bluuebunny/crossref_metadata_2025 huggingface dataset:
Epoprostenol in Primary Pulmonary Hypertension
Authors: Herner Sheryl J , Mauro Laurie S
Published: March 2004

OBJECTIVE:

To review briefly the epidemiology, pathophysiology, and current treatment of primary pulmonary hypertension (PPH) and review the available clinical data on epoprostenol in PPH.

DATA SOURCES:

A MEDLINE search (January 1966–August 1998) was used to identify case reports and clinical studies pertaining to epoprostenol in PPH. Bibliographic lists were also used.

STUDY SELECTION:

All English-language clinical studies of epoprostenol in PPH were included. Incomplete study descriptions (abstracts) were not included.

DATA EXTRACTION:

Study design, population, methods, clinical outcomes, and adverse effects were evaluated.

DATA SYNTHESIS:

PPH is a relatively rare disease that results in symptoms of congestive heart failure and has a five-year survival rate of 34%. Therapy has consisted of vasodilators, anticoagulation, oxygen, and ultimately lung transplantation. Epoprostenol, which has recently become available as an integral pharmacotherapeutic option, has been shown to improve hemodynamic parameters such as cardiac output, pulmonary artery pressure, and pulmonary vascular resistance. It has been shown to improve exercise parameters, New York Heart Association (NYHA) functional class, and survival. Epoprostenol is indicated for patients with severe disease (NYHA class III or IV) who do not respond to acute vasodilator challenge or chronic calcium-channel blocker therapy. Its chronic administration is challenging as it requires continuous infusion via central venous catheter and a special infusion pump. Administration is further complicated by the 48-hour expiration of reconstituted epoprostenol and the need to refrigerate the reconstituted drug.

CONCLUSIONS:

Epoprostenol improves hemodynamics and clinical outcome in patients with severe PPH. Epoprostenol therapy requires intensive patient education and medical monitoring, but it can improve well-being and delay the need for lung transplantation.
Torsade De Pointes Resulting from the Addition of Droperidol to an Existing Cytochrome P450 Drug Interaction
Authors: Michalets Elizabeth Landrum , Smith Laura K , Van Tassel Eric D
Published: March 2004

OBJECTIVE:

To report a case of QT prolongation associated with concomitant cyclobenzaprine and fluoxetine administration followed by torsade de pointes potentiated by droperidol.

CASE SUMMARY:

A 59-year-old white woman who had been receiving long-term fluoxetine and cyclobenzaprine therapy was admitted for Achilles tendon repair. Baseline QTc was prolonged at 497 msec. Prior to surgery, the patient received droperidol, an agent known to prolong the QT interval. During surgery the patient developed torsade de pointes, which progressed into ventricular fibrillation. On postoperative day 1, after cyclobenzaprine discontinuation, the QTc decreased toward normal (440 msec).

DISCUSSION:

Cyclobenzaprine shares anticholinergic effects, tachycardia, and dysrhythmic potential with the tricyclic antidepressants (TCAs). Fluoxetine is a known inhibitor of the CYP2D6 isoenzyme (along with CYP3A4 and CYP2C) and has been shown to increase TCA serum concentrations. The combination of cyclobenzaprine and fluoxetine resulted in significant QT prolongation in our patient that progressed to torsade de pointes after preoperative droperidol administration. Resolution of QT abnormalities after cyclobenzaprine discontinuation provided further evidence of a drug-induced etiology. Other possible medical and drug-related causes of torsade de pointes are reviewed and ruled out.

CONCLUSIONS:

Clinicians should be aware of the dysrhythmic potential of cyclobenzaprine and fluoxetine, monitor for other cytochrome P450 inhibitors, and avoid concomitant drugs known to prolong the QT interval.
Pharmacokinetics of Anticancer Drugs in Cerebrospinal Fluid
Authors: Morikawa Norifumi , Mori Teruaki , Kawashima Hisanori , Takeyama Masaharu , Hori Shigeaki
Published: March 2004

OBJECTIVE:

To examine the pharmacokinetics of anticancer drugs in the cerebrospinal fluid (CSF) during chemotherapy by the lumbar– ventricular (LV) and ventricular–lumbar (VL) routes.

CASE SUMMARY:

A 69-year-old Japanese woman with disseminated glioblastoma received two LV and four VL courses of CSF perfusion chemotherapy with methotrexate, nimustine, and cytarabine hydrochloride. Samples of CSF from the ventricles and lumbar spinal canal were obtained via Ommaya reservoirs during one LV and one VL course. Drug concentrations in the CSF were measured by fluorescence polarization immunoassay or HPLC.

