Zidovudine update: 1990.

Zidovudine (ZDV) is the only approved antiviral for the treatment of human immunodeficiency virus infection (HIV) in the U.S. Although newer antivirals have reached Phase II testing, ZDV is now the accepted therapy against which all other agents will be compared. Zidovudine 1500 mg/d was previously prescribed only to adult HIV-infected patients who had developed AIDS or AIDS-related complex (ARC). However, results obtained from recently completed studies indicate that a lower daily dose (500 mg) appears to be equivalent. In addition, ZDV therapy appears to be beneficial to asymptomatic HIV-infected patients with CD4+ counts less than 500/mm3. The toxicity profile of ZDV, previously obtained from patients receiving 1500 mg/d, consisted of either acute (e.g., fever, rash, headache) or chronic (e.g., anemia, neutropenia, myopathy) adverse effects. ZDV pharmacokinetics are variable within and between the different subpopulations of HIV-infected patients who have been studied. Bioavailability ranges from 50 to 70 percent, and values for half-life, total body clearance, and volume of distribution are 1-2 h, 20-40 mL/min/kg, and 1-2 L/kg, respectively. Drug interactions occur primarily between ZDV and other agents that undergo hepatic glucuronidation (e.g., probenecid, sulfamethoxazole) resulting in decreased ZDV clearance. ZDV is currently measured by HPLC, radioimmunoassay and FPIA; however, the role of therapeutic monitoring is currently under investigation. Studies of ZDV therapy in neonates, pediatric patients, patients with resistant isolates of HIV, and HIV-infected patients receiving combined treatment with other reverse transcriptase inhibitors or immunomodulators are ongoing.

Clinical considerations and costs associated with formulary conversion from tobramycin to gentamicin.

The clinical and financial effects of replacing tobramycin with gentamicin on the formulary of a 550-bed teaching hospital were studied. On the recommendation of the pharmacy and therapeutics committee, the formulary aminoglycoside was changed from tobramycin to gentamicin in June 1985; the nonformulary status of amikacin was unchanged. Five weeks later, physician compliance was assessed and the reasons for prescribing nonformulary aminoglycosides were determined. Two four-month-long evaluations were done at 6 and 18 months after implementation to assess patterns of use of nonformulary aminoglycosides. The impact on costs was determined after one and two years by considering use patterns of formulary and nonformulary aminoglycosides, as well as those of third-generation cephalosporins and mezlocillin. Resistance patterns of two gram-negative organisms, Pseudomonas aeruginosa and Serratia marcescens, were assessed for 1982-1987. Finally, the rate of nephrotoxicity in gentamicin-treated patients was determined. During the first five weeks after the formulary conversion, 80.3% (106 of 132) of the aminoglycoside orders received were for gentamicin. After telephone follow-up by the pharmacy department, that figure rose to 93.9%. During the four-month reviews beginning at 6 and 18 months, nonformulary orders accounted for 10.9% and 7.4%, respectively, of the total number of courses of aminoglycosides prescribed. In the majority of these cases, tobramycin and amikacin were used to treat infections caused by organisms with documented resistance to gentamicin or to gentamicin and tobramycin, respectively. No clear-cut changes in resistance patterns for Ps. aeruginosa or S. marcescens could be associated with the formulary conversion.(ABSTRACT TRUNCATED AT 250 WORDS)

Life-threatening tardive dyskinesia caused by metoclopramide.

A case of severe life-threatening tardive dyskinesia resulting in esophageal and respiratory difficulties due to metoclopramide therapy is presented. A 66-year-old man with a primary diagnosis of clear cell carcinoma of the biliary duct was treated with metoclopramide for gastrointestinal symptoms related to his chemotherapy regimen. The patient initially presented with tremor and rigidity in the upper extremities. On antiparkinsonian therapy, symptoms progressed to hemiballism and involuntary movements of the face, mouth, and tongue, with respiratory and esophageal dyskinesia. Despite discontinuance of metoclopramide, severe tardive dyskinetic symptoms resulted in placement of a gastrostomy tube to maintain nutritional support. This case along with others in the literature should emphasize the need for continuous reevaluation of metoclopramide during long-term therapy, since serious side effects have been reported to occur.

Effect of warfarin on the activated partial thromboplastin time.

Outpatients followed in an anticoagulation clinic were studied retrospectively to determine the effect of warfarin on the activated partial thromboplastin time (APTT). Twenty-nine patients were studied in part 1 of the trial to determine whether their APTT values were elevated when their prothrombin time (PT) was within 1.5 to 2.5 times the control PT. Part 2 was carried out using the data of 32 patients to determine whether a correlation existed between the degree of elevation of the patients' PT values due to warfarin and the concurrent degree of elevation of their APTT results. Baseline PT and APTT values and a minimum of three concurrent PT and APTT values determined during anticoagulation therapy with warfarin were used. Data were collected by chart review and review of Hematology Department records. Results indicated that a statistically significant difference was evident between the baseline APTT (30.79 sec) and the mean APTT (55.10 sec) when the PT was within the therapeutic range of 1.5 to 2.5 times the control while on warfarin therapy. Good linear correlation was evident (r = 0.821) between the degree of elevation of the PT and the degree of elevation of the APTT for the group. In most cases, a good linear correlation was also evident for individual patients. Routine ordering of concurrent APTT and PT tests for patients receiving warfarin therapy is not needed since the PT alone can be monitored under most circumstances.

Primary cardiac osteosarcoma: multidisciplinary aspects applicable to extraskeletal osteosarcoma generally.

An osteosarcoma, primary in the right ventricular epicardium, produced pericardial constriction. Intense activity on technetium-99m bone scintigraphy led to a correct preoperative diagnosis. Biopsy of unrepresentative tissue clouded the diagnosis, and autopsy resolved the issue. Several clinicopathologic correlations are presented. Major therapeutic advances mandate early recognition of extraskeletal osteosarcoma, and the topic is reviewed in regard to cardiac cancers in general. The need to biopsy both hard and fleshy areas of unusual tumors is reviewed.