Hematology and Oncology Pharmacology Flashcards
(130 cards)
1
Q
heparin–mechanism
A
lowers the activity of thrombin and factor Xa
short half life
2
Q
heparin–use
A
immediate anticoagulation for pulmonary embolism (PE), acute coronary syndrome, MI, deep vein thrombosis (DVT),
used during pregnancy–does not cross placenta
follow PTT
3
Q
heparin–toxicity
A
bleeding
thrombocytopenia (HIT)
osteoporosis
drug-drug interactions
4
Q
heparin–antidote
A
use protamine sulfate–positively charged mc that binds negatively to heparin
5
Q
what are the advantages/disadvantages to using low molecular weight heparins?
A
low molecular weight heparins–enoxaparin, dalteparin
advantages:
act more on factor Xa
have better bioavailability
2-4 times longer half life
can be administered subcutaneously and w/o lab monitoring
disadvantage:
not easily reversible
6
Q
explain heparin induced thrombocytopenia (HIT)
A
development of IgG antibodies against heparin bound platelet factor 4 (PF4)
antibody heparin PF4 complex activates platelets –> thrombosis and thrombocytopenia
7
Q
name the direct thrombin inhibitor
A
bivalirudin–related to hirudin, the anticoagulant used by leeches
8
Q
direct thrombin inhibitor–mechanism
A
directly inhibits activity of free and clot-associated thrombin
9
Q
direct thrombin inhibitor–use
A
venous thromboembolism
atrial fibrillation
can be used in HIT
doe not require lab monitoring
10
Q
direct thrombin inhibitors–toxicity
A
bleeding
11
Q
antidote for direct thrombin inhibitors
A
no specific reversal agent
can attempt to use activated prothrombin complex concentrates (PCC) and/or fibrinolytics (eg. transexamic acid)
12
Q
warfarin–mechanism
A
interferes with gamma carboxylation of vitamin K dependent clotting factors II, VII, IX, X, and proteins C and S
metabolism affected by polymorphisms in the gene for vitamin K epoxide reductase complex (VKORCI)
in lab–effect on EXtrinsic pathway and inc PT, long half life
“the EX-President went to WAR(farin).”
13
Q
warfarin–use
A
chronic anticoagulation–venous thromboembolism prophylaxis and prevention of stroke in atrial fibrillation
follow PT/INR
14
Q
can warfarin be used in pregnant women? why?
A
no, b/c crosses placenta (unlike heparin)
15
Q
warfarin–toxicity
A
- bleeding
- teratogenic
- skin/tissue necrosis
- drug-drug interactions
- proteins C and S have shorter half lives than clotting factors II, VII, IX, X which results in early transient hypercoagulability with warfarin use
- skin/tissue necrosis within first few days of large doses believed to be due ot small vessel microthromboses
16
Q
antidote for warfarin
A
vitamin K
17
Q
how would you rapidly reverse warfarin?
A
fresh frozen plasma
18
Q
explain heparin “bridging”
A
- heparin frequently used when starting warfarin
- heparin’s activation of antithrombin enables anticoagulation during initial, transient hypercoagulable state caused by warfarin
- initial heparin therapy reduces risk of recurrent venous thromboembolism and skin/tissue necrosis
19
Q
compare and contrast heparin vs. warfarin
A
20
Q
name direct factor Xa inhibitors
A
ApiXaban
rivatoXaban
21
Q
direct factor Xa inhibitors–mechanism
A
bind to and directly inhibit factor Xa
22
Q
direct factor Xa inhibitors–use
A
- treatment and prophylaxis for DVT and PE (rivaroxaban)
- prophylaxis in patients with atrial fibrillation
- oral agents do not require coagulation monitoring
23
Q
direct factor Xa inhibitors–toxicity
A
bleeding–no reversal agent is available
24
Q
name the thrombolytics
A
Alteplase (tPA)
Reteplase (rPA)
streptokinase
tenecteplase (TNK-tPA)
25
thrombolytics--mechanism
* directly or indirectly aid conversion of plasminogen to plasmin, which cleaves thrombin and fibrin clots
* inc PT
* inc PTT
* no change in platelet count
26
thrombolytics--use
* early MI
* early ischemic stroke
* direct thrombolysis of severe PE
27
thrombolytics--toxicity
* bleeding
28
when are thrombolytics contraindicated?
