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PHARMACOLOGY - Heme > Drug Treatment of Hematologic Malignancies > Flashcards

Drug Treatment of Hematologic Malignancies Flashcards

1
Q

What are two important risks you run by suppressing WBC production and damaging DNA?

A
  • 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
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2
Q

What is the general dosing pattern used in the treatment of lymphomas, leukemias, and myelomas?

A

HIGH dose Induction Therapy followed by LOW dose consolidation therapy

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3
Q

What are the guidlines for combination chemotherapy?

A
  • Drugs MUST show activity against a tumor type
  • NO two drug should have the same MOA
  • TOXICITIES should be Different
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4
Q

Imatinib
• Cancer treated
• MOA

A

ALL

MOA:
• Blocks the BCR-ABL tyrosine Kinase

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5
Q

Dexamethasone

A

ALL

MOA:
• Steroid that induces apoptosis through the mitochondrial pathway with BAX/BAK, cyt c, and caspase 3

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6
Q

Interferon Alfa-2a

A

CML

  • Prolongs all phases of the cell cycle
  • Induces Differentiation (cells enter G0)
  • ACTIVATES NK CELLS as well as macrophages
  • Stimulates cytokine production
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7
Q

Fludarabine
• Cancer Treated
• MOA

A

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.
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8
Q

Rituximab

A

CLL

MOA:
• Binds to CD20 promoting ADCC, Complement fixation, and Triggers a CD20 pathways resulting in Apoptosis

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9
Q

What are the main two drugs are used to treat Acute Promyelocytic Leukemia?
• MOA

A

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

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10
Q

What drugs are often given to complement the action of ATRA and As2O3 in the treatment of APL?

A

ANTHRACYCLINE (chelating agent) ± Cytarabine

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11
Q

How are the drugs given to treat APL [t(15,17)] administered?
• BLACK BOX WARNINGS???

A

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

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12
Q

What 2 reasons might you give a corticosteroid in treatment of ALL (acute lymphomablastic leukemia)?
• MOA (if applicable)

A

INDUCTION OF APOPTOSIS
• Glucocorticoid Receptor causes Apoptosis via downstream Bax/Bak –> Mitochondria –> Cyto C –> Caspase 3 path (mitochondrial path)

ANTI-EMETIC, decrease edema, pain

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13
Q

Suppose you give an allogenic transplant to a patient with ALL. Would you need to cease treatment with Imatinib?

A

NO - Imatinib should only act on BCR-ABL which is an abnormal fusion protein so normal tissues shouldn’t be affected

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14
Q

What is the inherent disadvantage of tyrosine kinase inhibitors?
• What common suffix do these drugs share?

A

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”

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15
Q

What are some of the downfalls to the Tyrosine kinase inhibitors?

A
  • 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)
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16
Q

T or F: its important to monitor blood counts in Fludarabine therapy because it can cause lymphopenia, anemia, thrombocytopenia, and neutropenia.

A

True, but this is true of most drugs in this treatment of this disorder because they are designed to kill blood cells

17
Q

What is often give to patients receiving chemotherapy to keep them from getting sick so frequently?

A

G-CSF (filgrastim) is often given to keep the neutrophil count up

GM-CSF (sargramostin)

18
Q

Which of the CD20 binding drugs binds at a different site than the rest?
• what is the advantage?

A

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

19
Q

What reaction do you risk causing in patients anytime you give a monoclonal antibody drug?

A

• Infusion reactions

20
Q

Idelalisib
• MOA
• Drug Type
• Administration

A

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

21
Q

What are the general adverse effects of the nibs (tyrosine kinase inhibitors), sibs (PI3K inhibitors), and mibs (BTK inhibitors)?

A
  • Rash
  • GI upset
  • Teratogenesis
22
Q

Idelalisib Black Box Warning

A
  • Intestinal Perforation

* Severe Diarrhea/Colitis

23
Q

What cancer is treated by Ibrutinib?

• MOA

A

MCL (mantle cell lymphoma)

MOA:
• Inhibits Bruton’s Tyrosine Kinase (BTK)

24
Q

Panobinostat
MOA
Cancer Treated

A

Myeloma Treatment

MOA
• Histone Deactylase Inhibitor - allows for continuous activation of p53, proteosomes, etc

• Cause Apoptosis ultimately

25
Q

Daratumumab

MOA

A

Myeloma Treatment

MOA
CD38 transmembrane glycoprotein HIGHLY AND UNIFORMLY EXPRESSED ON MYELOMA (plasma) CELLS (low on other lymphoid cells)

26
Q

Elotuzumab
MOA
Unique Toxicity?

A

Myeloma Treatment

MOA
SLAMF7 (CS1) is expressed on NK cells and MYEOMA (plasma) cells

  • Elotuzumab binding on NK cells activates them
  • its an Antibody so NK cells recognize it by ADCC
  • Prevents adhesion to bone marrow

Causes peripheral n. disease (not that remarkable)

27
Q

Ixazomib

MOA

A

Myeloma Treatment

MOA
Reversible Proteasome Inhibitor (hence the mib suffix)

28
Q

What are the 4 drugs mentioned to treat myeloma?

• which is the most specific?

A

Panobinostat
Daratumumab - MOST SPECIFIC b/c of CD38 binding
Elotuzumab
Ixazomib

29
Q

Would you expect the nibs to cause transfusion reactions? why or why not?

A

NO they are given orally so infusion reactions aren’t an issue like they are with the mAbs.

30
Q

Why is Ixazomib thought to be better than its earlier drugs like Bortezomib and carfilzomib?

A

It can be taken orally rather than parenterally

31
Q

Azacitidine
• Administration method
• MOA

A

Administration
• IV infusion

MOA:
• CYTIDINE ANALOGS
• Incorporate into DNA and INHIBIT DNA methyltransferases resulting in depletion of active enzymes

PHARMACOLOGY - Heme (4 decks)

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