Management of orthostatic hypotension.

The pathogenesis, clinical manifestations, and management of orthostatic hypotension (OH) are reviewed. OH is a decline in blood pressure that occurs when one moves from a lying to a standing position that results in symptoms of cerebral hypoperfusion, most commonly lightheadedness and syncope. The disorder may result from primary autonomic disorders, such as Shy-Drager syndrome; reversible nonautonomic causes, such as reduced blood volume; underlying diseases, such as diabetes mellitus; and drugs. Elderly people are predisposed to OH. The diagnosis of OH is based on the documentation of postural hypotension accompanied by symptoms of cerebral ischemia. The goal of therapy is to relieve symptoms. Nonpharmacologic approaches are preferred and include increasing sodium intake, avoiding rapid postural changes, and wearing elastic garments. OH is difficult to treat pharmacologically because of varying responses and adverse effects. The drug of choice for all types of OH is fludrocortisone acetate, although caution must be used in patients with congestive heart failure. Prostaglandin synthetase inhibitors can also be used for all types of OH but have had more limited success. Sympathomimetics with or without monoamine oxidase inhibitors, beta-adrenergic antagonists, and ergot alkaloids should be administered only to patients with certain types of OH, and patients must be monitored closely. Clonidine, midodrine, yohimbine, octreotide, dopamine antagonists, desmopressin, and epoetin alfa have not been well studied and should be limited to patients with severe, refractory disease. Although no uniformly effective treatment regimen exists, OH can often be adequately managed with a combination of nondrug and drug therapies.

The use of norfloxacin in a university hospital.

Because of increasing norfloxacin use and the development of resistant organisms, an evaluation was undertaken in a University Hospital to assess the appropriateness of norfloxacin for the treatment of urinary tract infections and to calculate the potential cost savings associated with more cost-effective antibiotic therapy. Medical records of 64 patients receiving norfloxacin for a 31-day period were concurrently reviewed. Of these, 58 patients were treated for urinary tract infections and four patients received urinary tract infection prophylaxis. Fourteen patients were prescribed solely empiric therapy whereas an additional 44 patients received definitive treatment confirmed by culture results. Based on the predetermined criteria, norfloxacin use for the definitive treatment of urinary tract infections was deemed to be appropriate in 34 of the 44 patients. Three additional courses of therapy were also judged to be appropriate due to documented signs and symptoms associated with urinary tract infections, despite cultures with less than 10(5) colony forming units per mL urine. Reasons for inappropriate use in the remaining seven patients included isolation of fewer bacteria than required by the criteria in asymptomatic patients (3 cases), isolation of organisms not sensitive to norfloxacin (1 case) and lack of dosage adjustment for renal insufficiency (3 cases). Nineteen of 32 evaluable inpatients (59%) received norfloxacin when a less expensive, equally effective agent was available. Although savings from more cost-effective therapy of urinary tract infections are minimal, due to the potential emergence of resistant organisms, norfloxacin should be reserved for infections not amenable to treatment with other oral antibiotics.

Use of albumin in a university hospital: the value of targeted physician intervention.

Results of a preliminary study of albumin use at the University of Michigan Hospital were shared with one surgical service (thoracic surgery) that had a documented high rate of inappropriate use. To determine the effectiveness of this targeted educational intervention in reducing inappropriate use and associated drug costs, albumin prescribing for all adult inpatients at University Hospital over a 30-day period was assessed in a retrospective review. Eighty-six patients used a total of 843 units, a ten percent reduction in total albumin use. Albumin administration to thoracic surgery patients decreased by 38 percent. The 35 percent reduction in inappropriate albumin use by this service (Fisher's exact test, p less than 0.001) was associated with an estimated annual cost savings of +83,500. Inappropriate albumin use by other medical services generally increased over previously measured levels. This study demonstrated the effectiveness of targeted educational interventions in reducing inappropriate albumin use and thereby controlling rising healthcare costs.

Fatal hepatotoxicity induced by hydralazine or labetalol.

Antihypertensive agents have been associated with adverse reactions that, if unrecognized by health practitioners, may have devastating consequences. The pattern of hepatotoxicity observed during therapy with the vasodilator hydralazine is highly variable, often making its diagnosis difficult. Serious hepatic injury induced by the alpha- and beta-adrenergic receptor antagonist labetalol has only recently been reported and therefore, many clinicians may be unaware of this adverse effect. Familiarity with the clinical features and course of hydralazine- and labetalol-induced hepatic injury is necessary to ensure prompt recognition and discontinuation of the agent.

Management of uremic bleeding.

The pathogenesis, clinical manifestations, and management of uremic bleeding are discussed, and the role of pharmacologic intervention in the treatment of this disorder is emphasized. Care of the patient with uremia is frequently complicated by spontaneous, life-threatening bleeding episodes. Although not completely elucidated, this bleeding tendency may be associated with ineffective binding of the von Willebrand Factor (a component of factor VIII) to platelet membranes, acquired storage-pool deficiency, and anemia. Uremic patients may develop a number of clinical manifestations, including epistaxis, purpura, and bleeding from the gastrointestinal tract. Dialysis, while frequently effective for the short term, does not completely correct platelet dysfunction. Red-blood-cell transfusions may partially reduce bleeding time; however, their use places the patient at risk for viral infection. Cryoprecipitate is often used in acute situations because of its short onset of action. Desmopressin is likewise effective when an immediate effect is desired. Conjugated-estrogen therapy appears beneficial for patients in whom a long-lasting effect is desired. Management of uremic bleeding may include dialysis, red-blood-cell transfusions, cryoprecipitate, desmopressin, and conjugated estrogens. Adverse effects, particularly the risk of viral infection, as well as duration of action, must be considered in therapy selection.

