Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Effective monitoring of chronic hemodialysis patients treated with recombinant human erythropoietin (r-HuEPO; EPOGEN [epoetin alfa], AMGEN Inc, Thousand Oaks, CA) includes an initial evaluation of the patient, the patient's anemia, and the patient's iron stores. Assessment of iron stores includes obtaining hematocrit and hemoglobin levels, reticulocyte count, red cell indices, serum ferritin level, transferrin percent saturation, and the patient's transfusion history. If iron stores are inadequate to support the increased erythropoiesis induced by the therapy, appropriate iron replacement therapy should be provided. Monitoring also involves assessment of BP (and its control), because development or exacerbation of hypertension is the most significant side effect associated with this treatment. Because the dose-response relationship for r-HuEPO therapy has been clearly documented, a target hematocrit and target rate of increase in hematocrit can be established. As anemia improves, continued monitoring of hematocrit, hemoglobin, red cell indices, serum ferritin level, and transferrin percent saturation will ensure that depleted iron stores are noted and treated as necessary. Heparin requirements during dialysis, blood chemistries, and blood access problems should also be monitored. No data currently exist suggesting that dialyzer reuse is compromised by r-HuEPO therapy. Quality-of-life surveys show improvement with r-HuEPO treatment and effective reduction of anemia. There is also some indication that morbidity is lessened and survival improved when anemia is treated with r-HuEPO therapy.
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PMID:Monitoring considerations in recombinant human erythropoietin therapy. 266 80

Onset or exacerbation of hypertension has been observed as a possible complication of recombinant human erythropoietin (r-HuEPO; EPOGEN [epoetin alfa], AMGEN Inc, Thousand Oaks, CA) therapy for the anemia of end-stage renal disease. This effect is attributed to an overly rapid rise in the hematocrit level and the accompanying consequences, which include increased hemoglobin, blood viscosity, and red cell mass, as well as normalization of the cardiac index of anemia. The sluggish response to these changes by compensatory mechanisms, resulting in increased peripheral vascular resistance, may be the means by which BP becomes elevated during therapy. Although more than one third of patients receiving r-HuEPO therapy have developed sustained increases in diastolic pressure of 10 mmHg or more, this potential problem is controllable. Prevention or correction of hypertension is accomplished by initiating therapy with a low-dose regimen that is slowly increased, thereby preventing a rapid rise in the hematocrit level. Drug intervention, together with dialysis prescription modification and restriction of dietary salt and fluid to regulate weight, can effectively control BP. Discontinuation of therapy for severe and uncontrollable hypertension rarely becomes necessary.
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PMID:Management of blood pressure changes during recombinant human erythropoietin therapy. 266 81

The treatment of severe anemia related to end-stage renal disease with recombinant human erythropoietin (r-HuEPO; EPOGEN, [epoetin alfa] AMGEN Inc, Thousand Oaks, CA) has been investigated in more than 1,500 hemodialysis patients worldwide. The goal of r-HuEPO therapy is to maintain the hematocrit level at 35%, with a recommended starting dose of 150 mg/kg of body weight, administered intravenously after each dialysis three times a week for 6 to 12 weeks. Hematocrit levels should be measured at least once a week and the dose adjusted in increments or decrements of 10 mg/kg to 25 mg/kg to keep the hematocrit level between 33% and 40%. Patients receiving r-HuEPO must be normotensive. A history of seizures has been cause for exclusion from clinical trials. Patients' iron status should also be adequate at the onset of therapy, which is defined as a serum ferritin level of 100 ng/mL or more, and a transferrin saturation of more than 20%. Iron status and BP must be carefully monitored, and abnormalities corrected with iron supplementation, ultrafiltration, or antihypertensive medication. The lack of controlled studies makes determination of the actual incidence of side effects difficult, but it appears to be minimal. Possible side effects of r-HuEPO therapy include hypertension, seizures, myalgia, malaise, headache, gastrointestinal distress, and injected conjunctiva. The major benefits of r-HuEPO therapy are reduced need for transfusion and marked improvement in quality-of-life parameters.
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PMID:Who should receive recombinant human erythropoietin? 266 84

