Chemotherapy drugs Flashcards
(96 cards)
1
Q
alkylating agents
A
form covalent adducts with DNA bases resulting in tumor cell death
- bischloroethyl amines (nitrogen mustards)
- nitrosoureas
- Mechlorethamine
- can be bifunctional or monofunctional
- can mutagenic (secondary cancers can result from chemotherapy)
- myelosuppression and oral/GI mucositis = dose limiting
2
Q
nitrosourea
A
- alkylating agent
- little cross over with other alkylating agents so can use if resistance to other drugs is formed
- crosses blood brain barrier
- useful against brain tumors
- has chloroethyl group
3
Q
Methotrexate
A
- inhibitor of human dihydrofolate reductase (DHFR)
- depletes cells of tetrahydrofolate which is needed for thymine synthesis
- accumulates in cells as a polyglutamate derivative
- folic acid analog
- S phase specific
- myelosuppressive effects can be ameliorated by combination with Leucovorin
4
Q
5-fluorouracil
A
- pyrimidine antagonist
- S phase specific
- administered by IV (variable absorption po)
- direct inhibition of thymidylate synthetase
- works synergistically with leucovorin for colon cancer treatment
5
Q
anti-tumor antimetabolites
A
- agents that inhibit metabolic processes essential in the S phase of the cell cycle
- methotrexate and purine/pyrimidine antagonists
6
Q
DNA intercalating agents
A
- bind to DNA and interfere with DNA replication causing mutations
- anthracyclines (doxorubicin and daunorubicin)
- interfere with DNA topoisomerase II function
- cardiac toxicity = dose limiting factor
7
Q
bleomycin
A
- cytotoxic action: DNA strand scission
- generates free radicals
- pulmonary fibrosis = side effect
- good in ABVD Hodgkin lymphoma combo treatment therapy
8
Q
Mitotic spindle poisons
A
- M phase specific agents interfere with mitotic spindle function during mitosis
- bind to tubulin protein subunits of microtubule with polymerization or depolymerization
- Vinca alkaloids (vincristine/ vinblastine)
- Taxanes (paclitaxel)
9
Q
vincristine
A
- mitotic spindle poison
- non-dose limiting bone marrow depression
- dose limitied neurotoxicity
- MOPP regime hodgkins-lymphoma
10
Q
Vinblastine
A
- mitotic spindle poison
- bone marrow depression = dose limiting
11
Q
Topoisomerase inhibitors
A
- elicit DNA damage via interaction with DNA topoisomerase/DNA complexes
- interfere with the religation of single or double stranded DNA stranded breaks
- DNA topoisomerase I: topotecan and irinotecan
- DNA topoisomerase II: etoposide, daunorubicin, and doxorubicin
12
Q
cisplatin and carboplatin
A
- platinum cooridation complex
- forms adducts with DNA bases and exert toxicity in similar mechanism of classical alkylating agents
- causes nephrotoxicity (reversible with hydration)
13
Q
aromatase inhibitors
A
- block estrogen synthesis through aromatase enzyme
- Ietrozole, anastrozole, exemestane
14
Q
Leuprolide
A
- synthetic gonadotropin-releasing hormone (GnRH) receptor agonist
- prostate cancer treatment
15
Q
flutamide
A
- prostate cancer treatment
- ineffective against prostate cancer alone
- used in combo with leuprolide
16
Q
Enzalutamide
A
alternative hormonal therapies for treatment of castration-resistant prostate cancers
-androgen receptor antagonists used in conjunction with GnRH agonists
17
Q
prednisone
A
- adrenocorticosteroid
- multidrug regimen used for leukemia, lymphoma, and myeloma
- anti-proliferative and lymphocytic effects on immune cells
- used as palliative agents in other cancers to reduce inflammation and nausea
18
Q
Erlotinib
A
- epidermal growth factor (EGF) receptor protein tyrosine kinase inhibitor
- mutationally activated
- NSCLC (non-small cell lung cancer)
- head and neck cancers
19
Q
Lapatinib
A
- HER2 receptor protein tyrosine kinase inhibitor
- overexpressed by gene amplification
- breast cancer
20
Q
Imatinib
A
- Abl protein tyrosine kinase inhibitor
- activated by rearrangement/fusion of Bcr and Abl protein tyrosine kinase genes in chronic myelogenous leukemia
21
Q
Venmurafenib
A
- B-raf protein kinase inhibitor
- mutationally activated in melanomas
22
Q
Cetuximab
A
- EGF receptor protein tyrosine kinase inhibitor
- chimeric EGFR antibody
- colon cancer
- head and neck cancer
23
Q
Trastuzumab
A
- HER2 receptor protein tyrosine kinase inhibitor
