bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ciprofloxacin-Induced Toxic Epidermal Necrolysis
Authors: Moshfeghi Mersedeh , Mandler Hilary D. 
Published: January 2017

OBJECTIVE: To report a case of probable ciprofloxacin-induced toxic epidermal necrolysis (TEN) in an adult with systemic lupus erythematosus (SLE). CASE SUMMARY: A 31-year-old woman with SLE developed a pruritic rash following her first dose of oral ciprofloxacin. She continued taking ciprofloxacin, and the rash progressively worsened, becoming painful and covering her entire body. She discontinued the ciprofloxacin six days later and presented to the hospital, where two days later, her rash began to desquamate with epidermal erosions and a positive Nikolsky's sign. Skin biopsy was positive for TEN. She then was transferred to a burn-treatment unit because of the severity of the skin involvement. The patient recovered following prolonged hospitalization and rehabilitation. CONCLUSIONS: Although TEN occurs rarely with ciprofloxacin, extensive postmarketing surveillance needs to be performed to determine other risk factors for its development and to establish the incidence of TEN and other severe cutaneous reactions caused by ciprofloxacin or the other fluoroquinolones.
ATOVAQUONE: A Review
Authors: Haile Lydia G. , Flaherty John F. 
Published: January 2017

OBJECTIVE: To review the chemistry, pharmacology, pharmacokinetics, clinical efficacy, and safety of atovaquone. DATA IDENTIFICATION: An English-language literature search using MEDLINE (1984-1993), programs and abstracts of the 30th, 31st, and 32nd Interscience Conferences on Antimicrobial Agents and Chemotherapy, program and abstracts of the VIII International Conference on AIDS, and unpublished information from Burroughs Wellcome, the manufacturer of atovaquone. STUDY SELECTION: All available pharmacokinetic and clinical trials were reviewed. DATA EXTRACTION: Study quality was assessed by a critical appraisal of study design and methods. Pharmacokinetic studies were evaluated for sampling, methods used to determine pharmacokinetic properties, and the presence of concentration-response and concentration-toxicity relationships. Clinical trials were assessed primarily for comparative efficacy and toxicity. RESULTS: Atovaquone is a novel hydroxynaphthoquinone with potent activity against Pneumocystis carinii and Toxoplasma gondii. Its pharmacokinetic properties are characterized by relatively poor bioavailability, excretion almost exclusively through the feces, lack of hepatic metabolism and urinary excretion, low steady-state plasma concentrations, high protein binding, and a long elimination half-life (50-70 h). Results from comparative clinical trials in AIDS patients with mild-to-moderate P. carinii pneumonia (PCP) reveal similar overall treatment success rates for atovaquone, trimethoprim/sulfamethoxazole (TMP/SMX), and pentamidine. Treatment failure because of lack of therapeutic response was significantly greater in patients who received atovaquone compared with those treated with TMP/SMX (p=0.002). More atovaquone-patients experienced treatment failure compared with their pentamidine-treated counterparts, although statistical significance was not achieved. Treatment failure secondary to drug toxicity was significantly higher in the TMP/SMX- and pentamidine-treated patients (p<0.01). Atovaquone has not been studied for PCP prophylaxis. Limited data exist on the use of atovaquone for toxoplasmic encephalitis (TE); however, results from an open trial reveal that the drug may be useful in treating this disorder. To date, atovaquone has been well tolerated by most patients administered the drug. The most common adverse effects include maculopapular rash, gastrointestinal disturbances, and fever. Atovaquone is considerably more costly than other oral agents used to treat PCP. CONCLUSIONS: Atovaquone appears to be better tolerated but less effective than TMP/SMX and pentamidine in the treatment of mild-to-moderate PCP. There is not enough information available on the use of atovaquone for PCP prophylaxis or the treatment of TE to definitively describe its efficacy. Comparative clinical trials are needed to assess its role in this clinical setting.
So Much Writing, So Little Science: A Review of 37 Years of Literature on Edetate Sodium Chelation Therapy
Authors: Grier Michael T. , Meyers David G. 
Published: January 2017

