bluuebunny/crossref_metadata_2025_split huggingface dataset:
Drug-and Nutrition-Induced Hypophosphatemia: Mechanisms and Relevance in the Critically Ill
Authors: Brown Glen R. , Greenwood Jan K. 
Published: January 2017

OBJECTIVE: To provide an outline of the drugs and nutritional therapy that could contribute to the development of hypophosphatemia in the critically ill patient. DATA SOURCES: Computerized abstracting services, references to primary literature articles, and review publications were screened for references to drug- or nutrition-related hypophosphatemia. STUDY SELECTION: Studies primarily describing responses in adults were selected. Animal research is described that illustrates findings in humans. DATA EXTRACTION: Information was abstracted from the findings of individual case reports and clinical trials. DATA SYNTHESIS: Data are organized by mechanism of possible effect on serum phosphate concentration. No reference is made to drugs that do not have an effect on phosphate metabolism. CONCLUSIONS: Hypophosphatemia can have significant effects that would hinder recovery of the critically ill patient. Antacids, catecholamines, beta-adrenergic agonists, sodium bicarbonate, and acetazolamide are commonly used therapeutic agents that could contribute significantly to the development of hypophosphatemia. Provision of nutrition 10 the chronically malnourished individual or chronic administration of phosphate-depleted parenteral nutrition could produce symptoms associated with hypophosphatemia. Other drugs could have a mild effect on lowering serum phosphate concentrations, but would be unlikely to produce symptoms unless combined with other etiologies of hypophosphatemia.
Steady-State Pharmacokinetics of Cefoperazone and Sulbactam in Patients with Acute Appendicitis
Authors: Danziger Larry H. , Piscitelli Stephen C. , Occhipinti Donna J. , Resnick Daniel J. , Rodvold Keith A. 
Published: January 2017

OBJECTIVE: To determine the steady-state pharmacokinetics of intravenously administered cefoperazone and sulbactam when given in combination to patients with acute appendicitis. METHODS: Six patients with normal renal and hepatic function received cefoperazone 2 g with sulbactam 1 g prior to appendectomy and then every 12 hours. Serial blood samples were collected after each patient received at least three doses of cefoperazone/sulbactam. RESULTS: Cefoperazone and sulbactam could be best described by a two-compartment model. Mean ± SD values for cefoperazone steady-state volume of distribution (Vssd), elimination half-life (t1/2β), clearance (Cl), and area under the curve (AUC0-t) were 19.8 ± 8.0 L, 3.97 ± 1.06 h, 62.6 ± 16.3 mL/min, and 556.9 ± 122.0 mg·h/L, respectively. Sulbactam Vssd, t1/2β, Cl, and AUC0-t were 34.7 ± 13.9 L, 1.39 ± 0.4 h, 288.6 ± 68.2 mL/min, and 64.8 ± 24.5 mg·h/L, respectively. CONCLUSIONS: Compared with data from healthy volunteers, cefoperazone exhibited a decreased Cl and increased Vssd and t1/2β in patients with acute appendicitis. An increased Vssd also was observed for sulbactam. The disposition of cefoperazone/sulbactam is altered in this group of patients; however, these changes are not likely to warrant a dosage reduction.
Assessment of Methods and Outcomes: Using Modified Inpatient Ciprofloxacin Criteria in Community-Based Drug Use Evaluation
Authors: Rovers John P. , Bjornson Darrel C. 
Published: January 2017