Erythropoietin is produced mainly by the kidneys and stimulates erythropoiesis in the bone marrow. Chronic renal failure is characterized by anemia, which is principally caused by erythropoietin deficiency. Recombinant human erythropoietin (r-hEPO) corrects the anemia of chronic renal disease and improves patient well-being, exercise tolerance, and cognitive function. The clinical pharmacology, efficacy, safety, and tolerance of r-hEPO are presented. Four major studies attest to r-hEPO's efficacy in the treatment of anemia of chronic renal disease and document potential toxicities of hypertension, iron deficiency, thrombosis, and bone pain. Careful attention to the extent of correction of the hematocrit, increased heparinization during hemodialysis therapy, and compliance with dietary restrictions may minimize the incidence and severity of adverse reactions. Resistance to r-hEPO may be due to iron deficiency, aluminum toxicity, or inflammation, including infection. Potential future uses of r-hEPO include the treatment of various other anemias, such as those seen in sickle cell anemia, rheumatoid arthritis, and autologous blood donation. Controlled clinical studies in these areas have not been reported.
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PMID:Recombinant human erythropoietin. 266 69

The chemistry, pharmacology, pharmacokinetics, clinical uses and efficacy, adverse effects, drug interactions, dosage and administration, and formulary considerations of epoetin are described. Erythropoietin, a glycoprotein hormone primarily synthesized in the kidney, is the chief regulator of red blood cell production. Erythropoietin concentrations increase in response to a hypoxic state, resulting in increased red blood cell formation, accelerated hemoglobin production, and premature movement of reticulocytes into the circulation. The human gene responsible for the production of erythropoietin recently was cloned, and the recombinant product--epoetin--has been made available through mass production. The apparent volume of distribution of i.v. epoetin approximates the assumed plasma volume both in healthy volunteers and in patients with chronic renal failure. Little is known about the metabolism and route of elimination of epoetin and erythropoietin. Epoetin recently was approved by the FDA for treatment of anemia associated with chronic renal failure. Clinical trials in patients receiving hemodialysis or peritoneal dialysis and in predialysis patients with renal dysfunction demonstrate epoetin's efficacy. Other potential indications include augmentation of blood production in patients enrolled in autologous blood donation programs and treatment of anemias associated with rheumatoid arthritis, sickle cell disease, acquired immunodeficiency syndrome, cancer, and premature birth. The most frequent adverse effect associated with epoetin therapy is the worsening or development of hypertension. Other adverse effects include thrombocytosis, hyperkalemia, rise in serum urea concentration, iron deficiency, and flu-like symptoms. No drug interactions with epoetin have been reported in humans. The recommended starting epoetin dosage in patients with chronic renal failure is 50-100 IU/kg three times weekly. Epoetin is available only as an injection for i.v. or s.c. administration. Epoetin provides a new therapeutic approach to the treatment of anemia associated with chronic renal failure in hemodialysis, peritoneal dialysis, and predialysis patients. Benefits of epoetin therapy include reduced need for blood transfusions, the amelioration of anemic symptoms, and an improved quality of life.
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PMID:Epoetin: human recombinant erythropoietin. 268 Feb 41

Juxtaglomerular cell tumor of the kidney is an uncommon neoplastic cause of surgically curable hypertension. We report a case of erythrocytosis due to elevated serum erythropoietin with a renin secreting juxtaglomerular cell tumor.
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PMID:Juxtaglomerular cell tumor with elevation of serum erythropoietin. 268 72

Twenty patients treated with human recombinant erythropoietin (EPO) for 9 months were studied. The patients were randomly allocated to high flux (HF) or conventional dialysis (CD). Patients on HF used the F-60 or F-80 dialyzer, with a polysulfone membrane; QB: 470 ml/min; QD: 800 ml/min; t: 127 min; Kt/V: 1.01. Conventional dialysis patients used regenerated cellulosic membranes; QB: 297 ml/min; QD: 500 ml/min; t: 193 min; Kt/V: 1.05. Mean dose of EPO was 103 U/kg for HF patients and 112.4 U/kg for patients on CD. At 9 months, no significant differences were observed in HCT (HF 33.6% vs. CD 33.2%), BUN, serum creatinine, potassium, or phosphorus. Hemoconcentration during dialysis was 12% for HF and 17% for CD. Urea clearance decreased 7% for HF and 9% for CD, while clearance of creatinine, potassium, and phosphorus decreased between 14 and 18% with both treatments. Heparin requirements increased 10% in HF and 16% in CD. Hypertension was similar in both groups. One HF patient withdrew from the study because of hypertension and one HF patient had seizures related to hypertension. Vascular access clotting or hospitalizations were no different. High flux dialysis patients on EPO over a 9 month period did not have any catastrophic complications when HCT was maintained between 30 and 35%.
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PMID:Are high flux dialysis and erythropoietin treatment in a collision course? 268 11

