Acute renal failure associated with immunoglobulin therapy.

Four cases of acute renal failure induced by intravenous immunoglobulin are presented, and the literature on the subject is reviewed. The clinical course varies from asymptomatic serum creatinine elevation to anuric renal failure occurring within days of the institution of therapy, followed by the rapid recovery of renal function after termination of therapy. The renal histology demonstrates severe tubular vacuolization with cellular swelling and preservation of the brush border. Glomerular endothelial, mesangial, and epithelial cells also may demonstrate swelling and vacuolization. There is no evidence for inflammatory or immune complex-mediated etiologies. The immunoglobulins or carbohydrate additives in the preparations appear to have a unique and reversible effect on the glomerular and tubular cell function.

Serum vancomycin concentrations: reappraisal of their clinical value.

Although monitoring serum vancomycin concentrations in clinical practice is commonplace, the data supporting this practice are meager. The rationale for monitoring these concentrations is to improve the effectiveness and/or reduce the toxicity of the drug. However, there are no data to suggest that monitoring serum vancomycin concentrations improves the effectiveness of therapy. In addition, despite many case reports of vancomycin-associated nephrotoxicity and ototoxicity, it is unclear whether this agent truly causes such conditions. Moreover, there is no evidence that adherence to specific ranges of vancomycin concentrations will preclude these events. Finally, vancomycin pharmacokinetics are sufficiently predictable that adequate serum drug concentrations can be obtained with dosing methods that take into account the patient's age, weight, and renal function. Safe and effective vancomycin dosage regimens can be constructed with these empirical dosing methods, whereas monitoring vancomycin levels increases the cost of therapy without improving the safety or efficacy of treatment.

Drug prescribing for patients with changing renal function.

The prevalence and course of renal dysfunction in hospitalized patients and the prescribing of renally eliminated drugs in these patients were studied. All adult inpatients at a large teaching hospital who had a serum creatinine concentration assay performed were screened for renal dysfunction (an estimated creatinine clearance of < 40 mL/min). Renally compromised patients were monitored for changes in renal function. The regimens of selected renally eliminated drugs prescribed for these patients were compared with the manufacturers' recommended dosages for patients with renal compromise. Of the 3800 patients screened, 195 (5%) had renal dysfunction; most of these patients were older than 65 years. Although improvements in renal function were noted in 49 (30%) of the 169 patients with renal dysfunction who were not receiving hemodialysis, elderly patients were less likely to show an improvement in renal function. Of the 60 patients with renal dysfunction for whom a renally eliminated drug was prescribed, 27 (45%) were receiving dosages in excess of the manufacturers' recommendations. Changes in creatinine clearance estimates are common in hospitalized patients with renal impairment. Programs designed to alert physicians to potentially excessive dosages of renally eliminated drugs need to be sensitive to these changes.

Central nervous system reactions to histamine-2 receptor blockers.

PURPOSE: To review the incidence, risk factors, pharmacology, and management of central nervous system reactions to histamine-2 receptor (H2) blockers. DATA IDENTIFICATION: English-language articles were identified through a search of the MEDLINE and Current Contents data-bases. Bibliographies of retrieved articles were examined for relevant articles. Case reports submitted to the Food and Drug Administration through 19 September 1989 were obtained. STUDY SELECTION: Studies on the association between central nervous system toxicity (psychosis, agitation, hallucinations, delirium, mental status changes, disorientation, confusion, irritability, obtundation, or hostility) and H2 blockers were analyzed. DATA EXTRACTION: All data on the incidence of and potential predisposing factors for central nervous system reactions to H2 blockers were analyzed. Limitations of the data are discussed. RESULTS OF DATA SYNTHESIS: Central nervous system toxicities have been associated with all H2 blockers. These reactions generally occur during the first 2 weeks of therapy and resolve within 3 days of drug withdrawal. The estimated incidence of central nervous system reactions is 0.2% or less in outpatients and 1.6% to 80% in hospitalized patients. Cimetidine is most frequently associated with these reactions; however, no clear evidence exists that one H2 blocker is more likely than another to cause a reaction. Risk factors for central nervous system reactions have been proposed, but only advanced age has some, albeit limited, data to support it as a risk factor. Studies have only infrequently established causality and there have been difficulties in establishing risk factors for an relative incidences of a phenomenon that occurs infrequently in outpatients and that can be multifactorial in origin. CONCLUSIONS: All H2 blockers are associated with central nervous system reactions. There is no clear evidence of a higher rate of reactions with one H2 blocker compared with another.

Protein binding of vancomycin in a patient with immunoglobulin A myeloma.

Atypical vancomycin pharmacokinetics were observed in an immunoglobulin A myeloma patient. Drug concentrations in serum were extremely elevated, the elimination half-life was prolonged despite normal renal function, and the vancomycin therapy was ineffective. Extensive binding of vancomycin, presumably by high concentrations of an aberrant immunoglobulin A protein, may have accounted for these observations.

Monoamine oxidase inhibitors and weight gain.

Weight gain associated with antidepressant therapy is a common problem that often results in noncompliance. Some authors suggest that monoamine oxidase inhibitors (MAOI) are less likely to produce weight gain than tricyclic antidepressants. This paper addresses the relative potential for weight gain with the MAOI. Assessing the potential for antidepressant-induced weight gain necessitates separating the weight changes associated with alterations in mood disorders from those due to drug-induced alterations in appetite control. The mechanisms of appetite control are reviewed briefly followed by proposed mechanisms by which the MAOI may alter this control. A literature review suggests that phenelzine is the MAOI most likely to induce weight gain; reports of isocarboxazid-induced weight gain are less common. There are no cases of tranylcypromine-induced weight gain in the literature that are clearly associated with the drug. The MAOI probably have different effects on the mechanisms of appetite control.

Development of a hospital-based adverse drug reaction reporting program.

The development of an adverse drug reaction (ADR) reporting program at a university hospital is described in this article. Critical steps in the development process included identifying the personnel responsible for the program, defining ADRs and reportable ADRs, developing an ADR data form, promoting the program, and providing feedback to the health care professionals of the institution. A standing ADR subcommittee was formed to develop, implement, and coordinate the program. Two approaches to data collection were used: the standard format of voluntary reporting and a targeted drug method (targeting specific agents, typically newly approved drugs or those in which new, or potentially serious adverse reactions have been noted). The program was promoted through memorandums to department chairpersons and through a P & T Committee newsletter. The number of ADRs reported per quarter steadily increased from nearly zero to approximately 60 cases per quarter. Details on the implementation of this ADR program, its limitations and successes, are described.