bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety and Tolerance of Intravenous Nimodipine
Authors: Sramek John J. , Heller Allen H. , Sundaresan Pavur R. , Lettieri John , Sawin Suzanne , Cutler Neal R.
Published: January 2017

OBJECTIVE:

To evaluate the safety and tolerance of intravenous nimodipine administered via a peripheral vein in healthy male volunteers.

DESIGN:

Double-blind, placebo- and vehicle-controlled trial with three fixed-dose panels.

SETTING:

Inpatient infusion and observation periods.

SUBJECTS:

61 healthy male volunteers, aged 18–40 years.

METHODS:

Subjects in panel 1 received nimodipine 0.4 mg/h, vehicle 2 mL/h, or placebo 2 mL/h; subjects in panel 2 received nimodipine 1 mg/h, vehicle 5 mL/h, or placebo 5 mL/h; subjects in panel 3 received nimodipine 2 mg/h, vehicle 10 mL/h, or placebo 10 mL/h. All infusions were administered intravenously for 48 hours and volunteers were observed for 48 hours after cessation of the infusion. In addition to standard safety assessments (physical examination, electrocardiogram, laboratory studies, and adverse event reporting), supine and standing blood pressures and pulse rates were measured frequently. Plasma samples were also analyzed for nimodipine and its two demethylated metabolites.

RESULTS:

Of 61 subjects, 55 completed the 48-hour infusion and 6 discontinued the study because of adverse events. Intravenous nimodipine was well tolerated at 0.4 and 1 mg/h. However, all six subjects who received nimodipine 2 mg/h experienced moderate-to-severe adverse events, and one subject was discontinued because of dizziness, diaphoresis, and postural hypotension. The matched vehicle (10 mL/h) also was not well tolerated, with three subjects who discontinued because of phlebitis. Two subjects who received placebo were also discontinued during the study. Small (2 mm Hg) decreases in mean supine diastolic blood pressure were observed in the 0.4- and 1-mg/h nimodipine groups, but the 2-mg/h group showed a slight (5 mm Hg) increase in blood pressure. These changes were not clinically significant. Clearance and half-life of nimodipine and its metabolites were similar at all three dosages.

CONCLUSIONS:

Using peripheral vein administration, nimodipine 2 mg/h and matched vehicle at 10 mL/h were not well tolerated in this healthy normal population. The maximum tolerated dose of nimodipine was found to be 1 mg/h.
Hydroxyurea-Induced Fever: Case Report and Review of the Literature
Authors: Lossos Izidore S. , Matzner Yaacov
Published: January 2017

Objective:

To describe a patient with hydroxyurea-induced fever.

Case Summary:

A patient with essential thrombocythemia developed a fever 12 hours after beginning hydroxyurea therapy. The diagnosis of drug fever was established by resolution of the fever after withdrawal of hydroxyurea and its recurrence on reexposure to the drug.

Discussion:

Hydroxyurea-induced fever is rare. In the present case, a short lag period between commencement of hydroxyurea therapy and appearance of fever may suggest either direct toxicity or an idiosyncratic reaction. In previous reports, a hypersensitivity drug reaction was implicated.

Conclusions:

The mechanism of hydroxyurea-induced fever remains unclear. Clinicians should be aware of this rare adverse effect.
Low Itraconazole Serum Concentrations Following Administration of Itraconazole Suspension to Critically Ill Allogeneic Bone Marrow Transplant Recipients
Authors: Kintzel Polly E. , Rollins Carol J. , Yee Walter J. , List Alan F.
Published: January 2017

Objective:

To report itraconazole serum concentrations following administration of itraconazole suspension via orogastric feeding tubes to 2 critically ill allogeneic bone marrow transplant recipients.

Case Summaries:

A 38-year-old man and a 29-year-old man, each allogeneic bone marrow transplant recipients, were treated with oral itraconazole for documented fungal infections. Intubation and mechanical ventilation impeded ingestion of itraconazole capsules. Itraconazole was prepared initially as a suspension in intravenous lipid emulsion 20% and later as a suspension in citric acid 1.5% in D5W USP. Itraconazole serum concentrations were assayed using HPLC. Predose itraconazole serum concentrations were undetectable to 72 ng/mL. Postdose itraconazole serum concentrations were 5–97 ng/mL. Itraconazole concentrations measured in these patients were markedly lower than serum concentrations reported in the literature for similar doses administered to fed subjects.

Discussion:

Efficacy of this antifungal agent is limited currently by the patient's ability to ingest and absorb the itraconazole capsules. Pathophysiologic factors and suspension formulation issues that likely contributed to decreased itraconazole absorption are discussed.

Conclusions:

Preparation and administration of itraconazole as a suspension did not enhance drug absorption in these patients. Furthermore, efficacy of itraconazole suspension may be affected by physical compatibility and chemical stability of the extemporaneous preparations.
Stereochemistry in Pharmacotherapy: When Mirror Images are Not Identical
Authors: Tracy Timothy S.
Published: January 2017

Objective:

To describe how drug stereoisomers may differ in pharmacokinetic and pharmacodynamic properties and how these differences may affect therapeutic outcomes.

Study Selection:

Representative studies were chosen from the drug literature demonstrating stereoisomeric differences in drug absorption, protein binding and distribution, metabolism, and elimination. Furthermore, examples of pharmacodynamic differences between drug stereoisomers are presented to demonstrate that these stereoisomers not only may differ in pharmacologic potency, but may possess entirely different pharmacologic actions.