OBJECTIVE: To determine the safety and efficacy of edetate sodium (ethylenediamine tetraacetic acid; EDTA) chelation therapy for atherosclerosis. METHODS: Literature search using MEDLINE, encompassing 1966 through May 1993. Further references were obtained from articles and books, and from citations obtained from the American Academy of Medical Preventics. RESULTS: 16 case reports or case series, 2 longitudinal studies, and 3 clinical trials were reviewed, along with testimonials cited in 19 books. CONCLUSIONS: Little valid scientific evidence is available. Although the postulated mechanisms of action for EDTA are biologically plausible and EDTA appears to be safe, it has not been proven effective. Indeed, the best evidence shows it to be ineffective. Therefore, EDTA chelation therapy should not be used in clinical practice to treat atherosclerosis.
Evaluation of The Pharmacokinetic Interaction Between Cemetidine or Famotidine and Cyclosporine in Healthy Men
Authors: Shaefer Mark S , Rossi Stephen J , Mcguire Timothy R , Schaaf Larry J , Collier Dean S , Stratta Robert J 
Published: January 2017

Objective: To investigate the potential interaction between cimetidine or famotidine and cyclosporine in healthy men. Design: All subjects received oral cyclosporine at baseline, after the first week of 1 histamine2 (H2)-blocker, and a third time after a 1-week washout plus 1 week of the second H2-blocker. Blood samples were collected just before each dose of cyclosporine and for up to 36 hours afterward for pharmacokinetic analysis. Setting: A college of pharmacy in a university teaching hospital. Participants: The study population consisted of 8 healthy men at least 19 years of age. Main Outcome Measures: Cyclosporine concentrations in whole blood were measured using a polyclonal fluorescence polarization immunoassay. Cyclosporine pharmacokinetic parameters during each of the 3 treatment periods were compared. Results: The average times to maximum cyclosporine concentrations were similar between baseline (3.2 h), cimetidine (2.9 h), and famotidine (3.6 h) dosing periods. There were no significant differences in area under the curve, half-life, or maximum concentration during the 3 dosing periods. Conclusions: Neither cimetidine or famotidine produced a significant change in the pharmacokinetics of single-dose oral cyclosporine in healthy men.
Difference Between the Measured and Ordered Dose of Catecholamine Infusions
Authors: Allen Elizabeth M , Boerum Don H Van , Olsen Alice F , Dean J Michael 
Published: January 2017

Objective: To measure the actual concentrations of dopamine, dobutamine, and epinephrine in infusates prepared for patients, and to compare these concentrations with those of the dopamine HCl, dobutamine, and epinephrine HCl infusates that had been prescribed to evaluate drug preparation accuracy. Design: Prospective, unblind study. Setting: Pediatric intensive care unit in a tertiary-care teaching hospital. Participants: All dopamine, dobutamine, and epinephrine infusions ordered for patients during the 2-month study period were eligible for inclusion in the study. Measurements: Daily samples of dopamine, dobutamine, and epinephrine infusates that were prepared for 41 pediatric patients were obtained; the infusate catecholamine concentration was measured by HPLC and compared with the ordered concentration. The concentration then was multiplied by the rate of infusion to determine the catecholamine dose. Main Results: There were significant differences between the measured doses of dopamine, dobutamine, and epinephrine and the dopamine HCl, dobutamine, and epinephrine HCl doses (p = 0.0001, p = 0.039, and p = 0.0009, respectively) that had been ordered because of preparation inaccuracies. Failure to account for the HCl salt in the stock drug accounted for some, but not all, of the inaccuracy of the dopamine HCl and epinephrine HCl infusates. There was a wide interday variability in the measured catecholamine dosage in patients receiving the same dose for 3 days or more. Conclusions: There are daily fluctuations in the preparation of dopamine, dobutamine, and epinephrine infusates that could alter the amount of drug actually delivered to critically ill patients and potentially contribute to their hemodynamic instability.
Compatibility of Ondansetron Hydrochloride with Meperidine Hydrochloride for Combined Administration
Authors: Xu Quanyun A , Trissel Lawrence A , Fox Janet L 
Published: January 2017

