Drug Treatment of Hematologic Malignancies Flashcards
(31 cards)
What are two important risks you run by suppressing WBC production and damaging DNA?
- By suppressing WBC production you run the risk of opportunistic infection and reactivation or latent infections such as TB, or Hepatis B
- DNA damage in a rapidly dividing cell population
What is the general dosing pattern used in the treatment of lymphomas, leukemias, and myelomas?
HIGH dose Induction Therapy followed by LOW dose consolidation therapy
What are the guidlines for combination chemotherapy?
- Drugs MUST show activity against a tumor type
- NO two drug should have the same MOA
- TOXICITIES should be Different
Imatinib
• Cancer treated
• MOA
ALL
MOA:
• Blocks the BCR-ABL tyrosine Kinase
Dexamethasone
ALL
MOA:
• Steroid that induces apoptosis through the mitochondrial pathway with BAX/BAK, cyt c, and caspase 3
Interferon Alfa-2a
CML
- Prolongs all phases of the cell cycle
- Induces Differentiation (cells enter G0)
- ACTIVATES NK CELLS as well as macrophages
- Stimulates cytokine production
Fludarabine
• Cancer Treated
• MOA
CLL
MOA:
• PHOSPHORYLATED Purine analog that gets TRAPPED IN BLOOD b/c of phosphate
- Dephosphorylated to be taken into cells the TRI-phosphorylated
- Inhibits RNA reductase and DNA pols.
Rituximab
CLL
MOA:
• Binds to CD20 promoting ADCC, Complement fixation, and Triggers a CD20 pathways resulting in Apoptosis
What are the main two drugs are used to treat Acute Promyelocytic Leukemia?
• MOA
ATRA (all-trans-retanoic acid)
• UNBINDS CO-REPRESSORS (CoR) from RARa allowing for cell differentiation
As2O3
• Causes PML sumoylation and degradation
• CREATES ROS (and Down Regulates Bcl-2) causing APOPTOSIS
What drugs are often given to complement the action of ATRA and As2O3 in the treatment of APL?
ANTHRACYCLINE (chelating agent) ± Cytarabine
How are the drugs given to treat APL [t(15,17)] administered?
• BLACK BOX WARNINGS???
ATRA
• Oral - Extensive Hepatic Metabolism
As2O3
• IV - drawback
• AV block and QT prolongation
DIFFERENTIATION SYNDROME (Retinoic acid syndrome) occurs with BOTH drug*
• Pulmonary Infiltrates
• Pulmonary and Pericardial Effusions
- fever, dyspnea, weight gain
What 2 reasons might you give a corticosteroid in treatment of ALL (acute lymphomablastic leukemia)?
• MOA (if applicable)
INDUCTION OF APOPTOSIS
• Glucocorticoid Receptor causes Apoptosis via downstream Bax/Bak –> Mitochondria –> Cyto C –> Caspase 3 path (mitochondrial path)
ANTI-EMETIC, decrease edema, pain
Suppose you give an allogenic transplant to a patient with ALL. Would you need to cease treatment with Imatinib?
NO - Imatinib should only act on BCR-ABL which is an abnormal fusion protein so normal tissues shouldn’t be affected
What is the inherent disadvantage of tyrosine kinase inhibitors?
• What common suffix do these drugs share?
Inherent Disadvantage is that they rely on binding to the ATP binding site so any mutations or polymorphisms here will render the drug ineffective
All end in “nib”
What are some of the downfalls to the Tyrosine kinase inhibitors?
- Orally active so CYP3A4 metabolized causing Drug-Drug and Food interactions, Hepatoxicity
- Edema with Severe Fluid Retention in ELDERLY patients
- RASH, SOMETIMES USED TO KNOW THE DRUG IS WORKING (sibs do this too)
- Endocrine Dysfunction (pancreas, thyroid, etc)
T or F: its important to monitor blood counts in Fludarabine therapy because it can cause lymphopenia, anemia, thrombocytopenia, and neutropenia.
True, but this is true of most drugs in this treatment of this disorder because they are designed to kill blood cells
What is often give to patients receiving chemotherapy to keep them from getting sick so frequently?
G-CSF (filgrastim) is often given to keep the neutrophil count up
GM-CSF (sargramostin)
Which of the CD20 binding drugs binds at a different site than the rest?
• what is the advantage?
Ofatumumab binds at the SMALL loop of CD20 all others (rituximab, tositumomab, and obinutuzumab) bind at LARGE loop.
• Small loop is closer in proximity to the cells surface and may give it an advantage by being closer
What reaction do you risk causing in patients anytime you give a monoclonal antibody drug?
• Infusion reactions
Idelalisib
• MOA
• Drug Type
• Administration
MOA:
•binds and inhibits PI3 Kinase (PI3K) and enzyme between the B-cell receptor and BTK
Drug Type:
• PI3K inhibitor “-sib”
Administration:
• ORAL administration –> CYP3A4 metabolism
What are the general adverse effects of the nibs (tyrosine kinase inhibitors), sibs (PI3K inhibitors), and mibs (BTK inhibitors)?
- Rash
- GI upset
- Teratogenesis
Idelalisib Black Box Warning
- Intestinal Perforation
* Severe Diarrhea/Colitis
What cancer is treated by Ibrutinib?
• MOA
MCL (mantle cell lymphoma)
MOA:
• Inhibits Bruton’s Tyrosine Kinase (BTK)
Panobinostat
MOA
Cancer Treated
Myeloma Treatment
MOA
• Histone Deactylase Inhibitor - allows for continuous activation of p53, proteosomes, etc
• Cause Apoptosis ultimately
