Heme-Pharm Flashcards
Deferoxamine
chelating drug used to irrigate the bowel after an iron overdose
dihydrofolate reductase
enzyme that switches dietary folate to tetrahydrofolate (middle man) to active folate - once active folate can assist in DNA synthesis
What do these drugs do?
Methotrexate, trimethoprim, pyrimethamine
target dihdyrofolate reductase inhibiting the action of the enzyme that converts folic acid to active form
Apoetin alfa (epogen)
erythropoietin stimulating agent
3x a week
Darbepoetin alfa (mircera)
erythropoietin stimulating agent
1x a week
Epoetin beta (aranesp)
erythropoietin stimulating agent
every other week/monthly
don’t use on cancer patients due to increased risk of death
3 iron salts
ferrous sulfate, ferrous fumarate, ferrous gluconate
sodium ferric gluconate (ferrlecit)
Iron sucrose (venofer)
Iron dextran (infed)
ferumoxytol (feraheme)
what kind of drugs are these)
parenternal iron preparations
Filgrastim (neupogen)
myeloid growth factor - granulocyte
administer daily due to 2-7 hr half life
pegfilgrastim (neulasta)
myeloid growth factor - granulocyte
administer once per chemo cycle
sagramostim (leukine)
myeloid growth factor - granulocyte macrophage
administer daily (1/2/ life 2-7 hrs)
oprelvekin (recombinant IL-11 or Neumega)
megakaryocyte growth factor
administer daily half life 7-8 hrs
antidote for nitrogen mustard
thiosulfate
antidote for vinca alkaloids
hyaluronidase
antidote for anthracyclines
dexrazoxane
what is the active and inactive form of folic acid
active: folinic acid
inactive: folic acid
folic acid
- mechanism of action
- pharmacokinetics
synthesis of purines/pyrimidines
oral, absorbed in jejunum
B12
- mechanism of action
- pharmacokinetics
cofactor required for enzymatic rxns (succinyl co-A)
IM/SubQ or oral for maintenance
iron salts (3)
- MOA
- Pharmacokinetics
attached “salt” helps iron absorption
- Ferrous sulfate, ferrous fumarate, ferrous gluconate
oral, absorbed in duodenum
what do Erythropoietin stimulating agents do?
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)
Erythropoietin stimulating agents pharmacokinetics
IV/SC administration
Granulocyte colony stimulating factor (G-CSF)- myeloid
- MOA
- pharmacokinetics
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)
Granulocyte-macrophage colony stimulating factor (GM-CSF)- myeloid
- MOA
- pharmacokinetics
- why take it?
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
Megakaryocyte growth factor
- pharmacokinetics
-MOA
- why take it?
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
5-Fu pharmacokinetics
IV (adrucil)
topical (fluorplex)
5-fu MoA
inhibits thymidylate synthetase which feeds to folic acid cycle = no DNA synthesis
5-FU indications
breast tumors
colorectal tumors
non-invasive skin cancers (topical)
5-FU OD treat with?
uridine-triacetate (vistogard)
Mercaptopurine(purinethol) pharmacokinetics
- Oral
- Metabolized by xanthine oxidase
Mercaptopurine(purinethol) MoA
converted to ribonuceotide by HGPRT and acts as fake NT putting itself into DNA and making it nonfunctional
Mercaptopurine(purinethol) indications
- Acute lymphocytic leukemia (remission maintenance w/ methotrexate)
- Chronic myeloid leukemia
Mercaptopurine(purinethol) interacts with?