* patients with:
* active bleeding
* history of intracranial bleeding
* recent surgery
* known bleeding diatheses
* severe hypertension
29
how to treat toxicity of thrombolytics
* aminocaproic acid, an inhibiotr or fibrinolysis
* can also use fresh frozen plasma and cryoprecipitate to correct factor deficiencies
30
name the ADP receptor inhibitors
clopidogrel
prasugrel
ticagrelor (reversible)
ticlopidine
31
ADP receptor inhibitors--mechanism
* inhibit platelet aggregation by irreversibly blocking ADP receptors
* prevent expression of glycoproteins IIb/IIIa on platelet surface
32
ADP receptor inhibitors--use
* acute coronary syndrome
* coronary stenting
* decrease incidence or recurrence of thrombotic stroke
33
ADP receptor inhibitors--toxicity
* neutropenia (ticlopidine)
* TTP may be seen
34
cilostazol, dipyridamole--mechanism
* phosphodiesterase III inhibitor
* inc cAMP in platelets
* results in inhibition of platelet aggregation
* vasodilators
35
cilostazol, dipyridamole--use
* intermittent claudication
* coronary vasdilation
* prevention of stroke or TIAs (combined with aspirin)
* angina prophylaxis
36
cilostazol, dipyridamole--toxicity
* nausea
* headache
* facial flushing
* hypotension
* abdominal pain
37
name the glycoprotein IIb/IIIa inhibitors
* abciximab
* eptifibatide
* tirofiban
38
glycoprotein IIb/IIIa inhibitors--mechanism
* bind to the glycoprotein receptor IIb/IIIa on activated platelets
* prevent aggregation
39
what is abciximab made from?
(glycoprotein IIb/IIIa inhibitors)
monoclonal antibody Fab fragments
40
glycoprotein IIb/IIIa inhibitors--use
* unstable angina
* percutaneous transluminal coronary angioplasty
41
glycoprotein IIb/IIIa inhibitors--toxicity
* bleeding
* thrombocytopenia
42
what are the anti-metabolite drugs?
* azathiprine and 6-mercaptopurine
* cladribine
* cytarabine
* 5-fluorouracil
* methotrexate
43
azathiprine, 6-mercaptopurine--mechanism
* purine analogs --\> dec de novo purine synthesis
* activated by HGPRT
* azathioprine is metabolized into 6-MP
44
azathiprine, 6-mercaptopurine--use
* prevent organ rejection
* rheumatoid arthritis
* IBD
SLE
* used to wean patients off steroids in chronic dz and to treat steroid refractory chronic disease
45
azathiprine, 6-mercaptopurine--toxicity
* myelosuppression
* GI
* liver
46
how are azathiprine and 6-mercaptopurine metabolized, and how does this affect toxicity?
* they are metabolized by xanthine oxidase
* so, they have inc toxicity with allopurinol or febuxostat
47
cladribine--mechanism
* purine analog
* multiple mechanisms--inhibition of DNA polymerase, DNA strand breaks
48
cladribine--use
* hairy cell leukemia
49
cladribine--toxicity
* myelosuppression
* nephrotoxicity
* neurotoxicity
50
cytarabine (arabinofuranosyl cytidine)--mechanism
* pyrimidine analog
* inhibition of DNA polymerase
51
cytarabine (arabinofuranosyl cytidine)--use
* leukemias (AML)
* lymphomase
52
cytarabine (arabinofuranosyl cytidine)--toxicity
* myelosuppression with megaloblastic anemia
* **CYT**arabine causes pan**CYT**openia
53
5-fluorouracil--mechanism
* pyrimidine analog bioactivated to 5-FdUMP--covalently complexes folic acid
* this complex inhibits thymidylate synthase --\> dec dTMP --\> dec DNA synthesis
54
5-fluorouracil--use
* colon cancer
* pancreatic cancer
* basal cell carcinoma (topical)
* effects enhanced with the addition of leucovorin
55
5-fluorouracil--toxicity
* myelosuppression
* worsened with addition of leucovorin (folinic acid)
56
methotrexate--mechanism
* folic acid analog--competitively inhibits dihydrofolate reductase --\> dec dTMP --\> dec DNA synthesis
57
methotrexate--use
* cancers:
* leukemias (ALL)
* lymphomas
* choriocarcinoma
* sarcomas
* non-neoplastic:
* ectopic pregnancy
* medical abortion (with misoprostol)
* rheumatoid arthritis
* psoriasis
* IBD
* vasculitis
58
methotrexate--toxicity
* myelosuppression
* reversible with leucovorin "rescue"
* hepatotoxicity
* mucositis (ie. mouth ulcers)
* pulmonary fibrosis
59
name the antitumor antibiotics
* bleomycin
* dantinomycin (antinomycin D)
* doxorubicin, daunorubicin
60
bleomycin--mechanism
induces free radical formation --\> breaks in DNA strands
61
bleomycin--use
* testicular cancer
* Hodgkin lymphoma
62
bleomycin--toxicity
* pulmonary fibrosis
* skin hyperpigmentation
* minimal myelosuppression
63
dactinomycin (actinomycin D)--mechanism
intercalates in DNA
64
dactinomycin (**ACT**inomycin D)--use
* Wilms tumor
* Ewing sarcoma
* rhabdomyosarcoma
* used for childhood tumors
* "children **ACT** out"
65
dactinomycin (actinomycin D)--toxicity
myelosuppression
66
doxorubicin, daunorubicin--mechanism
* generate free radicals
* intercalate in DNA --\> breaks in DNA --\> dec replication
67
doxorubicin, daunorubicin--use
* solid tumors
* leukemias
* lymphomas
68
doxorubicin, daunorubicin--toxicity
* cardiotoxicity (dilated cardiomyopathy)
* myelosuppression
* alopecia
69
what can be used to prevent cardiotoxicity that may result from using doxorubicin, daunorubicin?