Objective: To determine the physical compatibility and chemical stability of ondansetron hydrochloride 0.1 and 1 mg/mL with meperidine hydrochloride 4 mg/mL admixed in NaCl 0.9% injection USP. Design: Triplicate test solutions of the drugs in NaCl 0.9% injection USP were prepared and stored at 4,22, and 32 °C. Samples were removed initially and at various time points over 31 days and were stored at −70 °C until they were analyzed. Physical compatibility was assessed by measuring solution turbidity with a color-correcting turbidimeter and particle content with a light-obscuration particle sizer/counter, as well as by visual assessment. Chemical stability of the drugs was determined using a stability-indicating HPLC analytic method. Duplicate determinations were performed on each sample to measure the concentration of each drug. Results: All admixtures were found to exhibit no visual or subvisual changes of consequence in turbidity or particle content at all observation points. Further, little or no loss of any of the drugs occurred in any concentration throughout the study. Conclusions: The physical compatibility and chemical stability of ondansetron hydrochloride with meperidine hydrochloride under the conditions of this study have been established for 7 days at 32 °C and 31 days at 4 and 22 °C.
Opioid-Induced Muscle Activity: Implications for Managing Chronic Pain
Authors: Sylvester Robert K , Levitt Ralph , Steen Preston D 
Published: January 2017

Objective: To increase awareness of opioid-induced involuntary muscle hyperactivity and to present management options. Case Summary: A ventilator-dependent 71-year-old man presented with pain caused by metastatic lung cancer. Transdermal fentanyl therapy was titrated to 200 μg/h. Two days later a continuous morphine infusion was initiated because of frequent administration of oral morphine solution for breakthrough pain. The patient became progressively less responsive and began exhibiting involuntary muscle hyperactivity thought to represent breakthrough pain. Despite the inability to assess pain control effectively in this unresponsive patient, the morphine infusion rate was increased from 22 to 717 mg/h within 7 days. No change in muscle hyperactivity was observed. Discussion: Over the last decade involuntary muscle hyperactivity has been documented as an adverse effect of chronic opioid therapy. The literature describing the incidence of this toxicity, possible risk factors for its development, and recommendations for its management are discussed. Conclusions: The occurrence of muscle hyperactivity in an unresponsive patient receiving chronic opioid therapy may represent opioid toxicity. Recommendations for managing opioid-induced muscle hyperactivity include reduction of the opioid dosage and/or administration of clonazepam therapy.
Pseudomonas Aeruginosa as a Cause of Infectious Diarrhea Successfully Treated with Oral Ciprofloxacin
Authors: Porco Frank V , Visconte Ernest B 
Published: January 2017

Objective: To describe an immunocompromised patient (without AIDS) with nosocomial infectious diarrhea caused by Pseudomonas aeruginosa. Oral ciprofloxacin therapy proved to be effective. Case Summary: An 80-year-old woman with type II diabetes mellitus and hypertension developed progressive renal insufficiency, was hospitalized because of uremia, and underwent hemodialysis. When the patient developed hematochezia, Duke's C sigmoid colon cancer was detected and successfully resected. She received broad-spectrum antibiotics in the perioperative period. The patient then developed profuse diarrhea associated with abdominal cramping, a low-grade fever, prostration, and headache. The patient then started to receive vancomycin 500 mg po qid empirically. Four days later, the diarrhea continued unabated, the Clostridium difficile titer was negative, and the vancomycin therapy was stopped. However, the stool culture was positive for heavy growth of P. aeruginosa sensitive to ciprofloxacin. The patient then began to receive ciprofloxacin 500 mg po bid. Within 3 days the diarrhea stopped. Oral ciprofloxacin therapy was continued for 10 days and the patient remained free of symptoms with formed stools thereafter. Discussion: Diarrhea following the use of broad-spectrum antibiotics implicates pseudomembranous colitis as the cause. The patient did not respond to oral vancomycin therapy and had a negative stool assay for C. difficile toxin. This patient was believed to have Pseudomonas enteritis, which was confirmed by 2 positive stool cultures. The administration of oral ciprofloxacin therapy stopped her diarrhea with a rapid resolution of symptoms. Conclusions: P. aeruginosa as a cause of infectious diarrhea is unusual. When it occurs, it usually represents a nosocomial infection in an immunocompromised host. This report illustrates that oral ciprofloxacin therapy is effective for Pseudomonas enteritis, with rapid resolution of symptoms.
Mechanism of Anaphylactoid Reactions: Improper Preparation of High-Dose Intravenous Cyclosporine Leads to Bolus Infusion of Cremophor El and Cyclosporine
Authors: Liau-Chu Merry , Theis Jochen GW , Koren Gideon 
Published: January 2017

