pharmacology overview Flashcards
log kill hypothesis:
- doubling time of tumor assumed to be ______ regardless of tumor size
- fraction of cells killed with each cycle of therapy is constant through growth of tumors may be ____
- assumes __________sensitivity to therapy
- doubling time of tumor assumed to be constant regardless of tumor size
- fraction of cells killed with each cycle of therapy is constant through growth of tumors may be exponential
- assumes homogeneous sensitivity to therapy
Goldie-Coldman hypothesis:
- takes into account property of drug _______
- proposes that best strategy for treatment is to
- goals is prevention of tumor__________
- takes into account property of drug resistance
- proposes that best strategy for treatment is to initiate therapy early (small tumor) with combinations of active drugs
- goals is prevention of tumor resistance
types of treatment (5)
- single
- sequential
- combination
- immunotherapy
- Hormonal therapy
liquid tumors types of therapy (3)
- induction
- consolidation
- maintenance
solid tumors types of therapy (3)
- adjuvant therapy
- neoadjuvant therapy
- palliation
intial treatment to get patient into complete remission
induction
used in leukemia to eradicate micrometastatic disease
consolidation
prolonged therapy; often used in ALL
maintenance
used after definitive solid surgery to eradicate micro-metastatic disease
adjuvant
used to reduce tumor burden prior surgical intervention
neoadjuvant
used to reduce symptoms and improve quality of life
palliative
disappearance of all evidence of tumor
complete response
decrease of at least 50% in diameter of all measurable lesions
partial response
decrease of less than 50% to increase of less than 25% in diameter product of lesion
stable disease
increase of more than 25% in diameter product of any lesion
progressive disease
there are many factors that might affect response to therapy
yep, such as tumor burden, diagnosis, stage/grade, tumor cell heterogeneity, drug resistance such as in AML in elderly, and diseases like Fanconi that are mores susceptible to adverse SE of chemo due to chromosome fragility
medical therapies for cancer are often administered according to a schedule based on ____ why?
cycles . after chemo is given there is usually a “rest period” during which no treatment is given, allowing normal cells to recover from chemo effects
affect microtubule formation and work in M-phase
vinca alkaloids
are incorporated as false analogues in DNA and RNA synthesis and work in S-phase
anti-metabolites
cell cycle non-specific therapies include (2) meaning that they occur independently of phase in which the cycle is occurring
- alkylating agents
2. anti-tumor antibiotics
form inter- and intra- strand crosslinks in DNA
alkylating agents
intercalate into DNA
anti-tumor antibiotics
exert their effects through binding a particular molecular on the cell surface
monoclonal ab
exert their effects through manipulation of the immune system
biologic agents
the vomiting center is in the
medulla
the chemoreceptor trigger zone which sens info to the vomiting center is found in the
fourth ventricle
vagal and sympathetic afferents from GI tract stimulate
vomiting center and chemoreceptor trigger zone
serotonin is released from
enterochromaffin cells in GI tract
ACUTE chemotherapy-induced nausea and vomiting:
- occurs in the ____ hr after chemo
- peaks _____ hr after start of infusion
- typical drugs used to treat include
- occurs in the first 24 hr after chemo
- peaks 3-4 hr after start of infusion
- typical drugs used to treat include serotonin antagonists, corticosteroids and dopamine antagonists
DELAYED chemotherapy-induced nausea and vomiting:
- occurs after the ____ hr of chemo
- it can lasts for ___days and typically peaks ____ days after infusion
- associated with specific chemo agents-
- drugs used for the prophylaxis and treatment of delayed N/V include
- occurs after the first 24 hr of chemo
- it can lasts for 3-5 and typically peaks 2-3 days after infusion
- associated with specific chemo agents- cisplatin, cyclophosphamide and doxorubicin
- drugs used for the prophylaxis and treatment of delayed N/V include serotonin antagonists, NK-1 antagonists, corticosteroids, dopamine antagonists
ANTICIPATORY chemotherapy-induced nausea and vomiting
- response is _______ occurring before chemo is administered
- best treated prophylactivally with
- response if conditioned occurring before chemo is administered
- best treated prophylactivally with benzodiazepines
Serotonin antagonists:
- block the action of serotonin in the periphery and at the CTZ at the _______
- major side effects include (3)
- high doses are associated with this ekg abnormality-
- examples include (2)
- block the action of serotonin in the periphery and at the CTZ at the type 3 receptor
- major side effects include headache, hiccups and constipation
- high doses are associated with this ekg abnormality- QTc prolongation
- examples include ondansetron and palonosetron
difference between ondansetron aand palonosetron
ondansetron needs to be given at least one time per day while palonosetron has a long half life and thus only needs a one time IV dose
NK-1 antagonists
- block the substance ___at the neurokinin-1 reception in the CNS and the periphery
- indicated in the treatment(2)
- major SE include (2)
- multiple drug interactions to ____system leading to a decrease in the efficacy of (2), and increasing the serum concentration of (1)
- example includes
- block the substance P at the neurokinin-1 reception in the CNS and the periphery
- indicated in the treatment of both acute and delayed N/V
- major SE include fatigue, hiccups.