OBJECTIVE: To determine if published drug use evaluation (DUE) criteria for inpatients could be modified to describe and evaluate drug therapy in outpatients. DESIGN: Retrospective review of drug profiles and diagnostic codes in outpatients included in the Iowa Medicaid Management Information System database. METHODS: Criteria specifying clinical indication, process indicators, complications, and outcomes were modified from existing inpatient DUE criteria for ciprofloxacin. The Iowa Medicaid database provided demographics, drug profiles, and diagnostic codes for outpatients prescribed ciprofloxacin between March 1 and March 15, 1993. RESULTS: 539 patients were evaluated. Mean (±SD) age was 62.1 ± 23.8 years; 70.9 percent were women, 44.9 percent were nursing home patients who received lower doses (p=0.04). Of 146 patients (27.1 percent) with infection-related International Classification of Diseases-Clinical Modification, 9th Revision (ICD-9CM) codes, 43.8 percent did not meet indication for use criteria, 15.8 percent met criteria, and 40.4 percent were equivocal/other. Process indicators in 539 patients revealed that 2.4 percent were <18 years old and potential interactions existed for theophylline (9.3 percent), iron (9.7 percent), warfarin (4.8 percent), sucralfate (2.2 percent). Two patients (0.4 percent) received prenatal vitamins. Dosage and duration of therapy could not be linked to disease severity. Complications of therapy were not evaluable. Outcomes were assessed indirectly by using concurrent antibiotic histories. These histories showed that patients received a mean 2.7 ± 2.4 (median 2, range 1–16) ciprofloxacin prescriptions during the study period. There was frequent concurrent use of antibiotics, and 29 percent of prescriptions were preceded or followed by additional quinolone therapy within 30 days. CONCLUSIONS: Evaluating appropriateness of therapy with this methodology is feasible if validated ICD-9CM codes are reported consistently in sufficient numbers of patients. Low levels of reporting of relevant disease codes require that large numbers of patients be screened to use this method effectively. Descriptive use data are readily obtained. Data obtained by this method indicated several apparent deficiencies in ciprofloxacin therapy.
Cough Induced by Quinapril with Resolution after Changing to Fosinopril
Authors: Sharif M. Nabi , Evans Barb L. , Pylypchuk George B. 
Published: January 2017

OBJECTIVE: To report a case of chronic, nonproductive cough secondary to the angiotensin-converting enzyme (ACE) inhibitor quinapril, with complete resolution after switching to another ACE inhibitor, fosinopril. DATA SOURCES: All relevant articles from January 1985 through February 1993 were identified, primarily through MEDLINE search and review of pertinent articles' bibliographies. CASE SUMMARY: A 68-year-old woman developed a dry, irritating cough within one month of starting quinapril therapy for the treatment of essential hypertension. The patient was a nonsmoker with no respiratory illnesses. The cough continued for the duration of therapy with quinapril. One month after changing to fosinopril therapy, the patient reported complete resolution of the cough. She remains cough-free to date. DISCUSSION: Cough induced by ACE inhibitors is a frequently documented adverse effect. It is severe enough to require discontinuation of therapy in 1–10 percent of patients. The cough is considered to be a class-related adverse effect with cross-reactions between ACE inhibitors routinely reported. At this time, changing to another ACE inhibitor or additive therapy with nonsteroidal antiinflammatory drugs is not recommended. Discontinuation of the ACE inhibitor results in rapid alleviation of the cough, although this is not always necessary, as most patients may experience a cessation or decrease in cough. We report a case of cough following the administration of quinapril, with complete resolution after changing to the alternative ACE inhibitor fosinopril in a patient with essential hypertension. CONCLUSIONS: Cough has been encountered commonly after the administration of ACE inhibitors. Frequency of cough is variable and although this complication has been described as a class effect, patients with a persistent, severe ACE inhibitor-induced cough may benefit from a trial of fosinopril therapy. This may be particularly useful in patients unable to tolerate an alternative class of antihypertensive agents.
Inaccurate Assessment of Drug-Induced Thrombocytopenia: Reason for Concern
Authors: Burnakis Thomas G. 
Published: January 2017

OBJECTIVE: To report two cases in which patients were reputed to have exhibited thrombocytopenia secondary to the histamine-receptor blocking agent ranitidine. Evaluation and the associated time frame of events failed to confirm these observations. DESIGN: Two case studies. RESULTS: Ranitidine was ordered as part of the therapeutic course of two patients admitted to the medicine service. The development of thrombocytopenia in both patients was attributed to this agent and it was discontinued. In addition to ranitidine, both patients received several other agents with greater potential to cause thrombocytopenia, and had a time course of development of the adverse effect that would not support ranitidine as the offending agent. Both patients required histamine-receptor antagonists at some point following their discontinuation and, based on the available evidence, the pharmacy suggested that these agents be restarted. In neither case did restarting the histamine-receptor antagonist lead to recurrence of thrombocytopenia. CONCLUSIONS: Although ranitidine can cause thrombocytopenia, the reported incidence is very low. Spontaneous reporting of adverse effects is essential in establishing a true pattern of safety for a drug. However, reports need to be scrutinized before they are rolled into the collective intelligence. Overzealous or incomplete reporting will lead to cautions that are either unnecessary or, because they deny people necessary treatment, dangerous.
Sertraline-Phenelzine Drug Interaction: A Serotonin Syndrome Reaction
Authors: Graber Mark A. , Hoehns T. Brent , Perry Paul J. 
Published: January 2017