Pharmacologic management of Paget's disease.

The pathogenesis, clinical features, indications for therapy, and current pharamacologic management of Paget's disease are reviewed. Paget's disease is a bone disorder of unknown etiology primarily affecting the elderly. Overactive bone resorption leads to the accelerated formation of disorganized, weak bone. Pain and fractures are common clinical features. Neurologic, cardiovascular, metabolic, and neoplastic complications are also reported. Because most patients are asymptomatic, the disease is often detected during routine roentgenography or laboratory tests. Primary indications for pharmacologic intervention include bone pain, neural compression, immobilization hypercalcemia or hypercalciuria, cardiac failure, and orthopedic surgery. Recurrent or non-healing fractures and rapidly progressing complications are additional indications. Drugs used in the management of Paget's disease include calcitonin, etidronate disodium, and plicamycin. Although these agents are efficacious, each has disadvantages. Clinical resistance to animal calcitonins may develop, and the cost of therapy may be prohibitive. Etidronate may induce ostemalacia. The use of plicamycin is limited by potentially severe toxicities. Dichloromethylene and aminohydroxypropylidene are promising diphosphonate compounds but are still investigational In those patients who are unresponsive to single-agent regimens, combination therapy may prove effective. Although many patients with Paget's disease do not require pharmacologic therapy, calcitonin and etidronate are the agents of choice when it is indicated.

Albumin utilization in a university hospital.

The inappropriate use of high-priced agents such as human serum albumin significantly contributes to the rising cost of medical care. A utilization review was conducted at the University of Michigan Hospital in order to identify the appropriateness of use of this agent. Criteria were developed and prescribing was retrospectively evaluated for 81 patients. Of the 935 units administered to these patients, 692 (74 percent) were judged to be inappropriate. This inappropriate use accounted for a projected annual expenditure of nearly $281,000. Interventions have previously demonstrated success in improving prescribing.

Drug therapy of hypertensive crises.

The clinical features, pathogenesis, and pharmacologic management of hypertensive crises are reviewed, with emphasis on newer therapies. Hypertensive crises may be divided into hypertensive emergencies and hypertensive urgencies. Hypertensive emergencies, in which acute organ damage exists, require blood pressure reduction within one hour. In hypertensive urgencies no acute end-organ damage has yet occurred; however, blood pressure should be controlled within 24 hours. Factors that may precipitate a hypertensive crisis include renovascular hypertension, acute glomerulonephritis, head injuries, renin- or catecholamine-secreting tumors, antihypertensive-therapy withdrawal syndromes, eclampsia, and ingestion of tyramine by patients receiving monoamine oxidase inhibitors. The traditional drug of choice for therapy of hypertensive emergencies is sodium nitroprusside. Intravenous labetalol produces a prompt, controlled reduction in blood pressure and is a promising alternative. Other agents used are diazoxide, trimethaphan camsylate, hydralazine, nitroglycerin, and phentolamine. However, all these agents have disadvantages, including unpredictable antihypertensive effects, difficult blood pressure titration, and serious potential adverse effects such as profound hypotension, reduced renal blood flow, and increased myocardial workload. Most patients with hypertensive urgencies can be effectively treated with orally or sublingually administered agents. Older regimens of reserpine, methyldopa, or guanethidine, with their slow onsets and long durations of action, have been largely replaced by clonidine and nifedipine. Captopril and minoxidil have also been used with some success. Despite the lack of comparative trials with traditional agents, demonstrated efficacy and desirable pharmacologic characteristics have made several new agents acceptable for therapy of hypertensive crises.

Crossed-immunoelectrophoretic analyses of Trypanosoma cruzi epimastigote, metacyclic, and bloodstream forms.

Sonicated suspensions of epimastigote, metacyclic, or bloodstream forms of Trypanosoma cruzi were emulsified in Freund's complete adjuvant. Rabbits immunized with epimastigotes or metacyclics received five intramuscular (i.m.) injections of 1 x 10(9) sonicated trypanosomes at weekly intervals. Immunization with bloodstream forms included three i.m. injections of 5 x 10(7) and six injections of 2 x 10(8) sonicated trypanosomes. Selected antisera from these rabbits were employed in crossed immunoelectrophoretic studies against the homologous or heterologous extracts of sonicated trypanosomes. Extracts of epimastigote, metacyclic, and trypomastigotes produced 31, 29, and 11 precipitin peaks respectively against the homologous rabbit antisera. Tandem, crossed-immunoelectrophoresis of these extracts against antiepimastigote or antimetacyclic sera revealed that epimastigotes or metacyclics may each have at least four antigens that did not appear to be shared by the other, whereas each of these forms may have at least eight or nine antigens that were not detected with extracts from trypomastigotes. Cross-absorptions of antiepimastigote or antimetacyclic sera with live trypanosomes caused marked reductions in the numbers of precipitin peaks formed against the homologous extracts, but cross-absorptions with sonicated suspensions of epimastigotes or metacyclics showed that epimastigotes or metacyclics each have at least two antigens that were not detected in extracts of the other. Differentiation appeared to be accompanied by antigenic change. More antigens appear to be shared by epimastigotes and metacyclic forms than by trypomastigotes and epimastigotes or metacyclics.