- humanized HER2 antibody
- Treat breast cancer
24
Q
Rituximab
A
- monoclonal antibody directed against CD20 surface antigen on B cells
- expressed on non hogkin lymphoma
- chronic lymphocytic leukemia
- chimeric IgG
- Adverse: association with PML (progressive multifocal leukoencephalopathy)
25
Brentuximab Vedotin
- CD30 surface antigen
- expressed on some hodgkin and non-hodgkin lymphoma cells
- chimeric IgG conjugated to mitotic spindle poison vedotin
26
BCG - TheraCys
- adjuvant immune system (immunostimulant)
- live attenuated bacillus calmette-guerin
- increase APC (antigen presenting cell) activity
- Bladder cancer treatment
- direct activation of leukocytes (macrophages) can result in systemic inflammation and septic shock
27
Aldesleukin, Proleukin (IL-2)
IL-2 cytokine (immunostimulant)
- increased proliferation of activated T cells, production of IFN-gamma, and cytotoxic killer cell activity
- side effects arise as it amplifies all immune responses in host
28
Actimmune (IFN-gamma)
IFN-gamma (immunostimulant)
| - treats severe recurrent infections
29
Betaseron, Extavia, Avonex, Rebif (IFN-beta)
IFN- beta (immunostimulant)
- multiple sclerosis
- reduction of pro-inflammatory cytokines
30
Ipilimumab
immune checkpoint inhibitor
- fully human antibody to CTLA-4
- activates naive T cell in lymph node
- can cause severe and fatal immune mediated rxns cased by t cell activation and prolifereation esp in GI tract
31
Nivolumab
immune checkpoint inhibitor
- fully human antibody to PD-1
- effector T cell function in the periphery
- synergistic effects on tumor regression with ipilimumbab in metastatic melanoma, colorectal, and renal cell cancer
32
Cyclophosphamide - (cytoxan)
immunosuppression by cross-linking DNA and killing proliferating cells:
AKA an alkylating agent
- causes hemorrhagic cystitis which is reversible with Mesna
33
Azathioprine - Imuran
- metabolized to 6-mercatopurine
- further metabolized to: 6-thioguanine
- metabolized product inhibit purine synthesis
- inactivated by xanthine oxidase which is:
* **DECREASED when combined with ALLOPURINOL
34
Mycophenolate Mofetil (Cell-Cept)
hydrolyzed to mycophenolic acid (active form)
| -prevents purine synthesis
35
Methotrexate
- inhibits dihydrofolate reductase (DHFR)
- prevent synthesis of thymidine and purine nucleotides
- treatment for Rheumatoid arthritis
36
Leflunomide - Arava
decreased pyrimidine synthesis
| - similar to methotrexate
37
Prednisone
Glucocorticosteroid
- immunosuppressive and anti-inflammatory
- ligands for glucocorticoid receptors affecting gene transcription
- immunosuppressive effect: inhibition of cytokine gene expression from antigen activated T cells (thus reduced B cell antibody production as well)
- first line for solid organ and hematopoietic stem cell transplantation
- Side effects:
- - Adrenal suppression (suppresses endogenous production of glucocorticosteroids)
- - GI ulceration
- - no serious marrow toxicity
reduced expression of inflammatory cytokines
- reduced expression of chemokines
- increased expression of annexins inhibits PLA2 activity and reduces Arachidonic Acid production
- reduced expression of COX2 leads to reduced prostanoid production
38
Calcineurin inhibitors
cytokine gene expression in antigen activated T cells results from calcineurin dependent dephophorylation of the transcription factor NF-AT
- calcineurin is inhibited by complex formed between endogenous proteins: immunophilins and immuno-suppressive drugs
39
Cyclosporine (sandimmune)
- used in kidney, liver, & cardiac transplants
- calcineurin inhibitor
- adverse effect: Nephrotoxicity (bc NF-AT works in kidney)
- increased cancer indcidence documented
40
Tacrolimus (Prograf, FK506)
- calcineurin inhibitor
| - same as cyclosporine
41
Mammalian target of rapamycin (mTOR) inhibitors
serine/threonine kinase important for regulating translation of proteins required for *cell proliferation*
- inhibited by complex bw endogenous immunophilin, FKBP12, and sirolimus
42
Sirolimus (Rapamune, Rapamycin)
- mTOR inhibitor
- can be used alone or in combo to preserve solid organ transplants
- antagonizes tacrolimus effects (bc competitor for same receptor FKBP12
- synergizes with cyclosporine
- myelosuppression (bc bone marrow proliferation uses same pathway)
