Annals of Pharmacotherapy

Rathbun, R. Chris; Martin, Emory S.

doi: 10.1177/106002809202601101pmid: 1362093

OBJECTIVE:To examine the effect of didanosine (2′,3′-dideoxyinosine, ddI) on surrogate markers of HIV infection (CD4+ lymphocyte count, p24 antigen) and to evaluate the incidence of adverse effects from ddI.DESIGN:This study was performed as a retrospective chart review of patients who were enrolled in Bristol-Myers Squibb's expanded-access program for ddI.SETTING:Patient records were obtained from primary care physicians' offices.PATIENTS:Twenty-five HIV-infected patients diagnosed with AIDS or AIDS-related complex (ARC) who were intolerant of zidovudine (ZDV) therapy or deteriorating clinically despite ZDV therapy and were eligible for inclusion in the ddI expanded-access program.INTERVENTION:ddI was administered orally in a citrate-phosphate buffer every 12 hours. Patients were followed by their private physician on a monthly basis.MAIN OUTCOME MEASURES:Laboratory analysis at each month included CD4+ lymphocyte count, hemoglobin, hematocrit, serum amylase, uric acid, serum triglycerides, and p24 antigen. Mean CD4+ cell count, serum amylase, hemoglobin, and uric acid at each month during ddI therapy were compared with baseline concentrations for nine months.RESULTS:Patients had received prior ZDV therapy for an average of 15.5 months before starting ddI. Mean CD4+ cell counts increased from 53.9/mm3 at baseline to 72.4/mm3 after 4 months of therapy (p=0.04) but returned to concentrations comparable with those at baseline after 5 months. One case of documented pancreatitis, two cases of suspected pancreatitis, and nine cases of peripheral neuropathy occurred during ddI therapy. The estimated mean cumulative dose for the development of neuropathy was 1.16 g/kg, which is lower than previously reported.CONCLUSIONS:Patients who have received prolonged therapy with ZDV or who have low initial CD4+ counts may not have sustained increases in CD4+ counts from ddI therapy. Also, development of peripheral neuropathy may occur at lower cumulative doses in these patient populations.

Mohiuddin, Syed M.; Gupta, Naresh C.; Esterbrooks, Dennis J.; Siffring, Patricia A.; Frick, Mathis P.; Hilleman, Daniel E.; Sketch, Michael H.

doi: 10.1177/106002809202601102pmid: 1477436

OBJECTIVE:To compare thallium-201 (201Tl) myocardial perfusion imaging following intravenous adenosine and oral dipyridamole.DESIGN:Open-label, randomized, comparison.SETTING:Outpatient, university-affiliated clinic.PATIENTS:Fifteen patients with angiographically documented coronary artery disease.INTERVENTIONS:Planar 201Tl myocardial perfusion imaging following both intravenous adenosine 140 μg/kg/min for six minutes and oral dipyridamole suspension 300 mg.MAIN OUTCOME MEASURES:A comparison between adenosine and dipyridamole was made in the following areas: concordance in interpretation of 201Tl scintigrams, cardiac and noncardiac 201Tl uptake and clearance, hemodynamic and electrocardiographic changes, and adverse effects.RESULTS:The scintigraphic studies showed perfusion defects in 13 patients (87 percent) after dipyridamole and in 15 patients (100 percent) after adenosine. 201Tl uptake and clearance were quantitated in nine myocardial segments and in four extracardiac segments in each patient. 201Tl uptake was not significantly different between adenosine and dipyridamole studies in most cardiac regions. Extracardiac 201Tl uptake was significantly less in the liver and splanchnic regions following adenosine compared with dipyridamole. 201Tl clearance was not significantly different following adenosine and dipyridamole except in the anterolateral region in the anterior view. Hemodynamic changes following administration of intravenous adenosine and oral dipyridamole were not significantly different. Adverse effects were more common with adenosine than with dipyridamole. Adverse effects with adenosine were transient; however, adverse effects with dipyridamole were prolonged and required reversal with aminophylline in 2 patients. No patients required termination of the adenosine infusion or administration of aminophylline.CONCLUSIONS:These preliminary data suggest that adenosine 201Tl imaging may be a useful alternative to dipyridamole 201Tl imaging. Although adenosine produces more frequent adverse effects, they are generally better tolerated than those associated with dipyridamole.