Data Synthesis:

Examples are presented demonstrating that when stereoisomeric differences in pharmacokinetics are linked to pharmacodynamic differences, alterations in therapeutic effect can result. Additionally, drug interactions are discussed in which 1 isomer is affected to a greater extent than the other, potentially causing not only an increase or decrease in effect, but also a change in pharmacologic action. Examples also are presented of the marketing of single isomer entities, with a discussion of the use of these products. Finally, preliminary policies of the Food and Drug Administration are discussed, as well as the potential implications of these policies.

Conclusions:

Drugs that are administered as stereoisomers can differ with respect to both pharmacokinetics and pharmacodynamics, and these differences may have profound implications in pharmacotherapy. All future investigations of drugs that exist as stereoisomers must take into account the pharmacokinetics and pharmacodynamics of both isomers to understand fully the observed phenomena.
Pharmacoeconomic Benefit of Antibiotic Step-Down Therapy: Converting Patents from Intravenous Ceftriaxone to Oral Cefpodoxime Proxettl
Authors: Hendrickson Joseph R , North Donald S
Published: January 2017

Objective:

To evaluate the economic benefit associated with the early conversion of therapy from intravenous ceftriaxone to the comparable oral third-generation cephalosporin, cefpodoxime proxetil.

Design:

Open-label, unblind, nonrandomized clinical trial.

Setting:

A 360-bed Veterans Affairs Medical Center.

Patients:

Forty patients who began receiving intravenous ceftriaxone for either a community-acquired pneumonia or a complicated urinary tract infection.

Intervention:

Twenty patients were selected, based on clinical assessment, to be converted from intravenous ceftriaxone to oral cefpodoxime proxetil. Twenty other comparable patients, who would have been appropriate for step-down therapy, did not receive pharmacy intervention and were used as a control group.

Measurements:

Both groups were assessed and compared for length of ceftriaxone therapy, length of oral follow-up therapy (if any), length of hospitalization, results of culture and sensitivity testing, treatment success and readmissions, and cost of respective therapeutic regimens.

Results:

In the cefpodoxime study group, the average time receiving intravenous and oral antibiotics was 9.1 days at a total cost of $3040.26 for the 20 patients. In the control group, the average time receiving intravenous and oral antibiotics was 11.9 days at a total cost of $3961.26. A savings of $46.05 per patient was achieved. Patients receiving step-down therapy averaged 1 fewer day of hospitalization.

Conclusions:

Pharmacist intervention and cefpodoxime step-down therapy were associated with decreased overall antibiotic costs in our intravenous-to-oral program.
Prescription Drug and Healthcare Use Among Swedish Patients Treated with Antidepressants
Authors: Bingefors Kerstin Al , Isacson Dag Gl , Knorring Lars Von , Smedby Björn
Published: January 2017

Objective:

To analyze healthcare and prescription drug use among patients taking and those not taking antidepressant drugs in a Swedish community.

Design:

Cross-sectional study.

Setting:

General population of the rural Swedish municipality Tierp of approximately 20 000 inhabitants.

Participants:

All residents of Tierp aged 25 years or older during 1988.

Main Outcome Measures:

Mean number of ambulatory care visits, hospital bed days, and prescriptions per person; proportion of those taking prescription drugs in different pharmacologic classes.

Results:

Patients treated with antidepressant drugs had a significantly (p < 0.05) greater use of ambulatory care, hospital care, and prescription drugs than those who did not take antidepressants in the study population. They also had an increased frequency of use of prescription drugs from virtually all pharmacologic classes. Furthermore, the risk for polypharmacy was high in patients treated with antidepressant medications.

Conclusions:

Those who took antidepressant drugs consumed more health services and prescription drugs than did those not taking an antidepressant. Patients receiving antidepressant treatment may be at serious risk for iatrogenic disease and should be evaluated carefully with respect to concomitant drug use.
Diabetes and Related Metabolic Risk Factors Among Arab Americans
Authors: Jaber Linda A , Slaughter Richard L , Grunberger George
Published: January 2017

Objective:

To estimate the incidence of noninsulin-dependent diabetes mellitus (NIDDM) and associated metabolic abnormalities such as impaired glucose tolerance, increased blood pressure, hyperinsulinemia, and obesity in the Arab-American community in the Detroit metropolitan area.

Methods:

Subjects were selected randomly from a computer-generated list provided by the Arab-American Center for Economic and Social Services. Laboratory studies included a 2-hour, 75-g oral glucose tolerance test with glucose, insulin, and C-peptide determinations.

Results:

Of the 105 volunteers studied, 57 were women and 48 were men. Mean ± SD age was 46.0 ± 13.0 years. Body mass index was 30.4 ± 6.8 kg/m2, with 68% of subjects having a body mass index of 27 kg/m2 or more. Of the study participants, 33% had NIDDM, 8.6% had impaired glucose tolerance, and 58% had normal glucose tolerance. Subjects with diabetes, compared with subjects who had normal glucose tolerance, exhibited increased fasting insulin (98 ± 69 vs 55 ± 31 pmol/L; p = 0.00056); higher cholesterol (6.03 ± 1.03 vs 5.09 ± 1.22 mmol/L; p = 0.00073); marginally lower high-density lipoprotein cholesterol (0.98 ± 0.21 vs 1.14 ± 0.31 mmol/L; p = 0.054); higher triglycerides (7.84 ± 5.79 vs 3.83 ± 2.15 mmol/L; p = 0.00002); and higher diastolic (83.7 ± 8.9 vs 78.3 ± 8.0 mm Hg; p = 0.014) as well as systolic (132.5 ± 16.0 vs 119.0 ± 10.6 mm Hg; p = 0.00001) blood pressures.

