Heme-Pharm Flashcards
1
Q
Deferoxamine
A
chelating drug used to irrigate the bowel after an iron overdose
2
Q
dihydrofolate reductase
A
enzyme that switches dietary folate to tetrahydrofolate (middle man) to active folate - once active folate can assist in DNA synthesis
3
Q
What do these drugs do?
Methotrexate, trimethoprim, pyrimethamine
A
target dihdyrofolate reductase inhibiting the action of the enzyme that converts folic acid to active form
4
Q
Apoetin alfa (epogen)
A
erythropoietin stimulating agent
3x a week
5
Q
Darbepoetin alfa (mircera)
A
erythropoietin stimulating agent
1x a week
6
Q
Epoetin beta (aranesp)
A
erythropoietin stimulating agent
every other week/monthly
don’t use on cancer patients due to increased risk of death
7
Q
3 iron salts
A
ferrous sulfate, ferrous fumarate, ferrous gluconate
8
Q
sodium ferric gluconate (ferrlecit)
Iron sucrose (venofer)
Iron dextran (infed)
ferumoxytol (feraheme)
what kind of drugs are these)
A
parenternal iron preparations
9
Q
Filgrastim (neupogen)
A
myeloid growth factor - granulocyte
administer daily due to 2-7 hr half life
10
Q
pegfilgrastim (neulasta)
A
myeloid growth factor - granulocyte
administer once per chemo cycle
11
Q
sagramostim (leukine)
A
myeloid growth factor - granulocyte macrophage
administer daily (1/2/ life 2-7 hrs)
12
Q
oprelvekin (recombinant IL-11 or Neumega)
A
megakaryocyte growth factor
administer daily half life 7-8 hrs
13
Q
antidote for nitrogen mustard
A
thiosulfate
14
Q
antidote for vinca alkaloids
A
hyaluronidase
15
Q
antidote for anthracyclines
A
dexrazoxane
16
Q
what is the active and inactive form of folic acid
A
active: folinic acid
inactive: folic acid
17
Q
folic acid
- mechanism of action
- pharmacokinetics
A
synthesis of purines/pyrimidines
oral, absorbed in jejunum
18
Q
B12
- mechanism of action
- pharmacokinetics
A
cofactor required for enzymatic rxns (succinyl co-A)
IM/SubQ or oral for maintenance
19
Q
iron salts (3)
- MOA
- Pharmacokinetics
A
attached “salt” helps iron absorption
- Ferrous sulfate, ferrous fumarate, ferrous gluconate
oral, absorbed in duodenum
20
Q
what do Erythropoietin stimulating agents do?
A
Raise erythroid proliferation/differentiation
Release of reticulocytes from bone marrow
Indications:
- Anemia secondary to chronic kidney dz
- Myeloid- suppressive cancer chemo (only give to improve QOL)
- Hgb below 10 mg (12 for those w/ kidney dz)
21
Q
Erythropoietin stimulating agents pharmacokinetics
A
IV/SC administration
22
Q
Granulocyte colony stimulating factor (G-CSF)- myeloid
- MOA
- pharmacokinetics
A
Pharmacokinetics: IV of SC administration
Mech of Action:
- Increase proliferation/differentiation of neutrophil progenitors
- Increase phagocytic activity of neutrophils
- Increase hematopoietic stem cell mobilization (make more myeloid)
23
Q
Granulocyte-macrophage colony stimulating factor (GM-CSF)- myeloid
- MOA
- pharmacokinetics
- why take it?
A
Pharmacokinetics: IV/SC (SC more common)
Mech of Action:
- Increase proliferation/differentiation of early/late granulocytic progenators
- Increase erythroid/megakaryocyte progenators
- Increase phagocytic activity of mature neutrophils
- Increase hematopoietic stem cell mobilization (less than G-CSF)
neutropenia, chemo induced myelosuppression
24
Q
Megakaryocyte growth factor
- pharmacokinetics
-MOA
- why take it?
