Week 7 - Chapter 56 - Hematopoietic Agents

Question 1

Colony Stimulating Factors …

Answer 1

This is a type of Hematopoetic growth factor that stimulates production of particular blood cell types (stem cells to form colonies of mature cells). Also, it is a normal components of human breast milk. Infant harm has not been demonstrated. No special precautions are required during breast-feeding.
(Burchum, p. 657)

Question 2

Erythropoietic Growth Factors (ESAs) …

Answer 2

This type of Hematopoetic growth factor stimulate RBC production. Because they increase RBC production, this growth factor represent an alternative to infusions for patients with low RBC counts, including patients with Chronic Renal Failure and cancer patients undergoing myelosuppressive chemotherapy. Unfortunately, although these drugs can be beneficial, postmarketing surveillance has shown clear evidence of harm. In all patients, this growth factor may increase the risk of stroke, heart failure, blood clots, myocardial infarction (MI), and death. In patients with cancer, this growth factor may shorten time to tumor progression and reduce overall survival. E.g of this growth factor is called Erythropoeitin.

Question 3

Hematopoiesis

Answer 3

[BLANK] is the process by which our bodies make red blood cells, white blood cells, and platelets. The process is regulated in part by hematopoietic growth factors—naturally occurring hormones that stimulate the proliferation and differentiation of hematopoietic stem cells, and enhance function in the mature forms of those cells.

Question 4

Leukocytosis …

Answer 4

When administered in doses greater than 5 mcg/kg/day, filgrastim has caused white blood cell counts to rise above 100,000/mm3 in 2% of patients. Although no adverse effects were associated with this degree of [BLANK], avoiding [BLANK] would nonetheless be prudent. Excessive white cell counts can be avoided by obtaining complete blood counts twice weekly during treatment and by reducing filgrastim dosage if [BLANK] develops.

Question 5

Leukopoietic Growth Factors …

Answer 5

The [BLANK] growth factors stimulate production of leukocytes (white blood cells). Three preparations are available: filgrastim, pegfilgrastim, and sargramostim.

Question 6

Neutropenia …

Answer 6

Filgrastim is given to elevate neutrophil counts, and thereby reduce the risk of infection. Specific indications are chronic severe [BLANK] and [BLANK] associated with cancer chemotherapy or BMT.

Question 7

Pure red-cell aplasia (PRCA)

Answer 7

Very, very rarely, treatment with epoetin leads to [BLANK], a condition characterized by severe anemia and a complete absence of erythrocyte precursor cells in bone marrow. The cause is production of neutralizing antibodies directed against epoetin itself as well as any native erythropoietin the body is still able to produce. In the absence of epoetin and erythropoietin, production of RBCs ceases. Because patients can no longer make erythrocytes, transfusions are required for survival. If evidence of [BLANK] develops, epoetin should be discontinued and blood should be assessed for neutralizing antibodies.

Question 8

Thrombocytopenia …

Answer 8

Oprelvekin is administered to patients undergoing myelosuppressive chemotherapy to minimize [BLANK] (platelet deficiency) and to decrease the need for platelet transfusions. Because it stimulates the bone marrow, oprelvekin should not be given to patients with cancers of myeloid origin.

Question 9

Thrombopoietic Growth Factors …

Answer 9

[BLANK] growth factors are endogenous compounds that stimulate production of platelets. At this time, oprelvekin is the only [BLANK] growth factor available. Two drugs with similar actions—romiplostim and eltrombopag

Question 10

Erythropoietin (Epoetin Alfa)

What is it used for?

Answer 10

USES:

• -Anemia associated with chronic renal failure
• -Chemotherapy-induced anemia;
• -For HIV-infected patients taking zidovudine
• -Anemia in patients facing surgery

Question 11

Erythropoietin (Epoetin Alfa)

What are the adverse effects?

Answer 11

ADVERSE EFFECTS:

• -Hypertension
• -Autoimmune pure red-cell aplasia (PRCA) which is very rare
• -Cardiovascular events (Cardiac arrest, Hypertension, Heart failure, Thrombotic events (stroke and MI))

Question 12

Erythropoietin (Epoetin Alfa)

What are some warnings to be aware of?

Answer 12

WARNINGS:

• -Excessive dosage
• -Cancer patients: ESAs can accelerate tumor progression and shorten life in certain cancer patients
• -Renal failure patients: ESAs can increase the risk of serious cardiovascular events and death if hemoglobin levels are driven too high,
• -Preoperative patients: Increased DVT risk. Premed with anticoagulants,
• -Risk evaluation and mitigation strategy (Formal risk communication/informed consent)

Question 13

Erythropoietin (Epoetin Alfa)

What are some safety alerts/warning for Dosage?
Important to understand

Answer 13

DOSAGE:

• -To minimize risks: Use minimum needed to gradually raise hemoglobin content to eliminate the need for RBC transfusions
• -Monitor: Hemoglobin, Iron, CBC, Serum chemistry

Question 14

Filgrastim

What is it?

