Erythropoietin

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Chapter: Essential pharmacology : Drugs Affecting Blood And Blood Formation

Erythropoietin (EPO) is a sialoglycoprotein hormone (MW 34000) produced by peritubular cells of the kidney. It is essential for normal erythropoiesis.


ERYTHROPOIETIN

 

Erythropoietin (EPO) is a sialoglycoprotein hormone (MW 34000) produced by peritubular cells of the kidney. It is essential for normal erythropoiesis. Anaemia and hypoxia are sensed by kidney cells rapid secretion of EPO acts on erythroid marrow and:

 

a)  Stimulates proliferation of colony forming cells of the erythroid series.

b)  Induces haemoglobin formation and erythroblast maturation.

c)   Releases reticulocytes in circulation.

 

EPO binds to specific receptors on the surface of its target cells. The EPO receptor is a JAKSTAT-kinase binding receptor that alters phosphorylation of intracellular proteins and activates transcription factors to regulate gene expression. It induces erythropoiesis in a dose dependent manner, but has no effect on RBC lifespan.

 

The recombinant human erythropoietin (Epoetin α, β) is administered by i.v. or s.c. injection and has a plasma t½ of 6–10 hr.

 

Use

 

The primary indication for epoetin is anaemia of chronic renal failure which is due to low levels of EPO; 25–100 U/kg s.c. or i.v. 3 times a week (max. 600 U/kg/week) raises haematocrit and haemoglobin, reduces need for transfusions and improves quality of life. It is prudent to start with a low dose and titrate upwards to keep haematocrit between 30–36%, and Hb 10–12 g/ dl. Some recent studies have indicated that dose reduction by about 30% is possible when epoetin is given s.c. compared to i.v. Exercise capacity and overall wellbeing of the patients is improved. Most patients have low iron stores; require concurrent parenteral/oral iron therapy for an optimum response. Other uses are:

 

·      Anaemia in AIDS patients treated with zidovudine.

·      Cancer chemotherapy induced anaemia.

·      Preoperative increased blood production for autologous transfusion during surgery.

 

Adverse Effects

 

Epoetin is nonimmunogenic. Adverse effects are related to sudden increase in haematocrit, blood viscosity and peripheral vascular resistance (due to correction of anaemia). These are—increased clot formation in the AV shunts (most patients are on dialysis) hypertensive episodes, occasionally seizures. Flu like symptoms lasting 2–4 hr occur in some patients.

 

HEMAX 2000 IU/ml and 4000 IU/ml vials; EPREX 2000 IU, 4000 IU and 10000 IU in 1 ml prefilled syringes; ZYROP (epoetin β) 2000 IU and 4000 IU vials.


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