allopurinol - raises serum levels (xanthine oxidase inhibitor
Methotrexate pharmacokinetics
- Oral/parenteral
- Bioavailability dose dependent
- Wide distribution EXCEPT CNS
Methotrexate MoA
- Inhibits dihydrofolate reductase which feeds into folic acid cycle
- No pyrimidine synthesis
Methotrexate indications
- Breast cancer
Methotrexate adverse effects
- MYELOSUPPRESSION – rescue w/ leucovorin
Pemetrexed (alimta) pharmacokinetics
IV ONLY
Pemetrexed (alimta) MoA
inhibits thymidylate synthetase and dihydrofolate reductase to block DNA synthesis
Pemetrexed (alimta) indications
non-small cell lung cancer
- In combination w/ cistplatin (alkalating agent)
Pemetrexed (alimta) adverse effects
- MYELOSUPPRESSION
- ORAL ULCERATION
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
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
Vincristine (cincasar, marquibo) indications
- Acute lymphoblastic leukemia
- Non-hodgkin lymphoma
- Hodgkin lymphoma
Vincristine (cincasar, marquibo) adverse effects
neurotoxicity
Docetaxel (taxotere) pharmacokinetics
V administration
- Give dexamethasone as pre-treatment to avoid fluid retention and hypersensitivity rxns
Docetaxel (taxotere) MoA
MT block and unable to divide into 2 cells, decreases tumor
Docetaxel (taxotere) indication
metastatic prostate and breast cancer
Docetaxel (taxotere) adverse effects
- MYELOSUPPRESSION (neutropenia)
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)
Cyclophosphamide (Cytoxan)- MoA
- Active metabolites form covalent bonds w/ N7 nitrogen of guanine
- Cross linking of DNA strands = no DNA replication/transcription
Cyclophosphamide (Cytoxan)- indication
- Non-hodgkin lymphoma
- Breast cancer
- Neuroblastoma (tumor on immature nerve cells)
Cyclophosphamide (Cytoxan)- adverse effects
- MYELOSUPPRESSION
Busulfan (myleran) pharmacokinetics
oral (low half life 2-2.5 hrs)
Busulfan (myleran) MoA
- Active metabolites form covalent bonds w/ N7 nitrogen of guanine
- Cross linking of DNA strands = no DNA replication/transcription
Busulfan (myleran) indications
acute myeloid leukemia, chronic myeloid leukemia
Busulfan (myleran) adverse effects
myelosuppression and pulmonary fibrosis (fatal)
Hyperpigmentation of skin creases
Cisplatin (platinol-aq) pharmacokinetics
: IV administration
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
Cisplatin (platinol-aq) indications
ovarian cancer and lung cancer
Cisplatin (platinol-aq) adverse effects
severe n/v
temozolomide (temodar) pharmacokinetics
oral/IV
temozolomide (temodar) MoA
- alkylating agent adds a methyl group to guanine residues
- DNA damage and tumor cell death
temozolomide (temodar) indications
astrocytoma or glioblastoma – cross BBB
Doxorubicin (Adriamycin)- pharmacokinetics
IV (widely distributed to tissues except CNS)
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
Doxorubicin (Adriamycin)-indications
- Breast, lung, thyroid cancer
- Hodgkin and non-hodgkin lymphoma
Bleomycin (blenoxane) pharmacokinetics
IV
- Widely distributed to tissues except CNS
- Inactivated by aminohydrolase
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
Bleomycin (blenoxane) indications
- Testicular cancer, head/neck cancer
Irinoteca (camptosar) – topoisomerase I inhibitor pharmacokinetics
IV administration
- Metabolite has greater antitumor activity than parent compound
Irinoteca (camptosar) – topoisomerase I inhibitor MoA
- Permanent single strand break due to blockage of topoisomerase I nick does not get sealed back
Irinoteca (camptosar) – topoisomerase I inhibitor indicators
colon cancer, solid tumors of cervix/lung
Irinoteca (camptosar) – topoisomerase I inhibitor adverse affects
diarrhea
Etoposide (toposar) – topoisomerase II inhibitor pharmacokinetics
oral or IV (oral 50% bioavailability)
Etoposide (toposar) – topoisomerase II inhibitor MoA
irreversible double stranded break
Etoposide (toposar) – topoisomerase II inhibitor indications
testicular cancer and small cell lung cancer
Etoposide (toposar) – topoisomerase II inhibitor adverse effects
- MYELOSUPPRESSION
Dasatinib (vuman) BCR-ABL inhibitors pharmacoknetics
oral
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
