Pharmacotherapy
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Review Comparative Study
Dose conversion from recombinant human erythropoietin to darbepoetin alfa: recommendations from clinical studies.
Recombinant human erythropoietin (r-HuEPO, epoetin alfa), is an established and effective treatment for anemia associated with both chronic kidney disease (CKD) and cancer and has improved the management of anemia over alternatives such as transfusion. Darbepoetin alfa is a new erythropoietic agent with a 3-fold longer half-life and increased in vivo potency relative to r-HuEPO. These properties allow patients to be treated with longer dosing intervals than with r-HuEPO. ⋯ Appropriate guidance for conversion of patients with CKD from r-HuEPO to darbepoetin alfa is provided in the approved United States package insert for darbepoetin alfa. In patients who are prescribed darbepoetin alfa, either by conversion from r-HuEPO or as de novo treatment, therapy should begin according to recommendations in the package insert, after which, doses should be titrated individually according to each patient's hemoglobin response. Dosing data from oncology clinical studies, although not necessarily applicable to CKD, indicate similar potency ratios between r-HuEPO and darbepoetin alfa, and in addition affirm the finding that, as the interval between doses of darbepoetin alfa is increased, hemoglobin response is maintained.
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Sepsis and acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) are associated with high mortality rates despite recent therapeutic advances. Both disease states involve uncontrolled host defense responses that lead to inflammation, endothelial damage, enhanced coagulation, diminished fibrinolysis and fibroproliferation to produce microthrombi, and relative adrenal insufficiency. Corticosteroids inhibit the host defense response and may offer an inexpensive therapeutic option. ⋯ A multicenter study investigating stress-dose methylprednisolone for ARDS is under way and should provide valuable information. Sufficient data support stress-dose hydrocortisone therapy for vasopressor-dependent septic shock. Stress-dose methylprednisolone therapy for ALI-ARDS requires further study but may be warranted in cases of refractory infection-induced ARDS when impending mortality is likely.
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Case Reports
Angiotensin II receptor blocker-associated angioedema: on the heels of ACE inhibitor angioedema.
Angioedema and cough are known side effects of angiotensin-converting enzyme (ACE) inhibitors. Angiotensin-converting enzyme is a potent inhibitor of kinase II, which facilitates the breakdown of bradykinin. An increase in bradykinin levels results in continued prostaglandin E2 synthesis, vasodilation, increased vascular permeability, and increased interstitial fluid. ⋯ We report angioedema associated with losartan (an ARB) in a patient who had experienced angioedema secondary to enalapril (an ACE inhibitor). Almost half of patients with ARB-associated angioedema also had developed angioedema while receiving ACE inhibitor therapy. Clinicians should exercise caution when using ARBs in patients with a history of angioedema secondary to ACE inhibitors.