bluuebunny/crossref_metadata_2025 huggingface dataset:
Haloperidol Decanoate: A Depot Antipsychotic
Authors: Hemstrom Carl Arthur , Evans R. Lee , Lobeck Frank G.
Published: May 2017

This article reviews the role of a new depot antipsychotic dosage form, haloperidol decanoate (HD), in relationship to other comparable pharmacotherapies (oral and injectable). The chemistry, indications, contraindications, and pharmacokinetics of HD are discussed. The available clinical research in humans is presented and evaluated with respect to efficacy, adverse effects, and dosing. HD is clearly an effective antipsychotic dosage form. Certainly, HD can improve compliance and possibly outcome for selected patients. HD should be reserved for chronic relapsing schizophrenic patients who have responded to oral haloperidol. Considering the pharmacokinetics, potential risks, and cost of HD, the clinician needs to be prepared with recommendations to effect optimal use of HD (guidelines are presented).
Vancomycin Serum Protein Binding Determination by Ultrafiltration
Authors: Ackerman Bruce H. , Taylor E. Howard , Olsen Keith M. , Abdel-Malak Wedad , Pappas Alexandras A.
Published: May 2017

Sixty-two serum concentrations were obtained from 12 infected patients enrolled in a vancomycin pharmacokinetic study. Both unbound and total serum vancomycin concentrations were measured using ultrafiltration and a commercial fluorescent polarization immunoassay. Ultrafiltrates were obtained by centrifugation at 1000 × g for ten minutes at room temperature and their assay indicated a range in protein binding from 7.9 to 71 percent. The mean protein binding (mean ±SD) was 41.95 ± 14.15 percent. No measurable adsorption of vancomycin onto the ultrafiltration membrane was noted. Orthogonal regression of unbound versus total vancomycin concentrations was described by the equation y=0.597x-0.362 with a correlation coefficient of 0.948.
Stability of Terbutaline Sulfate Injection Stored in Plastic Tuberculin Syringes
Authors: Raymond Glynn G.
Published: May 2017

Terbutaline sulfate injection was drawn up into plastic tuberculin syringes and stored under four conditions: exposed to ambient (fluorescent) light at room temperature (23-25 °C) and under refrigeration (2-8 °C) and protected from light at room temperature and under refrigeration. The terbutaline sulfate content was determined one, two, three, four, five, six, and seven weeks after initial storage. The analytical method employed was the United States Pharmacopeia XXI colorimetric procedure. Under all four storage conditions terbutaline sulfate concentration was >90 percent of initial concentration at all time periods.
Major Depression with Psychotic Features Associated with Acyclovir Therapy
Authors: Sirota Pinkhas , Stoler Moshe , Meshulam Betty
Published: May 2017

Psychiatric side-effects associated with acyclovir therapy are very rare in the medical literature. We present a case of depression with paranoid delusions in a patient with chronic lymphocytic leukemia that appeared after intravenous acyclovir treatment for herpes simplex infection. The clinical picture resolved following discontinuation of acyclovir and treatment with haloperidol and maprotiline. The patient's status was intact at an eight-month follow-up check. The few reports of psychiatric disorders due to acyclovir are reviewed and discussed.
Is There Significance beyond the T-Test?
Authors: Boyce Eric G. , Nappi Jean M.
Published: May 2017

Choosing the most appropriate statistical test may be routine for statisticians, but not for clinicians. The t-test, a parametric statistical test, may be used inappropriately. This commentary describes the assumptions of and alternatives to the t-test.

T-tests are used to compare two groups of data that are from a continuous scale and normally distributed. Determining if data are normally distributed can be difficult but selected methods can be useful. Two nonparametric tests, the Mann-Whitney U test and the Wilcoxon rank sum test, may be more appropriate in analyzing data that are neither continuous nor normally distributed. Statistical results may vary with the test chosen. Investigators are responsible for using the appropriate statistical tests. Statisticians and texts can be consulted. Pharmacy educational and training programs may need further emphasis in the area of statistics.
Effects of Magnesium Citrate and Clidinium Bromide on the Excretion of Activated Charcoal in Normal Subjects
Authors: Vuignier Barbara Insley , Oderda Gary M. , Gorman Richard L. , Klein-Schwartz Wendy , Watson William A.
Published: May 2017

The efficacy of cathartics in shortening the gastrointestinal transit time of activated charcoal (AC) in the presence of drugs that alter gastrointestinal motility has not been determined. We evaluated the effects of magnesium citrate (MC) on the excretion of activated charcoal in healthy volunteers alone and with concurrent administration of the anticholinergic drug clidinium bromide. Forty subjects were randomized to clidinium bromide 5 mg or placebo capsule (PC), followed by activated charcoal 15 g and magnesium citrate or a placebo liquid (PL). The onset and duration of excretion of activated charcoal were noted. Mean onset times for activated charcoal were: group I (CB, MC) 4.5 ± 2.1 h; group II (CB, PL) 17.0 ± 10.0 h; group III (PC, MC) 6.3 ± 5.8 h; and group IV (PC, PL) 20.6 ± 8.4 h. The onset of excretion of activated charcoal was statistically different in both magnesium citrate groups as compared with the placebo liquid groups. The duration of activated charcoal in the stool was similar among the groups. The addition of clidinium bromide did not appear to affect gastrointestinal transit time. These results support previous studies of the effects of cathartics on the excretion of activated charcoal, and suggest that cathartic efficacy is not inhibited by anticholinergic drugs when used in therapeutic doses.
Impact of a Clinical Pharmacokinetic Service on Patients Treated with Aminoglycosides for Gram-Negative Infections
Authors: Destache Christopher J. , Meyer Sharon K. , Padomek Michael T. , Ortmeier Brian G.
Published: May 2017

