrosine kinases including VEGF receptors and PDGF beta receptors
|
|
|
What are the adverse effects associated with sorafenib and sunitinib
|
hypertension
hand-foot syndrome possible heart failure (sunitinib) rash |
|
|
How does all-trans retinoic acid work and what cancer is it used to treat?
|
It induces the differentiation of cancer cells in acute promyelocytic leukemia
|
|
|
What is the mechanism of arsenic trioxide and what toxicities are associated with it?
|
It induces differentiation but can cause QT prolongation, arrhythmias, and retinoic acid syndrome
|
|
|
What is the mechanism of action of bortezomib?
|
It is a proteasome inhibitor
|
|
|
What is the mechanism of action of hydroxyurea and what are the side effects?
|
It inhibits ribonucleotide reductase but causes bone marrow suppression, N and V, skin reactions
|