dexrazoxane--iron chelating agent
70
name the alkylating agents
* busulfan
* cyclophosphamide, ifosfamide
* nitrosoureas
* carmustine
* lomustine
* semustine
* streptozocin
71
busulfan--mechanism
crosslinks DNA
72
busulfan--use
* CML
* also used to ablate patient's bone marrow before bone marrow transplantation
73
busulfan--toxicity
* severe myelosuppression--in almost all cases
* pulmonary fibrosis
* hyperpigmentation
74
cyclophosphamide, ifosfamide--mechanism
* cross link DNA at guanine N-7
* require bioactivation by the liver
75
cyclophosphamide, ifosfamide--use
* solid tumors
* leukemia
* lymphomas
76
cyclophosphamide, ifosfamide--toxicity
* myelosuppression
* hemorrhagic cystitis
77
how can you prevent hemorrhagic cystitis that may result from using cyclophosphamide, ifosfamide?
* prevented by using mesna (thiol group of mesna binds toxic metabolites) or N acetylcysteine
78
nitrosoureas--mechanism
* requires bioactivation
* cross blood brain barrier --\> CNS
* cross link DNA
79
nitrosoureas--use
brain tumors--including glioblastoma multiforme
80
nitrosoureas--toxicity
* CNS toxicity
* convulsions
* dizziness
* ataxia
81
name the microtubule inhibitors
* paclitaxel, other taxols
* vincristine, vinblastine
82
paclitaxel, other taxols--mechanism
* hyperstabilize polymerized microtubules in M phase so that mitotic spindle cannot break down
* anaphase cannot occur
83
paclitaxel, other taxols--use
* ovarian carcinomas
* breast carcinomas
84
paclitaxel, other taxols--toxicity
* myelosuppression
* neuropathy
* hypersensitivity
85
vincristine, vinblastine--mechanism
* vinca alkaloids that bind beta tubulin and inhibit its polymerization into microtubules --\> prevent mitotic spindle formation
* M phase arrest
86
vincristine, vinblastine--use
* solid tumors
* leukemias
* Hodgkin (vinblastine) lymphomas
* non Hodgkin (vincristine) lymphomas
87
vincristine, vinblastine--toxicity
* vincristine
* neurotoxicity--areflexia, peripheral neuritis
* consipation--including paralytic ileus
88
cisplatin, carboplatin--mechanism
cross link DNA
89
cisplatin, carboplatin--use
* testicular carcinomas
* bladder carcinomas
* ovary carcinomas
* lung carcinomas
90
cisplatin, carboplatin--toxicity
* nephrotoxicity
* peripheral neuropathy
* ototoxicity
91
how would you prevent nephrotoxicity that may result from use of cisplatin, carboplatin?