OBJECTIVE: To report a serious drug interaction possibly occurring with the monoamine oxidase inhibitor phenelzine and the selective serotonin reuptake inhibitor sertraline. CASE SUMMARY: A 61-year-old woman with treatment-refractory major depressive disorder was being treated unsuccessfully with lithium, phenelzine, thioridazine, and doxepin. Sertraline 100 mg/d was added to the patient's therapy. Within three hours of ingesting the first dose, the patient experienced a dramatic increase in her temperature, pulse, and respirations along with labile blood pressure, and symptoms of rigidity, diaphoresis, shivering, and decreased sensorium. The patient was transported to the emergency room and treated with diazepam 10 mg iv, followed by midazolam 10 mg iv for control of rigidity. She was also intubated. The patient then experienced precipitous falls in her blood pressure and respiratory rate. Ice packs combined with a cooling blanket and dantrolene 80 mg iv were administered to control fever and rigidity, respectively. She had an initial working diagnosis of neuroleptic malignant syndrome, which was later changed to serotonin syndrome. Dantrolene was continued for 72 hours at which time the patient was extubated and transferred to a psychiatric unit. CONCLUSIONS: Selective serotonin reuptake inhibitor antidepressants should not be combined with monoamine oxidase inhibitor antidepressants because of the risk of serotonin syndrome.
Safety and Tolerance of Intravenous Nimodipine
Authors: Sramek John J. , Heller Allen H. , Sundaresan Pavur R. , Lettieri John , Sawin Suzanne , Cutler Neal R. 
Published: January 2017

OBJECTIVE: To evaluate the safety and tolerance of intravenous nimodipine administered via a peripheral vein in healthy male volunteers. DESIGN: Double-blind, placebo- and vehicle-controlled trial with three fixed-dose panels. SETTING: Inpatient infusion and observation periods. SUBJECTS: 61 healthy male volunteers, aged 18–40 years. METHODS: Subjects in panel 1 received nimodipine 0.4 mg/h, vehicle 2 mL/h, or placebo 2 mL/h; subjects in panel 2 received nimodipine 1 mg/h, vehicle 5 mL/h, or placebo 5 mL/h; subjects in panel 3 received nimodipine 2 mg/h, vehicle 10 mL/h, or placebo 10 mL/h. All infusions were administered intravenously for 48 hours and volunteers were observed for 48 hours after cessation of the infusion. In addition to standard safety assessments (physical examination, electrocardiogram, laboratory studies, and adverse event reporting), supine and standing blood pressures and pulse rates were measured frequently. Plasma samples were also analyzed for nimodipine and its two demethylated metabolites. RESULTS: Of 61 subjects, 55 completed the 48-hour infusion and 6 discontinued the study because of adverse events. Intravenous nimodipine was well tolerated at 0.4 and 1 mg/h. However, all six subjects who received nimodipine 2 mg/h experienced moderate-to-severe adverse events, and one subject was discontinued because of dizziness, diaphoresis, and postural hypotension. The matched vehicle (10 mL/h) also was not well tolerated, with three subjects who discontinued because of phlebitis. Two subjects who received placebo were also discontinued during the study. Small (2 mm Hg) decreases in mean supine diastolic blood pressure were observed in the 0.4- and 1-mg/h nimodipine groups, but the 2-mg/h group showed a slight (5 mm Hg) increase in blood pressure. These changes were not clinically significant. Clearance and half-life of nimodipine and its metabolites were similar at all three dosages. CONCLUSIONS: Using peripheral vein administration, nimodipine 2 mg/h and matched vehicle at 10 mL/h were not well tolerated in this healthy normal population. The maximum tolerated dose of nimodipine was found to be 1 mg/h.
Hydroxyurea-Induced Fever: Case Report and Review of the Literature
Authors: Lossos Izidore S. , Matzner Yaacov 
Published: January 2017