The present study was a retrospective, case-control design aimed at evaluating whether the clinical pharmacokinetic service (CPS) is cost-effective, as assessed by lengths of hospital stay and aminoglycoside therapy, incidence of a decrease in renal function, and time for resolution of infection as determined by vital signs. Forty-six patients were entered into this study, and were matched by defined criteria. The results of the study demonstrated a six-day difference in hospital stay for the CPS group (p < 0.05). Length of aminoglycoside therapy was 33 hours shorter for the CPS group. Additionally, the time necessary for resolution of the infection was significantly shorter for this group, as assessed by vital signs returning to normal or baseline. Three patients in each group expired. Two patients in the CPS group and five in the control group developed aminoglycoside-associated increases in serum creatinine. No significant difference was found between the two groups in age, weight, or APACHE II score. Additionally, the two groups were similar with respect to concomitant diseases and concomitant antibiotics used. The approximate cost of the CPS was calculated as $56 per patient. Use of the CPS decreasing hospital stay by six days (mean $1875/patient) would translate to an annual savings of $654 375 in hospital charges, assuming 365 patients received aminoglycoside therapy per year.
Allergic Reaction to Antipyrine, A Marker of Hepatic Enzyme Activity
Authors: Mccrea Jacqueline B. , Vlasses Peter H. , Rocci Mario L.
Published: May 2017

Antipyrine is a pyrazole derivative used extensively as a marker for hepatic drug metabolizing enzyme activity. A subject participating in a clinical trial employing antipyrine experienced an acute allergic reaction to the drug which was characterized by diaphoresis, flushing, swelling of the throat, difficulty in breathing, vomiting, swelling of the upper lip, and a diffuse urticarial rash. Intravenous administration of diphenhydramine markedly improved the symptomatology. Clinical investigators as well as study participants should be alerted to the potential for antipyrine to cause an acute allergic reaction.
Prolonged Use of Intravenous Isoniazid and Rifampin
Authors: Koestner James A. , Jones Linda Keck , Polk William H. , Sawyers John L.
Published: May 2017

We present a case of a 55–year-old woman requiring prolonged therapy with intravenous isoniazid and rifampin secondary to extensive bowel disease. We believe that this is the first U.S. report of a patient receiving both medications by the iv route. After months of therapy the patient has not experienced side effects secondary to this route of administration. We believe that iv isoniazid and rifampin provides a safe alternative method of delivery when clinical situations dictate this route.
Amoxapine-Induced Neuroleptic Malignant Syndrome
Authors: Madakasira Sudhakar
Published: May 2017

Amoxapine is a second-generation antidepressant possessing significant dopamine-blocking activity and extra-pyramidal side effects. The occurrence of neuroleptic malignant syndrome is described in a patient treated with amoxapine. The syndrome resolved rapidly following discontinuation of the drug. Older patients may be particularly at risk for this adverse reaction with amoxapine.
Accuracy of Two Equations in Determining Normalized Phenytoin Concentrations
Authors: Mauro Laurie Slack , Mauro Vincent F. , Bachmann Kenneth A. , Higgins James T. , Robinson J. Daniel
Published: May 2017

The accuracy of two equations in normalizing total phenytoin concentrations in the presence of renal failure or hypoalbuminemia was evaluated in 11 renal failure and 23 hypoalbuminemic patients. Blood samples were obtained from hospitalized patients receiving phenytoin and were assayed for free and total phenytoin concentrations. Estimated normalized phenytoin concentrations based on free drug concentration were compared statistically with normalized concentrations calculated from the two equations via Student's t-test. The equation for normalizing phenytoin concentrations in hypoalbuminemic patients significantly underpredicted normalized phenytoin concentrations 15.7 ± 8.5 versus 19.9 ± 12.1 mg/L(p<0.001). In patients with renal failure, the mean phenytoin concentration from the respective equations and that based on free concentration were 14.1 ± 6.2 and 14.0 ± 7.9 mg/L, respectively. However, in 5 of 11 renal failure patients the equation resulted in over- or underprediction by at least 25 percent. Neither equation should be used clinically to normalize phenytoin concentrations in these patient populations.
Survival of Beta-Lactamase-Producing and -Nonproducing Bacteria in Intravenous Solutions
Authors: Hugbo Peter G. , Akpan Udo E.
Published: May 2017