Conclusions:

This pilot study demonstrates that diabetes may be a frequent medical problem in the Arab-American community. A well-designed epidemiologic study is warranted to validate these results and to elucidate the underlying mechanisms responsible for these findings.
Carbamazepine Phakmacokinetics in Obese and Lean Subjects
Authors: Caraco Yoseph , Zylber-Katz Ester , Berry Elliot M , Levy Micha
Published: January 2017

Objective:

To compare carbamazepine pharmacokinetic parameters between obese and lean subjects following the administration of a single 200-mg tablet.

Design:

Single-dose intervention, open study.

Setting:

Teaching university hospital.

Subjects:

Eighteen obese (group A) otherwise healthy subjects, referred to the metabolic outpatient clinic, and 13 healthy lean (group B) volunteers. Inclusion criterion for the obese subjects was a body mass index (BMI = weight/height2) of more than 30 kg/m2. In the obese group, mean ± SD total body weight (TBW), BMI, and percent of ideal body weight (IBW) were 111.4 ± 19.9 kg, 38.8 ± 6.0 kg/m2, and 182.7% ± 30.7%, respectively. These values were significantly greater than the respective values of 63.2 ± 8.3 kg, 22.4 ± 1.6 kg/m2, and 105.8% ± 5.8% obtained in the lean group (p < 0.001).

Intervention:

Single-dose oral administration of carbamazepine 200-mg tablet (Teril, Taro, Israel).

Outcomes:

Carbamazepine elimination half-life (t1/2), apparent volume of distribution (Varea/F), and its oral clearance (Clpo/F) were derived from the drug concentration-time curves.

Results:

Carbamazepine Varea/F and t1/2 were significantly greater in group A than in group B (98.4 ± 26.9 vs. 60.7 ± 8.5 L, respectively, p < 0.001; and 59.4 ± 14.7 vs. 31.0 ± 5.0 h, respectively, p < 0.001), but its Clpo/F was reduced only slightly in obese as compared with lean subjects (19.8 ± 5.2 vs. 23.0 ± 4.6 mL/min, respectively, p = 0.07). Correction for IBW yielded similar results for Varea/F and t1/2, but Clpo/F per kg of IBW was significantly smaller in the obese than in the lean subjects (0.32 ± 0.07 vs. 0.39 ± 0.06 mL/min/kg of IBW, respectively, p < 0.02). Linear correlations were observed between Varea/F and TBW for both group A (r = 0.92, p < 0.001) and group B (r = 0.77, p < 0.002).

Conclusions:

In comparison with lean subjects, carbamazepine Varea/F is significantly greater in obese subjects and its t1/2 is markedly prolonged. The minor nonsignificant effect of obesity on carbamazepine Clpo/F suggests that in obese subjects the carbamazepine daily dose should be based on IBW, not on TBW.
In Vitro Stability of Ranitidine Hydrochloride in Enteral Nutrient Formulas
Authors: Crowther Roger S , Bellanger Renee , Szauter Karen EM
Published: January 2017

Objective:

To determine the chemical stability and physical compatibility of ranitidine in enteral nutrient formulas.

Measurements:

A stability-indicating HPLC assay was used to measure the recovery of ranitidine from tablet (dissolved in water) or syrup after up to 24 hours of in vitro incubation in a variety of enteral nutrient formulas. Ranitidine binding to components of the formulas was measured after ultrafiltration.

Results:

Eight enteral nutrient formulas were studied, and more than 90% of added ranitidine was recovered from each formula after 24 hours. The amount of ranitidine bound to components of the formulas varied between 8% and 29%. No gross physical incompatibilities were seen and the pH of each formula changed by less than 0.1 pH units over 24 hours.

Conclusions:

Ranitidine from either tablet or syrup was stable in the enteral nutrient formulas studied. Administration of ranitidine by admixture into these enteral formulas may be feasible.
Topical Fumagillin in The Treatment of Microsporidial Keratoconjunctivitis in Aids
Authors: Garvey Michael J , Ambrose Paul G , Ulmer Jack L
Published: January 2017

Objective:

To report microsporidial keratoconjunctivitis in a patient infected with HIV who was treated with topical fumagillin.

Case Summary:

A 37-year-old white man who was experiencing redness, pain, irritation, decreased vision, and a foreign body sensation occurring in both eyes was referred to the ophthalmology clinic. The patient had a medical history significant for AIDS, Pneumocystis carinii pneumonia, and Cytomegalovirus retinitis. Conjunctival smears were taken and stained positive for the presence of Microsporidia. The patient was diagnosed with bilateral microsporidial keratoconjunctivitis and fumagillin therapy was initiated. After 5 days of therapy, the patient repotted significant improvements characterized by a decrease in blurred vision with only slight blurring in the left eye, decrease in headache, and decreased foreign body sensation. The patient continued topical fumagillin therapy for more than 14 months, with only slight blurring in the left eye and no apparent ocular toxicity as a result of fumagillin therapy.

Discussion:

Although rare in occurrence, increasing numbers of documented microsporidial infections are being reported in the medical literature, particularly in individuals who are seropositive for HIV. Clinicians need to be cognizant of microsporidial keratoconjunctivitis as another opportunistic infection in this patient population.

Conclusions:

Although a curative agent has yet to be discovered, fumagillin represents a safe, effective, low-cost, topical agent for the treatment of microsporidial keratoconjunctivitis.
Self-Initiated Modification of Hypertension Treatment in Response To Perceived Problems
Authors: Wallenius Sirpa H , Vainio Kirsti K , Korhonen Maarit Jh , Hartzema Abraham G , Enlund Hannes K
Published: January 2017

Objective:

To assess the prevalence of patient-initiated modification of drug instructions and the association between different classes of problems and the modification of hypertension therapy.

