Chemotherapeutic Drugs

britt611's version from 2017-01-19 19:32

Section 1

Question Answer
What are 5 types of therapeutic modalities in oncologSurgery, Radiaiton, chemotherapy, immunotherapy, targeted therapy
what is an example of why you would do radiation before surgery?If tumor is located in Brain, lung, thyroid. Areas that are hard to perform surgery
what is an example of why you should perform surgery before before radiationeasy to remove, faster recover period
Define: Adjuvant therapyTreatment with chemotherapeutic agent after achieving control of the primary tumor with surgical resection or radiation therapy
Define: neoadjuvant therapyChemotherapy used prior to treatment with other modalities for local tumor contol, with the intent of deceasing tumor size
Define: induction therapyChemotherapy treatment with the intention of a cure
Define: Rescue therapyIs the use of chemotherapy after a tumor fails to respond to a previous therapy or after tumor recurrence
Define: Palliative chemotherapy Aims to decrease clinical sign in the case of unresectable or disseminated disease and associated with pain
Define: Therapeutic indexThe ratio between the toxic dose and the therapeutic dose for that drug
Define: MTDMaximal tolerated dose- the highest dose of a drug that can be administered in the absence of unacceptable or irreversible side effects
What phase in the cell cycle are the majority of cell in healthy tissues in?G0 phase
When does the cell cylce become self directed?when it crosses the restriction point. Rb gene is in charge of this
What is required for CDK activity?cyclins to be activated

Section 2

Question Answer
how do cell cycle non specific drugs kill cells?kills resting cells and dividing cells
How do cell cycle specific drugs kill cellskills actively dividing cells
Name 6 drugs that are classified as Cell cycle non specific1. Cyclophosphamide 2. Chlorambucil 3. Cisplatin/carboplatin 4. actinomycin D 5. adriamycin 6. L-asparginase
Name 2 drugs that effect the S phase of the cell cylce1. Methotrexate 2. 5-fluorouacil
Name 2 drugs that effect the G2 phase of the cell cycle1. Etoposide 2. Bleomycin
Name 3 drugs that effect the M phase of the cell cycle1. Vincristine 2. vinblastine 3. paclitaxel

Section 3

Question Answer
What is the limit of detection of cells that shows clinical signsapprox. 10^9 cells
What is the range of number of cancer cells in a patient are tumors usually diagnoses 10^9- 10^12
What is a adjuvant chemotherapy?this is an example of giving a drug after srugery, there for you can use less drug to curve animal of that disease
Define Clinical remissionwhen the number of cancer cells decreases to a point where the animal is not showing any clinical signs but still have disease
What is the chemotherapy dose calculation of BSAM^2 = [ A x (weight in grams)^2/3] / 10,000. where A= 10 in cats and 10.1 in dogs
What is the use of BSA?for current drug- dosing convention for cancer chemotherapeutic agents (BSA = mg/m^2)
how are the units different for small dogs and cats?for dogs less then 15kg, it is calculated based on bodyweight mg/kg
What are 2 ways cancers become drug resistant?1. Cellular mechansim 2. Anatomical resistance

Section 4

Question Answer
what are 3 ways cancer becomes drug resistance via cellular mechanism?1. Enhance survival 2. Alteration of drug targets 3. multi drug resistance
How do they enhance survival?1. Evade apoptosis 2. increase DNA repair
How do they alter drug targets?1. up regulation of target protein 2. mutation of target binding sites
How does multi drug resistance occur?1. Drug efflex pumps (Pgp) 2. drug conjugation with glutathione
What are 2 ways cancer become anatomical resistance1. Tumor hypoxia 2. Physiological barriers
How does tumor hypoxia occur?1. physical distance form BV 2. imperfection of malignant blood vessels
what are 2 examples of physiological barriers1. BBB, skin, Bone marrow 2. limited penetration of drug to mass

Section 5

Question Answer
What can chemotherapy cause? CANCER
Who can give chemo?tranied professonal
Where should chemo be mixed?in fume hood- it is a class II B
Protection gear should include what?Chemotherapy gloves, face mask, eye protection (face shield), chemo gown

Section 6

Question Answer
What are the 3 categories of akylating agents?1. nitrogen mustards 2. Nitrosoureas 3. Traizenes
What are 5 nitrogen mustards agents?1. Mechlorethamine (mustargen) 2. Cyclophosphamide (cytoxan) 3. chlorambucil (leukeran) 4. melphalan (alkeran) 5. Ifosfamide
What are 2 nitrosoureas?1. lomustine (CCNU) 2. Streptozocin
What is 1 traizenesDacarbazine
What is the function of alkylating agents?introduce alkyl groups that bind covalently into nucleophilic site of DNA and RNA
What do alkylating agents induce?monofunctional or bifunctional adducts that generate interstrand or intrastrand cross-links
Where do alkylating agents mostly react?7th position of guanine in each of the DNA strands causing cross linking and interfering with strand separation
What is the end result of alkylating agents?Misreading of codons and signal strand breakage
Are they effected by the MDR1 gene?NO
Is there cross drug resistance?NO
What are 5 mechanism of resistance to alkylating agent mechanism?1. decrease of drug influx, 2. increase production of nucleophilic substance (glutathione) that compete for the target, 3. increase of DNA repair mechansim, 4. Increase metabolic inactiation of drug, 5. Not effected by Pgp