Luzier, Aileen; Goss, Thomas F.; Cumbo, Thomas J.; Schentag, Jerome J.

doi: 10.1177/106002809202601103pmid: 1477437

OBJECTIVE:In order to quantitatively express the important, time-related aspects of response to antimicrobial therapy in patients with pneumonia, we required validated measures of the time course of events during the infection. To quantitate the changes in clinical status in relation to changes in cultures, we developed a scoring system to be used for patient assessment during therapy.DESIGN:Retrospective data collection, prospective analysis of factors.SETTING:Intensive care unit, Millard Fillmore Hospital.PATIENTS:Twenty-eight patients with nosocomial pneumonia.MAIN OUTCOME MEASURES:Clinical parameters were assessed daily for the duration of antimicrobial therapy. Using linear regression, the rate of clinical change in each patient treated was quantified. Eradication of the pathogen was determined by serial cultures of the infection site.RESULTS:Seventeen of the patients demonstrated eradication of the organism, and 11 demonstrated persistence of the pathogen (7 were considered colonization). The system described the patients at baseline in that the mean baseline scores were similar in both groups of patients (p=0.79). Patients in whom the pathogen was eradicated showed a rate of clinical improvement significantly different from those who had persistence of the organism (p=0.04). In patients demonstrating eradication, the time to eradication inversely correlated with the rate of clinical improvement (p<0.05). Of the ten parameters descriptive of the disease, those most sensitive to change after eradication of bacteria were body temperature, bacterial Gram stain, white blood cell Gram stain, and volume of sputum.CONCLUSIONS:In this set of pneumonia patients, the scoring system effectively quantified both baseline and time-related changes in clinical status. The system distinguished between the clinical course of the patient with organism eradication versus organism persistence. A shorter time to eradication was associated with a better clinical response. Prospective study of the system will determine its sensitivity.

Cortese, Linda M.; Gasser, Robert A.; Bjornson, Darrel C.; Dacey, Michael J.; Oster, Charles N.

doi: 10.1177/106002809202601104pmid: 1477438

OBJECTIVE:To report a case of recurrent pentamidine-induced torsades de pointes (TdP) and to review previously reported cases in the literature.DATA SOURCES:Medical records of the subject patient, case reports, and relevant studies identified by MEDLINE.DATA EXTRACTION:Data were abstracted from pertinent published sources by one author and reviewed by the remaining authors.DATA SYNTHESIS:A 43-year-old woman with AIDS experienced pentamidine-induced TdP. TdP and other cardiac arrhythmias recurred repeatedly for 13 days after pentamidine therapy was discontinued and in the presence of normal magnesium and potassium serum concentrations. Infusions of magnesium, lidocaine, and isoproterenol were used to treat the arrhythmias. The exact mechanism of pentamidine-induced TdP has not been clearly established. It is postulated, however, that the similarity of pentamidine's structure to procainamide may contribute to its proarrhythmic effects. The tissue-binding capacity of pentamidine may result in a prolongation of its effects. No distinctive characteristic appears to predispose people to the development of cardiac arrhythmias. Laboratory values that should be monitored include serum magnesium, potassium, and creatinine. The corrected QT interval also should be monitored.CONCLUSIONS:Recurrent arrhythmias may be seen for many days after intravenous administration of pentamidine has been discontinued. Clinicians should consider this phenomenon as they decide how to monitor patients who have received this drug.

Yamreudeewong, Weeranuj; Henann, Neil E.; Fazio, Anthony; Rangaraj, Uma

doi: 10.1177/106002809202601105pmid: 1477439

OBJECTIVE:To report a case of possible severe thrombocytopenia associated with administration of a single dose of plicamycin.CASE SUMMARY:A 73-year-old man with prostate cancer was admitted to the hospital with hypercalcemia (total serum calcium concentration 4.02 mmol/L) and a low baseline platelet count (152 × 109/L). Because of his symptomatic hypercalcemia, he was treated with NaCl 0.9%, furosemide, oral inorganic phosphate, and a single dose of plicamycin (15 μg/kg). Five days after plicamycin administration his platelet count decreased to 52 × 109/L, and continued to decrease further even after the transfusion of four units of platelets to a nadir of 7 × 109/L (hospital day 20). A second transfusion produced a small increase in his platelet count. The patient's clinical status continued to deteriorate, however, and he subsequently died.DISCUSSION:Plicamycin and other drugs that may induce thrombocytopenia are reviewed. The time course between plicamycin administration and the development of thrombocytopenia in our patient is assessed. Other contributing factors such as a low baseline platelet count and advanced age are also addressed.CONCLUSIONS:It is likely that the severe thrombocytopenia experienced by our patient was caused by a single dose of plicamycin. Adjusting the dosage for a patient's renal function as well as close monitoring of the platelet count are necessary when administering this drug. We report this case to remind clinicians of the potential for the development of severe thrombocytopenia following administration of a single dose of plicamycin.

Watling, Sharon M.; Crain, Judy L.; Edwards, Todd D.; Stiller, Ronald A.