BACKGROUND: During a Phase I/II trial of high-dose intravenous cyclosporine, a high incidence of anaphylactoid reactions was observed. Epidemiologic investigations revealed that the occurrence of anaphylactoid reactions was significantly associated with improper mixing during preparation of the infusions. It was hypothesized that improper mixing during the preparation of the infusion may have caused initial bolus infusions of the vehicle, Cremophor EL. These inadvertent bolus infusions may have caused the anaphylactoid reactions. OBJECTIVE: To investigate the effect of different mixing techniques on the distribution of the components of cyclosporine concentrate for infusion: cyclosporine, Cremophor EL, and ethanol in the infusions administered to the patients. METHODS: Infusions were prepared in a similar fashion as those administered to study patients enrolled in a high-dose cyclosporine therapy protocol. Samples were collected at defined time points of the infusions. Concentrations of cyclosporine and Cremophor EL were spectrophotometrically determined; ethanol concentrations were measured enzymatically. RESULTS: Cyclosporine and Cremophor EL concentrations were up to ninefold higher than intended during the first 10 minutes of the infusions that were not appropriately mixed. In contrast, the concentrations of cyclosporine and Cremophor EL were similar to the intended concentrations in all of the well-mixed infusions. CONCLUSIONS: Inappropriate mixing of high-dose cyclosporine infusions can lead to initial bolus infusion of cyclosporine and Cremophor EL. Bolus infusions of Cremophor EL have been associated with anaphylactoid reactions. Thus, thorough mixing of high-dose cyclosporine infusions may be important to reduce the possibility of life-threatening anaphylactoid reactions.
Formulation and Stability of Naltrexone Oral Liquid for Rapid Withdrawal from Methadone
Authors: Fawcett J Paul , Morgan Nicola C , Woods David J 
Published: January 2017

OBJECTIVE: To assess the stability of naltrexone oral liquid prepared from tablets and powder, and to evaluate its use in precipitating rapid withdrawal from methadone. DESIGN: Naltrexone 1 mg/mL oral liquids were prepared from tablets and powder and stored in the dark at 4, 25, and 70 °C. Similar formulations containing 5 mg/mL were stored at 70 °C. The 1-mg/mL formulation prepared from tablets was clinically evaluated in inducing rapid withdrawal in two drug-dependent individuals receiving methadone maintenance treatment using a naltrexone dose titration protocol. SETTING: A university pharmacy school and affiliated urban teaching hospital. MAIN OUTCOME MEASURES: Samples removed at six time points were analyzed for naltrexone concentration to assess decomposition over 90 days. An opioid withdrawal symptom checklist was used to assess the severity of the withdrawal symptoms prior to, and 30 minutes after, each dose of naltrexone. RESULTS: Decomposition of naltrexone in all formulations stored at 4 and 25 °C was not significant over 90 days. Both patients tolerated naltrexone 1 mg/mL oral liquid, but found it bitter and gritty. Withdrawal symptoms were experienced immediately after the first dose, but were resolving by the end of day 3 of naltrexone treatment, at which stage both patients were able to tolerate a 50-mg tablet of naltrexone as maintenance. CONCLUSIONS: Naltrexone 1 mg/mL oral liquids prepared from tablets or powder are stable when stored in the dark for 60 days at 4 °C and for 30 days at 25 °C. The formulation prepared from tablets provides flexible dosing in patients undergoing rapid withdrawal from methadone.
Drug Samples and Family Practice Residents
Authors: Shaughnessy Allen F , Bucci Kathryn K 
Published: January 2017