Design And Methods:

In this cross-sectional study, all patients (n = 1215) who had been examined at a hypertension clinic during a 1-year period were surveyed. The response rate to the questionnaire was 85%. of the 1035 respondents, 623 currently taking antihypertensive medication (self-report) were included in the study.

Results:

Of the patients taking antihypertensive drugs, 36% admitted that they had tried to manage their condition with a lower dosage and/or fewer drugs than prescribed. The percentage of patients who modified their drug regimen decreased with increasing age. One or more problems with the treatment of hypertension were reported by 79% of the respondents. The odds ratio (95% confidence interval) for modification among patients who reported 1 or more problems compared with those not reporting any problem was 3.5 (2.12 to 5.67). The prevalence of modification increased with the number of problems; this was seen in all age groups and among men and women.

Conclusions:

Perceived problems in drug taking in the treatment of hypertension have an important impact on the prevalence of modifying drug instructions.
Exacerbation of Congestive Heart Failure After Administration of Polyethylene Glycol–Electrolyte Lavage Solution
Authors: Granberry Mark C , White Laura M , Gardner Stephanie F
Published: January 2017

Objective:

To report a patient with exacerbation of congestive heart failure after administration of polyethylene glycol–electrolyte lavage solution (PEG–ELS).

Methods:

A MEDLINE search was performed, using the terms congestive heart failure (CHF), gastric lavage, colonoscopy, irrigation, and gastroparesis, of English-language articles published from January 1980 through January 1995, as well as review of pertinent articles' bibliographies.

Case Summary:

A 45-year-old white woman with left ventricular systolic dysfunction and diabetic gastroparesis received 4 L of a PEG–ELS as preparation for colonoscopy. Within 24 hours she presented to the emergency department with shortness of breath and increased bilateral lower extremity edema. She was admitted and treated with intravenous furosemide therapy. After aggressive diuresis her symptoms returned to baseline and she was discharged.

Discussion:

The literature search revealed no report of a patient requiring hospitalization as a result of sodium and water retention after bowel preparation with PEG–ELS. CHF is not considered a contraindication to the use of this solution; however, most studies that included patients with heart failure did not describe the degree of left ventricular dysfunction. Our patient's severe CHF, in combination with chronic renal insufficiency, resulted in significant retention of sodium and water.

Conclusions:

Patients with severe left ventricular dysfunction and chronic renal insufficiency who are being considered for procedures that necessitate bowel cleansing with PEG–ELS may be at risk for sodium and water retention and exacerbation of CHF.
Adverse Interactions Between Warfarin and Nonsteroidal Antiinflammatory Drugs: Mechanisms, Clinical Significance, and Avoidance
Authors: Chan Thomas Yk
Published: January 2017

Objective:

To review the mechanisms and clinical significance of adverse interactions between warfarin and nonsteroidal antiinflammatory drugs (NSAIDs) and discuss how these interactions can be avoided.

Data Sources:

Previous studies of interactions between warfarin and NSAIDs or reports of adverse interactions were identified from a MEDLINE search (1976 to present) and from the reference lists of pertinent articles.

Study Selection And Data Extraction:

All articles were considered for inclusion in the review. Pertinent information was selected for discussion.

Data Synthesis:

All NSAIDs can prolong bleeding time by inhibiting platelet function. High-dose aspirin has a direct hypoprothrombinemic effect. Phenylbutazone and its analogs enhance the hypoprothrombinemic effect of warfarin through a pharmacokinetic interaction by inhibiting the hepatic metabolism of warfarin. Mefenamic acid also enhances the anticoagulant effect of warfarin, but the mechanism is not known. The clinical relevance of protein binding displacement in the interaction between warfarin and NSAIDs has been overstated, although a significant one may be more likely in the presence of high concentrations of NSAIDs in patients with slow elimination of warfarin (e.g., those with severe heart failure or impaired liver function). NSAIDs can induce gastrointestinal bleeding, which is likely to be more severe if warfarin is also given.

Conclusions:

The combined use of warfarin and NSAIDs is generally discouraged because of the increased risk of bleeding in these patients. In patients receiving warfarin who also require NSAIDs, phenylbutazone and its analogs, high-dose aspirin, mefenamic acid, excessive use of topical methyl salicylate, and NSAIDs that are associated with a higher risk of bleeding peptic ulcers should be avoided. Patients should be closely monitored for anticoagulant control and bleeding complications during the combined use of warfarin and NSAIDs.
Population Pharmacodynamics: Strategies for Concentration- and Effect-Controlled Clinical Trials
Authors: Ebling William F , Levy Gerhard
Published: January 2017

OBJECTIVE:

To explore and evaluate various strategies for drug concentration- and effect-controlled clinical trials, respectively, in the context of studies of population pharmacodynamics (concentration—effect relationships).

METHODS:

The relative utility of drug concentration- and pharmacologic effect-controlled, randomized clinical trials with two or three concentration—effect measurements for each subject has been explored by computer simulation. The basis for these simulations was a sigmoid-Emax (maximum effect) pharmacodynamic model with Emax = 100%, EC50 (drug concentrations required to produce an effect intensity of 50%) = 10 concentration units, gamma = 2, and no hysteresis. Emax and gamma were held constant whereas EC50 was assumed to be log-normally distributed with a 26% coefficient of variation of the natural log-normalized data. A smaller random variability and variability due to measurement error also were incorporated in the simulations. To explore the implications of variable and unknown and gamma values, the suitability of linear and log—linear interpolation procedures for two-point concentration—effect data in different regions of the sigmoid-Emax curve was compared.

