Heme-Onc Drugs Flashcards
1
Q
A
2
Q
Heparin mechanism
A
cofactor for the activation of antithrombin leading to decreased thrombin and factor Xa
3
Q
Use of Heparin
A
immediate anticoagulation for PE, acute coronary syndrome, MI, DVT **Follow PTT
4
Q
Heparin can be used during pregnancy bc…
A
it does not cross the placenta. Warfarin cannot be used in pregnancy.
5
Q
Toxicity of Heparin
A
-bleeding -HIT -osteoporosis
6
Q
For rapid reversal of Heparin, use…
A
protamine sulfate (which is a positively charged molecule that binds negatively charged heparin).
7
Q
Low-molecular weight heparins (2)
A
- Enoxaparin 2. Dalteparin
8
Q
Low-molecular weight heparins act more on…
A
factor Xa, have better bioavailablity and 2-4x longer half life.
9
Q
Heparin Induced Thrombocytopenia (HIT)
A
-development of IgG antibodies agaisnt heparin bound to platelet factor 4 (PF4) -Ab-heparin-PF4 complex activates platelets leading to thrombosis and thrombocytopenia
10
Q
Argatroban, Bivalirudin MOA
A
Inhibit thrombin directly
11
Q
Argatroban and Bivalirudin are used…
A
instead of heparin for anticoagulating pts with HIT.
12
Q
Warfarin MOA
A
-interferes with normal synthesis and gamma-carboxylation of vitamin-K dependent clotting factors II, VII, IX and X and proteins C and S
13
Q
Warfarin is metabolized by…
A
the CYP450s.
14
Q
In lab assays, Warfarin has an effect on the…
A
extrinsic pathways and increases PT.
15
Q
Use of Warfarin
A
-chronic anticoagulation (after STEMI, venous thromboembolism prophylaxis, stroke prevention) **Follow PT/INR values.
16
Q
Toxicity of Warfarin
A
-bleeding -teratogenic -skin/tissue necrosis
17
Q
For reversal of warfarin overdose
A
-give vitamin K -if rapid reversal is necessary, give FFP
18
Q
Apixaban and Rivaroxaban MOA
A
bind and directly inhibit activity of factor Xa
19
Q
Use of Apixaban and Rivaroxaban
A
-treatment and prophylaxis of DVT and PE (rivaroxaban) -stroke prophylaxis
20
Q
Thrombolytics (3)
A
- Alteplase (tPA) 2. Reteplase (rPA) 3. Tenecteplase (TNK-tPA)
21
Q
MOA of thrombolytics (tPA, etc)
A
directly or indirectly aid conversion of plasminogen to plasmin, which cleaves thrombin and fibrin clots -increases PT and PTT
22
Q
Use of thrombolytics
A
-MI -ischemic stroke -directy thrombolysis of severe PE
23
Q
Thrombolytics are contraindicated in…
A
pts with active bleeding, hx of intracranial bleed, recent surgery, known bleeding diathesis or HTN.
24
Q
Treat thrombolytic toxicity with…
A
aminocaproic acid (inhibitor of fibrinolysis).
25
Aspirin MOA
irreversibly inhibits COX1 and COX2 by covalent acetylation; platelets cannot synthesize new enzyme so the effects last until new platelets are produced
26
Aspirin effects
-increased bleeding time -decreased TXA2 and prostaglandins -no effect on PT or PTT
27
Use of Aspirin
-antipyretic -analgesic -anti-inflammatory -antiplatelet (decreased aggregation)
28
Toxicity of aspirin
-gastric ulceration -tinnitus -reye syndrome in children with viral infxn
29
Chronic use of aspirin can lead to...
acute renal failure, interstitial nephritis and upper GI bleeding.
30
Overdose of aspirin causes....
respiratory alkalosis initially which is then superimposed by metabolic acidosis.
31
ADP receptor inhibitors (4)
1. Clopidogrel 2. Ticlopidine 3. Prasugrel 4. Ticagrelor
32
MOA of ADP recpetor inhibitors
inhibit platelet aggregation by irreversibly blocking ADP receptors; inhibit fibrinogen binding by preventing glycoprotein IIb/IIIa binding
33
Use of ADP receptor inhibitors
-acute coronary syndrome -coronary stenting (decreased risk of thrombotic stroke)
34
Toxicity of ADP receptor inhibitors
-Neutropenia (Ticlopidine) -may see TTP/HUS
35
Cilostazol and Dipyridamole MOA
phosphodiesterase III inhibitors leading to increased cAMP in platelets, thus inhibiting platelet aggregation vasodilators
36
Use of Cilostazol and Dipyridamole
-intermittent claduication -coronary vasodilation -prevention of stroke/TIA/angina
37
GP IIb/IIIa inhibitors (3)
Abciximab Eptifibatide Tirofiban
38
GpIIb/IIIa inhibitor MOA
bind to the glycoprotein receptor IIb/IIIa on activated platelets, inhibiting aggregation
39
Abciximab is made from...
monoclonal antibody Fab fragments.