Section 7

Question Answer
Mechlorethamine is a..Alkylating agent, strong vesicant
how is Mechlorethamine givenIV
Mechlorethamine is used for what?rescue protocols for relapsed lymphoma
What is a major disadvantage for Mechlorethamineit is a mutagenic and carcinogenic to bone marrow stem cells
what are the toxicities of MechlorethamineGI and BM are dose limiting toxicities --- VERY TOXIC
Melphalan is a..DNA cross-linking agent
how does Melphalan get into cells?it actively transported into tumor cells by amino acid transporters (can be blocked by the amino acid leucine). Does NOT require activation
What is Melphalan limiting toxicity?myelosuppression
What is Melphalan clinical use?used in combination with prednisone for multiple myeloma
Describe the PK(PD?) of cyclophophamideinactive before it gets metabolized in the liver
What is the most active cyclophophamide metabolite?phosphoramide mustadard- it induces bifunctional alkylation and cross- link production
How can cyclophophamide be given?PO or IV
How does PO route effect cyclophophamide?cyclophophamide (CP) is decreased following oral dosing, but with proper dosing the overall exposure is similar between IV and PO
Which enzyme in the liver makes cyclophophamide active?P450
What does the active phosphoramide mustard react with?alkylates DNA
what is the limiting toxicity of cyclophophamideNeutropenia and thrombocytopenia, GI toxcity is not common, Hemorrhagic cysistis is uncommon
how do you prevent cyclophophamide causing hemorrhagic cystitis?1. give drug orally 2. use Na-2 mercaptoethane sulfonate (Mesna) 3. Diuresis with fluids and diuretics
What is the clinical use of cyclophophamideAs part of the CHOP protocol for lymphoma
What is the CHOP protocol?Prednisone for the first month, Week 1: vincristin week2: cyclophophamide, week 3: vincristin week 4: adryamincin week 5: NO treatment, Repeat 4 times
What is Metronomic therapy?The use of very low dosing for prolonged periods mostly to inhibit angiogenesis in solid tumors. This targets the healthy progenitor cells so new BV can not be formed
how does Chlorambucil enter cells?enters cells by passive diffusion. Needs to be activated by the liver
what type of alkyation does Chlorambucil cause?bifunctional alkylation
how is Chlorambucil given?rapidly absorbed PO- take home drug
What is the dose limiting toxicity of Chlorambucilneutropenia and thrombocytopenia, has the lowest toxcity from all the alkylating agents
which alkylating agent has the lowest toxicity?Chlorambucil
What is the clinical use of ChlorambucilChronic lymphocytic leukemia (CLL) and low-grade GI lymphoma (cats
How is Lomustine (CCNU) given?PO
how is Lomustine (CCNU) classified?classified as a nitrosoureas
How does Lomustine (CCNU) enter cells?highly lipophilic - enters cells via passive diffusion
How does Lomustine (CCNU) effect cancer cells?alkylation, DNA-DNA and DNAprotein cross-links
What type of metabolism does Lomustine (CCNU) undergo?extensive hepatic metabolism-- toxic to liver- have to monitor liver values closely
describe Lomustine (CCNU) distributionextensive distribution to tissues, including BBB and skin
What is NADIR?is the time we see effects of toxic material on healthy cells
What is the NADIR of Lomustine (CCNU)LONG! around 3 eeks for dogs and up to 6 weeks in cats
what is the dose limiting toxicity of Lomustine (CCNU)neutropenia and thrombocytopenia. If chronic administration- can result in liver toxicity
What is recommended with Lomustine (CCNU) causing liver toxicity?prophylactic treatment with liver protectants (ex. SAM-e)
what is the clinical use of Lomustine (CCNU)Histiocytic sarcoma (DOC), lymphoma rescue, Epitheliotropic lymphoma, Malignancies of the brain, Mast cell tumor
Streptozotocin is a product of what?streptomyces achromogenes- initially investigated as an antibiotic that can cause alkylation of bacterial and mammals DNA
What is the cellular uptake of StreptozotocinCellular uptake to B-cells by GLUT2
What is the dose limiting toxicity of StreptozotocinInduced diabetes, severe renal toxicity (INCLUDES diuresis), almost NO bone marrow toxicities
what is the clinical use of Streptozotocininsulimona
How is dacarbazine (DTIC) given?IV- has poor oral absorption
How is dacarbazine (DTIC) product activated?in the liver by p450. Also in the lungs but less often
how does dacarbazine (DTIC)work?induced methylation
describe the metabolism and excretion of dacarbazine (DTIC)?heavily metabolized in the liver and excreted by urine
What barrier can dacarbazine (DTIC) cross? BBB
What 2 drugs can cross the BBBdacarbazine (DTIC) and lomustine (CCNU)
What is the dose limiting toxicity of dacarbazine (DTIC)GI and BM (neutropenia and thrombycytopenia)
What is the clinical use of dacarbazine (DTIC)lymphoma rescue, melanoma, brain malignancies