A
Pharmacokinetics: SC daily
Mech of Action
- Increase growth in multiple myeloid and lymphoid cells
- Increase circulating platelets and neutrophils
Indications:
- Prevention of thrombocytopenia due to cytotoxic chemo for non-myeloid cancers
25
5-Fu pharmacokinetics
IV (adrucil)
topical (fluorplex)
26
5-fu MoA
inhibits thymidylate synthetase which feeds to folic acid cycle = no DNA synthesis
27
5-FU indications
breast tumors
colorectal tumors
non-invasive skin cancers (topical)
28
5-FU OD treat with?
uridine-triacetate (vistogard)
29
Mercaptopurine(purinethol) pharmacokinetics
- Oral
- Metabolized by xanthine oxidase
30
Mercaptopurine(purinethol) MoA
converted to ribonuceotide by HGPRT and acts as fake NT putting itself into DNA and making it nonfunctional
31
Mercaptopurine(purinethol) indications
- Acute lymphocytic leukemia (remission maintenance w/ methotrexate)
- Chronic myeloid leukemia
32
Mercaptopurine(purinethol) interacts with?
allopurinol - raises serum levels (xanthine oxidase inhibitor
33
Methotrexate pharmacokinetics
- Oral/parenteral
- Bioavailability dose dependent
- Wide distribution EXCEPT CNS
34
Methotrexate MoA
- Inhibits dihydrofolate reductase which feeds into folic acid cycle
- No pyrimidine synthesis
35
Methotrexate indications
- Breast cancer
36
Methotrexate adverse effects
- MYELOSUPPRESSION – rescue w/ leucovorin
37
Pemetrexed (alimta) pharmacokinetics
IV ONLY
38
Pemetrexed (alimta) MoA
inhibits thymidylate synthetase and dihydrofolate reductase to block DNA synthesis
39
Pemetrexed (alimta) indications
non-small cell lung cancer
- In combination w/ cistplatin (alkalating agent)
40
Pemetrexed (alimta) adverse effects
- MYELOSUPPRESSION
- ORAL ULCERATION
41
Vincristine (cincasar, marquibo) pharmacokinetics
IV administration (no CNS penetration)
- Vincasar: conventional
- Marquibo: liposomal
--encapsulated in liposomes which slows down the release and decreasing side effects/toxicity
42
Vincristine (cincasar, marquibo) MoA
- MT built and disassembled
- Blocks assembly of MT to cell division
- Disassembly process continues as normal but MT nonfucnitonal to divide into two cells
43
Vincristine (cincasar, marquibo) indications
- Acute lymphoblastic leukemia
- Non-hodgkin lymphoma
- Hodgkin lymphoma
44
Vincristine (cincasar, marquibo) adverse effects
neurotoxicity
45
Docetaxel (taxotere) pharmacokinetics
V administration
- Give dexamethasone as pre-treatment to avoid fluid retention and hypersensitivity rxns
46
Docetaxel (taxotere) MoA
MT block and unable to divide into 2 cells, decreases tumor
47
Docetaxel (taxotere) indication
metastatic prostate and breast cancer
48
Docetaxel (taxotere) adverse effects
- MYELOSUPPRESSION (neutropenia)
49
Cyclophosphamide (Cytoxan)- pharmacokinetics
- Oral and IV administration (90-95% bioavailability)
- Prodrug converted to phosphoramide (active)
- Acrolein formed as a byproduct (no therapeutic value, can cause side effects)
50
Cyclophosphamide (Cytoxan)- MoA
- Active metabolites form covalent bonds w/ N7 nitrogen of guanine
- Cross linking of DNA strands = no DNA replication/transcription
51
Cyclophosphamide (Cytoxan)- indication
- Non-hodgkin lymphoma
- Breast cancer
- Neuroblastoma (tumor on immature nerve cells)
52
Cyclophosphamide (Cytoxan)- adverse effects
- MYELOSUPPRESSION
53
Busulfan (myleran) pharmacokinetics
oral (low half life 2-2.5 hrs)
54
Busulfan (myleran) MoA
- Active metabolites form covalent bonds w/ N7 nitrogen of guanine
- Cross linking of DNA strands = no DNA replication/transcription
55
Busulfan (myleran) indications
acute myeloid leukemia, chronic myeloid leukemia
56
Busulfan (myleran) adverse effects
myelosuppression and pulmonary fibrosis (fatal)