Objective: To describe a patient with hydroxyurea-induced fever. Case Summary: A patient with essential thrombocythemia developed a fever 12 hours after beginning hydroxyurea therapy. The diagnosis of drug fever was established by resolution of the fever after withdrawal of hydroxyurea and its recurrence on reexposure to the drug. Discussion: Hydroxyurea-induced fever is rare. In the present case, a short lag period between commencement of hydroxyurea therapy and appearance of fever may suggest either direct toxicity or an idiosyncratic reaction. In previous reports, a hypersensitivity drug reaction was implicated. Conclusions: The mechanism of hydroxyurea-induced fever remains unclear. Clinicians should be aware of this rare adverse effect.
Low Itraconazole Serum Concentrations Following Administration of Itraconazole Suspension to Critically Ill Allogeneic Bone Marrow Transplant Recipients
Authors: Kintzel Polly E. , Rollins Carol J. , Yee Walter J. , List Alan F. 
Published: January 2017

Objective: To report itraconazole serum concentrations following administration of itraconazole suspension via orogastric feeding tubes to 2 critically ill allogeneic bone marrow transplant recipients. Case Summaries: A 38-year-old man and a 29-year-old man, each allogeneic bone marrow transplant recipients, were treated with oral itraconazole for documented fungal infections. Intubation and mechanical ventilation impeded ingestion of itraconazole capsules. Itraconazole was prepared initially as a suspension in intravenous lipid emulsion 20% and later as a suspension in citric acid 1.5% in D5W USP. Itraconazole serum concentrations were assayed using HPLC. Predose itraconazole serum concentrations were undetectable to 72 ng/mL. Postdose itraconazole serum concentrations were 5–97 ng/mL. Itraconazole concentrations measured in these patients were markedly lower than serum concentrations reported in the literature for similar doses administered to fed subjects. Discussion: Efficacy of this antifungal agent is limited currently by the patient's ability to ingest and absorb the itraconazole capsules. Pathophysiologic factors and suspension formulation issues that likely contributed to decreased itraconazole absorption are discussed. Conclusions: Preparation and administration of itraconazole as a suspension did not enhance drug absorption in these patients. Furthermore, efficacy of itraconazole suspension may be affected by physical compatibility and chemical stability of the extemporaneous preparations.
Stereochemistry in Pharmacotherapy: When Mirror Images are Not Identical
Authors: Tracy Timothy S. 
Published: January 2017

Objective: To describe how drug stereoisomers may differ in pharmacokinetic and pharmacodynamic properties and how these differences may affect therapeutic outcomes. Study Selection: Representative studies were chosen from the drug literature demonstrating stereoisomeric differences in drug absorption, protein binding and distribution, metabolism, and elimination. Furthermore, examples of pharmacodynamic differences between drug stereoisomers are presented to demonstrate that these stereoisomers not only may differ in pharmacologic potency, but may possess entirely different pharmacologic actions. Data Synthesis: Examples are presented demonstrating that when stereoisomeric differences in pharmacokinetics are linked to pharmacodynamic differences, alterations in therapeutic effect can result. Additionally, drug interactions are discussed in which 1 isomer is affected to a greater extent than the other, potentially causing not only an increase or decrease in effect, but also a change in pharmacologic action. Examples also are presented of the marketing of single isomer entities, with a discussion of the use of these products. Finally, preliminary policies of the Food and Drug Administration are discussed, as well as the potential implications of these policies. Conclusions: Drugs that are administered as stereoisomers can differ with respect to both pharmacokinetics and pharmacodynamics, and these differences may have profound implications in pharmacotherapy. All future investigations of drugs that exist as stereoisomers must take into account the pharmacokinetics and pharmacodynamics of both isomers to understand fully the observed phenomena.
Pharmacoeconomic Benefit of Antibiotic Step-Down Therapy: Converting Patents from Intravenous Ceftriaxone to Oral Cefpodoxime Proxettl
Authors: Hendrickson Joseph R , North Donald S 
Published: January 2017