RESULTS:

Pharmacologic effect-controlled clinical trials with 300 hypothetical subjects and targeted effect intensities of 25% and 75% yielded very good estimates of drug concentrations required to produce effect intensities of 35%, 50%, and 65%, whereas concentration-controlled trials yielded much poorer estimates. Moreover, the concentration-controlled trials, despite optimum choice of targeted concentrations, yielded a large number of data points with poor information content (effect intensities of <15% or >85%). Determinations based on targeted effect intensities of 25% and 75% yielded better estimates of individual EC50 values than those targeted for 25% and 50% or 50% and 75% effect intensity. Results were not significantly improved by adding a third measurement (targeted to 50% effect) to the 25% and 75% effect design. Estimations of drug concentrations required to produce an effect intensity of 50%, based on log—linear interpolation of exact concentration—effect data at 25% and 75%, yielded exact results independent of gamma value (0.5–8.0) whereas linear interpolation produced large overestimates at gamma = 0.5 or 1.0 but satisfactory estimates at gamma ≤ 2.0. Similar calculations for an effect intensity of 15% based on exact concentration—effect data at 5% and 25% yielded reasonably good estimates by both methods of interpolation over a wide range of gamma values. A review of the clinical literature showed that gamma values are usually 2 or higher.

CONCLUSIONS:

Population pharmacodynamic studies of reversibly acting drugs without pharmacodynamic hysteresis or time dependency (e.g., tolerance) can be successfully conducted using a pharmacologic effect-controlled randomized clinical trial design with only two properly selected target effect intensities per subject.
Steady-State Plasma Concentrations of Midazolam in Critically Ill Infants and Children
Authors: Hughes Julie , Gill Andrea M , Mulhearn Helen , Powell Edward , Choonara Imti
Published: January 2017

OBJECTIVE:

To determine the steady-state plasma concentrations of midazolam in critically ill infants and children.

DESIGN:

Prospective uncontrolled study conducted over 18 months.

SETTING:

Regional pediatric intensive care unit in a children's hospital.

PATIENTS:

Thirty-eight infants and children, aged 1 month to 13 years, requiring midazolam as sedation during mechanical ventilation. The patients were divided into three age groups: (1) infants less than 12 months (n = 16); (2) children 1–2 years (n = 12); and (3) children aged 3 years and older (n = 10).

MAIN OUTCOME MEASURES:

A single blood sample was collected once steady-state plasma concentrations of midazolam were achieved during a continuous intravenous infusion. Plasma clearance was calculated from the plasma concentrations and infusion rate.

RESULTS:

The plasma clearance was higher in children aged 3 years and older (median plasma clearance 13.0 mL/min/kg) than in infants and children 1–2 years old (median plasma clearance 3.1 and 2.3 mL/min/kg, respectively) (Kruskal-Wallis analysis of variance, p < 0.01). The midazolam infusion rates were similar for the three groups studied (Kruskal-Wallis analysis of variance, p > 0.05). The plasma concentrations of midazolam were significantly lower in children 3 years and older (median plasma concentration 128 ng/mL) than in infants and children 1–2 years old (median plasma concentrations 395 and 790 ng/mL, respectively) (Kruskal-Wallis analysis of variance, p < 0.05).

CONCLUSIONS:

The plasma clearance in children 3 years and older was higher than in infants and children up to 2 years old. There was considerable interindividual variation in the steady-state plasma concentrations of midazolam in critically ill infants and children.
Sulfadiazine-Induced Multiple Urolithiasis and Acute Renal Failure in a Patient with AIDS and Toxoplasma Encephalitis
Authors: Díaz Fernando , Collazos Julio , Mayo José , Martínez Eduardo
Published: January 2017

OBJECTIVE:

To report a patient with sulfadiazine-induced urolithiasis and acute renal failure.

CASE SUMMARY:

A patient with AIDS who was being treated with pyrimethamine and sulfadiazine for Toxoplasma encephalitis developed lumbar pain, dysuria, urinary frequency, and hematuria. Acute renal failure was found and numerous crystals of sulfadiazine were seen in the urine. Multiple calculi of up to 2 cm in diameter in both kidneys were noted on ultrasound. The patient was treated with intravenous fluids and alkalinization of the urine with rapid improvement. An intravenous urographic study performed 2 days later showed no evidence of calculi and renal function was normal.

DISCUSSION:

Patients with AIDS and Toxoplasma encephalitis may have several predisposing conditions that can lead to the development of sulfadiazine-induced crystalluria, including poor fluid intake, fever, diarrhea, and hypoalbuminemia, in addition to the high doses of the drug required and the prolonged period of treatment.

CONCLUSIONS:

This potentially serious complication can be managed easily with conservative treatment. Clinicians should be aware of this complication as it is expected to occur more frequently as more patients are treated with sulfonamides and patients with AIDS experience longer survival rates.
Comparison Oftheocular Beta-Blockers
Authors: Sorensen Suellyn J , Abel Steven R
Published: January 2017

OBJECTIVE:

To compare the similarities and differences among the ocular beta-blockers. Important considerations when comparing these agents are the differences in systemic adverse effects, local tolerability, and cost.

DATA SOURCE:

Information was retrieved from a MEDLINE search of the English-language literature and bibliographic reviews of review articles. Index terms included beta-blockers, glaucoma, timolol, levobunolol, betaxolol, metipranolol, and Carteolol.

STUDY SELECTION:

Emphasis was placed on eyedrop studies, as well as properly designed and executed clinical trials that assessed dosage, dosing interval, therapeutic response, adverse effects, and cost.

