Lecture 24 - Agents for Anemias; Hematopoietic growth factors

Question 1

Nutrient Factors (Drug list)

Answer 1

• Iron and combinations
• Folic acid derivatives and combinations
• Cyanocobalamin (vit B12)

Question 2

Growth and Stimulating Factors (Drug list)

Answer 2

• Sargramostim (GM-CSF)
• Filgrastim (G-CSF)
• Epoetin Alfa
• Oprelvekin

Question 3

Iron deficiency anemias

Answer 3

Result in microcytic, hypochromic anemia

Megaloblastic Anemias
- Deficiency in vitamin B12 or folic acid

Pernicious Anemias
- Lack of intrinsic factor due to gastric mucosal atrophy
- Results in marrow changes (hyperplasia), subacute combined degeneration of the spinal cord, and peripheral neuropathy.

Question 4

Oral Iron

Answer 4

Iron is a component of hemoglobin and myoglobin.
- Ferrous salts are absorbed 3x more readily than ferric form
- Iron enters mucosal cell through apical uptake transporter (DMT-1) and combines with apoferritin to be retained in the cell as ferritin.
- Iron leaves through ferroportin

Adverse toxicity:
- GI irritation, nausea, vomiting, constipation.
- Lethal dose if too much

Treatment of toxicity: Deferoxamine Mesylate - chelates iron

Uses: Prevent and treat iron deficiency anemias

Question 5

Iron Dextran

Answer 5

Parenteral Iron; Complex of ferric hydroxide and dextran

FDA BOX WARNING: Anaphylactic-type reactions. Also hypersensitivity reactions

IV injected; Test dose of 0.5 ml to test anaphylactic reactions

For iron deficiency in which oral administration impossible

Question 6

Folic Acid

Answer 6

Required for nucleoprotein synthesis (Requires dihydrofolate reductase) and erythropoiesis
- Dietary folic acid present in foods
- Metabolized in the liver. Normal serum levels of 5-15 ng/ml; Below 5ng/ml indicate deficiency and below 2ng/ml results in megaloblastic anemia

Adverse effects: Don’t give if anemia undiagnosed, may result in severe nerve damage. Also hypersensitivity, GI, and CNS effects

Used for the treatment of megaloblastic anemias due to a deficiency of folic acid.

Contraindicated in treatment of pernicious anemia and other megaloblastic anemias where vitamin B12 is deficient

Take if pregnant! Folic acid deficiency is common and can result in child spina bifida

Question 7

Vitamin B12

Answer 7

Required for DNA synthesis by participating in two essential enzymatic reactions
1) Cofactor of methylmatonyl-CoA mutase -> lack = abnormal fatty acid
2) Cofactor of methionine synthesis

Takes long time to exhaust all stored B12. Uptake through binding to intrinsic factor in the presence of calcium in the terminal ileum. Transcobalamin II delivers protein for vitamin B12.

Adverse effects:
- 3 months w/o = permanent degenerative lesions of spinal cord.
- Optic nerve atrophy
- Folic acid - irreversible neural degeneration

Drug interactions: Hypersensitivity may result in anaphylactic shock and death

USE:
- Vitamin B12 deficiency
- 2.2 ug/day for pregnant women

Question 8

Erythropoietin (Epoetin Alfa)

Answer 8

Regulates erythropoiesis by stimulating the bone marrow to create RBC; absence leads to anemia
- Highly effective for treatment of anemias of chronic disease
– Chronic renal disease
– AIDS induced anemia treated with zidovudine
– Cancer induced anemia

FDA BOXED WARNINGS:
- Cardiovascular events: myocardial infarction, stroke, venous thromboembolism
- Chronic kidney disease
- Cancer: increase risk of tumor progression or recurrence

Question 9

Filgrastim (G-CSF)

Answer 9

Human Granulocyte Colony Stimulating Factor
- Regulates neutrophil production

Used for chemotherapy induced neutropenia, bone marrow transplants, and HIV neutropenia.

Question 10

Sargramostim (GM-CSF)

Answer 10

Human Granulocyte-Macrophage Colony Stimulating Factor
- Support growth and differentiation of stem cells into granulocytes and macrophages.

Used for myeloid recovery in cancer patients and bone marrow transplants