Hyperpigmentation of skin creases
57
Cisplatin (platinol-aq) pharmacokinetics
: IV administration
58
Cisplatin (platinol-aq) MoA
INTRAstrand cross link
- Same strand of DNA becomes stuck together distorting/bending the shape and making it unfit to be unzipped
59
Cisplatin (platinol-aq) indications
ovarian cancer and lung cancer
60
Cisplatin (platinol-aq) adverse effects
severe n/v
61
temozolomide (temodar) pharmacokinetics
oral/IV
62
temozolomide (temodar) MoA
- alkylating agent adds a methyl group to guanine residues
- DNA damage and tumor cell death
63
temozolomide (temodar) indications
astrocytoma or glioblastoma – cross BBB
64
Doxorubicin (Adriamycin)- pharmacokinetics
IV (widely distributed to tissues except CNS)
65
Doxorubicin (Adriamycin)- MoA
- Inhibition of topoisomerase II (uncoiler)
- Formation of free radicals
- Drug jams itself between DNA leading to distortion and generation of hydroxyl radicals causing strands to break
66
Doxorubicin (Adriamycin)-indications
- Breast, lung, thyroid cancer
- Hodgkin and non-hodgkin lymphoma
67
Bleomycin (blenoxane) pharmacokinetics
IV
- Widely distributed to tissues except CNS
- Inactivated by aminohydrolase
68
Bleomycin (blenoxane) MoA
- Inhibition of topoisomerase II (uncoiler)
- Formation of free radicals
- Drug jams itself between DNA leading to distortion and generation of hydroxyl radicals causing strands to break
69
Bleomycin (blenoxane) indications
- Testicular cancer, head/neck cancer
70
Irinoteca (camptosar) – topoisomerase I inhibitor pharmacokinetics
IV administration
- Metabolite has greater antitumor activity than parent compound
71
Irinoteca (camptosar) – topoisomerase I inhibitor MoA
- Permanent single strand break due to blockage of topoisomerase I nick does not get sealed back
72
Irinoteca (camptosar) – topoisomerase I inhibitor indicators
colon cancer, solid tumors of cervix/lung
73
Irinoteca (camptosar) – topoisomerase I inhibitor adverse affects
diarrhea
74
Etoposide (toposar) – topoisomerase II inhibitor pharmacokinetics
oral or IV (oral 50% bioavailability)
75
Etoposide (toposar) – topoisomerase II inhibitor MoA
irreversible double stranded break
76
Etoposide (toposar) – topoisomerase II inhibitor indications
testicular cancer and small cell lung cancer
77
Etoposide (toposar) – topoisomerase II inhibitor adverse effects
- MYELOSUPPRESSION
78
Dasatinib (vuman) BCR-ABL inhibitors pharmacoknetics
oral
79
Dasatinib (vuman) BCR-ABL inhibitors MoA
- Acts on BCR/ABL kinase expressed on Philadelphia chromosome for chronic myeloid leukemia
- Oncoprotein results in transition swap in chromosomes leading to abnormal TK expression and hematopoietic stem cells
- See malignant cell proliferation and kinase is not able to inhibit nfkb so you dis-inhibited the apoptotic pathway
80
Dasatinib (vuman) BCR-ABL inhibitors indicators
chronic myeloid leukemia
81
Erlotinib (tarceva) pharmacokinetics
oral
- Need to test tumor cells whether they have the EGFR mutation before you can use the drug
82
Erlotinib (tarceva) moA
- Specific inhibition of epidermal growth factor receptor tyrosine kinase
--prevents GTPase activation of DNA synthesis and cell proliferation
83
Erlotinib (tarceva) indications
metastatic non-small cell lung cancer (second line)
84
Sunitinib (sutent) pharmacokinetics
oral
85
Sunitinib (sutent) indications
- Advanced renal cell carcinoma
- Gastrointestinal stromal tumor resistant to imatinib
86
Sunitinib (sutent) MoA
blocks angiogenesis
- Vascular endothelial growth factor binds to receptor
- When activated it increases vascular permeability promoting cell proliferation and migratin
- Angiogenesis forms new blood vessels – how tumors survive
