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96 Cards in this Set

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Cancer Biology/Cell Kinetics
Similar to bacterial kinetics
Doubling time = 1 g to 2 g
Generation time = 1 cell to 2 cells (controls growth rate)
Growth is exponential
Cell Cycle
G1 = protein and RNA synthesis
S = DNA synthesis
G2 = protein and RNA synthesis
M = mitosis/cell division
G0 = non-dividing
Total Kill Concept
One L1210 Leukemia cell is FATAL to a mouse
- a given dose will kill a constant percentage of cells per unit time
- # of original cells before therapy will determine # of cells surviving therapy
Combination Chemotherapy
ABVD
BACOP
CHOP
CMF
CVP
MOPP
POMP
Carmustine-Cimetidine
Additive bone marrow depression
Cimetidine inhibits Carmustine metabolism
Cyclophosphamide-Allopurinol
Bone marrow depression
Allopurinal alters the liver metabolism of cyclophosphamide
Mercaptopurine - Allopurinol
Increased mercaptopurine toxicity
Allopurinol inhibits xanthine oxidase which is involved in mercaptopurine metabolism
Methotrexate - Ethyl Alcohol
Hepatotoxicity
Methotrexate-Aspirin
Increased serum concentration of free MTX
Aspirin displaces MTX from plasma proteins and competes for its elimination
MTX-Cytarabine
Syngeristic effects
MTX-Neomycin
Decreased MTX absorption
MTX-Probenecid
Increased MTX in serum
Probenecid inhibits MTX excretion
MTX-Sodium Bicarb
Increased renal elimination of MTX due to alkalinization of urine
MTX-Sulfisoxazole
Decreased plasma binding and renal clearance of MTX
Antineoplastic Agents
General Toxicities
-pancytopenia
-thinning and denudation of mucosa
-hair loss, skin lesions
-teratogenic, sterility
-immunosuppression
-cancer
-gout
Alkylating Agents MOA
alkylate nucleic acids and proteins
Alkylating Agents Kinetics
quickly metabolized, distributed, excreted
Alkylating Agents Toxicities
Nausea, vomiting
Alopecia
Thrombocytopenia
Hemorrhagic cystitis
Increased skin pigmentation
Alkylating Agents Resistance
Decreased take up of drug
Increased ability to excise cross-linked residues and repair the defect
Mechlorethamine Uses
Hodgkin's
Lymphosarcoma
Wilm's Tumor
Chlorambucil Uses
Lymphosarcoma
CLL
Ovarian CA
Hodgkin's
Cyclophosphamide Uses
ALL
Neuroblastoma
Myeloma
Wilm's tumor
Melphalan uses
Multiple myeloma
Melanoma
ThioTEPA uses
Ovarian CA
Lymphosarcoma
Busulfan Uses
CML
Uracial Mustard Uses
CLL
Lymphoma
Hodgkin's
Pipobroman Uses
Polycythemia vera
Chronic granulocytic leukemias
BCNU Uses
Astrocytoma (CNS tumors)
Procarbazine Uses
Hodgkin's
Dacarbazine Uses
Hodgkin's
Altretamine Uses
Ovarian CA
cis-DDP MOA
Alkylates DNA, forms coordination complexes
cis-DDP Toxicity
Kidney damage
cis-DDP uses
Testicular CA
Ovarian CA
Bladder CA
Head and neck CA
Carboplatin
Similar to cis-DDP
Less toxic
6-Mercaptopurine
Purine analogue/anti-metabolite
6-Mercaptopurine MOA
Suppression of de novo purine biosyntheis (due to psuedo-feedback inhibition)
Inhibition of adenylate and guanylate formation
Inhibition of interconversion reactions in purine metabolism
6-Mercaptopurine Kinetics
Oral
Complete GI absorption
90% protein bound
t1/2 = 90 minutes
6-Mercaptopurine Toxicities
Leukopenia, thrombocytopenia, anemia
Anorexia
Jaundice
6-Mercaptopurine Uses
Antileukemic
Azathioprine
Less toxic than 6-MP
Prevents transplant rejection
Used in RA and SLE
Pyrimidine Analogues
5-FU
ARA-C
5-FU MOA
Blocks thymidylate/DNA synthesis
Depresses RNA synthesis
5-FU Kinetics
IV
Excreted as expired CO2 after 24 hours
5-FU Toxicities
Leukopenia, thrombocytopenia
Anorexia, diarrhea, stomatitis
5-FU USes
GI neoplams
Female genital tract CA
Breast CA
ARA-C MOA
Inhibits DNA synthesis
Incorporated into internucleotide linkages
ARA-C Kinetics
IV
Cleared in 15-30 minutes
Metabolism inactivates
ARA-C Toxicities
Leukopenia, thrombocytopenia, anemia