Dasatinib (vuman) BCR-ABL inhibitors indicators
chronic myeloid leukemia
Erlotinib (tarceva) pharmacokinetics
oral
- Need to test tumor cells whether they have the EGFR mutation before you can use the drug
Erlotinib (tarceva) moA
- Specific inhibition of epidermal growth factor receptor tyrosine kinase
–prevents GTPase activation of DNA synthesis and cell proliferation
Erlotinib (tarceva) indications
metastatic non-small cell lung cancer (second line)
Sunitinib (sutent) pharmacokinetics
oral
Sunitinib (sutent) indications
- Advanced renal cell carcinoma
- Gastrointestinal stromal tumor resistant to imatinib
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
Debrafinib (tafinlar) + trametinib (mekenist) pharmacodynamics
oral
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
Debrafinib (tafinlar) + trametinib (mekenist) indicators
inoperable and metastatic melanoma
Bortezomib (velcade) pharmacokinetics
subQ or IV
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
Bortezomib (velcade) indications
- Multiple myeloma
Alemtuzumab (lemtrada)pharmacokinetics
SC or IV
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
Alemtuzumab (lemtrada) indications
- B-cell chronic lymphocytic leukemia
- Relapsing MS
Bevacizumab(avastatin) pharmacokinetics
IV
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
Bevacizumab(avastatin) indications
colorectal cancer and lung cancer
Cetuximab (erbutix) pharmacokinetics
IV
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
Cetuximab (erbutix) indications
metastatic colorectal cancer
Ipilimumab (yervoy) pharmacodynamics
IV
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
Ipilimumab (yervoy) indications
metastatic melanoma and unresectable melanoma
Ipilimumab (yervoy) adverse effect
Colitis, neuropathy, hepatitis, pneumonitis, progressive multifocal leukoencephalopathy – severe/possibly fatal
Pembrolizumab (keytruda) pharmacokinetics
IV
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
Pembrolizumab (keytruda) Indications
non-small cell lung cancer
Rituximab (rituxan)pharmacokinetics
IV administration
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
Rituximab (rituxan) Indications
- Relapsed or refractory B-cell non Hodgkin lymphoma
- Chronic lymphoid leukemia
Trastuzumab (Herceptin) pharmacokinetics
IV
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
Trastuzumab (Herceptin) indications
metastatic breast cancer
Mycophenolate Mofetil (cellcerpt) pharmacokinetics
oral or IV
- Oral gets meatabolized to mycophenolic acid
Mycophenolate Mofetil (cellcerpt) MoA
- inhibition of ionsine monophosphate dehydrogenase to decrease synthesis of nucleic acids and suppress immune system
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
Azathioprine pharmacokinetics
oral or IV
- prodrug converted to 6-mercaptopurine
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
Azathioprine indications
prevention of renal transplant rejection
Basiliximab (simulect) pharmacokinetics
IV administration
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
Basiliximab (simulect) indication
prevention of renal transplant rejection
Belatacept (nulojix) pharmacokinetics
IV administration
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
Belatacept (nulojix) indications
prevention of renal transplant rejection
- In combination w/ basiliximab and mycophenolate mofetil
Cyclosporine pharmacokinetics
oral, iv, or topical ocular administration (oral 20-50%)
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
Cyclosporine indications
- Prevention of organ transplant rejection
- Idiopathic urticaria
- Psoriasis
Tacrolimus (profraf) pharmacokinetics
oral/IV or topical
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
Tacrolimus (profraf) indications
- prevention of organ transplant rejection
- Atopic dermatitis
Sirolimus(rapamune) pharmacokinetics
ORAL ONLY half life of 60 hrs
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
Sirolimus(rapamune) indications
- Prevention of organ transplant rejection
- Graft vs host dz
Sirolimus(rapamune) adverse rxn
- Profound myelosuppression thrombocytopenia
- Hepatotoxicity
- Hypertriglyceridemia
Pneumonitis
