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Onco, Drugs and Markers Flashcards

1
Q

Alkylating Agents

A

CELL CYCLE NON-SPECIFIC DRUGS (CCNS) Crosslink DNA, Lipids, and Carbs with Methyl groups.

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2
Q

Cyclophosphamide Melphalan Chlorambucil

A

Nitrogen Mustard Alkylating agents. CCNS Tx: Hodgkins/Non-Hodgkins Lymphoma SEs: GI, Myelosuprresion, alopecia, sterility, Vescication, secondary malignancies

Cyclophosphamide: CHOP Regiment for CLL, neuroblastoma, rhabdomosarcoma, breast/ovarian, soft tissue sarcoma. Hemorrhagic Cystitis** (and bladder cancer)

Melphalan: Multiple myeloma, breast cancer, ovarian cancer.

Chlromabuicl: CLL and NHL

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3
Q

ThioTEPA

A

Arizidine type Alkylating Agent (CCNS) Breast, Ovarian, and superficial bladder cancer SEs: Myelosupression

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4
Q

Carmustin Lomustin Stretozocin

A

Nitrosoureas type Alkylating Agent (CCNS)

CNS Use (Lipid Soluable). SEs: Myelosuppresion, Interstitial Lung Disease, Interstial Nephritis

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5
Q

Busulfan

A

Alkyl Sulfonate type Alkylating Agent (CCNS)

CML

PULM FIBROSIS****, skin pigmentation , adrenal insufficiency

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6
Q

Mechlorethamine

A

Alkylating Agent (CCNS) Hodgkins and NLH VESICANT******, GI distress, myelosuprresion, alopecia

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7
Q

Procarbazine Dacarbazine Bendamustine

A

Nonclassical Alkylating Agents (CCNS) Procarbazine: Highest risk of secondary cacners. Metabolites act as MOA Dacarbazine: potent VESICANT Bendamustine: Nasuea vomtiging, myelosurpession

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8
Q

Platinum Analogs

A

DNA crosslinkers, synergist effects with alkylating agents, flouropyrimidines and taxanes. Hydration issues

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9
Q

Carbopaltin Cisplatin Oxaliplatin

Can be given concurrently to reduce tox?

A

CCNS Carboplatin: No hydration issues, fever renal and GI tox Cisplatin: Irreversible peripheral neuropathies Oxaliplatin (part of FOLFOX)–REVERSIBLE peripheral neuropathies

Amifostine: Free radical scavenging agent decreasing cumulative nephrotox

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10
Q

AntiMetabolites

A

CCS in S phase Goal is to disrupt DNA precursor production/synth

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11
Q

Methotrexate Pemetrexed

A

Antifolate type antimetabolite CCS Methotrexate hits DHFR and thymidylate synthase. Rescue with Leucovorin Pemetrexed: Thymidlate synthase inhibitor

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12
Q

5-fluororuracil Capecitabine

A

Prodrog antimetablite CCS 5-flourouracil: DHPD converts to FdUMP inhibiting dna synth of thymine (thymineless death) and FUTP (inhibiting RNA processing and translation). Patients lacking DHPD get severe tox. Capecitaine: Fluoropyridine prodrug. SEs: Hand foot syndrome

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13
Q

Cytarabine Gemcitabine

A

Deoxycitidine Pyrimide Analog Antimetabolite (CCS) Cytarabine: RAPID CLEARANCE–continous IV infusion, hematological malignancies (AML first line drug)–makes sense since maintain a high concentration in blood but not anywhere else dt clearance. Gemcitiabine: Inhibits RBR thus inhibiting DNA pol, DNA syth/repair, causing Chain term. BROAD cancer tx, SEs: Neutropenia and Renal Microangiopathy.

