bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reassessing the Lower end of the Phenytoin Therapeutic Range: A Review of the Literature
Authors: Hayes Grace , Kootsikas Maria E. 
Published: January 2017

OBJECTIVE: To critically review available data on the effective lower end of the phenytoin therapeutic range for the treatment of seizure disorders. DATA SOURCES: Relevant articles were identified from an English-language search of MEDLINE 1982-1992. Additional references were found in bibliographies of these articles. STUDY SELECTION/DATA EXTRACTION: We reviewed articles that included data on serum phenytoin concentrations (SPCs) and seizure control. Data on concurrent anticonvulsants, seizure diagnosis, and seizure severity were extracted when available. DATA SYNTHESIS: The original study defining the phenytoin therapeutic range as 10–20 mg/L is analyzed; it was based on a small, homogeneous sample that cannot be generalized to a more diverse epileptic population. Many studies report patients obtaining seizure control with SPCs below 10 mg/L. Studies including a range of seizure diagnoses and severity have a larger variability in effective SPCs; however, effective SPCs are reproducible. CONCLUSIONS: The therapeutic range of phenytoin is defined on an individual basis. Some patients, especially those with infrequent, primary tonic-clonic seizures, may be controlled with phenytoin concentrations below the recognized reference range of 10–20 mg/L.
Measured versus Estimated Creatinine Clearance in Patients with Low Serum Creatinine Values
Authors: Bertino Joseph S. 
Published: January 2017

OBJECTIVE: To examine, in patients with a serum creatinine (SCr) <85 μmol/L, whether the use of actual SCr versus the use of an SCr set at 85 μmol/L and applied to the Cockcroft-Gault method for calculation of creatinine clearance (Clcr), resulted in a similar ability to explain variance in prediction of Clcr. DESIGN: Included in the study were patients with stable renal function receiving total parenteral nutrition, who underwent a 24-hour urine collection and had an SCr <85 μmol/L. Clcr was calculated (CalcClcr) using the Cockcroft-Gault method, and actual SCr, and an SCr value set at 85 μmol/L (AdjCalcClcr). Calculated values were compared with 24-hour measured Clcr (MeasClcr). SETTING: Inpatient, acute-care hospital. PATIENTS: 33 patients having 33 urine-collection periods. All patients were receiving total parenteral nutrition as their only form of nutritional supplement. Patients who had liver disease, trauma, or burns, or who were receiving certain pharmacologic agents, were excluded from the study. MAIN OUTCOME MEASURES: MeasClcr based on the 24-hour urine collection, CalcClcr computed using the actual measured SCr, and SCr adjusted to 85 μmol/L. RESULTS: A higher proportion of the variance of measured versus calculated Clcr was explained by the using the actual measured SCr value (r2=0.68) than SCr adjusted to 85 μmol/L (r2=0.32). When analyzed by gender, adjusting the SCr to 85 μmol/L was somewhat better at explaining the variance of measured versus calculated Clcr, but still explained less than 50 percent of the variance. However, the use of the actual SCr explained more of the variance of measured versus calculated Clcr than the use of the SCr value adjusted to 85 μmol/L. CONCLUSIONS: In patients with an SCr <85 μmol/L, the actual measured SCr should be used when calculating Clcr (regardless of the patient's gender), by the Cockcroft-Gault method.
Prescribing Attitudes of Different Physician Groups regarding Fluoxetine
Authors: Levin Gary M. , DeVane C. Lindsay 
Published: January 2017