Anorexia, nausea, vomiting
ARA-C Uses
Acute granulocytic leukemias
Folic Acid Analogues (MTX)Kinetics
Absorbed well
Peak levels in 1 hour
50% protein bound
24 hour, complete excretion
MTX Toxicities
Anorexia, weight loss, bloody diarrhea
Leukopenia
Depression, coma
Severe hemorrhagic enteritis
Dermatitis, GI ulceration, infection, bleeding
MTX Uses
Choriocarcinoma
ALL
Psoriasis
Vinca Alkaloids (Vinblastine/Vincristine)MOA
Bind microtubular proteins
Prevent spindle formation
Inhibit cell cycle
Vinca Alkaloids (Vinblastine/Vincristine) Toxicities
Bone marrow depression
Pancytopenia
Neurological Problems
Vinca Alkaloids (Vinblastine/Vincristine) Uses
Solid tumors
Lymphosarcoma
Hodgkin's
Lymphoma
Choriocarcinoma
Acute leukemias
Epipodophyllotoxins
Etoposide
Teniposide
Epipodophyllotoxins MOA
Block S-G2 phase of cell cyle
Affect topoisomerase II
Epipodophyllotoxins Toxicities
Leukopenia, thrombocytopenia
Nausea, vomiting, stomatitis, diarrhea
Alopecia
Hepatic toxicity
Epipodophyllotoxins USes
Testicular tumors
NHL
AML
Breast CA
Kaposi's sarcoma
ALL
Taxol MOA
Binds tubulin dimers
Disrupts mitosis
Taxol Toxicities
Myelosuppression
Alopecia
Peripheral neuropathies
Muscle and joint pain
CV problems
Hypersensitivity
Taxol Uses
Breast CA
Ovarian CA
Lung CA
Head and neck CA
Daunorubicin/Adriamycin MOA
Intercalate DNA
Prevent replication
Inhibit topoisomerase II
Daunorubicin/Adriamycin Kinetics
t1/2 = 45 minutes
Bile excretion
Daunorubicin Toxicities
Bone marrow depression
Tachycardia, arrhythmias
Cardiorespiratory symptoms
Adriamycin Toxicities
Bone marrow depression
CHF
Nausea
Daunorubicin Uses
Acute leukemias
Adriamycin Uses
Lung CA
Breast CA
Bladder CA
Lymphoma
Sarcomas
Plicamycin MOA
Binds DNA
inhibits RNA synthesis
Requires guanine
Plicamycin Uses
Embryonal cell testicular tumors
Paget's, hypercalcemia
Dactinomycin MOA
Prevents DNA synthesis by binding DNA
Guanine and helical configuration required
Dactinomycin Kinetics
IV
Bile and urine excretion
Dactinomycin Toxicities
Hematopoietic depression, leukopenia, anemia, pancytopenia
Nausea, vomiting, stomatitis
Erythema, acne, alopecia
Fatigue, fever, myalgia
Dactinomycin Uses
Wilm's Tumor
Rhabdomyosarcoma
Ewing's sarcoma
Osteogenic sarcoma
Choriocarcinoma
Uterine and testicular CA
Bleomycin MOA
Inhibit DNA synthesis
Bleomycin Toxicities
Pulmonary fibrosis
Bleomycin Uses
Squamous cell carcinoma of skin
Testicular tumor
Lymphoma
Mitomycin MOA
Alkylating agent
Mitomycin Toxicities
Myelosuppression
Renal toxicity
Mitomycin Uses
Gastric adenocarcinoma
Tumors of cervix, colon, rectum, pancreas, breast, bladder, lung
Prednisone MOA
Inhibit RNA and protein synthesis
Prednisone Toxicities
Fluid disturbances
Hyperglycemia, glycosuria
Peptic ulceration
Infection
Psychiatric disturbances
Skeletal atrophy
Predinose Uses
ALL
Other Hormone Therapies
Progesterone (endometrial CA)
Diethylbestrol
Flutamide (antiandrogen)
Estramustine (estrogen + alkylating agent)
Leuprolide (GnRH analog)
Testosterone proprionate
Antiestrogens
Aminoglutethimide
Estrogen/Androgen MOA
Change hormonal environment of tumor
Estrogen/Androgen Uses
Prostatic CA
Mammary CA
Monoclonal Antibody (Herceptin) MOA
Inhibits tumor cell growth by binding to HER2
Monoclonal Antibody (Herceptin) Toxicities
Weakening of heart muscles leading to CHF
Leukopenia, anemia
Diarrhea, abdominal pain
Chills, fever, pain, weakness, anusea, vomiting, headache
Monoclonal Antibody (Herceptin) Uses
Advanced breast CA
Hydroxyurea MOA
inhibits ribonucleoside diphosphate reductase
Hydroxyurea Uses
Chronic granulocytic leukemia
Polycythemia vera
Solid tumors
Mitotane Uses
Adrenocortical CA (Palliative tx)
L-asparaginase Uses
ALL
(SE: nausea, liver dysfunction, hypersensitivity)
Gold-198 Uses
Pleural effusions and ascites secondary to cancer
Sodium Phosphate P 32 Uses
Polycythemia Vera
CML