Objective: To evaluate the economic benefit associated with the early conversion of therapy from intravenous ceftriaxone to the comparable oral third-generation cephalosporin, cefpodoxime proxetil. Design: Open-label, unblind, nonrandomized clinical trial. Setting: A 360-bed Veterans Affairs Medical Center. Patients: Forty patients who began receiving intravenous ceftriaxone for either a community-acquired pneumonia or a complicated urinary tract infection. Intervention: Twenty patients were selected, based on clinical assessment, to be converted from intravenous ceftriaxone to oral cefpodoxime proxetil. Twenty other comparable patients, who would have been appropriate for step-down therapy, did not receive pharmacy intervention and were used as a control group. Measurements: Both groups were assessed and compared for length of ceftriaxone therapy, length of oral follow-up therapy (if any), length of hospitalization, results of culture and sensitivity testing, treatment success and readmissions, and cost of respective therapeutic regimens. Results: In the cefpodoxime study group, the average time receiving intravenous and oral antibiotics was 9.1 days at a total cost of $3040.26 for the 20 patients. In the control group, the average time receiving intravenous and oral antibiotics was 11.9 days at a total cost of $3961.26. A savings of $46.05 per patient was achieved. Patients receiving step-down therapy averaged 1 fewer day of hospitalization. Conclusions: Pharmacist intervention and cefpodoxime step-down therapy were associated with decreased overall antibiotic costs in our intravenous-to-oral program.
Prescription Drug and Healthcare Use Among Swedish Patients Treated with Antidepressants
Authors: Bingefors Kerstin Al , Isacson Dag Gl , Knorring Lars Von , Smedby Björn 
Published: January 2017

Objective: To analyze healthcare and prescription drug use among patients taking and those not taking antidepressant drugs in a Swedish community. Design: Cross-sectional study. Setting: General population of the rural Swedish municipality Tierp of approximately 20 000 inhabitants. Participants: All residents of Tierp aged 25 years or older during 1988. Main Outcome Measures: Mean number of ambulatory care visits, hospital bed days, and prescriptions per person; proportion of those taking prescription drugs in different pharmacologic classes. Results: Patients treated with antidepressant drugs had a significantly (p < 0.05) greater use of ambulatory care, hospital care, and prescription drugs than those who did not take antidepressants in the study population. They also had an increased frequency of use of prescription drugs from virtually all pharmacologic classes. Furthermore, the risk for polypharmacy was high in patients treated with antidepressant medications. Conclusions: Those who took antidepressant drugs consumed more health services and prescription drugs than did those not taking an antidepressant. Patients receiving antidepressant treatment may be at serious risk for iatrogenic disease and should be evaluated carefully with respect to concomitant drug use.
Diabetes and Related Metabolic Risk Factors Among Arab Americans
Authors: Jaber Linda A , Slaughter Richard L , Grunberger George 
Published: January 2017

Objective: To estimate the incidence of noninsulin-dependent diabetes mellitus (NIDDM) and associated metabolic abnormalities such as impaired glucose tolerance, increased blood pressure, hyperinsulinemia, and obesity in the Arab-American community in the Detroit metropolitan area. Methods: Subjects were selected randomly from a computer-generated list provided by the Arab-American Center for Economic and Social Services. Laboratory studies included a 2-hour, 75-g oral glucose tolerance test with glucose, insulin, and C-peptide determinations. Results: Of the 105 volunteers studied, 57 were women and 48 were men. Mean ± SD age was 46.0 ± 13.0 years. Body mass index was 30.4 ± 6.8 kg/m2, with 68% of subjects having a body mass index of 27 kg/m2 or more. Of the study participants, 33% had NIDDM, 8.6% had impaired glucose tolerance, and 58% had normal glucose tolerance. Subjects with diabetes, compared with subjects who had normal glucose tolerance, exhibited increased fasting insulin (98 ± 69 vs 55 ± 31 pmol/L; p = 0.00056); higher cholesterol (6.03 ± 1.03 vs 5.09 ± 1.22 mmol/L; p = 0.00073); marginally lower high-density lipoprotein cholesterol (0.98 ± 0.21 vs 1.14 ± 0.31 mmol/L; p = 0.054); higher triglycerides (7.84 ± 5.79 vs 3.83 ± 2.15 mmol/L; p = 0.00002); and higher diastolic (83.7 ± 8.9 vs 78.3 ± 8.0 mm Hg; p = 0.014) as well as systolic (132.5 ± 16.0 vs 119.0 ± 10.6 mm Hg; p = 0.00001) blood pressures. Conclusions: This pilot study demonstrates that diabetes may be a frequent medical problem in the Arab-American community. A well-designed epidemiologic study is warranted to validate these results and to elucidate the underlying mechanisms responsible for these findings.