- multiple drug interactions due to the effects on the p450 system leading to a decrease in the efficacy of oral contraceptives and warfarin, and increasing the serum concentration of corticosteroids
- example includes aprepitant
corticosteroids:
- mechanism is
- major SE include (4)
- it increases the
- example is (1)
- mechanism is unknown- anti-emetic
- major SE include glucose intolerance, HTN, insomnia and agitation/jitteriness
- it increases the efficacy of other drugs by 20%
- example is dexamethasone
Olanzapine
- it is considered to be
- mechanism of action is that it modulates ____ and _____ activity
- it is used more in
- it is considered to be a atypical antipsychotic
- mechanism of action is that it modulates central dopaminergic and serotonergic activity
- it is used more in acute vs delayed CINV
Dopamine antagonists:
- blocks D1 and D2 receptors in (2)
- indicated for the treatment of
- major toxicities of dopamine antagonists include (2)
- examples include (2)
- mild toxicities of these drugs can be treated with (2)
- often used for
- blocks D1 and D2 receptors in CTZ and peripherally
- indicated for the treatment of acute and delayed N/V
- major toxicities of dopamine antagonists include extrapyramidal side effects (EPS) and akathisia.
- examples include prochloreperazine and metoclopramide
- mild toxicities of these drugs can be treated with diphenhydramine or benztropine
- often used for breakthrough (prn)
benzodiazepines:
- acts on (3)
- action is mediated via ___
- side effects include (2)
- often used for
- acts on limbic, thalamic and hypothalamic areas of CNS
- action is mediated via GABA
- side effects include sedation, retrograde amnesia
- often used for breakthrough (prn)
chemo can result in the suppression of psecific hematopoietic cell lines or all three leading to cytopenias
yep
glycoproteins produced by recombinant DNA technology that mimic endogenous erythropoetin, triggering the bone marrow to produce RBCs
Erythropoietin stimulating agents
how many people respond to ESAs
30-50% of patients with chemo induced anemia respond
all patients receiving ESAs should have iron studies performed before being started on the drugs… why?
adequate iron stores are required for these agents to work
Side effects of ESAs include (3)
- HTN
- arthralagias
- rash
a neutropenia with an absolute neutrophil count (ANC) of less than 500 found that risk of infection is related to severity and duration of neutropenia
yep
what is used to lessen the depth and length of neutropenia and enhances proliferation and differentiation of myeloid cell lines and function of the cell that they stimulate
myeloid growth factors
adverse effects of myeloid growth factors (4)
- fever
- bone pain
- increases in uric acid, LDH and alkaline phosphatase which represent cells turning over
- splenic infarct which is rare
myeloid growth factors are indicated:
- primary prophylaxis:
- secondary prophylaxis:
- established neutropenia:
- primary prophylaxis: for regiments know to cause neutropenia
- secondary prophylaxis: curative intent; maintain dosse density
- established neutropenia: febrile neutropenia is reduced by 1-3 days
long acting formulation of G-CSF which is dosed once after chemo; the clearance is via neutrophil mediated endocytosis and degradation and is thus auto-regulated as the neutrophil count recovers
Neulasta
2 forms of myeloid growth factors
- granulocyte colony stimulating factor used to enhance proliferation and differentiation of neutrophils
- granulocyte macrophage colony stimulating factor used to enhance proliferation and differentiation of granulocytes and macrophages
filgrastim
granulocyte colony stimulating factor used to enhance proliferation and differentiation of neutrophils
sargramostim
granulocyte macrophage colony stimulating factor used to enhance proliferation and differentiation of granulocytes and macrophages