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14
Q

6-mercaptopurine Cladribine 6-thiopurine Fludarabine

A

Purine antagonist type antimetabolite (CCS) 6-mercaptopurine–metabolixed by HPRT. SEs: Def of TPMT causes toxicity which is exacerbated with Allopurinol Cladribine: Immunosupression of CD4/8 T-cells

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15
Q

Vinblastine Vincristine

A

Vinca Alkyloid (CCS) Microtubule destabilizers arresting cell in mitosis (no spindle assembly). Vinblastine–vessicant (BLAST forms BLISTERS, and used for BONE marrow)

Vincristine: Neurotox w/ peripheral neuropathy, SIADH, ANS dysfunction

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16
Q

Paclitaxel Abraxane Docetaxel Ixebepilone

A

Taxane class (CCS) Microtbuule stabilizers, cleared by Cyp 450s Paclitaxel–breast, ovarian (solid tumors) SEs: Hypersensitivy and neurotoxicities Abraxane–Paclitaxel with albumin to prevent hypersensitivity Ixebepilone: Nontaxane. Binds Beta-tubulin subunits causing stabilization

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17
Q

Etoposide

Teniposide

A

Epipodophylotoxins CCS Etoposide: Inhbits Topoisomerase 2**. SEs: HOTN, myelosupresion, alopecia, nausea, vomitiging

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18
Q

Topotecan Irinotecans

A

Camptothecans (CCS) Inhibits Topoisomerase I Irinotechan: Prodrug. COLORECTAL CANCER first line (“irin-to the butt”). Diarrhea (first dt cholinergic stim, then more severe from toxicity)

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19
Q

Doxorubicin (adriamycin) Daunorubicin Idarubicvin Epirubicin Mitoxantrone

A

Anthracyline type drugs CCNS** Hodgkins 1) Inhibit Topoisomerase II, 2) DNA intercalation, 3) Semiquinone free-radical production (causes cardiac tox), 4) Binding to cell membranes (altering fluidity, and ion transport) CARDIAC TOX (arrythmias and conduction abnormalities progressing to dilated cardiomyopathy)

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20
Q

Mitomycin C

A

CCNS Prodrug. HEMOLYTIC UREMIC SYNDROME

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21
Q

Bleomycin

A

CCS drug inhibitng G2 phase by binding DNA. Hodkins and testicular cancer. PULM FIBROSIS from progressive pneumonitis

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22
Q

Prednisone

A

Glucocorticoid. Causes Apoptosis of immune cells (early on during low dose it will actually cause marrow release of myeloid/lymphoid cells into blood)

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23
Q

Tamoxifen

A

Estrogen antagonist in breast, estrogen agonist in ovaries/uterus. SEs: prothrombotic state, endometrial hyper/neoplasia.

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24
Q

Flutamide

A

Androgen Receptor Antagonists used in prostate cancer. Given initially before GnRH agonists as they initially cause an increase in GnRH levels.