doi: 10.1177/106002809202601106pmid: 1477440

OBJECTIVE:To report the presentation and controversies regarding therapy of an 18-year-old man following a life-threatening ingestion of verapamil.CASE SUMMARY:An 18-year-old man ingested large quantities of dipyridamole, trimethoprim/sulfamethoxazole, amoxicillin, and verapamil. He presented to an outlying hospital and was initially conscious. Soon thereafter, the patient had a seizure; he required intubation, developed cardiac conduction abnormalities, and became hypotensive. The patient required pharmacologic pressors and a pacemaker for transfer to our institution. At our institution, vigorous fluid resuscitation, cardiac pacing, and careful attention to acid/base and electrolyte management provided the basis of therapy. The patient recovered without deficit and was discharged from the intensive care unit five days later.DISCUSSION:Current controversies regarding the management of verapamil overdose are reviewed. Removal of the drug by gastric lavage is a mainstay of therapy. Administration of syrup of ipecac is contraindicated. Although specific recommendations for calcium dosing in the overdose situation have not been rigorously studied, maintenance of a normal serum ionized calcium concentration is suggested. An exogenous catecholamine, rather than dopamine, may be the drug of choice for treating hypotension. Cardiopulmonary bypass provides a method for drug removal in cases of severe toxicity; however, this invasive method requires further study. Management of fluid/electrolyte, acid/base, and ventilation abnormalities is required to treat large ingestions of verapamil. Treatment guidelines for critical care clinicians are provided.

Cohen, Herman A.; Ashkenazi, Arie; Nussinovitch, Moshe; Gross, Shmuel; Frydman, Moshe

doi: 10.1177/106002809202601107pmid: 1477441

OBJECTIVE:To report two cases of fixed drug eruption induced by methylphenidate.CASE SUMMARY:Two children with attention deficit disorder treated with methylphenidate as a simple drug developed fixed drug eruption of the scrotum. Drug discontinuation was followed by a complete resolution of the skin eruption. Rechallenge resulted in the same drug rash. Macrophage migration-inhibiting factor (MIF) assay with methylphenidate was positive.DISCUSSION:The pathogenesis of fixed drug eruption and the role of MIF assay in the diagnosis of adverse drug reaction is discussed.CONCLUSIONS:Fixed drug rash induced by methylphenidate is a possible but rare phenomenon.

Geraets, Douglas R.; Scott, Shane D.; Ballew, Kenneth A.

doi: 10.1177/106002809202601108pmid: 1477442

OBJECTIVE:To report a case of toxicity from orally administered lidocaine in a patient with cardiomyopathy receiving concurrent mexiletine therapy.DATA SOURCES:Case reports, review articles, and studies identified by search of the MEDLINE database and Current Contents.STUDY SELECTION:All reports of toxicity from orally administered lidocaine were reviewed.DATA SYNTHESIS:Lidocaine, a local anesthetic, is widely used to treat cardiac arrhythmias. Toxicity with the parenteral form occurs frequently. In contrast, there are few reports of toxicity with oral lidocaine, most of them occurring in children receiving large doses relative to body weight. We report a case of intoxication in an adult with severe cardiomyopathy and concurrent mexiletine therapy who received only two doses of oral lidocaine.CONCLUSIONS:Although it is rarely reported in adults, clinicians must be alert to the possibility of toxicity from orally administered lidocaine. This is most likely to occur in patients with conditions known to reduce lidocaine clearance, when higher-than-usual doses are administered, or when concurrent therapy with oral lidocaine analogs may be present.

Savino, Lee B.; Haushalter, Nikki M.

doi: 10.1177/106002809202601109pmid: 1335803

OBJECTIVE:To report a case of “scalded mouth syndrome” (SMS) caused by lisinopril.PATIENT:A woman being treated with lisinopril for hypertension developed a burning sensation of her lips and buccal mucosa. The condition persisted with continued use of lisinopril and subsided when the medication was discontinued.CONCLUSIONS:The symptoms described by our patient were similar to those reported in previous cases of SMS associated with the use of enalapril and captopril, two other angiotensin-converting enzyme (ACE) inhibitors. This reaction to ACE inhibitors appears to be dose related, and subsides with a decreased dosage or discontinuation of the medication.

Gonzalez, Edgar R.; Jones, Lori A.; Ornato, Joseph P.; Bleecker, Giselle C.; Strauss, Michael J.; ,

doi: 10.1177/106002809202601110pmid: 1362094

OBJECTIVE:To describe the use of adjunctive therapies in patients with acute myocardial infarction receiving thrombolytic agents.DESIGN:Data were collected prospectively by the study-site investigator or the emergency department physician caring for the patient. Study participation did not influence thrombolytic regimen selection or the adjunctive therapies ordered.SETTING:Thirteen Virginia hospitals representing a cross-section of hospitals in the state. Eleven are urban medical centers; four have graduate medical education programs.PARTICIPANTS:Patients were included in the study if the decision to administer thrombolytic therapy was made in the emergency department.MAIN OUTCOME MEASURES:Concomitant medications administered during the first six hours after initiation of thrombolytic therapy.RESULTS:Two hundred ten patients (aged 57 ± 14.1 y) were evaluated. Ninety-five percent of these patients were treated with tissue plasminogen activator, 3 percent received anisoylated plasminogen streptokinase activator complex, and 2 percent received streptokinase. Ninety-one percent of the patients also received heparin, the most commonly used adjunctive medication; 77 percent concomitantly received lidocaine; 62 percent received aspirin; and only 19 percent received a beta-blocker.CONCLUSIONS:Our data provide a reference point for future studies to determine factors that influence the selection of adjunctive agents for treating patients with acute myocardial infarction receiving thrombolytics.