Erythropoietin absorption

WARNING Anaphylactic Rxns w/ use use only if oral Fe not possible administer where resuscitation techniques available Uses Fe deficiency when cannot supl PO Action Fe supl Dose Adul. Iron defic anemia Estimate Fe deficiency, give 25-100 mg IM/IV /d until total dose total dose (mL) = [-.0442 x (desired Hgb - observed Hgb) x LBW] + (0.26 x LBW) Iron replacement, blood loss Total dose (mg) = blood loss (mL) x Hct (as decimal fraction) max 100 mg/d Peds >4 mo. As for adults max 0.5 mL (wt <5 kg), 1 mL (5-10 kg), 2 mL (>10 kg) p dose IM or direct IV Caution [C, M] Contra Anemia w/o Fe deficiency. Disp Inj SE Anaphylaxis, flushing, dizziness, inj site inf Rxns, metallic taste Interactions X Effects W/ chloramphenicol, X absorption of oral Fe EMS Anaphylactic Rxns common taking oral Fe t risk of tox and SEs OD May cause N/V, HA, muscle/joint pain and fev symptomatic and supportive Iron Sucrose (Venofer) [Iron Supplement] Uses Fe deficiency anemia w/ chronic HD in those receiving erythropoietin Actions Fe r lacement. Dose 5 mL (100 mg) IV on dialysis, 1 mL (20 mg)/min max Caution [C, M] Contra Anemia w/o Fe deficiency Disp Inj SE Anaphylaxis, -1- BP, cramps, N/V/D, HA Interactions i Absorption OF oral Fe supls EMS See Iron Dextran OD See Iron Dextran... 

Iron deficiency anemia is treated with oral or parenteral iron preparations. Oral iron corrects the anemia just as rapidly and completely as parenteral iron in most cases if iron absorption from the gastrointestinal tract is normal. An exception is the high requirement for iron of patients with advanced chronic kidney disease who are undergoing hemodialysis and treatment with erythropoietin for these patients, parenteral iron administration is preferred. 

Mizuno, A., M. Ueda, and G. Kawanishi. 1992. Effects of salicylate and other enhancers on rectal absorption of erythropoietin in rats. J Pharm Pharmacol 44 570. 

Epoetin alfa, recombinant erythropoietin, is a glycoprotein that simulates erythrocyte production. Epoetin alfa is administered three times weekly subcutaneously or intravenously. Epoetin is used to treat anemia in patients with chronic renal failure, HIV infection, and patients receiving chemotherapy [104]. Development of a safe, effective nasal formulation of epoetin alfa, containing an absorption enhancer could once again improve the efficacy of epoetin alfa therapy, and reduce the number of injections required in these sensitive patient populations. 

Anemia is observed in some CF patients despite chronic hypoxia. The apparent deficient erythroid response occurs, at least in part, from disturbances in erythropoietin regulation and iron availabihty (impaired gastrointestinal absorption). Despite chronic hypoxia in some patients with CF, erythropoietin concentrations are normal or low. The condition is characterized by decreased hematocrit and serum ferritin, increased carboxyhemoglobin, and normal or low hemoglobin. Vitamin E concentrations may be normal. Many patients may have iron deficiency owing to decreased dietary intake, malabsorption, or blood loss. 

Many PD patients secrete large quantities of fibrinogen into the peritoneal cavity, which results in fibrin formation. This can lead to intraperitoneal adhesions and outflow obstruction. Intraperitoneal heparin may prevent this complication as a result of its local an-tiflbrin effect. Because standard heparin has a molecular weight of 12,000 to 15,000 daltons, it is minimally absorbed and thereby has limited systemic effects. The absorption of intraperitoneal erythropoietin has also been studied. Its bioavailability is low, but may be increased when added into a dry peritoneum. ... 

A severe decrease in P-globin levels leads to the precipitation of the a-chain, which in turn causes a defect in the maturation of the erythroid precursor, and erythropoiesis thus reducing red cell survival. The profound anemia in the affected individual stimulates the production of erythropoietin leading to the expansion of bone marrow and subsequent skeletal deformities. The hyperplasia of the bone marrow induces increased iron absorption leading to the deposition of iron in tissues. If the concentration of iron in the tissues becomes too high, it can lead to organ failure and death if appropriate therapeutic steps are not taken. 

Patients with anemia secondary to chronic kidney disease are ideal candidates for epoetin alfa therapy. The response in predialysis, peritoneal dialysis, and hemodialysis patients is dependent on the severity of renal failure, erythropoietin dose and route of administration, and iron availability. The subcutaneous route of administration is preferred to the intravenous route because absorption is slower and the amount of drug required is reduced by 20 to 40%. 

Iron-deficiency anemia results from dietary intake of iron that is inadequate to meet normal requirements (nutritional iron deficiency), blood loss, or interference with iron absorption. Most nutritional iron deficiency in the U.S. is mild. More severe iron deficiency is usually the result of blood loss, either from the GI tract, or in women, from the uterus. Impaired absorption of iron from food results most often from partial gastrectomy or malabsorption in the small intestine. Finally, erythropoietin therapy can result in a functional iron deficiency. 

Complicating iUness also can interfere with the response of an iron-deficiency anemia to iron therapy. By decreasing the number of red cell precursors, intrinsic disease of the marrow can blunt the response. Inflammatory illnesses suppress the rate of red cell production, both by reducing iron absorption and reticuloendothelial release and by direct inhibition of erythropoietin and erythroid precursors. Continued blood loss can mask the response as measured by recovery of the Hb or hematocrit. 

Anemia resulting from decreased production of erythropoietin (renal system) and decreased vitamin absorption (gastrointestinal system) can result in decreased oxygenation and tissue hypoxia (lactic acidosis). 

A multiple-step mechanism could also control iron absorption through the intestine. For example, it has been proposed that the bone marrow controls the secretion of a specific humoral factor responsible for regulating the intestinal absorption of iron. If such a hormone exists, it is unlikely to be erythropoietin. Erythropoietin administration to animals has no effect on iron absorption. Conversely, intestinal absorption and the iron stores influence the rate of erythropoiesis. Iron loading of anemic dogs considerably stimulates hemoglobin synthesis. 

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