Drug Used for Treatment of Anemia Flashcards
what are 3 types of iron and vitamin deficiency anemias?
– Hypochromic, microcytic anemia (small red cells with low hemoglobin; caused by chronic blood loss giving rise to iron deficiency)
– Megaloblastic anemia (large red cells, few in number); caused by a deficiency of Vit B12 or folic acid
– Pernicious anemia (fewer normal-sized red cells, each with a normal hemoglobin content); caused by a deficiency of Vit B12 due to defect in intrinsic factor
what other blood cell deficiencies might there be?
– Erythrocytes, neutrophils and platelets
causes of anemia
which nutrients necessary for haemopoiesis might be deficient?
– iron
– folic acid and vitamin B 12
– pyridoxine (vit B6) and vitamin C (important for iron abs)
common causes of depression on bone marrow?
– drug toxicity (e.g. anticancer drugs, clozapine )
– exposure to radiation, including radiotherapy
– diseases of the bone marrow (e.g. idiopathic aplastic
anaemia, leukaemias)
– reduced production of, or responsiveness to, erythropoietin
(e.g. chronic renal failure, rheumatoid arthritis, AIDS)
what other cause is ther for anemia?
Excessive destruction of red blood cells (i.e.
haemolytic anaemia)
- EPO that synthesized RBCs, most synthesized in kidneys
- Chronic renal failure - less synthesis of RBCs
what are 2 categories for treating anemia?
hematinic agents
hematopoietic growth factors
name 2 hematinic agents
- Iron
- Folic acid and Vit B12
name 4 Hematopoietic Growth Factors
- Erythropoietin
- Granulocyte Colony-Stimulating Factor (G-CSF)
- Granulocyte-Monocyte Colony-Stimulating Factor (GM-CSF)
- Megakaryocyte (Thrombopoietic) Growth Factors
Hematinic agents: Iron
where is iron in the body?
normal daily requirement for men, growing children, menstruating womem?
pregnant women?
• The body of a 70 kg man contains about 4 g of iron
• 65% of which circulates in the blood as hemoglobin.
• About one-half of the remainder is stored in the liver,
spleen and bone marrow, as ferritin and hemosiderin .
• Normal daily requirement for iron is 5 mg for men, and 15 mg for growing children and for menstruating women
• A pregnant woman needs between 2 and 10 times this
amount because of the demands of the fetus.
• The average diet provides 15–20 mg of iron daily, mostly in meat.
• Iron in meat is generally present as heme, and about 20– 40% of hem iron is available for absorption.
Hematinic agents: Iron
how much is absorbed daily?
pathway?
how much is lost daily?
plasma iron goes to bone marrow in RBC precursors
- 24mg go to Hb in RBC
- 6mg go to mononuclear phagocytes (mnp) representing aborted cells that fail to develop into functional RBCs
- 24 mg from Hb in rbc to stores in mnp
- we lose 1-2 mg daily, maintain fixed amount
Hematinic agents: Iron
which form of iron is absorbed?
where is it absorbed?
what is a transport protein for iron?
• Ferric iron (Fe3+) must be converted to ferrous iron (Fe2+, reduced form) for absorption (by ferric reductase enzyme) in the GI tract.
• Absorption involves active transport into mucosal cells in the duodenum and jejunum (the upper ileum), from where it can be transported into the plasma and/or stored intracellularly as ferritin.
• Total body iron is controlled exclusively by absorption; in iron deficiency, more is transported into plasma than is stored as ferritin in jejunal mucosa.
• Iron that is released is transported by transferrin (the
transport protein).
• Transferrin delivers the iron to either the liver for storage or to bone marrow for further hemoglobin and RBC production
Hematinic agents: Iron
name oral and IV common drugs
Iron formulations are used for treatment of iron deficiency
Oral: ferrous sulfate, ferrous fumarate, ferrous gluconate, polysaccharide-iron complex
IV: iron dextran, sodium ferric gluconate, iron sucrose
Hematinic agents: Iron
iron formulations MOA
• Most iron is recycled through the body; RBCs contain the majority of iron in hemoglobin. Because the life span of an RBC is about 120 days, in 1 day about 0.8% of the RBCs are broken down, and their iron is recycled:
-Senescent (old) RBCs are taken up by the reticular system (spleen and macrophages) and are relieved of their iron
Lose 0.8% RBC everday - broken down and iron is released because of their lifespan
Hematinic agents: Iron
Pharmacokinetics
what inhibits its absorption?
- Ferrous iron (Fe2+) is better absorbed than ferric iron (Fe3+) and is absorbed in the duodenum. About 25% of ferrous iron is absorbed.
- Iron from animals (heme iron) is ferrous; iron from vegetarian foods (nonheme iron) is ferric, and so a smaller percentage is available for absorption.
- Iron should be taken on an empty stomach; many foods inhibit iron absorption. Other factors that markedly decrease absorption include antacids, H2 blockers, proton pump antagonists, and calcium supplements.
- Most ingested iron either is not absorbed or is lost with the enterocytes when their turnover results in shedding into the lumen of the GI tract.
- Some oral compounds are combined with ascorbic acid, which is designed to enhance absorption.
- Vegetarians - iron supplements
Nonheme iron for vegetarian foods - PPIs, H2RAs, calc supplement inhibit iron abs
- tale orange juice, ascorbic acid enhances abs
Hematinic agents: Iron
clinical uses
• To treat iron deficiency anaemia, which can be
caused by:
• Chronic blood loss (e.g. with menorrhagia, hookworm, colon cancer)
• Increased demand (e.g. in pregnancy and early infancy)
• Inadequate dietary intake (uncommon in developed countries)
• Inadequate absorption (e.g. following gastrectomy, or in diseases such as celiac disease, where the intestinal mucosa is damaged by an immunologically based intolerance to the wheat protein gluten)
- more common in females with menstruation
celiac disease often accompanied with T1 Diabetes