OBJECTIVE: To determine the attitudes and prescribing patterns of family medicine and psychiatric physicians regarding fluoxetine. DESIGN: A three-part questionnaire was distributed to the Departments of Family Medicine and Psychiatry. The survey included topics associated with fluoxetine use that have received broad professional attention, such as drug-induced suicidal and aggressive behavior. SETTING: The Family Practice Medical Group and the Department of Psychiatry at the University of Florida. PARTICIPANTS: Mailing lists from both above departments were used to distribute surveys to residents, fellows, and attending/faculty members of each department. Eighty-seven surveys were mailed. MAIN OUTCOME MEASURES: Survey questions were divided into three sections to help determine current attitudes of prescribing fluoxetine: eight short cases, 16 statements, and demographic data. RESULTS: The return rate was 69 percent following a mailing and a hand-delivered copy. Responses were dichotomized to agree or disagree and were analyzed by Fisher's exact test. Psychiatrists were much more likely than family practitioners to prescribe fluoxetine for obsessive-compulsive disorder (OCD), and more likely to prescribe for a patient with a history of substance abuse or seizure disorder. Psychiatrists were more aware of safety issues; however, drug-interaction knowledge was weak in both groups. CONCLUSIONS: Family practitioners, being the most predominant of medical specialists, appeared equally comfortable with prescribing fluoxetine in most circumstances compared with psychiatrists. However, there is a need for pharmacists to provide up-to-date drug information on fluoxetine to all healthcare professionals.
New Therapeutic Agents in the Management of Hypertension: Angiotensin II-Receptor Antagonists and Renin Inhibitors
Authors: Foote Edward F. , Halstenson Charles E. 
Published: January 2017

OBJECTIVE: To review the chemistry, pharmacokinetics, and clinical trials of two new classes of antihypertensive drugs, angiotensin II-receptor antagonists and renin inhibitors. DATA SOURCES: Primary literature on angiotensin II-receptor antagonists and renin inhibitors was identified through a comprehensive medical literature search from 1961 through 1993. This search included journal articles, abstracts, and reports of both animal and human research published in the English language. Indexing terms included renin-angiotensin aldosterone system, renin inhibitors, angiotensin II antagonists, DuP 753, losartan, MK954, A-64662, and Ro 42–5892. STUDY SELECTIONS: Emphasis was placed on clinical and pharmacokinetic studies in humans for drugs that are currently in Phase I—III research protocols in the US. DATA EXTRACTION: All available data from human studies were reviewed. DATA SYNTHESIS: Angiotensin II-receptor antagonists and renin inhibitors may be effective antihypertensives with few adverse effects noted in the small studies completed. Their potential advantage over angiotensin-converting enzyme (ACE) inhibitors includes a possible smaller adverse effect profile. In the past, the clinical utility of angiotensin II-receptor antagonists and renin inhibitors has been limited because of poor oral bioavailability, although newer agents are more readily bioavailable. CONCLUSIONS: Angiotensin II-receptor antagonists and renin inhibitors may be the next new classes of antihypertensives marketed. However, definitive conclusions about their roles in the management of hypertension are not possible until larger clinical trials assessing their efficacy and safety and comparing them with ACE inhibitors are completed.
Risk for Adverse Events among Patients Receiving Intravenous Histamine2-Receptor Antagonists
Authors: Hartzema Abraham G. , Porta Miquel S. , Tilson Hugh H. , Joseph Rami Ben , Segal Richard , Russell Wayne L. 
Published: January 2017

OBJECTIVE: To identify risk factors for adverse drug reactions (ADRs) in patients receiving intravenous histamine2-receptor antagonists (H2-RAs). DESIGN: The study hypothesis was evaluated by performing a logistic regression procedure with a backward elimination of the explanatory variables associated with ADRs. MAIN OUTCOME MEASURES: ADRs temporally associated with the use of intravenous H2-RAs served as the dependent variable. Background information about the patients and drug use evaluation criteria in three general areas were entered into the regression analysis. SETTING: Hospitals were selected from the southeastern US, based on their willingness to participate and their characteristics. Participating hospitals exhibited a variety of sizes and ownership arrangements. PATENTS: 1200 adult patients who were receiving intravenous H2-RAs. RESULTS: Seven percent of patients experienced a presumed ADR (PADR) to intravenous H2-RAs. The only risk factor for ranitidine was for patients who did not have their dosage corrected for renal function (“overdose”); these patients were twice as likely to experience a PADR compared with patients who received the correct dosage as determined by their renal function. Two risk factors for cimetidine were identified: (1) patients taking cimetidine with another medication known to cause a drug interaction; and (2) patient age. No risk factors were identified for famotidine. CONCLUSIONS: The two risk factors for ADRs identified in this study are preventable. Healthcare providers should strive to prevent ADRs by adjusting patients' dosages based on their renal function and by monitoring patients receiving cimetidine with another medication known to interact with cimetidine.
Bioelectrical Impedance Analysis as an Assessment of Diuresis in Congestive Heart Failure
Authors: Coodley Eugene L , Segal Jack L , Smith David Hg , Neutel Joel M 
Published: January 2017

