Agents used in anemias hematopoietic growth factors By

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

Agents used in anemias n n n Iron Vitamin B 12 Folic acid

Iron n Iron deficiency q q 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 Myoglobin and enzymes 31 6 28 5 Storage iron Total 13 50 4 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 Expansion of red cell mass 170 450 150 -200 200 -600 Fetal iron Iron in placenta and cord 270 90 200 -370 30 -170 Blood loss at delivery 150 90 -310 Total requirement* 980 580 -1340 Cost of pregnancya 680 440 -1050 *Blood loss at delivery not included. a. Iron 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 REQUIRE MENT, mg/kg AVAILABLE SAFETY FACTOR, IRON IN AVAILABLE POOR DIETIRON/REQUIRE GOOD DIET, MENT mg/kg Infant 67 33 -66 0. 5 -1 Child 22 48 -96 2 -4 Adolescent (male) 21 30 -60 1. 5 -3 Adolescent (female) 20 30 -60 1. 5 -3 Adult (male) 13 26 -52 2 -4 Adult (female) 21 18 -36 1 -2 Mid-to-late pregnancy 80 18 -36 0. 22 -0. 45

Clinical pharmacology n Indication for the use of iron q n Treatment or prevention of iron deficiency anemia Treatment q q Oral iron therapy Parenteral iron therapy

Some Commonly Used Oral Iron Preparations Preparation Tablet Size Elemental Iron per Usual Adult Tablet 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 n n n Nausea Epigastric discomfort Abdominal cramps Constipation Diarrhea

Clinical toxicity n Acute iron toxicity q q n Necrotizing gastroenteritis Vomiting, abdominal pain, bloody diarrhea Followed by shock, lethargy, dyspnea Severe metabolic acidosis, coma, death Chronic iron toxicity (hemochromatosis) q q Deposit of iron in the heart, liver, pancreas Can lead to organ failure and death

Vitamin B 12

The absorption and distribution of vitamin B 12

Enzymatic reactions that use vitamin B 12

Enzymatic reactions that use folate

Vitamin B 12: clinical pharmacology n Treat or prevent deficiency q q Megaloblastic anemia Neurologic syndrome n n n Degeneration of myelin sheaths Disruption of axons in the dorsal and lateral horns of spinal cord and in peripheral nerves Most cause of deficiency: q q Pernicious anemia, partial or total gastroctomy Disease affect the distal ileum: n n Inflammatory bowel disease Small bowel resection

Folic Acid

Enzymatic reactions that use folate

Folic acid: Clinical pharmacology n Deficiency q q n n 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 n n Erythropoietin Granulcyte colony-stimulating factor (G-CSF) Granulcyte-macrophage colony stimulating factor (GM-CSF) Interleukin 11

Clinical Uses of Hematopoietic Growth Factors Hematopoietic Growth Factor Clinical Condition Being Treated Recipients or Prevented 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 Neutropenia -CSF; filgrastim) Cancer patients treated with myelosuppressive cancer chemotherapy Granulocyte-macrophage colonystimulating factor (GM-CSF; sargramostim) Patients with severe chronic neutropenia Stem cell transplantation Mobilization of peripheral blood progenitor cells (PBPCs) Patients with nonmyeloid malignancies treated with stem cell transplantation 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