- Blocking vascularization helps kill the tumor
87
Debrafinib (tafinlar) + trametinib (mekenist) pharmacodynamics
oral
88
Debrafinib (tafinlar) + trametinib (mekenist) MoA
- Dabrafenib Drug targets gene mutation braf and trametinib blocks signaling downstream of gene mutation mek
- Synergistically work together to inhibit cell proliferation
- Ras gene
89
Debrafinib (tafinlar) + trametinib (mekenist) indicators
inoperable and metastatic melanoma
90
Bortezomib (velcade) pharmacokinetics
subQ or IV
91
Bortezomib (velcade) MoA
- Inhibition of catalytic site of 26S protease prevents degradation of ubiquitinated proteins (protease is trash that disposes tagged things)
- Drug inhibits proteasome to save proteins that shouldn’t be killed
92
Bortezomib (velcade) indications
- Multiple myeloma
93
Alemtuzumab (lemtrada)pharmacokinetics
SC or IV
94
Alemtuzumab (lemtrada) MoA
- IgG w/ kappa chain binds CD52 on B/T cell (normal and malignant)
- Lymphocyte targets cell for lysis/apoptosis
- Recommended to people who don’t respond to at least 2 other MS medications
95
Alemtuzumab (lemtrada) indications
- B-cell chronic lymphocytic leukemia
- Relapsing MS
96
Bevacizumab(avastatin) pharmacokinetics
IV
97
Bevacizumab(avastatin) MoA
- IgG binds to VEGF (vascularized endothelial growth factor) in membrane
- Binds and signaling cascades are activated angiogenesis
- Tumor grows w/ blood supply
- W/ drug it binds to ligand circulating VEGF via lock and key mechanism
- VEGF receptor won’t be able to fit it and activate the pathway
- Angiogenesis is decreased
98
Bevacizumab(avastatin) indications
colorectal cancer and lung cancer
99
Cetuximab (erbutix) pharmacokinetics
IV
100
Cetuximab (erbutix) MoA
- Epidermal growth factor receptor (tyrosine kinase)
- EGF ligand binds to receptor and activate signal transduction
- MAPK activated increased proliferation, decreased apoptosis, promotion of invasion/metastasis/angiongenesis
- W/ drug ligand is prevented from interacting w. receptor so as a result you get opposite – no proliferation, apoptosis promoted, decrease in metastasis and angiogenesis
101
Cetuximab (erbutix) indications
metastatic colorectal cancer
102
Ipilimumab (yervoy) pharmacodynamics
IV
103
Ipilimumab (yervoy) MoA
- MCH presents peptide to TCR for activation
- Costimulator interacts and T cell is activated
- CTLA-4 functions to prevent autoimmune dz by suppressing T-cell activation (interacts w. second signal)
- Drug can bind to CTLA4 so it can’t interact w. costimulatory and T-cell can activate
104
Ipilimumab (yervoy) indications
metastatic melanoma and unresectable melanoma
105
Ipilimumab (yervoy) adverse effect
Colitis, neuropathy, hepatitis, pneumonitis, progressive multifocal leukoencephalopathy – severe/possibly fatal
106
Pembrolizumab (keytruda) pharmacokinetics
IV
107
Pembrolizumab (keytruda) MoA
- Tumor cell interacts w/ T-cell ag and is presented to T-cell receptor
- Costimulatory PD1 interacts with PDL1 (programmed death)
- Interaction causes inhibition of T-cell from killing tumor
- Drug interacting with PD1 on T-cell blocks it and ligand can’t interact/block T-cell from activating so now the T-cell can promote death
108
Pembrolizumab (keytruda) Indications
non-small cell lung cancer
109
Rituximab (rituxan)pharmacokinetics
IV administration
110
Rituximab (rituxan) MoA
- Malignant cancerous B-cell w/ CD20 leads to increase in cell death, drug binds to cd20 ag found on non-hodgkin lymphoma
- Started for apoptosis
111
Rituximab (rituxan) Indications
- Relapsed or refractory B-cell non Hodgkin lymphoma
- Chronic lymphoid leukemia
112
Trastuzumab (Herceptin) pharmacokinetics
IV
113
Trastuzumab (Herceptin) MoA