Erythropoietin mRNA is detected primarily in kidney peritubular cells in response to hypoxia, and this tissue is the major adult source of the hormone. Erythropoietin can be assayed by in vivo or in vitro biological methods, or by radioimmunoassay, but only the in vivo assay can distinguish the most biologically active forms. The mature hormone consists of 166 amino acids and approximately 50% of the mature molecule (Mr 39,000) consists of carbohydrate. The gene is highly conserved among species studied, and is located on human chromosome 7, region q11-q22. Recombinant erythropoietin has been administered to haemodialysis patients and shown to increase haemoglobin levels, reticulocyte numbers and haematocrit. In transfusion-dependent patients, the need for regular transfusions was abrogated. Problems with hypertension have been noted in previously hypertensive patients, but the results of clinical trials with erythropoietin suggest that it will provide a valuable alternative therapy, for correcting some disorders of erythropoiesis.
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PMID:Erythropoietin. 268 15

The characteristics and uses of epoetin alfa (recombinant human erythropoietin) are described, and the issues associated with its use are discussed. The use of epoetin alfa was recently approved by FDA for the treatment of anemia associated with end-stage renal disease. Epoetin alfa acts on burst-forming and colony-stimulating units in the blood to raise hemoglobin and hematocrit levels, thus correcting the patient's anemia. It has a relatively short half-life and may be given either i.v. or s.c. Doses vary and must be adjusted according to the individual patient response. Clinical trials have involved doses ranging from 15 to 500 units/kg three times per week. Treatment causes a dose-related rise in the hematocrit, with subsequent improvement in the quality of life of dialysis patients. Adverse effects include hypertension, iron deficiency, and thrombocytosis. Additional research indicates that epoetin alfa may be effective in the correction of other uncomplicated anemias, such as those related to antineoplastic therapy. Issues facing hospital pharmacists and other health-care professionals include cost (the estimated cost of therapy is $4000 to $8000 per patient per year), appropriate use and potential misuse, use and reimbursement for indications not included in FDA-approved labeling, and restriction to particular prescribers. Because epoetin alfa does not produce therapeutic effects for at least 7 to 14 days, it is an ideal agent for formulary restriction. Epoetin alfa, like other products of biotechnology, will have substantial impact, both therapeutic and economic, on the practice of pharmacy. Hospital pharmacists need to be aware of these new therapies so that they may act quickly and decisively when issues associated with their use arise.
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PMID:Recombinant human erythropoietin. 269 Jun 6

Epoetin (recombinant human erythropoietin) is a sialoglycoprotein hormone that appears to be immunologically and biologically equivalent to the endogenous compound, enhancing erythropoiesis dose-proportionally. The therapeutic efficacy of epoetin in the treatment of anaemia associated with chronic renal failure has been established, with almost all patients responding with increases in haematocrit and haemoglobin levels, and improvements in quality of life. Some patients demonstrate relative epoetin resistance and require a higher dosage to achieve target haemoglobin and haematocrit levels. Maintenance of an adequate iron supply is essential and iron supplementation is recommended if serum ferritin is below 100 to 150 micrograms/L or transferrin saturation is less than 20%. The incidence of serious adverse effects may be reduced by maintaining a moderate rate of increase in the haematocrit with close monitoring of blood pressure and dialysis efficacy. Individual titration of epoetin dosage is recommended, with increases made in small increments to achieve haematocrit and haemoglobin levels of 30 to 33% and 10 to 12 g/dl, respectively, although the optimal haematocrit for each patient should be individually determined. Some patients will also require a modest increase in heparin dosage because of a possible increase in clotting tendency. Hypertension is the most common adverse effect in patients with chronic renal failure, occurring partially as a result of increasing blood viscosity and peripheral vascular resistance with the correction of anaemia. Maintenance epoetin therapy has been given for more than 2 years without a decrease in responsiveness and does not appear to adversely affect the outcome of renal transplantation. Thus, epoetin represents a significant therapeutic advance in the treatment of anaemia associated with chronic renal failure and should be considered a first option for these patients. Its potential value in the treatment of anaemia associated with other disorders and in facilitating autologous blood donation remains to be fully determined.
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PMID:Epoetin (recombinant human erythropoietin). A review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential in anaemia and the stimulation of erythropoiesis. 269 45


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