The survival of beta-lactamase-producing (β-lac+) and non-beta-lactamase-producing (β-lac-) Bacillus and Staphylococcus spp. has been investigated in dextrose 5% injection, NaCl 0.9%, and dextrose 5% in NaCl 0.9% solutions. Tests were performed under static and turbulent conditions of incubation, with and without antibiotics added to the fluids, and with or without 1% citrated blood. All solutions were inoculated with about 1000 organisms/mL, and sampled for viable bacteria at specific time intervals. Under static conditions, there was no significant decrease in viability (p > 0.01) of the bacilli, except for the staphylococci (p < 0.01). However, when cultures were agitated, all species showed significant decline in viability (p < 0.01). When antibiotics were present, S. aureus (β-lac+) declined gradually throughout 24 hours (p > 0.01). B. cereus (β-lac+) concentrations were static in all solutions. All organisms multiplied rapidly in solutions containing blood. The results suggest that the growth characteristics of both β-lac+ and β-lac- bacteria in intravenous fluids are essentially similar, except in solutions containing beta-lactamase-sensitive antibiotics in which (β-lac+ bacteria tend to survive.
Albumin Utilization in a University Hospital
Authors: Alexander Michael R. , Stumpf Janice L. , Nostrant Timothy T. , Khanderia Ujjaini , Eckhauser Frederic E. , Colvin Carol L.
Published: May 2017

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.
Phenytoin-Carbamazepine Cross-Sensitivity
Authors: Reents Stan B. , Luginbuhl William E. , Davis Steven M.
Published: May 2017

A case of phenytoin-carbamazepine cross-sensitivity is presented. Similar signs and symptoms occurred during administration of both drugs. A common metabolic intermediate is offered as a possible explanation of the mechanism. Clinicians should be careful when choosing alternatives in patients with hypersensitivity reactions to anticonvulsants. Valproic acid may be the safest choice in this setting.
Diabetogenic Effect of Nifedipine
Authors: Heyman Samuel N. , Heyman Ayelet , Halperin Itzchak
Published: May 2017

This case report describes a 60-year-old diabetic patient whose daily insulin requirements increased by 30 percent following nifedipine administration. Glucagon and intravenous glucose tolerance tests were performed with and without nifedipine treatment, in order to evaluate the roles of decreased pancreatic beta islet cell function and augmented insulin peripheral resistance in the diabetogenic effect of nifedipine. Insulin and calculated glucose peripheral utilization extrapolated from the glucose concentration curves were not significantly different. C-peptide levels tended to be lower with nifedipine treatment at baseline and during the glucagon tests. This may suggest that the altered glycemic control associated with nifedipine was mediated by a suppressed islet beta cell function. The effect of calcium channel-blockers upon glycemic control and the possible mechanisms involved are discussed.
Hemodynamic Vertebrobasilar Insufficiency as an Adverse Effect of Antihypertensive Therapy
Authors: Fagan Susan C. , Mccormick Patrick W. , Diaz Fernando G.
Published: May 2017

A 63-year-old white male with a 25-year history of hypertension experienced the onset of intermittent diplopia and gait disturbance 24 hours after a change in antihypertensive medication from atenolol 50 mg/d to enalapril 5 mg bid. Three weeks later, the patient was admitted with a worsening of symptoms. Cerebral arteriography revealed significant bilateral vertebral artery stenosis. Symptoms continued to progress in the hospital, and at the time of posterior circulation revascularization the patient had a persistent bilateral internuclear ophthalmoplegia and right ptosis. The need for a neurovascular workup and adjustment of therapy in patients with antihypertensive-associated cerebral ischemia is discussed.
Pharmacokinetics of Ranitidine in Morbidly Obese Women
Authors: Davis Robin L. , Quenzer Ronald W. , Bozigian Haig P. , Warner Christopher W.
Published: May 2017

The pharmacokinetics of a single dose of ranitidine 50 mg iv were determined in ten normal-weight and ten morbidly obese (>90 percent ideal body weight) age-matched female subjects. No significant difference between normal and obese subjects was found in ranitidine peak serum concentration, volume of distribution, clearance, and elimination rate constant. Ranitidine volume of distribution and clearance were significantly smaller in the obese subjects per kilogram of total body weight (1.45 vs. 0.80 L/kg and 0.59 vs. 0.33 L/h/kg, respectively; p<0.001) but not when normalized to ideal body weight (1.65 vs. 1.45 L/kg and 0.68 vs. 0.59 L/h/kg). We conclude that obese patients receiving ranitidine therapy should be treated with standard dosages or dosages based on ideal body weight.
Ketorolac: A Parenteral Nonsteroidal Antiinflammatory Drug
Authors: Resman-Thrgoff Beth H.
Published: May 2017

Ketorolac tromethamine is a pyrrolo-pyrrole nonsteroidal antiinflammatory drug (NSAID) with potent analgesic effects when administered intramuscularly for the treatment of acute pain. Ketorolac is well absorbed and has a rapid onset of action. Maximum plasma concentrations are achieved in 45-50 minutes and peak analgesic effects in about one to two hours following intramuscular injection. Ketorolac is more than 99 percent bound to plasma proteins and has a mean apparent volume of distribution of 0.11-0.25 L/kg. About 91 percent of a dose is excreted in urine, mostly as inactive metabolites, and approximately 6 percent is eliminated in feces. The elimination half-life, approximately four to six hours, increases in elderly patients and those with renal impairment. Its analgesic effectiveness was similar or superior to that of morphine, meperidine, or pentazocine in single-dose studies of patients with postoperative pain or renal colic and greater than that of placebo in patients with chronic cancer pain. The adverse effects are generally mild to moderate, self-limiting, and similar to those seen with other prostaglandin inhibitors. Ketorolac has a reversible inhibitory effect on platelet aggregation. It can cause dose-related gastric ulcerations, even when administered parenterally. Ketorolac is a promising parenteral alternative to oral NSAIDs and a nonnarcotic alternative to opioid analgesics. Additional multiple-dose studies are needed to more clearly define its place in therapy.
Fluosol: An Oxygen-Delivery Fluid for use in Percutaneous Transluminal Coronary Angioplasty
Authors: Garrelts James C.
Published: May 2017