DATA EXTRACTION:

Data from several studies were evaluated according to the study design, therapeutic response, and adverse effects.

DATA SYNTHESIS:

Timolol maleate, levobunolol, metipranolol, and Carteolol have similar effectiveness in lowering intraocular pressure; however, levobunolol and timolol gel forming solution may have an advantage of once-daily dosing. Studies have not been published comparing the clinical efficacy of timolol hemihydrate with that of other ocular beta-blockers. Metipranolol is cost effective in treating primary open-angle glaucoma; however, it has been associated with more ocular burning, stinging, and granulomatous anterior uveitis than other agents. The intrinsic sympathomimetic activity of Carteolol has not yet displayed a definite advantage over the other agents in terms of optic disk perfusion and systemic adverse effects. The control of intraocular pressure with betaxolol has not always been as good as with timolol; however, betaxolol has some advantages over timolol and the other topical beta-blockers in terms of systemic adverse effects.

CONCLUSIONS:

Considering cost, efficacy, and safety, timolol maleate is the recommended formulary agent because the other agents cannot consistently show an outstanding advantage.
Adverse Effects of the Angiotensin-Converting Enzyme Inhibitors
Authors: Alderman Christopher P
Published: January 2017

OBJECTIVE:

To review current literature relating to the adverse effects of the angiotensin-converting enzyme (ACE) inhibitors.

DATA SOURCES:

Online drug information sources, including MEDLINE (1966–November 1994), Iowa Drug Information Service, and the Australasian Medical Index (AMI), were used to identify relevant literature, including reviews.

DATA EXTRACTION:

Data were extracted from studies described in the English-language literature dealing with the adverse effects of ACE inhibitors. Comprehensive reviews and relevant case reports also were included.

DATA SYNTHESIS:

Important adverse effects of ACE inhibitors include first-dose hypotension, renal dysfunction, hyperkalemia, and cough. Less common adverse effects include angioedema, hepatotoxicity, skin rashes, and dysgeusia. ACE inhibitors also are associated with adverse fetal effects; thus, this class of drugs is contraindicated in pregnancy. Some adverse effects of ACE inhibitors are predictable on the basis of the fundamental pharmacology of this class of drugs. However, other effects are idiosyncratic in nature, although these reactions are generally much less common.

CONCLUSIONS:

Attention to the principles of risk assessment, risk minimization, and patient monitoring are important when ACE inhibitor therapy is used for any indication. Provided these steps are taken, ACE inhibitors are generally a safe and effective class of drugs.
Drug-Associated Guillain-Barré Syndrome: A Literature Review
Authors: Awong Ingrid E , Dandurand Kenneth R , Keeys Christopher A , Maung-Gyi Felix A Khin
Published: January 2017

OBJECTIVE:

To present an overview of reported drug-associated Guillain-Barré syndrome (GBS) and current management of the disease.

DATA SOURCES:

Case reports and reviews of drug-associated GBS published in the English-language literature from 1982 through 1994 were retrieved from MEDLINE. An additional search was done through the Iowa Drug Information System for the same period. This search yielded incidents that occurred as early as 1976. The key search terms were GBS, polyneuropathy, chemically induced polyradiculoneuropathy, and etiology of GBS. The searches were limited to human subjects.

DATA SYNTHESIS:

Drugs that have been associated with GBS are presented, and although no definite relationships have been established, selected reports attempt to show an increased incidence of GBS after drug therapy. Outcome of medical management of GBS has been variable; however, death occurs in less than 10% of those affected.

CONCLUSIONS:

GBS and clinically similar states have been reported to occur with a variety of drugs and biologics; however, because of the paucity of available data a well-defined cause and effect relationship has not been established between GBS and any drug. There appears to be no treatment of choice for this disorder. Further comparative studies should be done to determine the therapy with the most consistent outcome.
Quantifying the Clinical Significance of Drug—Drug Interactions: Scaling Pharmacists' Perceptions of a Common Interaction Classification Scheme
Authors: Roberts James S , Watrous Marc L , Schulz Richard M , Mauch Robert P , Nightengale Brian S
Published: January 2017

OBJECTIVE:

To develop a precise, interval level scale of the clinical significance of drug—drug interactions that reflects the professional judgments of practicing pharmacists.

PARTICIPANTS:

A convenience sample of 63 practicing pharmacists representing hospital (clinical and staff) and retail (chain and independent) practice settings.

METHOD:

Pharmacists judged the similarity among 15 interaction categories that have been commonly used to classify drug—drug interactions. A multidimensional scaling technique produced a spatial representation (i.e., a psychological map) of the structure inherent in those similarity judgments. Pharmacists' ratings of clinical significance were projected onto that same spatial representation using a multiple regression procedure, and the resulting information was used to develop a scale of clinical significance.

RESULTS:

The clinical significance scale developed from pharmacists' judgments was substantially different from a comparison scale published in a popular reference. The new scale was more precise than the comparison scale, and it also approximated an interval level of measurement. The judgments used to produce the new clinical significance scale were not reliably influenced by pertinent demographic characteristics of the sample.

CONCLUSIONS:

Inconsistencies between published clinical significance scales and the professional judgments of practitioners could affect patient care to the degree that a summary measure of clinical significance affects a practitioner's response to a potential drug—drug interaction. The clinical significance scale developed in this study has good measurement characteristics and reflects the professional judgments of practicing pharmacists. Use of the new scale is recommended on these grounds, although further assessment of its generality is warranted.
Cholestyramine Ointment to Treat Buttocks Rash and Anal Excoriation in an Infant
Authors: White C Michael , Gailey Ronald A , Lippe Scott
Published: January 2017

OBJECTIVE:

To describe a novel treatment for perianal excoriation in an infant receiving a promotility agent.