OBJECTIVE: To describe residents' knowledge, attitudes, and behaviors regarding sample medications and to determine the education provided in residency training regarding sample use. METHODS: A 6-item survey was sent to directors of US family practice residency programs. Residents of a sample of these programs were sent an anonymous, self-administered, 21-item questionnaire assessing knowledge, attitudes, and practices relating to sample use. Both surveys consisted of initial and follow-up mailings. RESULTS: The residency directors' survey was returned by 232 of the 436 residency directors (53%). Although 66% of the programs had a policy regarding samples, only 15% of the policies completely incorporated recommendations of the Society of Teachers of Family Medicine. After two mailings, 248 resident responses were received from 43 of 47 residencies (92%). Only 21% of respondents thought that they received adequate training about sample use in medical school; this number increased to 49% for residency training. Agreement with the adequate training statement was highest among respondents from residencies that had both a sample distribution policy and a pharmacist (p = 0.044). Fifty-five percent thought that samples influenced their prescribing and 70% thought that samples helped them to learn more about the sampled medication. CONCLUSIONS: Family practice residents value and use samples, although they are often unaware of the rules governing the labeling of samples. While reported distribution of samples by residents often is appropriate, education about effective sample use could be improved. Drug samples play a significant role in residency training.
Continuous Intrathecal Meperidine via an Implantable Infusion Pump for Chronic, Nonmalignant Pain
Authors: Harvey Susan C , O'Neil Michael G , Pope Catherine A , Cuddy Brian G , Duc Thomas A 
Published: January 2017

OBJECTIVE: To report a continuous infusion of intrathecal meperidine via an implanted infusion pump for nonmalignant, chronic pain. CASE SUMMARY: A 69-year-old white woman had chronic, nonmalignant low-back pain and bilateral leg pain. Multiple drug therapies and other interventional techniques had failed. The patient achieved significant pain relief by a continuous infusion of intrathecal meperidine via an implanted infusion pump. DISCUSSION: To our knowledge, this is the first report of meperidine administered intrathecally by continuous infusion. Continuous infusion of intrathecal and epidural opiates by implanted infusion pumps is becoming more widely recognized as an alternative treatment for patients with chronic, benign pain. Epidural and intrathecal meperidine is an effective analgesic for short-term surgical procedures. Data reporting effective relief and safety with continuous intrathecal meperidine remain limited. CONCLUSIONS: Continuous intrathecal meperidine via an implantable infusion pump may be an effective alternative in the treatment of chronic pain.
Olanzapine: A New Antipsychotic Agent with Efficacy in the Management of Schizophrenia
Authors: Kando Judith C , Shepski John C , Satterlee Winston , Patel Jayendra K , Reams Stephen G , Green Alan I 
Published: January 2017

OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy data, and adverse effects of olanzapine as a treatment for schizophrenia and to determine the advantages and disadvantages of this atypical antipsychotic agent compared with currently marketed agents. DATA SOURCES: A MEDLINE computer literature search was conducted to retrieve all English-language studies and review articles involving olanzapine published as of October 1, 1996. The manufacturer of the drug, Eli Lilly and Company, provided the clinical investigator's brochure and abstracts of unpublished Phase III clinical trials. STUDY SELECTION: Animal studies evaluating the pharmacology of olanzapine were evaluated, as were all open-label and double-blind studies involving the evaluation of olanzapine for the treatment of patients with schizophrenia. DATA EXTRACTION: All available clinical studies were reviewed and the interpretation of data for each study was influenced by the size of the study sample, the nature of the inclusion and exclusion criteria, and the data analysis techniques used. DATA SYNTHESIS: Olanzapine is a thienobenzodiazepine analog with an in vitro receptor affinity profile similar to that of clozapine. Olanzapine exhibits linear kinetics over the dosage range studied and is extensively metabolized in humans. Clinical evaluations to date have shown olanzapine to be at least as efficacious as typical antipsychotic agents in the treatment of the acute phase of schizophrenia. The drug was well tolerated, with significantly fewer extrapyramidal adverse effects than haloperidol. Current data suggest that olanzapine may be more effective than haloperidol for the treatment of negative symptoms; moreover, preliminary data suggest that fewer relapses occur over the course of treatment in patients treated with olanzapine compared with those taking haloperidol. CONCLUSIONS: The exact place of olanzapine in the therapy of psychotic patients remains unclear, as more data are needed to evaluate the long-term efficacy of this agent, its impact on negative symptoms, and its potential use in patients resistant to the standard agents. Despite limitations in the current database, olanzapine is a promising treatment option for patients with schizophrenia.