Fluosol (20% intravascular perfluorochemical emulsion) is an oxygen-carrying emulsion used to deliver oxygen to ischemic myocardium during percutaneous transluminal coronary angioplasty (PTCA). Fluosol is composed of two perfluorochemicals, perfluorodecalin and perfluorotripropylamine. It has a high capacity for oxygen solubility, a low viscosity, and a small particle size. Following administration, the perfluorochemicals in fluosol are not metabolized. Rather, most are expired as gaseous particles through the lungs; the remainder are taken up by the organs of the reticuloendothelial system and later expired. When administered during balloon inflation in PTCA, fluosol preserves ventricular wall motion and global left ventricular ejection fraction. In addition, it minimizes ST segment changes and preserves cardiac output. Fluosol may be especially useful in patients who have poor contractile reserve, multivessel disease, or serious underlying illness. Other uses under investigation include limitation of myocardial infarct size and chemosensitization or radiosensitization of malignant tumors. Adverse effects secondary to the use of fluosol include ventricular arrhythmias, pruritus, bradycardia, chest pain, dyspnea, and increased respiratory rate. Fluosol must be thawed, admixed, warmed to body temperature, and oxygenated prior to intracoronary administration. The usual administration rate is 60 mL/min during each balloon inflation.
Possible Serotonin Syndrome Associated with Tramadol and Sertraline Coadministration
Authors: Mason Barbara J , Blackburn Kate H
Published: May 2017

Objective

To report a possible case of serotonin syndrome associated with coadministration of tramadol hydrochloride and sertraline hydrochloride.

Case Summary

A 42-year-old woman developed atypical chest pain, sinus tachycardia, confusion, psychosis, sundowning, agitation, diaphoresis, and tremor. She was taking multiple medications, including tramadol and sertraline. The tramadol dosage had recently been increased, resulting in what was believed to be a serotonergic syndrome.

Discussion

Serotonin syndrome is a toxic hyperserotonergic state that develops soon after initiation or dosage increments of the offending agent. Patients may differ in their susceptibility to the development of serotonin syndrome. The (+) enantiomer of tramadol inhibits serotonin uptake. Tramadol is metabolized to an active metabolite, Ml, by the CYP2D6 enzyme. If this metabolite has less serotonergic activity than tramadol, inhibition of CYP2D6 by sertraline could have been a factor in the interaction.

Conclusions

Clinicians should be aware of the potential for serotonin syndrome with concomitant administration of sertraline and tramadol.
Seizure Resulting from a Venlafaxine Overdose
Authors: White C Michael , Gailey Ronald A , Levin Gary M , Smith Thomas
Published: May 2017

Objective

To report a case of venlafaxine overdose.

Case Summary

A 40-year-old white woman with major depression took an overdose of venlafaxine in an apparent suicide attempt. After the ingestion of 26 venlafaxine 50-mg tablets, the patient experienced a witnessed generalized seizure. She was admitted to the medical intensive care unit, venlafaxine was discontinued, and no further sequelae were seen.

Discussion

To our knowledge, this is the first reported case of venlafaxine overdose that resulted in a generalized seizure. Based on nonoverdose pharmacokinetics and pharmacodynamics of venlafaxine and the potential risks of available interventions, no emergent therapy was instituted.

Conclusions

The venlafaxine overdose in our patient resulted in a single episode of generalized seizure but elicited no further sequelae.
Valacyclovir
Authors: Acosta Edward P , Fletcher Courtney V
Published: May 2017

Objective

To discuss the clinical pharmacology, antiviral activity, clinical efficacy, and other therapeutic issues associated with valacyclovir use for the treatment of herpesvirus infections.

Data Source

Literature searches using MEDLINE were prospectively designed to include relevant articles and abstracts between January 1982 and March 1996. The searches focused on valacyclovir pharmacology, clinical efficacy, and issues associated with herpesvirus infections.

Study Selection

Selection of clinical and basic science studies were limited to those focusing on valacyclovir. All articles with pertinent information relevant to the scope of this article were reviewed.

Data Synthesis

Valacyclovir is an amino acid ester prodrug of acyclovir. It is currently approved for the treatment of herpes zoster infections in immunocompetent adults (1 g po tid for 7 d) and recurrent episodes of genital herpes in immunocompetent adults (500 mg bid for 5 d). Valacyclovir is rapidly and almost completely hydrolyzed to acyclovir prior to systemic exposure. The bioavailability of valacyclovir is 54% compared to approximately 20% for oral acyclovir. At higher dosages (2 g qid), the plasma AUC of acyclovir following oral valacyclovir administration approximates that seen after intravenous administration of 10 mg/kg every 8 hours. Clinical data indicate that valacyclovir is at least as effective as acyclovir in decreasing the duration of pain associated with postherpetic neuralgia, and in reducing time to genital lesion healing and the length of the episode.

Conclusions

Valacyclovir has improved bioavailability over acyclovir and is at least as efficacious. The favorable safety profile of acyclovir and increased systemic exposure make it a particularly ideal candidate for further studies of herpes group viral infections in immunocompromised patients.
Dalteparin: A Low-Molecular-Weight Heparin
Authors: Howard Patricia A
Published: May 2017

Objective

To discuss the chemistry, pharmacology, and pharmacokinetics of dalteparin, a low-molecular-weight heparin (LMWH), and to review the comparative clinical trial data evaluating the efficacy and safety of dalteparin and unfractionated heparin (UH) for the prophylaxis and treatment of venous thromboembolism.