Objective: To compare changes in bioimpedance parameters and calculated total body water (TBW) with conventional measurements used to assess the efficacy of diuretic therapy in the treatment of heart failure. Setting: A Veterans Affairs tertiary care, teaching hospital. Subjects: Twelve patients with New York Heart Association (NYHA) class HI congestive heart failure (CHF). Design: Prospective, consecutive sample, cohort, open label. Interventions: Parenterally administered furosemide; clinically dictated, outcome-oriented, adjunctive therapy of CHF. Outcomes: Bioelectrical impedance analysis (BIA) parameters, measured volume of diuresis and changes in body weight, defined clinical endpoints (NYHA criteria). Results: Three days of diuretic therapy with furosemide (oral and/or intravenous) for CHF was associated with a measured weight loss of 4.1 ± 0.6 kg and statistically significant increases in resistance and reactance of 20.8% ± 2.7% and 22.7% ± 6.1%, respectively (p < 0.005). Calculated TBW using BIA parameters and standard equations decreased on average by 6.1 ± 0.6 L or 11.2% ± 1.1% (p < 0.001). A significant inverse correlation was observed between change in measured body weight and total body reactance (p = 0.02). Conclusions: Single-frequency BIA appears to have limited clinical usefulness as a method of assessing diuretic therapy in the management of CHF. Its greatest usefulness appears to lie in the assessment of serial changes in individual patients and patient populations that are physiologically or metabolically homogeneous. Further studies are needed to establish the validity of BIA in patients with decompensated CHF.
Polyethylene Glycol Nephrotoxicity Secondary to Prolonged High-Dose Intravenous Lorazepam
Authors: Laine Gregory A , Hossain Sm Hamid , Solis R Thomas , Adams Stephen C 
Published: January 2017

Objective: To report a patient with a probable acute tubular necrosis (ATN) induced by chronic exposure to polyethylene glycol (PEG)-400 via long-term, massive dosage of intravenous lorazepam. Case Summary: A 57-year-old man with a history of alcohol abuse was admitted to the intensive care unit for acute respiratory failure. Lorazepam therapy was initiated in anticipation of alcohol withdrawal. Dosages up to 18 mg/h were required to provide adequate sedation and optimize ventilation. On day 43, the patient developed oliguric ATN of unknown etiology. The cumulative intravenous lorazepam dose was 4089 mg, equivalent to approximately 220 mL of PEG-400. Blood urea nitrogen concentrations followed a pattern that paralleled lorazepam dosage increases and decreases. Protein and granular casts were evident in urinalyses performed on days 12 and 29. The patient eventually experienced complete recovery. Discussion: ATN associated with intravenous PEG was last reported in 1959 in 6 of 32 patients receiving a cumulative PEG-300 dose of 120–200 mL over 3–5 days via an intravenous nitrofurantoin preparation. Two of the 6 patients died. Chronic administration of intravenous PEG to rabbits over a 5-week period has caused cloudy swelling of the renal tubular epithelium, increased blood urea concentrations, and death in some animals. Conclusions: ATN probably resulted from chronic PEG exposure via massive doses of lorazepam injection, possibly enhanced by concurrent administration of vancomycin.
Indapamide-Induced Severe Hyponatremia and Hypokalemia
Authors: Chan Thomas Yk 
Published: January 2017