- Directed against human epidermal receptor 2 HER2 that dimerizes with a partner
- Activates signaling cascade leading to transcription/dysregulation of cell cycle
- Drug binds to HER2 and inhibits cellular pathways normally activated and pro-apoptotic pathways are instead stimulated
114
Trastuzumab (Herceptin) indications
metastatic breast cancer
115
Mycophenolate Mofetil (cellcerpt) pharmacokinetics
oral or IV
- Oral gets meatabolized to mycophenolic acid
116
Mycophenolate Mofetil (cellcerpt) MoA
- inhibition of ionsine monophosphate dehydrogenase to decrease synthesis of nucleic acids and suppress immune system
117
Mycophenolate Mofetil (cellcerpt) indications
- prevention of solid organ transplant rejection
- alternative to cyclosporine or tacrolimus
- graft vs host dz (prophylaxis and ex in hematopoietic stem cell transplant recipients)
- long term administration bc immunosuppressants for rest of life
118
Azathioprine pharmacokinetics
oral or IV
- prodrug converted to 6-mercaptopurine
119
Azathioprine MoA
- converted to NT by addition of a ribose phosphate
- inhibits DNA synthesis required for B/T cell proliferation
- trying to suppress immune system
120
Azathioprine indications
prevention of renal transplant rejection
121
Basiliximab (simulect) pharmacokinetics
IV administration
122
Basiliximab (simulect) MOA
- drug binds to and blocks IL-2 receptor
- CD25 on surface of T-lymphocyte acts as a receptor that it binds to
- When IL-2 is activated a cascade causes proliferation of T-cells and decreases apoptosis
- When inhibited proliferation is lowed and apoptosis is slowed suppressing the immune system – T-cells decrease
123
Basiliximab (simulect) indication
prevention of renal transplant rejection
124
Belatacept (nulojix) pharmacokinetics
IV administration
125
Belatacept (nulojix) MoA
- Recombinant fusion protein made in lab CTLA4 is fused to IgG
- MHC interacts w/ TCR and second stimulation CD80/86 interacts w/ CD28
- Drug blocks activation of T-cell by binding to CD80 on APC preventing the second signaling co-stimulation.
- Second signal is not received and T-cell does not activate
126
Belatacept (nulojix) indications
prevention of renal transplant rejection
- In combination w/ basiliximab and mycophenolate mofetil
127
Cyclosporine pharmacokinetics
oral, iv, or topical ocular administration (oral 20-50%)
128
Cyclosporine MoA
- CSA = cyclosporine
- CSA crosses onto T-cell and interacts with CpN
- When they bind inhibits CaN (calcinurin)
- Inhibition will block singanling that would lead to increased production of IL-2 (pro-inflammatory)
- IL-2 shut down and suppresses immune system
129
Cyclosporine indications
- Prevention of organ transplant rejection
- Idiopathic urticaria
- Psoriasis
130
Tacrolimus (profraf) pharmacokinetics
oral/IV or topical
131
Tacrolimus (profraf) MoA
- Fk506 is tacrolimus
- Leads to decrase in IL-2 like cyclosporine by inhibiting calcinurin
- Interacts with FKBP to inhibit CaN which inhibits IL-2 cascade
132
Tacrolimus (profraf) indications
- prevention of organ transplant rejection
- Atopic dermatitis
133
Sirolimus(rapamune) pharmacokinetics
ORAL ONLY half life of 60 hrs
134
Sirolimus(rapamune) MoA
- Proliferation signal inhibitor
- Activation of IL-2 normally leads to activation of MTOR to increase proliferation and division
- SRL crosses T-cell and interacts with FKBP like tacrolimus
- This inhibits MTOR
- Decrease in normal IL-2 driven process
135
Sirolimus(rapamune) indications
- Prevention of organ transplant rejection
- Graft vs host dz
136
Sirolimus(rapamune) adverse rxn
- Profound myelosuppression thrombocytopenia
- Hepatotoxicity
- Hypertriglyceridemia
Pneumonitis
