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Pharmacology > Anemia and Hematopoietic Growth Factor Pharmacology > Flashcards

Anemia and Hematopoietic Growth Factor Pharmacology Flashcards

1
Q

What is the distribution of iron in your body?

A

Hemoglobin 70%
Myoglobin 10%
Ferritin and Hemosiderin (storage) 10-20%
Enzymes 1%

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2
Q

Describe the absorption of heme iron

A

Itron from animal sources (heme iron) may be absorbed intact

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3
Q

What form must non-heme iron be in for absorption?

A

Must be converted to ferrous (Fe2+) form

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4
Q

What is the protein transporter involved in iron absorption from the GI lumen?

A

DMT1

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5
Q

What will iron complex with if its destination is the bone marrow? What is that iron used for?

A

Transferrin.

That iron will be used for blood cell precursors.

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6
Q

What will iron complex with for storage?

A

Ferritin

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7
Q

Where is ferritin mainly present in the body?

A

Liver
Spleen
Plasma

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8
Q

What is the function of ferroportin?

A

Involved in the export of iron in the intestinal epithelium

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9
Q

How does hepcidin affect iron?

In what disease would high hepcidin play a role?

A

Hepcidin downregulates ferroportin, which can prevent macrophages in bone marrow from exporting iron to blood cell precursors. High levels of hepcidin play a role in ANEMIA OF CHRONIC DISEASE

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10
Q

Describe the pathogenesis of hemochromatosis

A

Low hepcidin levels lead to lots of iron being absorbed and released into the circulation. Leads to iron deposits in the lungs, heart, and liver, which is toxic
May cause organ failure

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11
Q

How does iron deficiency affect ferritin levels? Transferrin?

A

Low ferritin

High transferrin

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12
Q

How does iron overload affect ferritin levels? Transferrin?

A

High ferritin

Low transferrin

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13
Q

What are indications for iron therapy?

A

Prevention or treatment of iron deficient anemia

  • Increased requirements (premature infants, children, pregnant women)
  • Inadequate absorption
  • Blood loss (GI, menstrual)
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14
Q

How may iron therapy be administered?

A

Oral or parenteral (IM, IV)

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15
Q

When is parenteral iron indicated above oral iron?

A

When oral iron is not tolerated
Post GI resection
Malabsorption syndrome

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16
Q

Adverse Effects of Oral Iron therapy

A

Nausea
Vomiting
Black stools

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17
Q

What is a common cause of acute iron toxicity? How can acute iron toxicity be fatal?

A

Overingestion of iron tablets. Could be fatal due to necrotizing gastroenteritis

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18
Q

What could cause chronic iron toxicity?

A

Hemochromatosis

Multiple RBC transfusions

19
Q

What could chronic iron toxicity lead to?

A

Organ failure

20
Q

How should you treat acute iron toxicity?

A

Gastric aspiration
Gastric lavage with phosphate or carbonate solns
Iron chelation therapy (deferoxamine)

21
Q

How should you treat chronic iron toxicity?

A

Intermittent phlebotomy (if no anemia present)

Iron chelation (deferoxamine, deferasirox)

22
Q

What is required for B12 absorption? Where is the complex absorbed?

A

Complexation with IF.

Absorbed in the distal ileum

23
Q

After B12 absorption, how does it get transported to the sites where it is needed?

A

Complexation with transcobalamin II

24
Q

How is folic acid absorbed? Where is it stored?

A

Absorbed as monoglutamate. Stored mainly in the liver

25
Q

What are some signs of a B12 or folate deficiency?

A 
Deficient DNA synthesis
Megaloblastic anemia
Leukopenia with hypersegmented granulocytes
Atrophic glossitis
Chronic gastritis

B12 deficiency can cause CNS symptoms with subacute combined degeneration

26
Q

Treatment for B12 Deficiency

A

Pareneteral (IM) injections of cyanocobalamin or hydroxycobalamin

Now there is some evidence that oral B12 can be effective, even without IF

27
Q

Treatment for Folic Acid Deficiency

A

Oral folic acid

28
Q

What is the physiological function of Erythropoietin (EPO)?

Where is EPO made?

A

Stimulates proliferation and differentiation of erythroid cells

Stimulates release of reticulocytes form bone marrow

Produced in the kidney

29
Q

Indications for EPO Therapy

A 
Chronic Renal Failure
Aplastic anemia
Leukemias
HIV/AIDS
Associated anemias
Cancer
Anemia of prematurity
Post-phlebotomy
30
Q

What improvements should you expect to see after EPO injection?

A

Reticulocytes seen around 10 days

Increase in hemoglobin in 2-6 weeks

31
Q

EPO Toxicity and Black Box Warnings

A

HTN
Thrombosis
Anaphylaxis
Increased risk of tumor progression and recurrence

32
Q

G-CSF/GM-CSF

What is their physiological function?

A

Growth factors stimulating the proliferation and differentiation of myeloid, erythroid, and megakaryocytic cells

Promote release of hematopoietic cells into the peripheral circulation

33
Q

G-CSF/GM-CSF

What are the two pharmacological recombinant forms?

A 
Filgastim
Pegfilgastim (longer 1/2 life)
34
Q

G-CSF/GM-CSF

What are the therapeutic indications?

A

After chemotherapy to increase PMN counts

Used after chemo for AML (causes growth of normal cells that will outcompete the leukemia cells)

Mobilize blood stem cells into the periphery for easier collection for stem cell transplant

35
Q

G-CSF/GM-CSF

Toxicity

A

G-CSF: bone pain, allergies

GM-CSF: Fever, arthralgia, peripheral edema, pleural or pericardial effusion, allergy

G-CSF is generally preferred

36
Q

IL-11

Physiological function

A

Normally produced by bone marrow stromal cells to promote megakaryocytic progenitor proliferation.

Increases peripheral platelet counts

37
Q

Is recombinant TPO (thrombopoietin) useful?

A

No. It often induced an immune response from patients and did not ultimately increase peripheral platelet levels

38
Q

IL-11

Indications

A

Thrombocytopenia after chemo

39
Q

IL-11

Toxicity

A 
Fatigue
HA
Dizziness
Dyspnea
Arrhythmias
Hypokalemia
40
Q

What are the two new agents for treating thrombocytopenia?

A

Romiplostim

Eltrombopag

41
Q

Romiplostim

MOA

A

“Peptibody”
Peptide domain binds the TPO receptor
Antibody Fc domain increases its half life

42
Q

Eltrombopag

MOA

A

Small molecule TPO-receptor agonist

43
Q

What are the indications for Romiplostim and Eltrombopag?

A

ITP

Eltrombopag may also be used in aplastic anemia

44
Q

Romiplostim and Eltrombopag

Adverse Effects

A

Headache
Myalgia
Bone marrow fibrosis (reversible)

Pharmacology (67 decks)

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