losartan-potassium and Drug-Overdose

Observational studies have shown a strong positive correlation between the severity of anemia and the risk of poor outcomes in patients with chronic kidney disease (CKD). This observation was initially taken to imply that adverse outcomes in CKD are caused by anemia. However, the assumption of causality ignores the possibility that anemia and adverse outcomes might be unrelated and that both are caused by underlying inflammation, oxidative stress and comorbid conditions. Randomized clinical trials of anemia correction have revealed an increased risk of adverse cardiovascular outcomes in patients assigned to normal, rather than subnormal, hemoglobin targets. As a result, correction of anemia is now considered potentially hazardous in patients with CKD. Notably, individuals who did not reach the target hemoglobin level in the clinical trials, despite receiving high doses of erythropoietin and iron, experienced a disproportionately large share of the adverse outcomes. These observations point to overdose of erythropoietin and iron, rather than anemia correction per se, as the likely culprit. This Review explores the reasons for the apparent contradiction between the findings of observational studies and randomized clinical trials of anemia treatment in CKD. I have focused on data from basic and translational studies, which are often overlooked in the design and interpretation of clinical studies and in the formulation of clinical guidelines.

Topics: Anemia; Animals; Blood Platelets; Blood Pressure; Causality; Chronic Disease; Comorbidity; Dose-Response Relationship, Drug; Drug Overdose; Endothelin-1; Erythropoietin; Hemoglobins; Humans; Hypertension; Kidney Diseases; Kidney Failure, Chronic; Morbidity; Nitric Oxide; Oxidative Stress

The cytokine erythropoietin protects the heart from ischaemic injury, in part by preventing apoptosis. But appropriate dose of erythropoietin for the protection of injured heart has not been studied. While we were researching the cardiac protective effects of erythropoietin in acute myocardial infarction, we experienced two cases of accidental nearly ten times overdose administration of erythropoietin up to 318,000 units instead of 33,000 units on the second day of three scheduled days of treatment. So a total of 384,000 units of erythropoietin were administered during three days. In case 1, the ALT level soared up to 386 U/l on the second day of administration and decreased slowly. It was back to normal state 3 months later. The AST level increased slowly up to 391 U/l and normalized 3 months later. Haemoglobin level was elevated up to 15.7 g/dl (14.7 g/dl at admission) and, 3 months later, normalized to 14.8 g/dl. In case 2, the ALT level was elevated up to 98 U/l on the second day of administration and decreased slowly. Three months later, the ALT level was normalized. The AST level also increased slowly up to 71 U/l and normalized 3 months later. Haemoglobin level was elevated up to 15.6 g/dl (13.8 g/dl at admission) and, 3 months later, normalized to 13.6 g/dl. In these two cases reported, these patients, even after massive overdose, tolerated it relatively well and the only side-effects we found were elevated liver enzyme and haemoglobin levels.

Topics: Adult; Alanine Transaminase; Aspartate Aminotransferases; Drug Overdose; Erythropoietin; Hemoglobins; Humans; Liver; Male; Middle Aged; Myocardial Infarction; Recombinant Proteins

Topics: Anemia; Blood Transfusion, Autologous; Drug Overdose; Epoetin Alfa; Erythropoietin; Ferritins; Humans; Iron Deficiencies; Orthopedic Procedures; Platelet Count; Preoperative Care; Recombinant Proteins; Research Design; Sample Size

Erythropoietin (EPO) is commonly used to treat anemias secondary to renal failure, malignancy, and AIDS. Although therapeutic complications are well described, overdose is rare. A 42-y-o man with AIDS confused his instructions for self-administration of interferon and EPO and began injecting himself daily with 10,000 units of EPO for several weeks. He presented with confusion, pain in his abdomen and feet, and a hemoglobin of 23.2 g/dLwith a hematocrit of 77.1%. The patient was treated with iv fluids, phlebotomy and 2 sessions of erythropheresis which removed 898 mL and 640 mL of red blood cells, respectively; his hemoglobin remained between 12-14 g/dL and symptoms resolved. His only sequelae involved skin loss over his toes, which did not require grafting. This rare case of EPO overdose highlights the complications of essential erythrocytosis, with central nervous system, peripheral, and presumed mesenteric ischemia.

Topics: Acquired Immunodeficiency Syndrome; Adult; Cytapheresis; Diagnosis, Differential; Drug Overdose; Emergency Treatment; Erythropoietin; Humans; Male; Sarcoma, Kaposi

Deliberate self-administration of recombinant human erythropoietin (rHuEpo) in a patient without anemia has never been documented. The case of a 62-year-old man who worked in an allied health care field and surreptitiously injected the drug, causing his hematocrit to increase to a dangerously high level is presented. Resultant complications of the misuse of erythropoietin in this patient included worsening hypertension, exacerbation of chronic lung disease and development of new onset angina. Medical management consisted of endotracheal intubation with mechanical ventilation, intravenous hydration, and serial phlebotomy. The unusual possibility of erythropoietin abuse must be added to the differential diagnosis with a patient with unexplained polycythemia. This case highlights the potential abuse of biological growth factors that may mask medical conditions.

Topics: Angina Pectoris; Bloodletting; Delusions; Diagnosis, Differential; Drug Overdose; Erythropoietin; Fluid Therapy; Hematocrit; Humans; Hypertension; Lung Diseases, Obstructive; Male; Middle Aged; Polycythemia; Respiration, Artificial; Self Medication; Substance-Related Disorders