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25
Leuprolide, Goserelin, Nafarelin
GnRH analogs: Prostatic carcinomas Acute doses increase LH/FSH levels Chronic doses: lowers LH/FSH lvls
26
Anastrozole
Aromatase Inhibitors. Used for advanced breast cancer by lowering estrone levels
27
Imatinid Dastinib Nilotinib
tx for CML t(9;22). Inhibitors bcl-abl fusion kinase Dastinib--multi kinase inhibitor nilotinib--higher specificity for bcl-abl kinase both are newer and used when imatinib doesn't work
28
Trastuzamab (herceptin)
Inhibits HER-2/neu receptor (EGFR) in breast cancer Adverse Rxns: **CARDIAC TOX (CHF (LVFailure))**, and pulm toxicity
29
Cetuximab Panitumumab
Metastaic colon cancer. Inhibits extracelullar domain of EGFR. KRAS expressing cancers. Acneiform skin rash and hypomagnesmia SEs
30
Gefitinib Erlotinib
Moleclar inhibitors of the tyrosine kianse domain of EGFR. Non-small cell lung cancer.
31
Bevacibzumab Sorafenib Sunitinib
VEGF inhibitor. Metastaic Colorectal cacner, non-small lung cancer, and breast cacner Bevacibzumab:HTN increased incidence of arterial thromboembolic events (TIA, stroek, agnina, MI) Sunitinib: Advanced Renal cell cacner
32
Sirolimus, Tacrolimus, Tensirolimus, Everolimus
MTOR inhibitors (inhibit calcineurin) preventing T-cell formation
33
Bortezomib (velcade)
Boron containing molecule inhibitng proteasome, causing a pro-apoptosis, cell death effect. Works well for refractory cancers. SEs: Peripheral neuropathies
34
Rituximab (rituxan)
AntiCD20 Antibody---inhibits B-cells Lymphomas and Rheumatoid arthritis
35
Gemtuzumab ogozomicin
Anti-CD33 antibody
36
Alemtuzumab
AntiCD52 antibody
37
Aspariginase
**Childhood ALL.** Tumor cells lack asparagine synthesase, and this drug depletes asparagine which means inhibition of protein synth SEs: Hypersentivitiy. Bronchospasm resp failure and HTON
38
Alkaline Phosphatase
Mets to bone, liver, Pagets disease of bone Seminoma (from placental ALP)
39
Alpha Feto Protein
Hepatocellular Carcinoma, Hepatoblastoma Yolk Sac (endodermal sinus) tumor Testicular Cancer Mixed germ cell tumor (w/ BhCG)
40
CA-15-3
Breast Cancer
41
CA-27-29
Breast
42
CA-19-9
Pancreatic Adenocarcinoma
43
CA-125
Ovarian Cancer
44
Calcitonin
Medullary Thyroid Carcinoma (MEN2a/b)
45
CEA
CarcinoEmbryonic Antigen 70% of colorectal and panc Can be produced by Gastric, breast, medullary thyroid carcinomas
46
S-100
Nerual Crest Origin (melanomas, neural tumors, schwannomas, langerhans cell histiocytosis)
47
TRAP
Hairy Cell Leukemia (b cell neoplasm)
48
Adult have blood smear with B-cells having filamentous projections. Dx? Stain? Tx? Mechanism?
Hairy Celly Leukemia. TRAP + Cladribine (2-CDA): adeonsine analog that inhibits ADA
49
AFP?
HCC, Yolk sac tumor (endodermal sinus), Mixed germ cell tumors
50
Pancytopenia with: 1) Fatty inflitrate on bone marrow 2) Hepatosplenomegaly and fibrosis on bone marrow 3) Dissordered differentaiton on bone marrow (possible ringed sideroblasts and megaloblastic anemia) 4) Bone marrow being crowded out by tumor with some fibrosis
1) Aplastic Anemia 2) Myelofibrosis 3) Myelodysplastic syndrome 4) Myelophthisic anemia
51
Follate deprivation can be rescued somewhat by supplementing what?
Thymidine: allowing thymidine kinase to replete some of the dTMP stores
52
Irradiation does what?
1) Double Strand DNA breaks 2) Forms free radicals
53
ALL B vs T markers/presentation? Special about Tx?
TDT+ (marker of pre T and pre B cells) CD10+ (PreB cells only) T cell will tend to present with mediastinal mass (inspiratory stridor/dysphagia) B-ALL tx: treat their B-rains and B-alls (need chemo that passes thru the BBB, and Testis Blood barrier)
54
Difference between SLL and CLL?