Data Sources

A MEDLINE search identified pertinent English-language publications on dalteparin and venous thromboembolism. Key search terms were dalteparin, Fragmin, LMWH, and venous thromboembolism. The search was supplemented by review articles, articles obtained from the bibliographies of the review articles, and the dalteparin approval database.

Study Selection

The most pertinent studies describing the pharmacology and pharmacokinetics of dalteparin in humans were selected; all abstracts and clinical trials evaluating the use of dalteparin for antithrombotic therapy were reviewed. Review articles by authors of international reputation were selected.

Data Extraction

Pertinent information from the review articles on the pharmacology of LMWHs and UH was summarized. Clinical trial data were extracted for study design, patient demographics, therapeutic regimens, methods of evaluation, and outcomes.

Data Synthesis

Dalteparin is an LMWH indicated for patients undergoing abdominal surgery who are considered to be at risk for deep-vein thrombosis (DVT), which may lead to pulmonary embolism (PE). In this population, numerous clinical trials have demonstrated comparable efficacy between dalteparin and fixed-dose UH for DVT prophylaxis. Dalteparin has a predictable dose response and can be administered as a standard single daily subcutaneous dose for all patients. In therapeutic doses, dalteparin does not alter coagulation tests and therefore does not require routine laboratory monitoring, in contrast with adjusted-dose UH. Bleeding risks with dalteparin are comparable with and possibly less than those associated with UH. Preliminary studies suggest that dalteparin may be effective for other indications, including DVT prophylaxis for hip replacement surgery and the treatment of DVT and PE. Comparative cost-effectiveness data are not yet available.

Conclusions

Dalteparin is the second LMWH to receive approval by the Food and Drug Administration. Dalteparin is indicated for prophylaxis against DVT in patients undergoing abdominal surgery. Clinical studies have shown that single daily doses of dalteparin provide a safe and effective alternative to fixed-dose UH therapy. Additional studies are needed to determine the cost-effectiveness of dalteparin compared with UH and other LMWHs.
Antibiotic-Associated Hepatitis: Update from 1990
Authors: Vial Thierry , Biour Michel , Descotes Jacques , Trepo Christian
Published: May 2017

Objective

To review the literature on the recent available evidence of antibiotic-associated acute liver injury.

Data Sources

All published articles from January 1990 to July 1995 were extracted from the monthly updated HEPATOX database. Additional articles were found using MEDLINE, EMBASE, and PASCAL searches. Hepatic injuries associated with antituberculous, antimycotic, antiviral, antiprotozoal, and antiseptic compounds were excluded from this review.

Study Selection

As the amount of literature was large, only case reports, series, and epidemiologic data were used. Results from clinical trials were reviewed only when no other information was available.

Data Extraction

Original articles were reviewed to select relevant material. Information regarding the clinical description, histologic features, severity, outcome, and possible risk factors was extracted. Data on incidence were provided by epidemiologic studies or spontaneous reporting to regulatory agencies.

Data Synthesis

Antibiotic-associated acute liver injury is rare, with an incidence not exceeding 1 case per 10 000 users for most drugs. Among beta-lactams, amoxicillin/clavulanic acid and penicillinase-resistant penicillins are associated with predominant and sometimes protracted cholestasis. The hepatotoxic potential of all available erythromycin salts is confirmed, and recent evidence suggests that roxithromycin could be added to the list of antibiotic-induced liver injury. Among fluoroquinolones, only ciprofloxacin has been associated with serious hepatitis. Trimethoprim/sulfamethoxazole-induced hepatitis is often reported, but trimethoprim alone also appears as a possible cause of acute liver injury. Finally, acute bile duct injuries and ductopenia have been described with several antibiotics.

Conclusions

The most important recent information is the possibility of protracted liver cholestasis with bile duct injuries induced by several antibiotics, particularly penicillinase-resistant penicillins, and the identification of new potentially hepatotoxic antibiotics, namely, roxithromycin, ciprofloxacin, and trimethoprim.
General Medicine: Effects of Aspirin on Platelet Aggregation in Smokers and Nonsmokers
Authors: Chant Clarence , Fagan Susan C , Aurora Sheena K , Gidal Barry E , Joseph Rajiv
Published: May 2017

Objective

To assess the relative antiaggregatory ability of aspirin on platelets of smoking and nonsmoking healthy volunteers.

Design

Prospective, randomized, crossover study.

Setting

Tertiary-care teaching institution.

Subjects

Eighteen healthy smoking and nonsmoking male volunteers.

Interventions

Each subject received aspirin 325 mg or ticlopidine 250 mg bid as an active control for 7 days in a crossover manner separated by a 1-month washout period. Whole blood platelet aggregation was measured on four occasions, twice at baseline and once after each drug treatment.

Outcome Measurement

Whole blood ex vivo platelet aggregation in terms of impedance (Ω) and adenosine triphosphate (ATP) release (nmol), as assessed using Lumi-aggregometry.