CASE SUMMARY:

A 2-month-old boy with reflux and regurgitation was treated with cisapride. Shortly after cisapride therapy he developed a rash on his buttocks and anal irritation that progressed in severity despite the use of numerous topical products and extended diaper-free periods. A topical cholestyramine ointment compound was prepared and administered, resulting in complete resolution within 3 days.

DISCUSSION:

Cisapride can decrease the gastrointestinal transit time, which can lead to less time for bile acid reabsorption in the distal ileum. If high concentrations of bile acids are contained in the stool, they can irritate the anus and buttocks in a manner similar to the skin irritation experienced by patients with ostomies. Cholestyramine, a bile acid sequestrant, can irreversibly bind the bile when applied topically and bring relief to the patient.

CONCLUSIONS:

Topical cholestyramine ointment may be a safe and efficacious treatment option for perianal irritation due to bile acids.
Cetirizine versus Hydroxyzine and Placebo in Chronic Idiopathic Urticaria
Authors: Breneman Debra L.
Published: January 2017

OBJECTIVE:

To compare the safety and efficacy of cetirizine with that of hydroxyzine and placebo in the treatment of chronic idiopathic urticaria.

DESIGN:

A 4-week multicenter, randomized, double-blind, double-dummy, placebo-controlled safety and efficacy study.

SETTING:

Patients were treated in a variety of allergy practice settings.

PATIENTS:

The study population consisted of 188 patients who were at least 12 years of age, with symptomatic chronic idiopathic urticaria that had occurred episodically for at least 6 weeks.

INTERVENTIONS:

Patients were given either cetirizine 10 mg once daily, hydroxyzine 25 mg tid, or placebo for 4 weeks.

MAIN OUTCOME MEASURES:

Patients and investigators used a 4-point scale to evaluate symptoms of urticaria and adverse effects of treatment. Ratings were compared among those taking cetirizine, hydroxyzine, or placebo.

RESULTS:

After 1 day of treatment, patients randomized to receive cetirizine 10 mg/d exhibited a reduction in the number of episodes of urticaria (and a reduction in pruritus) compared with patients who received hydroxyzine 25 mg tid and patients who received placebo (p = 0.002). The number of urticarial episodes in patients treated with hydroxyzine did not reach significance until day 2 (p = 0.001). Compared with patients who received placebo, patients who received cetirizine and those who received hydroxyzine showed reductions during weeks 1, 2, and 3 and at end-point analysis in the number and size of lesions and in the severity of pruritus (p < 0.04). Patient and physician evaluations at the end of week 4 revealed an improvement in urticarial symptoms for the hydroxyzine and cetirizine groups compared with the placebo group (p < 0.001). Four patients in the hydroxyzine group, 1 patient in the cetirizine group, and 1 patient in the placebo group discontinued the study because of sedation. No patient withdrew because of lack of efficacy.

CONCLUSIONS:

Cetirizine 10 mg once daily was equivalent to hydroxyzine 25 mg tid in controlling the symptoms of patients with chronic urticaria, as assessed by patient and investigator evaluations.
Selegiline in Treatment of Behavioral and Cognitive Symptoms of Alzheimer Disease
Authors: Tolbert Sandra R. , Fuller Matthew A.
Published: January 2017

OBJECTIVE:

To evaluate the effects of selegiline on behavioral and cognitive symptoms of patients with Alzheimer disease.

DATA SOURCES:

An English-language MEDLINE search (1982–1995) was used to identify the review articles and human clinical trials discussed in this article.

STUDY SELECTION:

Double- and single-blind and open-label trials were reviewed. Studies were also reviewed if selegiline was evaluated comparatively with other agents. Review articles were used for background information.

DATA EXTRACTION:

Data were evaluated from human studies. Studies were critiqued on the basis of design, methodology, duration, sample size, and the degree to which neuropsychological tests used in each study were compared.

DATA SYNTHESIS:

Selegiline is a selective, irreversible inhibitor of monoamine oxidase type B. Eight of 11 controlled trials showed selegiline had a positive effect on cognition (e.g., word fluency, delayed recall, total recall). Two of 5 controlled trials evaluating selegiline's effect on behavior (e.g., anxiety, tension, excitement, depression) showed a positive effect.

CONCLUSIONS:

The role of selegiline remains to be determined by large well-controlled, long-term clinical trials. Selegiline may be a useful agent in managing behavioral and cognitive symptomatology associated with Alzheimer disease. Given that the management of Alzheimer disease is symptomatic and no standard treatment exists, selegiline should be considered among the various options.
Comparative Study of Bioavailability and Clinical Efficacy of Carbamazepine in Epileptic Patients
Authors: Silpakit Orawan , Amornpichetkoon Montri , Kaojarern Sming
Published: January 2017

OBJECTIVE:

To compare the bioavailability of three generic brands of carbamazepine tablets with that of a proprietary brand in adult patients with epilepsy.

DESIGN:

A double-blind, randomized, three-phase crossover study.

SETTING:

A psychiatric facility.

PARTICIPANTS:

Eighteen patients with epilepsy who had taken carbamazepine at least 5 months before entering the study.

MAIN OUTCOME MEASURES:

Ten blood specimens from each patient were collected at steady-state. Plasma concentration of carbamazepine was analyzed for pharmacokinetic parameters such as maximum plasma concentration (Cmax), mean time to reach maximum concentration (tmax), and mean AUC.

