Pharmacology of Anemia Flashcards
Where is most of the iron in the body found?
In hemoglobin
What form of iron is absorbed?
Ferrous (Fe2+)
Transferrin
Transferrin takes iron to bone marrow
Ferritin
Ferritin takes iron to plasma/liver/spleen
Ferroportin
Exports iron from the small intestine
What can be used to estimate iron stores in the body?
Ferritin in plasma is in equilibrium with body storage and can be used to estimate total body stores
Hepcidin
Downregulates ferroportin
How does anemia of chronic disease (ACD) affect hepcidin?
It increases hepcidin levels which will decrease ferroportin and decrease iron uptake
What are the transferrin and ferritin levels in iron deficiency?
Ferritin is low to store less iron
Transferrin is high
What are the transferrin and ferritin levels in iron overload?
Ferritin is high to store more iron
Transferrin is low
What population has increased iron requirements?
- premature infants
- children
- pregnant or lactating women
What is used as oral iron therapy?
Ferrous sulfate, ferrous gluconate, ferrous fumarate
When is parenteral iron therapy used?
Indicated when oral iron is not tolerated, post GI resection, malabsorption syndromes
What is acute iron toxicity?
(1) May be fatal in small children
(2) Necrotizing gastroenteritis
(3) After short improvement, metabolic acidosis, coma and death
What is chronic iron toxicity?
Seen in hemochromatosis, multiple red cell tranfusions and it leads to organ failure like heart failure
How is acute iron toxicity treated?
- Gastric aspiration
- Gastric lavage-phosphate or carbonate solutions
- Iron chelation (deferoxamine)
How is chronic iron toxicity treated?
- Intermittent phlebotomy (if no anemia)
- Iron chelation (deferoxamine, deferasirox)
What atom is in all vitamin B12 forms?
Cobalt
What is required for vitamin B12 absorption?
Intrinsic Factor
Where is vitamin B12 absorbed?
In the distal ileum
Where is folic acid stored?
In the liver
What are the effects of vitamin B12 or folate deficiency?
- Alimentary tract: atrophic glossitis, chronic gastritis
- Blood and bone marrow: megaloblastic anemia, leukopenia with hypersegmented granulocytes, mild to moderate thrombocytopenia
- CNS: “subacute combined degeneration”: spastic paraparesis, sensory ataxia, lower limb paresthesias (not seen in folic acid deficiency)
What is the treatment for vitamin B12 deficiency?
Vitamin B12 deficiency is treated by parenteral injections (IM) of cyanocobalamin or hydroxycobalamin
What is the treatment for folic acid deficiency?
Oral folic acid
Are CNS symptoms of B12 deficiency reversed with folic acid treatment?
NO
Does treatment of vitamin B12 deficiency with oral vitamin B12 work even if the patient cannot make IF?
YES. High doses of oral B12 can bypass IF absence
What is erythropoietin?
- Glycoprotein, binds to its receptor and stimulates proliferation, differentiation of erythroid cells
- Stimulates release of reticulocytes from bone marrow
- Produced by the kidney
What is the usual relationship between the levels of erytrhopoietin and Hb?
Inverse.
When is erythropoietin therapy necessary?
- Chronic renal failure
- Aplastic anemia
- Anemia of prematurity
ROA of erythropoietin
IV or subcutaneous
Erythropoietin SE
Hypertension, thrombotic complications , allergic reactions
What is a major black box warning of erythropoietin?
Erythropoietin not as safe as was thought - increased
risk of tumor progression or recurrence as many tumors have an erythropoietin receptor present on them
What are G-CSF and GM-CSF?
G-CSF and GM-CSF are growth factors that stimulate proliferation and differentiation of myeloid cells
What is a unique function of G-CSF?
G-CSF promotes release of hematopoietic stem cells from the bone marrow into the peripheral circulation (much better than GM-CSF)
What is a unique function of GM-CSF?
GM-CSF also stimulates proliferation and differentiation of erythroid and megakaryocytic cells
What are indications for G-CSF and GM-CSF use?
- After intensive chemotherapy
- Treatment of congenital neutropenia, cyclic neutropenia, neutropenia associated with myelodysplasia and aplastic anemia
- High dose chemotherapy with autologous stem cell rescue
Which of G-CSF or GM-CSF is better tolerated?
G-CSF preferred since it is better tolerated in general
G-CSF and GM-CSF SE
- G-CSF can cause bone pain, splenic rupture (very rare)
- GM-CSF can cause fever, arthralgia, myalgia, peripheral edema, pleural/pericardial effusion
IL-11 Actions
- Promotes proliferation of megakaryocytic progenitors
* Increases peripheral platelet counts
IL-11 Indications
• Patients with thrombocytopenia after chemotherapy
Romiplostim
A novel protein known as a “peptibody” with two domains; a peptide domain that binds the thrombopoietin receptor (MPL), and an antibody Fc domain that increases half-life. Romiplostim is FDA approved for the treatment of idiopathic thrombocytopenia purpura (ITP).
Eltrombopag
A small molecule thrombopoietin receptor agonist of the thrombopoietin receptor, approved for the treatment of ITP and new approval for the treatment of aplastic anemia.