Results

Aspirin was associated with significantly less ATP release in both smokers (p = 0.01) and nonsmokers (p = 0.003). No significant differences in platelet aggregation were found between smokers and nonsmokers at baseline or with any treatment phases. Sixty-seven percent and 17% of volunteers receiving ticlopidine and aspirin, respectively, reported adverse effects.

Conclusions

Twice-daily administration of aspirin for 7 days to healthy volunteers was well tolerated and also reduced platelet aggregation significantly regardless of smoking status.
Pediatrics: Bethanechol Chloride Oral Solutions: Stability and Use in Infants
Authors: Schlatter Joël L , Saulnier Jean-Louis
Published: May 2017

Objective

To assess the stability of a bethanechol chloride oral solution prepared from tablets.

Method

The initial concentrations were determined. These solutions were stored at 4 °C for 90 days. During this period, the concentrations of the bethanechol chloride solutions were determined by spectrophotometry. The clinical efficacy of the oral solution was tested in five infants with gastroesophageal reflux disease by comparison of gastric pH before and after treatment.

Results

Significant decomposition of bethanechol chloride occurred in the two formulations. Bethanechol oral solution in sterile water for irrigation was well tolerated by five pediatric patients, and the clinical efficacy was equivalent to that of the tablet formulation.

Conclusions

The bethanechol chloride oral solution 1 mg/mL in sterile water for irrigation was stable at least 30 days when stored at 4 °C and at an initial pH of 6.5. This formulation appears to be clinically acceptable and provides a convenient dosage form for use in pediatric patients.
Pediatrics: Treatment of Tinea Capitis
Authors: Abdel-Rahman Susan M , Nahata Milap C
Published: May 2017

Objective

To review the epidemiology, pathogenesis, mycology, clinical presentation, and pharmacotherapy of tinea capitis, and describe the role of newer antimycotic agents.

Data Sources

A MEDLINE search restricted to English-language articles published from 1966 through 1996 and journal references were used in preparing this review.

Data Extraction

The data on mycology, pharmacokinetics, adverse effects, and drug interactions were obtained from controlled studies and case reports appearing in the literature. Both open-label and comparative studies were evaluated to assess the efficacy of antimycotics in the treatment of this infection.

Data Synthesis

Griseofulvin is the drug of choice in the treatment of tinea capitis. Newer agents with greater efficacy or shorter treatment durations continue to be explored. Ketoconazole, the first azole studied for efficacy in tinea capitis, has not demonstrated any clinical advantage over griseofulvin in several controlled clinical trials. Itraconazole is effective, but the available data are limited to case reports and a single uncontrolled study. Terbinafine similarly has shown promise in the treatment of tinea capitis, but the oral formulation was only recently approved in the US. Existing studies reflect the results in infection with pathogens not seen in the US. Both itraconazole and terbinafine achieve high concentrations in the hair and stratum corneum that persist for several weeks following drug administration. This may enable shorter courses of therapy; however, comparative studies need to be conducted in the US.

Conclusions

Tinea capitis remains the most common dermatophyte infection in young urban children. Oral antifungal therapy is required for effective treatment, often for several months. The combination of griseofulvin with a selenium sulfide shampoo continues to be the mainstay of therapy until more experience is gained with the newer antimycotics.
Extent and Variation of Omeprazole Prescribing in an Elderly Population of Ontario
Authors: McBride John E , Pater Joseph L , Dorland John L , Lam Yuk-Miu
Published: May 2017

Objective

To determine the extent of omeprazole prescribing in the senior population of Ontario over a 1-year period; the variation in omeprazole prescribing for this population according to age group, gender, and geographic region; and the extent of inappropriate prescribing of omeprazole for this population.

Design

Retrospective drug utilization review of prescription drug insurance claims.

Data Source

The Ontario Drug Benefit (ODB) program claims database.

Outcome Measures

The following outcomes were measured: the proportion of seniors in Ontario who received a prescription for omeprazole from April 1,1992 to March 31,1993; effects of age group, gender, and geographic region of residence on omeprazole prescribing; and the extent of inappropriate omeprazole prescribing according to the ODB criteria for use. Prescribing of omeprazole was defined as inappropriate if a first-line antiulcer drug (i.e., histamine2-receptor antagonist) was not prescribed within 1-6 months of the first prescription claim for omeprazole.

Results

A total of 29 936 seniors in Ontario received omeprazole from April 1,1992 to March 31,1993 (2.53 recipients per 100 eligible population). The age-gender group most frequently prescribed omeprazole was women 65-74 years, followed by women and men 75 years or older, and then men 65-74 years. Omeprazole prescribing varied widely among the 48 provincial counties (range of 1.66 recipients per 100 eligible population to 4.52 recipients per 100 population, p < 0.001). There was no evidence of a clustering effect in omeprazole prescribing at the county level. Prescribing of omeprazole was considered to be inappropriate for 80.5% of recipients.

Conclusions

This study demonstrated the ineffectiveness of the ODB limited-use program in controlling omeprazole prescribing. Further study should be done to examine determinants of variation in prescribing by geographic region.
Drug Use by the Elderly in Italy
Authors: Nobili Alessandro , Tettamanti Mauro , Frattura Lucilla , Spagnoli Alberto , Ferraro Lorenza , Marrazzo Eleonora , Ostino Giuseppe , Comelli Mario
Published: May 2017

Objectives

To evaluate drug consumption in the elderly aged 75 years or more living at home.

Design

Cross-sectional study.