40
Use of GP IIb/IIIa inhibitors
-unstable angina -percutaneous transluminal coronary angioplasty
41
Antimetabolites (6)
1. Metotrexate 2. 5-Fluorouracil 3. Cytarabine 4. Azathioprine 5. 6-Mercaptopurine 6. 6-Thioguanine \*all are S-phase specific
42
Methotrexate MOA
folic acid analog that inhibits dihydrofolate reductase leading to decreased dTMP, DNA and protein synthesis.
43
Cancer uses of methotrexate
-leukemias/lymphomas -choriocarcinoma -sarcomas
44
Non-neoplastic uses of methotrexate
-abortion/ectopic pregnancy -RA -psoriasis -IBD
45
Toxicity of Methotrexate
-Myelosuppression -Macrovesicular fatty change in liver -mucositis -teratogenic
46
Myelosuppression from methotrexate is reversible with...
leucovorin.
47
5-FU MOA
pyrimidine analog bioactivated to 5F-dUMP which covalently complexes folic acid; this complex inhibits thymidylate synthase leading to decreased dTMP, DNA and protein synthesis
48
Clinical uses of 5-FU
-colon cancer -pancreatic cancer -basal cell carcinoma
49
Toxicity of 5-FU
-myelosuppression (not reversible w/ leucovorin; use uridine) -photosensitivity
50
Cytarabine MOA
-pyrimidine analog leading to inhibition of DNA polymerase
51
Clinical use of Cytarabine
-leukemias -lymphomas
52
Cytarabine toxicity
Pancytopenia (thrombocytopenia, leukopenia, megaloblastic anemia)
53
Azathioprine, 6-MP and 6-TG MOA
purine analogs that decrease de novo synthesis of purines; activated by HGPRT
54
Clinical uses of azathioprine, 6-MP and 6-TG
-preventing organ rejection -RA -SLE (azathioprine) -Leukemia/IBD (6-MP, 6-TG)
55
Toxicity of Azathioprine, 6-MP and 6-TG
-bone marrow, GI and liver
56
Azathioprine and 6-MP are metabolized by...
xanthine oxidase and thus both have increased toxicity with allopurinol.
57
Antitumor antibiotics (3)
1. Dactinomycin 2. Doxorubicin, Daunorubicin 3. Bleomycin
58
Dactinomycin MOA
intercalates in DNA
59
Use of Dactinomycin
-Wilms tumor -Ewing sarcoma -Rhabdomyosarcoma
60
Toxicity of Dactinomycin
myelosuppression
61
Doxorubicin, Daunorubicin MOA
generate free radicals; intercalate DNA decreasing replication
62
Clinical use of Doxorubicin
solid tumors lymphomas/leukemias
63
Toxciity of Doxorubicin
-Cardiotoxicity (DCM) -myelosuppression -alopecia
64
When giving Doxorubicin, cardiotoxicity can be prevented with...
Dexrazoxane.
65
Bleomycin MOA
induces free radical formation which causes breaks in DNA
66
Uses of Bleomycin
-testicular cancer -Hodgkin lymphoma
67
Toxicity of Bleomycin
-pulmonary fibrosis -skin changes -mucositis
68
Alkylating Agents
1. Cyclophosphamide, Ifosfamide 2. Nitrosoureas (Carmustine, Lomustine, Semustine, Streptozocin) 3. Busulfan
69
Cyclophosphamide and Ifosfamide MOA
covalently X-link (interstrand) DNA at guanine N-7; requires activation by liver
70
Clinical uses of cyclophosphamide/Ifosfamide
-solid tumors -leukemia/lymphomas -some brain tumors
71
Toxicity of Cyclophosphamide/Ifosfamide
-myelosuppression -hemorrhagic cystitis
72
Hemorrhagic cystitis from cyclophosphamide and Ifosfamide can be partiall prevented with...
mensa which binds toxic metabolites.