43
Rho(D) immune globulin
antibody used to suppress unwanted immune response
- Rh negative mothers can be sensitized to the foreign D antigen of the Rh-positive fetus
- mechanism of immune suppression by Rh(D) antibodies is mediated through opsonization and clearance of fetal Rh+ cells before an effective immune response can develop
44
Belatacept (Nulojix)
blocks co-stimulatory receptors for immunosuppression
- prevents interaction between B7 (on APC) and CD28 (on T cell)
- no proliferation
- no cytokine production
Adverse effects:
- posttransplant lymphoproliferative disorder (PTLD)
- contraindicated in EBV-negative patients (as they are more susceptible to PTLD)
45
Natalizumab (Tysabri)
blocks adhesion molecules for immunosuppression
- blocks interaction between VLA-4 and VCAM-1 (preventing lymphocytes migration from vasculature into inflamed tissue sites)
- used for: relapsing forms of MS and Crohn disease
Adverse effects:
-- increased risk of PML
46
Antibodies as immune depleting agents
- produce prolonged (up to one year) depletion of circulating lymphocytes
- immuno-suppressive at the time of organ transplantation (induction therapy)
47
Anti-T Cell globulin (ATG)
- product of repeated injection of human T cells into horse, rabbit, sheep, or goats
- blocks T cell surface receptors & opsonizes T cells
- prolonged T cell depletion
Adverse effects:
-- cytokine release syndrome
48
Alemtuzumab (campath)
```
humanized anti-CD52 antibody
- depletes a broad variety of cells involved in immune system
Adverse effects:
-- myelosuppression
-- flu-like symptoms
```
49
Basiliximab (simulect)
Humanized anti-IL 2 receptor (anti-CD25) antibody
- blocks and opsonizes the alpha chain of IL-2 receptor (CD25) that is present on activated T cells
- depletes only antigen activated T cells
50
Ocrelizumab
* *first and only approved theray for progressive forms of MS
- mostly human monoclonal antibody to CD20, a B cell surface antigen
- opsonizes B cells & reduces circulating numbers of B cells resulting in reduced antibody production
51
Ustekinumab
cytokine inhibitor
- human monoclonal antibody which binds to and interferes with IL-12 & IL-23
- interferes with development of Th1 and Th17 responses
- treats: Psoriasis and Crohn's disease
52
Ixekizumab
cytokine inhibitor
- humanized monoclonal antibody which binds to IL-17 and inhibits its interaction with its receptor
- inhibits release of proinflammatory cytokines associated with Th17 response
53
DMARDs (disease modifying antirheumatic drugs)
reduce communication of cytokines that promote inflammatory process
54
Infliximab (Remicade)
Anti-TNFalpha agent
- humanized antibody to TNFalpha
- binds to TNFalpha prevents interaction with its receptor; reduces circulation/localized levels of TNF alpha
Treatment: rheumatoid arthritis and Crohn's disease
- increased frequency of serious infections (respiratory/urinary)
55
Adalimumbab
human antibody to TNF alpha
| - similar infliximab
56
Etanercept
Fusion protein containing the ligand binding domain the TNFalpha receptor and the Fc domain of human IgG
- similar to infliximab
57
Anakinra
anti-IL1 agents
- competitive IL-1 receptor antagonist (IL-1Ra analog)
- short half life, daily injection required
58
Jak inhibitor
Jak kinases are required mediators of signaling pathways activated by many cytokines
59
Tofacitinib
general Jak kinase inhibitor
- oral administration
- inhibits all activity of cytokines required for adaptive immunity
-comparable to anti-TNFalpha agents in rheumatoid arthritis
Adverse effets:
-- anemia, neutropenia, general myelosuppression
60
Diphenhydramine (benadryl)
antihistamine - first generation
61
Dimenhydrinate (dramamine)
first generation anti-histamine
62
cyclizine (Marezine)
first generation anti-histamine
63
Promethazine
first generation anti-histaine
64
Loratadine (claritin)
second generation antihistamine
- highly selective for H1 sites with few anti-cholinergic side effets
- penetrate poorly into CNS reducing sedative effects
65
Cetirizine (zyrtec)
second generation antihistamine
- highly selective for H1 sites with few anti-cholinergic side effets
- penetrate poorly into CNS reducing sedative effects
66
Fexofenadine (Allegra)
second generation antihistamine