Setting

Old-old (i.e., >75 y) people living in central Turin, a city in northern Italy.

Participants

Thirty-four general practitioners (GPs), with 50 or more old-old people in their patient list, randomly chosen among the GPs working in the Unità Socio-Sanitaria Locale I (Local Health Unit I) of Turin; 261 old-old people (135 men and 126 women) randomly selected from the practice records.

Methods

Data were collected by the GP through a structured questionnaire during an office visit and by a social worker in a home interview within 14 days of the GP visit GPs were asked to record every diagnosis and drug currently taken by the patient; social workers were trained in the administration of a structured questionnaire exploring sociodemographic variables, drug use (following the medication inventory strategy), disability, cognitive functions, and depressive symptoms.

Results

Nearly all subjects (95% of the women and 91% of the men) were taking at least 1 drug. The overall number of drugs recorded was 917 (47.1% for men and 52.9% for women), of which 172 (18.8%) were not reported by the GP but were recorded during the social worker's visit. The mean number of drugs was 3.2 for men and 3.8 for women, with a statistically significant difference (p = 0.02), while the mean number of diagnoses was 2.3 and 2.6, respectively. The study of correlates of drug consumption showed a strong association with number of diagnoses at univariate analysis (p < 0.0001, with a linear correlation coefficient of 0.64). No multivariate model showed a clear superiority over the simple one containing only the number of diagnoses in predicting the total number of drugs taken. Cardiovascular, nervous system, and alimentary tract drugs were the most frequently used. A total of 107 subjects (41%) were taking at least 1 unreported drug.

Conclusions

Our study shows high drug consumption among old-old people, with nearly 20% of drugs taken not reported by the GP. These results emphasize the need for an essential therapeutic approach in old-old people, prescribing only drugs of scientifically proven efficacy. Furthermore, the GP must make more effort when collecting a drug history from old-old patients.
Quality Assessment of Pharmacoeconomic Abstracts of Original Research Articles in Selected Journals
Authors: Trakas Kostas , Addis Antonio , Kruk Dorothy , Buczek Yvona , Iskedjian Michael , Einarson Thomas R
Published: May 2017

Objective

To assess and compare the quality of pharmacoeconomic abstracts of cost-minimization analyses, cost–effectiveness analyses, cost–utility analyses, and cost-benefit analyses of original research articles in selected medical, pharmacy, and health economics journals.

Methods

MEDLINE was used to identify articles in selected medical, pharmacy, and health economics journals using the MeSH word “economic” and text words “cost” and “pharmacoeconomic”; the journal PharmacoEconomics was searched manually. All retrieved abstracts were evaluated. Original, comparative (at least one drug comparator) research articles (1990–1994) reporting both costs and clinical outcomes were included in the quality analysis. Abstract quality was assessed as a percentage by using a checklist with 29 objective criteria. Group consensus produced interrater reliability greater than 0.8.

Results

One thousand two published abstracts labeled with the above key words were identified. Of these, 951 were excluded from quality assessment because they were not original research (18%), were not pharmacoeconomic research (47%), lacked a drug comparator (35%), or did not report a clinical outcome (0.5%). Thus, the quality of 51 (5% of the total) remaining abstracts was assessed. Overall scores were 56% in 1990 and 58% in 1994 (p = 0.094). Medical articles scored highest (61.5%; n = 25), pharmacy articles were next (54.3%; n = 5), and health economics articles were lowest (53.4%; n = 21) (p = 0.091); structured abstracts scored significantly higher (62.5%; n = 20) than unstructured (53.3%; n = 31) (p = 0.003).

Conclusions

Abstract quality was generally poor, with no significant change in quality over time. Medical journals scored highest, probably because they use structured abstracts. Guidelines for structured pharmacoeconomic abstracts may assist in improving quality.
Acute Respiratory Distress Syndrome after Aprotinin Infusion
Authors: Vucicevic Zeljko , Suskovic Tomislav
Published: May 2017

Objective

To report a case of acute respiratory distress syndrome (ARDS) following first exposure to aprotinin.

Case Summary

A 24-year-old previously healthy white man was treated with aprotinin infusion because of bleeding following tonsillectomy. The patient had never been treated with aprotinin before, including local application of different hemostatics containing the aprotinin component. Two hours later, hypotension and severe ARDS developed. A full recovery was noted after discontinuation of the drug and prolonged ventilatory support.

Discussion

To our knowledge, this is the first reported case of ARDS following first administration of aprotinin, although serious adverse effects at first exposure have been reported. We propose two possible mechanisms for this adverse reaction: a nonallergic or anaphylactoid reaction with direct degranulation of mast cells and basophils by aprotinin, and microthrombosis of the small pulmonary arterioles precipitated by aprotinin.

Conclusions

Most clinicians consider aprotinin to be a safe drug, especially if it has not been administered before. Reexposure carries a high risk of allergic reactions because of possible sensitization. Nonimmunologic, toxic, or idiosyncratic adverse reactions can be expected at first exposure to any drug, as well as to aprotinin.
Pharmacotherapy of HIV Dementia
Authors: Melton Sarah T , Kirkwood Cynthia K , Ghaemi S Nassir
Published: May 2017

Objective

To review the clinical presentation and management of cognitive impairment associated with central nervous system HIV type 1 (HIV-1) infection.

Data Sources

A MEDLINE search pertaining to HIV-related dementia (HIV-D) and pharmacologic management was performed. Additional literature was obtained from reference lists of the identified articles.

