Drugs of today
-
Pain is probably one of the most common cancer symptoms. In addition to being a major source of suffering and disability, cancer pain is extremely frightening for patients and their families. This review discusses the current options for treating cancer pain, focusing on the pharmacological agents currently available and briefly exploring some of the surgical options for pain management. The authors propose to adjust the World Health Organization (WHO) pain management ladder from its current three-step approach to a more sophisticated five-step algorithm that includes physical and psychological modalities along the entire continuum of care and adds two more steps related to neuromodulative and neurodestructive procedures once the opioids fail.
-
This article will review the clinical development of ibritumomab tiuxetan, a yttrium-90-conjugated monoclonal antibody to CD20, for patients with relapsed B-cell non-Hodgkin's lymphomas. Ibritumomab is the murine parent anti-CD20 antibody that was engineered to make the human chimeric antibody rituximab. Tiuxetan is an MX-DTPA chelator that is linked to ibritumomab to form ibritumomab tiuxetan. ⋯ Finally, a fifth trial treated 30 patients with mild thrombocytopenia using 0.3 mCi/kg (90)Y-ibritumomab tiuxetan and found an overall response rate of 83%. (90)Y-ibritumomab tiuxetan radioimmunotherapy is a new treatment modality for patients with relapsed B-cell non-Hodgkin's lymphoma. The advantages of this therapy are that it utilizes targeted radiation in a single-dose, outpatient schedule that is well tolerated and accepted by the patient. Future trials will build on these results and determine at what point in the disease course this modality can best be utilized to maximize the benefits to the patient.
-
Many advances have improved the care of critically ill patients, but only a few have been through the use of pharmaceutical agents. Recently, the US Food and Drug Administration (FDA) approved drotrecogin alfa (activated), or recombinant human activated protein C, for the treatment of patients with a high risk of death from severe sepsis. Drotrecogin alfa (activated) has antiinflammatory, antithrombotic and fibrinolytic properties. ⋯ This rise in blood pressure is often significant enough that endogenous catecholamines can be decreased and frequently discontinued entirely. Early withdrawal of the vasopressin replacement infusion results in recurrent hypotension. Unfortunately, randomized, blinded, placebo-controlled trials showing improvement in long-term outcomes such as mortality and length of stay are still lacking.
-
Darbepoetin alfa is a novel erythropoiesis-stimulating protein developed for the treatment of anemia. It is a hyperglycosylated analog of recombinant human erythropoietin with the same mechanism of action as erythropoietin, but with a three-fold longer terminal half-life after intravenous administration than recombinant human erythropoietin and the native hormone both in animal models and in humans. Clinical studies in patients with chronic renal failure either receiving or not receiving dialysis have shown that darbepoetin alfa is equivalent to recombinant human erythropoietin in terms of increases in hemoglobin concentration, percentage of patients achieving target hemoglobin concentration and average time to reach target hemoglobin concentration, although darbepoetin alfa is administered less frequently (once weekly or every other week). ⋯ There are no reports of antibody formation associated with darbepoetin alfa in chronic renal failure patients, and three cases of antibody formation, with neutralizing activity in one of the cases, have been reported in cancer patients. However, no cases of antibody-mediated pure red cell aplasia have been reported. The longer half-life of darbepoetin alfa, together with a similar efficacy and safety profile, confers the clinical advantage over recombinant human erythropoietin of allowing a less frequent dosing (once weekly or every other week versus one to three times weekly in renal patients), thus reducing health-care utilization and probably improving patient compliance.
-
Upper gastrointestinal (GI) bleeding is a common cause of hospitalization and despite effective endoscopic treatments, it is responsible for a significant societal burden due to the associated morbidity, mortality and financial implications. As it has long been hypothesized that acid suppression may help to improve outcomes of patients with gastroduodenal ulcer bleeding, acid-suppressing agents such as histamine-2 receptor antagonists (H(2)RAs) and intravenous (i.v.) proton pump inhibitors (PPIs) have been the subject of study. However, results for H(2)RAs show little if any improvement in outcomes, which may be explained by their insufficient acid suppression and the existence of rapid drug tolerance. ⋯ Randomized trials and meta-analyses have shown that acute high-dose i.v. PPI administration leads to improvements in patients undergoing endoscopic hemostasis for bleeding gastroduodenal ulcers and who also show high risk for rebleeding. However, the optimum dose, timing of administration and subgroups of patients who will benefit most from such treatment need to be further characterized.