* use amifostine (free radical scavenger) and chloride (saline) diuresis
92
etoposide, teniposide--mechanism
e**TOPO**side inhibits **topo**isomerase II --\> inc DNA degradation
93
etoposide, teniposide--use
* solid tumors
* particularly testicular and small cell lung cancer
* leukemias
* lymphomas
94
etoposide, teniposide--toxicity
* myelosuppression
* alopecia
95
Irinotecan, topotecan--mechanism
* inhibits topoisomerase I
* prevents DNA unwinding and replication
96
Irinotecan, topotecan--use
* colon cancer (irinotecan)
* ovarian and small cell lung cancers (topotecan)
97
Irinotecan, topotecan--toxicity
* severe myelosuppression
* diarrhea
98
hydroxyurea--mechanism
inhibits ribonucleotide reductase --\> dec DNA **S**ynthesis (**S** phase specific)
99
hydroxyurea--use
* melanoma
* CML
* sickle cell disease (inc HbF)
100
hydroxyurea--toxicity
severe myelosuppression
101
prednisone, prednisolone--mechanism
* various
* bind intracytoplasmic steroid receptor
* alter gene transcription
102
prednisone, prednisolone--use
* most commonly used as glucocorticoids in cancer chemotherapy
* used in CLL, non Hodgkin lymphomas
* part of combination chemotherapy regimen
* used as immunosuppressants
* ie. in autoimmune diseases
103
prednisone, prednisolone--toxicity
* cushing like symptoms
* weight gain
* central obesity
* muscle breakdown
* cataracts
* acne
* osteoporosis
* HTN
* peptic ulcers
* hyperglycemia
* psychosis
104
bevacizumab--mechanism
* monoclonal antibody against VEGF
* inhibits angiogenesis
105
bevacizumab--use
* solid tumors
* colorectal cancer
* renal cell carcinoma
106
bevacizumab--toxicity
* hemorrhage
* blood clots
* impaired wound healing
107
erlotinib--mechanism
* EGFR tyrosine kinase inhibitor
108
erlotinib--use
* non small cell lung carcinoma
109
erlotinib--toxicity
* rash
110
cetuximab--mechanism
* monoclonal antibody against EGFR
111
cetuximab--use
* stage IV colorectal cancer--wild type KRAS
* head and neck cancer
112
cetuximab--toxicity
* rash
* elevated LFTs
* diarrhea
113
imatinib--mechanism
* tyrosine kinase inhibitor of BCR-ABL
* Philadelphia chromosome fusion gene in CML
* c-kit
* common in GI stromal tumors
114
imatinib--use
* CML
* GI stromal tumors
115
imatinib--toxicity
* fluid retention
116
rituximab--mechanism
* monoclonal antibody against CD20
* found on most B cell neoplasms
117
rituximab--use
* non Hodgkin lymphoma
* CLL
* ITP
* rheumatoid arthritis
118
rituximab--toxicity
* inc risk of progressive multifocal leukoencephalopathy
119
tamoxifen, raloxifene--mechanism
* selective estrogen receptor modulators (SERMs)
* receptor antagonists in breast
* receptor agonists in bone
* block the binding of estrogen in ER + cells
120
tamoxifen, raloxifene--use
* breast cancer treatment (tamoxifen only) and prevention
* raloxidene also used to prevent osteoporosis
121
tamoxifen, raloxifene--toxicity
* both drugs increase risk of thromboembolic events (ie. DVT, PE)
122
tamoxifen--toxicity
* partial agonist in endometrium
* inc the risk of endometrial cancer
* causes hot flashes
123
raloxifene--toxicity
* no in in endometrial carcinoma b/c it is an estrogen receptor antagonist in endometrial tissue
124
trastuzumab (herceptin)--mechanism
* monoclonal antibody against HER-2 (c-erbB2)--a tyrosine kinase receptor
* helps kill cancer cells that overexpress HER-2 through inhibition of HER2-initiated cellular signaling and antibody dependent cytotoxicity
125
trastuzumab (herceptin)--use
HER-**2** + breast cancer and gastric cancer
(trans**2**zumab)
126
trastuzumab (herceptin)--toxicity
* cardiotoxicity
* **HEART**ceptin damages the **heart**
127
vemurafenib--mechanism
* small molecule inhibitor of BRAF oncogene + melanoma
* **VEmuRAF-enib** is for **V**600**E**-**mu**tated B**RAF** **inhib**ition
128
vemurafenib--use
* metastatic melanoma
129
know the common chemotoxicities of the following:
1. **C**isplatin/**C**arboplatin
2. **V**incristine
3. **B**leomycin, **B**usulfan
4. **D**oxorubicin
5. **T**rastuzumab
6. **C**isplatin/**C**arboplatin
7. **CY**clophosphamide
8. **5**-FU
9. **6**-MP
10. **M**ethotrexate
1. **C**isplatin/**C**arboplatin --\> ototoxicity (and nephrotoxicity)
2. **V**incristine --\> peripheral neuropathy
3. **B**leomycin, **B**usulfan --\> pulmonary fibrosis
4. **D**oxorubicin --\> cardiotoxicity
5. **T**rastuzumab --\> cardiotoxicity
6. **C**isplatin/**C**arboplatin --\> nephrotoxic (and acoustic nerve damage)
7. **CY**clophosphamide --\> hemorrhage cystitis
8. **5**-FU --\> myelosuppression
9. **6**-MP --\> myelosuppression
10. **M**ethotrexate --\> myelosuppression
130