SLL is the same as CLL except that CLL has peripheral blood lymphocytosis or bone marrow involvement. (SLL=small lymphocytic LYMPHOMA, CLL is chronic lymphocytic leukEMIA) Both are found in 60+ yo. CD20+ 5+. Smudge Cells
55
Aplastic Anemia Myleofibrosis Myelodysplastic syndrome Myelophthisic anemia
Aplastic: Failure/destruction of myeloid SCs, usually dt offending agent/virus. PANCYTOPENIA with FATTY INFLITRATION (Dry bone tap). NO HSM Myelofibrosis: HSM\*\*\* dt chronicity (think of Aplastic progressing to this). Atypical megakaryocyte activation results in fibroblast activation=fibrosis Myelodysplastic=ineffective hemaotpoesis (DYSplastic NOT aplastic). Pancytopenia/or decrease in 1 cell type. Marrow shows disordered differentation Myelophthisic Anemia; Space occupying lesion of bone marrow (mets associated with fibrosis)
56
Difference between Leukemoid Rxn and CML?
Both will have increased WBC counts with left shift (more band cells). Leukemoid will have increased Leukocyte ALP ("these are functional WBCs") vs CML will have decreased Leukocyte ALP (non-functional cancerous type cells)
57
Translocations for what cancer and what gene is overexpressed: t(11;14) t(14;18) t(8;14) t(15;17); Tx? t(9;22) Tx? t(11;22)
1) Mantle (think of the 1's forming a mantle for 4 and D1) 2) Folicular Lymphoma (bcl-2), and DLBCL 3) Burkitt Lymphoma (c-myc) 4) Promyelocytic Leukemia (altered Retinoic Acid receptor that does not respond, thus the cell never gets the signal to differentate and stays as a blast), Auer Rods, ATRA (retinoic Acid) 5) Philadelphia chromo (bcr-abl fusion protein) tx with imatinib (SMALL MOLECULE (not antibody) tyrosine kinase inhibitor) 6) Ewing's Sarcoma (11+22=33)
58
Bilateral carpal tunnel with macroglossia in elderly male?
Multiple Myeloma (amyloid deposition in the median nerve and tongue)
59
DD btwn Waldenstrom's Macroglobinemia and Multiple Myeloma? What do you see on urinalysis with MM?
Both will have hypervisocity sxs and M spikes. However Waldenstrom's will NOT have lytic bone lesions. NOTHING on urinalysis, you see bence jones proteins on Urine Protein Electrophoresis
60
Old man presenting with easy fatiguabilty, constipation, bone pain and renal failure
Multiple Myeloma (anemia, hypercalcemia, axial bone pain from increased RANKL + IL1, Renal failure) Can have associated neurosxs from hyperviscosity syndrome
61
62
Paraneoplastic Cerebellar Degeneration associated with which antibodies?
Anti- Yo (ovary/breast) P/Q (Lung) Hu (Lung)
63
Methotrexate Inhibits what? Rescue? SEs? Antipyrimidine or purine?
Folic acid analog inhibiting DHFR Can recuse with leucovorin or Thymidine (increases the salvage pathway) Anti-pyrimidine
64
5-FU Inhibits what? Rescue? SEs? Antipyrimidine or purine?
Pyrimidine analog activated to 5F-dUMP. 5F-dUMP complexes with folic acid to inhibt thymidylate synthase. NOT reversible. Can tx an OD with Uridine
65
Cytarabine Inhibits what? Rescue? SEs? Antipyrimidine or purine?
Pyrimidine analog inhibiting DNA poly CYTarabine causes panCYTopenia No rescue
66
Azathioprine Inhibits what? Rescue? SEs? Antipyrimidine or purine?
Metabolized by HGPRT into an active form of 6-MP Anti-Purine de novo synth inhibitor Inactivated by Xanthine oxidase THUS ALLOPURINOL causes toxicity
67
Dactinomycin? MOA? SEs? Clinical Use?
Also know as Actinomycin D Intercalates DNA (**_D_**-act-**_IN_**-omycin=gets **_IN D_**NA) SEs: Myelosuprresion Used for Wilms tumor, Ewing sarcoma, rhabdommyosarcoma, CHILDHOOD TUMORS\*\*\* "ONION SKIN GROWTH OF BONE"
68
Anthracyclins Drug Names? MOA? SEs? Prevention of SEs? Clinical Use?
