Agents used in anemias &hematopoietic growth factorsBy: S.Bohlooli, Ph.D.

Agents used in anemias

Iron Vitamin B12 Folic acid

Iron

Iron deficiency most common nutritional cause of anemia result from inadequate iron intake, malabsorption,

blood loss, or an increased requirement, as with pregnancy

The Body Content of Iron

  MG/KG OF BODY WEIGHT

  Male Female

Essential iron    Hemoglobin 31 28Myoglobin and enzymes 6 5

Storage iron 13 4Total 50 37 

Pathways of iron metabolism in human beings

Absorption, transport, and storage of iron

Iron Requirements for Pregnancy   AVERAGE, mg RANGE, mg

External iron loss 170 150-200Expansion of red cell mass 450 200-600

Fetal iron 270 200-370Iron in placenta and cord 90 30-170

Blood loss at delivery 150 90-310Total requirement* 980 580-1340Cost of pregnancya 680 440-1050*Blood loss at delivery not included. aIron lost by the mother; expansion of red cell mass not included. SOURCE: Council on Foods and Nutrition. Iron deficiency in the United States. JAMA 1968, 203:407-412. Used with permission

Daily Iron Intake and Absorption SUBJECT IRON

REQUIREMENT, mg/kg

AVAILABLE IRON IN POOR DIET-GOOD DIET, mg/kg

SAFETY FACTOR, AVAILABLE IRON/REQUIREMENT

Infant 67 33-66 0.5-1Child 22 48-96 2-4Adolescent (male) 21 30-60 1.5-3Adolescent

(female)20 30-60 1.5-3

Adult (male) 13 26-52 2-4Adult (female) 21 18-36 1-2Mid-to-late

pregnancy80 18-36 0.22-0.45

Clinical pharmacology

Indication for the use of iron Treatment or prevention of iron deficiency anemia

Treatment Oral iron therapy Parenteral iron therapy

Some Commonly Used Oral Iron Preparations

Preparation Tablet Size Elemental Iron per Tablet

Usual Adult Dosage (Tablets per Day)

Ferrous sulfate, hydrated

325 mg 65 mg 3–4

Ferrous sulfate, desiccated

200 mg 65 mg 3–4

Ferrous gluconate 325 mg 36 mg 3–4

Ferrous fumarate 100 mg 33 mg 6–8

325 mg 106 mg 2–3

Oral iron therapy adverse effects Nausea Epigastric discomfort Abdominal cramps Constipation Diarrhea

Clinical toxicity

Acute iron toxicity Necrotizing gastroenteritis Vomiting, abdominal pain, bloody diarrhea Followed by shock, lethargy, dyspnea Severe metabolic acidosis, coma, death

Chronic iron toxicity (hemochromatosis) Deposit of iron in the heart, liver, pancreas Can lead to organ failure and death

Vitamin B12

The absorption and distribution of vitamin B12

Enzymatic reactions that use vitamin B12

Enzymatic reactions that use folate

Vitamin B12: clinical pharmacology Treat or prevent deficiency

Megaloblastic anemia Neurologic syndrome

Degeneration of myelin sheaths Disruption of axons in the dorsal and lateral horns of

spinal cord and in peripheral nerves Most cause of deficiency:

Pernicious anemia, partial or total gastroctomy Disease affect the distal ileum:

Inflammatory bowel disease Small bowel resection

Folic Acid

Enzymatic reactions that use folate

Folic acid: Clinical pharmacology Deficiency

result in megaloblastic anemia Often caused by inadequate dietary intake

Pregnant woman has increased folate requirement

A dose of 1 mg is sufficient

Hematopoietic growth factors Erythropoietin Granulcyte colony-stimulating factor (G-CSF) Granulcyte-macrophage colony stimulating

factor (GM-CSF) Interleukin 11

Clinical Uses of Hematopoietic Growth FactorsHematopoietic Growth Factor Clinical Condition Being Treated

or PreventedRecipients

Erythropoietin, darbepoetin alfa Anemia Patients with chronic renal failure

HIV-infected patients treated with zidovudine

Cancer patients treated with myelosuppressive cancer chemotherapy

Patients scheduled to undergo elective, noncardiac, nonvascular surgery

Granulocyte colony-stimulating factor (G-CSF; filgrastim)

Neutropenia Cancer patients treated with myelosuppressive cancer chemotherapy

Granulocyte-macrophage colony-stimulating factor (GM-CSF; sargramostim)

Patients with severe chronic neutropenia

Stem cell transplantation Patients with nonmyeloid malignancies treated with stem cell transplantationMobilization of peripheral blood

progenitor cells (PBPCs) Mobilization of peripheral blood progenitor cells (PBPCs)

Patients with nonmyeloid malignancies

Donors of stem cells for allogeneic or autologous transplantation

Interleukin-11 (IL-11, oprelvekin) Thrombocytopenia Patients with nonmyeloid malignancies who receive myelosuppressive cancer chemotherapy

Romiplostim Thrombocytopenia Patients with idiopathic thrombocytopenic purpura