Answer 14

Granulocyte colony-stimulating factor
Leukopoietic growth factor
Reduces the incidence of severe neutropenia
Produces dose-dependent increase in circulating neutrophils
Reduces the incidence of infection, need for hospitalization, and need for intravenous antibiotics

Question 15

Filgrastim

What is it’s therapeutic uses?

Answer 15

Patients Undergoing Myelosuppressive Chemotherapy.
-Filgrastim is given to reduce the risk of infection in patients undergoing cancer chemotherapy. Many anticancer drugs act on the bone marrow to suppress production of neutrophils, greatly increasing the risk of infection. By stimulating neutrophil production, filgrastim can decrease infection risk.

Patients Undergoing Bone Marrow Transplantation.
-Filgrastim is given to shorten the duration of neutropenia in patients who have undergone high-dose chemotherapy followed by Bone Marrow Transplant. As noted, the drug is not used when the cancer is of myeloid origin.

Severe Chronic Neutropenia.
-Filgrastim provides effective treatment for congenital neutropenia (Kostmann’s syndrome), a condition characterized by pronounced neutropenia and frequent, severe infections. Therapy helps resolve existing infections and decreases the incidence of subsequent infections. Because treatment is chronic, the cost is very high. In addition to congenital neutropenia, filgrastim is used in patients with idiopathic neutropenia and cyclic neutropenia.

Question 16

Filgrastim

What are the adverse effects?

Answer 16

When used short term, filgrastim is generally devoid of serious adverse effects. There are no drug interactions of note.

Bone Pain.
-Filgrastim causes bone pain in about 25% of patients. Pain is dose related and usually mild to moderate. In most cases, relief can be achieved with a nonopioid analgesic (eg, acetaminophen). If not, an opioid may be tried.

Leukocytosis.
-When administered in doses greater than 5 mcg/kg/day, filgrastim has caused white blood cell counts to rise above 100,000/mm3 in 2% of patients. Although no adverse effects were associated with this degree of leukocytosis, avoiding leukocytosis would nonetheless be prudent. Excessive white cell counts can be avoided by obtaining complete blood counts twice weekly during treatment and by reducing filgrastim dosage if leukocytosis develops.

Question 17

Oprelvekin

What is it?

Answer 17

Oprelvekin [Neumega] is a thrombopoietic growth factor produced by recombinant DNA technology. The drug is a protein nearly identical in structure and actions to human interleukin-11, a cytokine produced in bone marrow. Oprelvekin is given to stimulate platelet production in patients undergoing myelosuppressive chemotherapy for nonmyeloid cancers.

Question 18

Operlvekin

What is it’s mechanism of action?

Answer 18

Oprelvekin acts on platelet progenitor cells to increase platelet production. Specifically, it stimulates proliferation of hematopoietic stem cells and megakaryocyte progenitor cells, and thereby increases synthesis of megakaryocytes, the cells that fragment into large numbers of platelets. In addition to promoting megakaryocyte synthesis, oprelvekin induces megakaryocyte maturation. The net result is increased platelet production. In patients treated with oprelvekin daily for 14 days, platelet counts begin to increase 5 to 9 days after the first injection, peak about 7 days after the last injection, and return to baseline 14 days after that.

Question 19

Oprelvekin

What are it’s therapeutic effects?

Answer 19

Oprelvekin is administered to patients undergoing myelosuppressive chemotherapy to minimize thrombocytopenia (platelet deficiency) and to decrease the need for platelet transfusions. Because it stimulates the bone marrow, oprelvekin should not be given to patients with cancers of myeloid origin.

Question 20

Oprelvekin

What are it’s adverse effects?

Answer 20

• Fluid Retention (sodium and water by the kidney) [caution patients with hx of HF or pleural effusion.
• Peripheral edema
• Anemia (expansion of plasma volume decreases both the hematocrit and hemoglobin concentration)
• Dyspnea (shortness of breath on exertion).
• Cardiac Dysrhythmias (Tachycardia, atrial fibrillation, and atrial flutter are common)
• Severe Allergic Reactions including anaphylaxis. Signs of oprelvekin-induced allergy include rash, urticaria, flushing, fever, hypotension, joint pain, chest pain, wheezing, shortness of breath, and edema of the face, tongue, and larynx.
• Effects on the Eye.