Doxorubicin (Adriamycin), Daunorubicin Free Radicals, Intercalates into DNA causing breaks and decreased replciation. SEs: CARDIOTOXICITY (dilated cardiomyopathy), Myelosuppression, alopecia. Dexrazoxane can be given to chelate iron and prevent cardiotox. Used for Solid tumors, leukemias and lymphomas
69
Bleomycin MOA? SEs? Clinical Use (know this--step 1 likes to ask)?
Induces free radical formation causing DNA strand breaks **_PULM FIBROSIS_**, skin changes mucositis; minimal myelosuppression Used for **_Testicular cancer (B-leo is for your B-alls)_**, hodgkins lymphoma
70
Cyclophosphamide MOA? **SEs?** Clinical Use? **Rescue?**
Covalently cross links at Guanines. "Makes DNA cyclic=cyclo-phosphamide" **HEMORRHAGIC CYSTISIS** **Mesna: thiol group binds toxic metabolites**
71
Nitrosoureas MOA? SEs? Clinical Use? Examples?
Carmustine, Lomustine, semustine, Streptozocin (-mustines: "Put NITRO in your MUSTang") Crosses BBB and crosslinks DNA (needs bioactivation) Used for Brain tumors; has CNS toxicity (convulsions/dizziness, ataxia)
72
Busulfan MOA? SEs? Clinical Use?
Cross-links DNA CML and bone marrow ablation before transplant. Thus SEs are severe myelosuppression; PULM FIBROSIS\*\*\*\*\*, hyperpigmentation
73
Vinca alkaloids 2 examples? MOA? SEs? Clinical Use? What phase do they inhibit?
Vin**_C_**ristine **_C_**NS toxicity Vin**_B**_lastine _**B_**one marrow suppression Inhibits microtubule by binding to the BETA tubulin unit M phase arrest Used for solid tumors, leukemias and lymphomas
74
Taxanes MOA? SEs? Clinical Use?
Microtubule HYPERSTABILIZER preventing mitotic spindle from breaking down in M phase thus no anaphase Used in ovarian and breast cancer
75
Platinum Compounds 2 Examples? MOA? SEs? Clinical Use? Rescue?
"-platins" Carboplatin, Cisplatin Cross-links DNA NEPHROTOXICITY and acoustic Nerve damage. Can prevent npehrotox with amifostine (free radical scavenger) Used in testicular bladder ovarian and lung cancers
76
Topoisomerase II inhibitors 2 examples? MOA? SEs? Clinical Use?
Etoposide, Teniposide ("-SIDES" inhibit Topo II) Myelosuppression, GI irritation and alopecia
77
Topoisomerase I inhibitors 2 examples? MOA? SEs? Clinical Use?
Irinotecan, Topotecan Coloncancer (irinotecan--2 forms of GI issues---secretory diarrhea followed by true GI tox). Ovarian and small cell lung cancers (topotecan) Myelosuprresion
78
Trastuzumab Tox?
Cardiotox ("HEARTceptin" for herceptin) "**_T**_rastuzumab for _**T_**itties which close to the heart"
79
Vemurafenib MOA, Clinical use?
Small Molecule inhibitor of B-raf kinase with V600E mutation
80
Bevacizumab MOA, SEs
be**_V**_acizumab anti-_**V_**egf Hemorrhage and imparied wound healing
81
Myelodisplastic and myeloproliferative disorders tend to progress to?
AML
82
Tumor Supressor mutations associate with which cancer? p16 DPC DCC
p16=melanoma DPC=Panc Cancer ("D-eleted in P-anc C-ancer) DCC=Colon Cancer ("D-eleted in C-olon C-ancer)
83
Oncogene mutations in the following KRAS HRAS NRAS C-MYC L-MYC N-MYC ERB2
KRAS: K-olon, panKreatic, lung HRAS: Bladder and kidney ("h for hematuria") NRAS: melanoma and hematologic malignancies (and follicular thyroid) C-MYC: burCits L-MYC: Lung (Small cell carcinoma) N-MYC: Neuroblastoma (which is a tumor of the ADRENALS) ERB2: Breast, Ovarian and Gastric
84
Testicular Cancer drugs?
EBC: Eradicate Ball Cancer Etoposide, Bleomycin, Cysplatin
85
Two drugs with Pulm Fibrosis---what are their mechanism of actions?
Bleomycin: Fragments DNA by inducing free radical damage Busulfan: Cross links DNA
86
87
Difference between Sirolimus vs Cyclosporin/Tacrolimus
Sirolimus binds mTOR and has minimal nephrotox Cyclo/Tacro inhibit IL-2 thru calcineurin and have hepatotox

Tom (30 decks)

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