Objective: To describe 2 patients with severe indapamide-induced hyponatremia and hypokalemia and to discuss the incidence and mechanisms of diuretic-induced hyponatremia and hypokalemia. Case Summary: Two women aged 60 and 62 years presented with severe hyponatremia (plasma sodium concentrations of 103–104 mmol/L) and hypokalemia (plasma potassium concentrations of 1.6–2.2 mmol/L) 5–6 weeks after they received indapamide 2.5 mg/d therapy for arterial hypertension. Central nervous system symptoms of hyponatremia were observed in both patients. One patient experienced severe postural hypotension, a plasma potassium concentration of 1.6 mmol/L, and electrocardiographic abnormalities consistent with hypokalemia. Hyponatremia was initially mistaken in this patient for the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Both patients recovered completely after withdrawal of indapamide therapy and correction of the hyponatremia and hypokalemia. Discussion: Previous studies of administration of indapamide 2.5 mg/d for 10–24 months in hypertensive patients showed a low incidence (0.6–1.2%) of hypokalemia severe enough to require withdrawal of drug therapy. Serum sodium concentrations were unaltered in these studies. All case reports, except 1, of indapamide-induced electrolyte disturbances described only hypokalemia. Conclusions: Indapamide can cause both severe hypokalemia and hyponatremia. The predominant clinical features can be a result of severe hyponatremia. The latter can have diverse clinical presentations and may be mistaken for SIADH. As with other diuretics, plasma sodium and potassium concentrations must be monitored during indapamide therapy, especially in patients at risk for hyponatremia and hypokalemia.
Effect of Vitamin C on Plasma Lipids
Authors: Howard Patricia A , Meyers David G 
Published: January 2017

Objective: To review the effects of vitamin C (ascorbic acid) on plasma lipid concentrations, and to address the proposed mechanisms through which vitamin C may potentially alter lipid concentrations. Data Source: A MEDLINE search was performed to identify pertinent English-language literature including studies, abstracts, and review articles. Key search terms were vitamin C, ascorbic acid, lipoproteins, lipids, and atherosclerosis. Study Selection and Data Extraction: Studies examining the relationships between vitamin C and plasma lipid concentrations including animal, observational, and clinical trials were selected. Because there were no large randomized, controlled clinical trials, data were extracted from all clinical trials, regardless of design. Review articles discussing the effects of vitamin C on plasma lipid concentrations and the atherosclerotic process also were included. Pertinent information, as judged by the authors, was extracted for discussion. Data Synthesis: Evidence suggests an inverse relationship between vitamin C intake and the development of atherosclerosis, although the effect has not yet been proven in clinical trials. It has been postulated that this effect might be mediated not only through the antioxidant properties of vitamin C, but also through a plasma lipid-modifying effect. Data from animal and observational trials suggest that high vitamin C concentrations may correlate negatively with concentrations of total cholesterol, triglycerides, and low-density lipoproteins and positively with high-density lipoproteins. Other studies, however, have not confirmed these findings. Similarly, results from clinical trials have been widely variable and inconclusive. Conclusions: Analysis of the literature suggests an association between vitamin C and plasma lipid concentrations and a potential role in slowing the development of atherosclerosis. Significant variations and inadequacies in trial design, however, prohibit definitive conclusions. On the basis of these preliminary data, it appears that there is justification for additional well-designed trials to further evaluate the relationship between vitamin C and plasma lipid concentrations.
Cigarette Smoking and Clinically Significant Drug Interactions
Authors: Schein Jeffrey R 
Published: January 2017