73
Nitrosureas (carmustine, lomustine, semustine, streptozocin) MOA
cross BBB and cross-links DNA; requires activation
74
Use of Nitrosurease (carmustine, lomustine, semustine, streptozocin)
brain tumors (including glioblastoma multiforme)
75
Toxicity of Nitrosureas
CNS toxicity
76
Busulfan MOA
cross-links DNA
77
Clinical use of Busulfan
CML -and to ablate pts bone marrow before BMT
78
Toxicity of Busulfan
-severe myelosuppression -pulmonary fibrosis -hyperpigmentation
79
Microtubule Inhibitors
1. Vincristine/Vinblastine 2. Paclitaxel (-taxols)
80
MOA of Vincristine/Vinblastine
vinca alkaloids that bind beta-tubulin and inhibits its polymerization into microtubules, thereby preventing mitotic spindle formation (m-phase arrest)
81
Clinical use of Vincristine/Vinblastine
-solid tumors -leukemias/lymphomas
82
Toxicity of Vincristine/Vinblastine
-myelosuppression (vinblastine) -neuotoxicty, pralytic ileus (vincristine)
83
Paclitaxel MOA
hyperstabilizes polymerized microtubules in M-phase so that mitotic spindle cannot break down preventing anaphase
84
Use of Paclitaxel
-ovarian cancer -breast cancer
85
Toxicity of Paclitaxel
-myelosuppression -alopecia -hypersensitivity
86
Cisplatin and Carboplatin MOA
cross-link DNA
87
Cisplatin and Carboplatin Use
testicular, bladder, ovary and lung carcinomas
88
Cisplatin and Carboplatin toxicity
-nephrotoxicity -acoustic nerve damage
89
Nephrotoxicity from cisplatin and carboplatin can be prevented with...
amifostine and chloride diuresis.
90
Etoposide and Teniposide MOA
inhibits topoisomerase II leading to increased DNA degradation
91
Clinical use of Etoposide and Teniposide
-solid tumors (esp. testicular, small cell lung) -leukemias/lymphomas
92
Toxicity of Etoposide/Teniposide
-myelosuppression -GI irritation -alopecia
93
Irinotecan and Topotecan MOA
inhibit topoisomerase I and prevent DNA unwinding and replication
94
Use of Irinotecan and Topotecan
-colon cancer (irinotecan) -ovarian and small cell lung (topotecan)
95
Toxicity of Irinotecan and Topotecan
-severe myelosuppression -diarrhea
96
Hydroxyurea MOA
inhibits ribonucleotide reductase leading to decreased DNA synthesis
97
Use of Hydroxyurea
-melanoma -CML -sickle cell
98
Toxicity of Hydroxyurea
-myelosuppression -GI upset
99
MOA of Prednisone and Prednisolone
may trigger apoptosis
100
Use of Prednisone and Prednisolone
-most commonly used glucocorticoids in cancer chemo -used in CLL, non-Hodgkins -also as immunosuppressants
101
Toxicity of Prenisone and Prednisolone
-Cushing-like symptoms
102
Tamoxifen and Raloxifene MOA
selective estrogen reuptake modulators (SERMs) - receptor antagonists in breast and agonists in bone
103
Use of tamoxifen and raloxifene
-breast cancer treatment (tamoxifen) -osteoporosis prevention (raloxifene)
104
Tamoxifen toxicity
partial agonist in endometrium which increases risk of endometrial cancer
105
Trastuzumab MOA
monoclonal Ab against HER-2, a tyrosine kinase receptor; helps kill breast cancer cells through inhibition of HER2 cellular signaling and Ab-dependent cytotoxicity
106
Use of Trastuzumab
HER2 + breast and gastric cancer
107
Toxicity of Trastuzumab
Cardiotoxicity
108
Imatinib MOA
tyrosine kinase inhibitor of bcr-abl and c-Kit
109
Imatinib Use
-CML (bcr-abl) -GI stromal tumors (c-Kit)
110
Imatinib toxicity
fluid retention
111
Rituximab MOA
monoclonal antibody agaisnt CD20 which is found on most B-cell neoplasms
112
Use of Rituximab
-Non-hodgkins -RA -ITP
113
Toxicity of Rituximab
-incrneased risk of progressive multifocal leukoencephalopathy
114
Vemurafenib MOA
inhibitor of forms of B-Raf kinase with V600E mutation
115
Use of Vemurafenib
metastatic melanoma
116
Bevacizumab MOA
monoclonal Ab against VEGF; inhibits angiogenesis
117
Use of Bevacizumab
solid tumors (colorectal, RCC)
118
Toxicity of Bevacizumab
-hemorrhage -impaired wound healing