RESULTS:

There were no statistically significant differences in these parameters among four brands of carbamazepine. However, when comparing the 90% CI of AUC of three generic brands with that of the proprietary brand, the AUC of two generic brands lay within a range of 80% to 120%. The effects of gender and each brand of carbamazepine on these pharmacokinetic parameters were also analyzed. Breakthrough seizures occurred even though the plasma concentration of carbamazepine was therapeutic.

CONCLUSIONS:

The bioavailability of two generic brands of carbamazepine tablets (Carmapine and Carzepine) and the proprietary brand (Tegretol) were equivalent in this sample of adult patients with epilepsy.
Generalized Seizures Associated with the Use of Muromonab-CD3 in Two Patients after Kidney Transplantation
Authors: Seifeldin Raafat A , Lawrence Kenneth R , Rahamtulla Anisha F , Monaco Anthony P
Published: January 2017

OBJECTIVE:

TO report two cases of seizures associated with the use of muromonab-CD3.

CASE SUMMARY:

TWO uremic cadaveric kidney transplant recipients had developed generalized seizures following administration of muromonab-CD3 within the first 2 days after transplantation. Seizures were treated successfully with intravenous phenytoin, and muromonab-CD3 administration was discontinued.

DISCUSSION:

The overall frequency of seizures during muromonab-CD3 administration is 6%. Uremia in patients in the early posttransplant period appears to predispose them to seizures. Seizures that happened to our two uremic patients after transplant suggest that they had been induced by muromonab-CD3 administration. The mechanism of how this could have induced seizures is unknown.

CONCLUSIONS:

Prophylactic muromonab-CD3 should be used carefully in uremic kidney transplant recipients following surgery. If therapy with muromonab-CD3 is necessary, early hemodialysis should be considered in an effort to lower the risk of seizures.
Efficacy and Safety of Intravenous Phosphate Replacement in Critically Ill Patients
Authors: Perreault Marc M , Ostrop Nikola J , Tierney Michael G
Published: January 2017

OBJECTIVE:

To evaluate the efficacy and safety of intravenous potassium phosphate administered in a fixed-dose regimen in critically ill patients.

DESIGN:

Prospective, unblind study.

SETTING:

Surgical—medical intensive care unit (ICU).

PARTICIPANTS:

Patients who developed hypophosphatemia during their ICU admission.

INTERVENTIONS:

Patients with a serum phosphate concentration between 1.27 and 2.48 mg/dL (group 1) and those with a concentration of 1.24 mg/dL or less (group 2) received 15 and 30 mmol, respectively, of phosphate as a potassium salt via a central line over 3 hours.

MAIN OUTCOME MEASURES:

Normalization of serum phosphate within 6 hours of infusion, the development of arrhythmias during the infusion, and the development of hypocalcemia and hyperkalemia after the infusion were evaluated. Redevelopment of hypophosphatemia and the need for further therapy were also assessed.

RESULTS:

Thirty-seven episodes of hypophosphatemia were entered in this study: 27 in group 1 (17 patients) and 10 in group 2 (10 patients). The mean serum phosphate concentration increased significantly from 2.02 to 2.82 mg/dL in group 1 and from 0.83 to 2.17 mg/dL in group 2, with no change in calcium or potassium. Normalization of serum phosphate with this initial dose occurred in 81.5% of the episodes in group 1 and 30% in group 2. However, over the following 2 days, 45% of the patients in group 1 and 60% in group 2 required further phosphate supplementation. No arrhythmias occurred during the 3-hour infusion that were related to the potassium phosphate. A significant drop in total serum calcium concentrations occurred in 2 patients who were slightly hypercalcemic prior to the infusion. Serum calcium concentrations remained above normal, but this was not associated with any adverse effects.

CONCLUSIONS:

The administration of potassium phosphate 15 mmol to critically ill patients with mild-to-moderate hypophosphatemia over 3 hours is both effective and safe. The administration of potassium phosphate 30 mmol to severely hypophosphatemic patients was safe but achieved normalization of serum phosphate in a minority of patients. Either a higher dose or the subsequent administration of more potassium phosphate may be required to normalize serum phosphate concentrations. Once normalization has occurred, there is a high likelihood of redevelopment of hypophosphatemia over the following 2 days and supplementation should be given accordingly.
Severe Minocycline-Induced Eosinophilic Pneumonia: Extrapulmonary Manifestations and the Use of in Vitro Immunoassays
Authors: Bentur Lea , Bar-Kana Yaniv , Livni Ella , Finkelstein Renato , Ben-Izhak Ofer , Keidar Shlomo , Bentur Yedidia
Published: January 2017

OBJECTIVE:

To report a severe and unusual reaction to minocycline and the use of in vitro immunologic assays.

CASE SUMMARY:

A 46-year-old white man developed severe respiratory distress with pulmonary infiltrates on chest X-ray and eosinophilia in blood, bronchoalveolar lavage fluid, and biopsied lung tissue during exposure to minocycline. Additional manifestations included pleuropericardial effusion, liver function abnormality, and bone marrow eosinophilia. Macrophage inhibition factor and mast cell degranulation assays were positive to minocycline.

DISCUSSION:

The patient's manifestations were compatible with the diagnosis of eosinophilic pneumonia. After excluding other possible etiologies, minocycline was identified as the offending agent. Generalized damage was suggested by the presence of a combination of extrapulmonary manifestations previously not reported. Results of the in vitro immunologic assays supported the hypersensitivity nature of the disease and confirmed the diagnosis.

CONCLUSIONS:

Minocycline-induced eosinophilic pneumonia may involve extrapulmonary sites. It is suggested that in vitro immunoassays be used for confirmation of the diagnosis rather than rechallenge or invasive procedures.