Objective: To review clinically significant drug interactions associated with cigarette smoking. Data Sources: Data from scientific literature were identified by using a MEDLINE search. Data were extracted, evaluated, and summarized for this review. Study Selection: Findings and experiences were selected from clinical, epidemiologic, and pharmacokinetic studies; review articles; case studies; abstracts; letters to the editor; and proceedings. Data Extraction: Data from human studies published in English were evaluated. Only interactions deemed clinically significant are included in this review. Conclusions derived from review articles on the subject of smoking and drug interactions also were used. Data Synthesis: Cigarette smoking can affect drug therapy via pharmacokinetic and pharmacodynamic mechanisms. Pharmacokinetic drug interactions are presented for theophylline, tacrine, insulin, flecainide, propoxyphene, propranolol, diazepam, and chlordiazepoxide. Pharmacodynamic interactions are described for antihypertensive and antianginal agents, antilipidemics, oral contraceptives, and histamine2-receptor antagonists. Conclusions: Cigarette smoking can reduce the efficacy of certain drugs or make drug therapy more unpredictable. Pharmacokinetic interactions may cause smokers to require a larger dosage of certain drugs through an increase in plasma clearance, a decrease in absorption, an induction of cytochrome P450 enzymes, or a combination of these factors. Pharmacodynamic interactions may increase the risk of adverse events in smokers with cardiovascular or peptic ulcer disease, and in women who smoke and use oral contraceptives. Healthcare professionals should pay special attention to patients with these profiles and should try to prevent cigarette smoking or encourage patients to discontinue this addictive habit.
Potential Treatment of Amyotrophic Lateral Sclerosis with Gabapentin: A Hypothesis
Authors: Welty Devin F , Schielke Gerald P , Rothstein Jeffrey D 
Published: January 2017

Objective: To provide the biochemical rationale for the use of the new anticonvulsant agent gabapentin as a treatment for amyotrophic lateral sclerosis (ALS). Background: ALS is a neuropathologic disorder of the central nervous system characterized by a progressive loss of upper and lower motor neurons. Although the etiopathology of ALS is incompletely known, it is hypothesized that glutamatergic neurotransmission is related to neuropathology. Glutamate is an excitatory amino acid neurotransmitter that is cytotoxic when overexpressed at synaptic terminals, probably through a calcium-related mechanism. The concentration of glutamate in cerebrospinal fluid is increased in patients with ALS. The increased extracellular concentrations of glutamate may be caused by a decreased capacity of glutamate transport in brain tissue and/or abnormal glutamate metabolism. Recent success with the glutamate release inhibitor riluzole in well-controlled clinical trials supports the excitotoxic mechanism of neuropathology in patients with ALS. Potential Treatment For Als: Gabapentin has demonstrated neuroprotective properties in a model of chronic glutamate toxicity in vitro. Although the neuroprotective mechanism of action of gabapentin is currently unknown, it is hypothesized here that gabapentin decreases the rate of formation of glutamate derived from the branched-chain amino acids (BCAAs) leucine, isoleucine, and valine. The proposed decrease in formation of glutamate from BCAAs may decrease the pool of releasable glutamate and therefore compensate for diminished glutamate uptake capacity and/or abnormal glutamate metabolism in patients with ALS. Conclusions: Based on this rationale, it is proposed that gabapentin may provide a beneficial effect in the treatment of patients with ALS.
Consumer Requests for Information regarding Psychotropic Drugs: Experience from a National Medicines Phone-In
Authors: Alderman Christopher P , Ryan Michael J 
Published: January 2017

OBJECTIVE: To undertake a qualitative analysis of calls regarding psychotropic drugs that were received during a national medicines phone-in day. BACKGROUND: In July 1996, The Society of Hospital Pharmacists of Australia coordinated a national medications phone-in day, allowing consumers to seek information about medications from pharmacists and physicians using a toll-free telephone number. METHODS: Data collection forms were used to record the details of all calls answered during the phone-in day. Demographic data collected included the estimated age and gender of the caller. Other data collected included the drugs that were the subject of the inquiry and the category of questions. RESULTS: There were 42 096 attempted connections to the service, but because of limited telecommunications capacity, only 2245 callers were successfully connected. Psychotropic drugs were the primary subject of 367 calls, representing 16.4% of all inquiries for which data collection forms were completed. Antidepressants (56.1%) and benzodiazepines (24.8%) were the two most commonly encountered classes of psychotropic drugs. The greatest proportion of calls (57.2%) was related to adverse effects of medications. The nature of the inquiries regarding adverse drug effects was generally consistent with the adverse effects detailed in the scientific literature. CONCLUSIONS: The results of this 1-day, consumer-oriented drug information project suggest that there is a substantial need for this type of service. Patients treated with psychotropic medications should have access to unbiased, high-quality information about drug therapy.