- highly selective for H1 sites with few anti-cholinergic side effets
- penetrate poorly into CNS reducing sedative effects
67
Aspirin
- NSAID
- ASA (acetylsalicylic acid) rapidly converted to salicylic acid in circulation
- ASA acetylates and irreversibly inhibits COX1 and COX2
- salicylic acid a reversible inhibitor or COX1 and COX2
* *all NSAIDs besides ASA are reversible inhibitors**
* *only NSAID shown to reduce risk of adverse CV events** (mechanism: loss of cox2 dependant production of PGI2 which antagonizes platelet and vascular effects of TXA2 produced by COX1 dependent activities in platelets
68
Acetaminophen
reduced in the presence of peroxides that are elevated at sites of inflammation
- lacks signigicant effects on platelets, CV, & gastrointestinal systems
- analgesic and antipyretic effects equivalent to aspirin
69
Celecoxib (celebrex)
COX-2 selective NSAIDs
- GI side effects
- increased incidence of CV events: hypertension, heart attack, stroke (with long term continuous use)
70
Zileuton
leukotriene synthesis inhibitor
| - inhibition of 5-lipoxygenase inhibits synthesis of LTB4 and LTD4 in mast cells and eosinophils
71
LTD4
leukotriene product
- increase capillary permeability, promoting localized edema
- constrictor of bronchial smooth muscle (resulting in difficulty breathing)
- produced by mast cells
- attracts eosinophils (leukocytes) to airway leading to increased airway reactivity
72
LTB4
leukotriene product
| - attracts neutrophils (leukocytes) to airway leading to increased airway reactivity
73
Zafirlukast and Montelukast
leukotriene receptor antagonist
- long term therapy for asthma
- LTD4 receptor antagonists reduced bronchoconstriction and edema associated with inflammatory responses
74
Anastrozole
aromatase inhibitor
| - more effective than SERMs in treatment of ER+ breast cancer in postmenopausal women
75
Capecitabine
prodrug of 5-FU
- preferential activation in tumor cells
- activated by thymidine phosphorylase
76
Doxorubicin and Daunorubicin
Anthracycline which are DNA intercalating agents that bind to DNA and interfere with DNA replication cause DNA mutation
- anthracyclines also interfere with DNA topoisomerase II function
77
Diclofenac
nonselective cox inhibitor
78
Dimenhydrinate, diphenhydramine, cyclizine, promethazine
H1 receptor antagonists
- act as inverse agonists: prevent histamine activation of recpetor as well as reducing basal activity of receptor
- treats: allergic rhinitis, uticaria, motion sickness
Adverse:
-- sedation
-- non-H1 effects (anticholinergic effects, adrenoreceptor blockade, serotonin receptor blockade, local anesthesia)
79
Dimercaprol
used in Chelation therapy
80
EDTA
used in Chelation therapy
81
etoposide
interferes with DNA topoisomerase II
| - substrate transported by the MDR1 drug transporter leading to multidrug resistance
82
exemestane
aromatase inhibitors
| - more effective than SERMs in treatment of ER+ breast cancers in postmenopausal women
83
indomethacin
nonselective COX inhibitor
84
Topotecan and irinotecan
interferes with DNA topoisomerase I
| - interferes with the religation of the single or double stranded DNA breaks
85
Ketorolac
non-selective COX inhibitor
86
Letrozole
antagonist of hormone action
87
Leucovorin
anti-tumor metabolite
- "folinic acid rescue": amelioration of myelosuppressive effects of methotrexate when given in the interval between successibe methotrexate treatments
88
Misoprostol
- PGE1 analog
| - protects against COX1 inhibition
89
oxytocin
-used to induce uterine contractions
90
Paclitaxel
mitotic spindle poison
- block microtubule disassembly
- ovarian cancer
91
Procarbazine
monofunctional alkylating agent
| - mutagenic
92
Raloxifene
- antagonists of hormone action
| - SERM used for ER+ breast cancer
93
Tamoxifen
- antagonists of hormone action
| - SERM used for ER+ breast cancer
94
EDTA
- chelates Ca2+ and Mg2+
- treats lead poisoning
- administered as CaNa2EDTA to minimize chelation of Ca2+
95
Succimer
- orally effective chelator
- treatment for lead poisoning
- approved for children with lead levels of >45ug/dL
96
Penicillamine
```
chelator of choice for Wilson's disease
- being replaced by better tolerated trientine
Adverse effects:
-- cutaneous reactions
-- Lupus like effects
-- renal toxicity
```