Study Selection and Data Extraction

All clinical trials and case reports evaluating pharmacologic efficacy in terms of clinical response, cerebrospinal fluid (CSF) changes, and neuropathology were considered for inclusion. Selection was not restricted by study design because most information consists of open uncontrolled trials and case reports.

Data Synthesis

HIV-D is characterized by a triad of disturbances in cognition, motor performance, and behavior in adults. Children present with developmental delay, cognitive impairment, poor brain growth, and other neurologic symptoms. The exact pathophysiologic mechanisms of HIV-D are not known. Numerous pharmacologic agents (e.g., nucleoside reverse transcriptase inhibitors, pentoxifylline, nitroglycerin, memantine, nimodipine, peptide T) are under investigation for management of HIV-D. Zidovudine is the most thoroughly investigated medication, with patients developing HIV-D less frequently and showing improvement on neuropsychological, CSF, and neuropathologic evaluations. Sustained response to zidovudine lasts 6 months to 1 year and optimal response is achieved at higher, but less tolerated, dosages. HIV-D patients frequently have comorbid psychiatric disorders requiring psychopharmacologic agents and are sensitive to the adverse effects of these medications.

Conclusions

HIV-D is a devastating complication of HIV-1 infection. Zidovudine is the therapy of choice for prevention and management of cognitive impairment in symptomatic HIV-infected patients and patients with AIDS. Recommendations for other medications cannot be made secondary to lack of data. The management of HIV-D may include multiple agents as more data become available regarding combination therapy. Well-designed controlled trials are needed to evaluate the efficacy of established treatments and investigational medications in the management of HIV-D.
Metformin and Insulin: Is There a Role for Combination Therapy?
Authors: Daniel Jacqueline R , Hagmeyer Kathleen O
Published: May 2017

Objective

To review the literature on concomitant insulin and metformin therapy in patients with type 1 diabetes to determine the potential for combination therapy.

Data Sources

A MEDLINE and bibliographic search (1966–1996) of the literature pertaining to metformin and phenformin and their combined use with insulin in the treatment of patients with type 1 diabetes mellitus was performed.

Study Selection

All human studies using metformin with insulin were included in the analysis. Studies using phenformin with insulin were also included due to its similarities to metformin.

Data Synthesis

The recent availability of metformin provides some new options for treating diabetes mellitus. One possibility is the use of this medication in conjunction with insulin in patients with type 1 diabetes. Although this seems like a potentially beneficial combination, there is currently no recommendation for use in this manner. Experience with combination metformin and insulin therapy has consistently demonstrated a reduction in insulin requirements. Studies have not been of necessary size or duration to definitively prove the benefits of this insulin dose reduction or any other benefits of combination therapy.

Conclusions

When metformin is added to insulin therapy, insulin requirements are likely to decrease. Although one would anticipate benefits from reduction in circulating insulin concentrations, the studies do not provide data to determine if benefits of combination therapy outweigh risks. Further studies of larger size and longer duration are needed before the use of metformin with insulin can be routinely recommended in patients with type 1 diabetes.
Cost-Minimization Analysis of Intravenous Adenosine and Dipyridamole in Thallous Chloride ti 201 Spect Myocardial Perfusion Imaging
Authors: Hilleman Daniel E , Lucas B Daniel , Mohiuddin Syed M , Holmberg M Jeffrey
Published: May 2017

Objective

To conduct a cost-minimization analysis of intravenous adenosine and intravenous dipyridamole in thallous chloride TI 201 single-photon emission computed tomography (SPECT) myocardial perfusion imaging.

Design

A retrospective, open-label, cost-minimization analysis.

Setting

University hospital, outpatient nuclear medicine department.

Patients

Eighty-three patients undergoing dipyridamole TI 201 SPECT and 166 patients undergoing adenosine TI 201 SPECT.

Main outcome Measures

A cost-minimization analysis was conducted using a direct cost accounting approach estimating institutional costs. For the purpose of this study, sensitivity and specificity between adenosine SPECT and dipyridamole SPECT were assumed to be identical. Key costs evaluated included acquisition, administration, monitoring, treatment of adverse effects, follow-up care, and repeat tests.

Results

Adenosine increased heart rate and lowered blood pressure to a significantly greater extent than dipyridamole. The frequency of adverse reactions was not significantly different (p = 0.103) between adenosine (1.64 ± 1.32 per patient) and dipyridamole (1.36 ± 1.23 per patient). The frequency of prolonged and late-onset adverse effects was significantly greater for dipyridamole than for adenosine (p < 0.001). The frequency of adverse events requiring medical intervention was statistically greater for dipyridamole (24%) compared with adenosine (5%) (p < 0.00001). Total cost was significantly less for adenosine ($378.50 ± $128.20 per patient) compared with dipyridamole ($485.60 ± $230.40). Although adenosine had a significantly greater acquisition cost than dipyridamole (p < 0.0001), administration, monitoring, and adverse reaction costs were significantly less for adenosine than for dipyridamole.

Conclusions

The cost of using dipyridamole is significantly greater than the cost of using adenosine despite adenosine's high acquisition cost. Adenosine is less expensive to use because of lower administration costs, monitoring costs, and adverse effect costs. Adenosine should be the agent of choice for pharmacologic vasodilation in the setting of myocardial perfusion imaging.