RESULTS:

During LV CSF perfusion, the highest CSF drug concentrations in both the ventricles and the lumbar spinal canal were observed at the end of perfusion. During treatment, the concentrations of all three drugs in the lumbar spinal canal were higher than those in the ventricles. The CSF AUC of methotrexate in the ventricles was 16.1% of that in the lumbar spinal canal. During VL CSF perfusion, the highest drug concentrations were also observed at the end of perfusion. The drug concentrations in the lumbar spinal canal were initially lower than those in the ventricles. However, the concentrations of methotrexate and cytarabine in the lumbar spinal canal exceeded those in the ventricles 3 hours after perfusion. The AUC of methotrexate in the lumbar spinal canal was 174.9% of that in the ventricles.

CONCLUSIONS:

The pharmacokinetics of anticancer drugs in ventricular CSF differ from those in lumbar CSF during LV and VL perfusion chemotherapy.
Using Literature in Health Care: Reflections on “The Yellow Wallpaper”
Authors: Frye Carla B
Published: March 2004

OBJECTIVE:

To discuss how literature can be used to educate healthcare practitioners and students about the patient's physical and emotional response to treatment.

DATA SOURCES:

A MEDLINE search (January 1975-November 1997) of English-language literature pertinent to using literature in health care was performed. Additional literature was obtained from a search of the New York University Web site on medicine and humanities, biographies of Charlotte Perkins Gilman, and a search of the MLA and INFOTRAC database.

SELECTION AND DATA EXTRACTION:

All articles and literature were considered for possible inclusion in this article. Pertinent information, as judged by the author, was selected for discussion.

Literature can pose a wealth of information to the healthcare professional. The short story “The Yellow Wallpaper” is analyzed in this article as one example of how literature portrays the patient's emotional response to disease. This short story describes a 19th-century woman's “descent into madness” and the ineffective treatment attempted by her well-meaning physician husband. The author, Charlotte Perkins Gilman, loosely based the story on her own experience with the respected physician, S Weir Mitchell and his famous rest cure. Some biographical information about Mitchell and Perkins is included, as well as a commentary on the treatment of depression in the 19th century.

CONCLUSIONS:

Short stories such as “The Yellow Wallpaper,” novels, and other short stories can help to remind the healthcare professional of the subjective nature of even our most proven therapies. As we strive to teach and deliver pharmaceutical care, we can use literature to help us understand the emotional impact of our drug therapies.
Cost-Minimization Analysis of Piperacillin/Tazobactam versus Imipenem/Cilastatin for the Treatment of Serious Infections: A Canadian Hospital Perspective
Authors: Marra Fawziah O , Frighetto Luciana O , Marra Carlo A , Sleigh Kenna M , Stiver H Grant , Bryce Elizabeth A , Reynolds Robert P , Jewesson Peter J
Published: March 2004

BACKGROUND:

In 1998 we reported the first Canadian double-blind, randomized, clinical trial involving a comparison of piperacillin/tazobactam (P/T) with imipenem/cilastatin (I/C). The present study was conducted to determine the feasibility of replacing I/C at our institution.

OBJECTIVE:

To describe the outcome of a pharmacoeconomic analysis of the clinical trial from the perspective of a tertiary acutecare institution.

METHODS:

A total of 150 consenting adults originally prescribed I/C were randomly assigned to receive either P/T 4.5 g iv (n = 75) or I/C 500 mg iv (n = 75) every six hours. Actual direct medical resources used in relation to the treatment of bacterial infections were prospectively assessed during a clinical trial; these included cost of study and ancillary antibiotics, hospitalization, diagnostic testing (radiology, laboratory assessments), and labor, as well as treatment of adverse drug reactions, antibiotic failures, and superinfections.

RESULTS:

While costs for successful treatment courses were similar across treatment arms, hospitalization costs for treatment course failures were higher for P/T recipients. Direct medical costs for treatment courses associated with a superinfection were also higher in the P/T arm. Overall costs for treatment failures with either study drug were at least twofold those observed for successful treatment courses. Mean total management cost per patient in the P/T group was $15 211 ($ CDN throughout) (95% CI $11 429 to $18 993), compared with $14 232 (95% CI $11 421 to $17 043) in the I/C group (p = 0.32), resulting in a mean cost difference of $979. Sensitivity analyses revealed that the superiority of I/C over P/T for successful treatment of serious infections was sensitive to changes in the cost of hospitalization and drug efficacy for either drug.

CONCLUSIONS:

Based on the results of the clinical trial, P/T and I/C offer similar clinical, microbiologic, and toxicity outcomes in hospitalized patients with serious infections. Under base–case conditions, our pharmacoeconomic analysis showed that I/C was a cost-effective alternative to P/T at the dosage regimens studied. However, this finding was sensitive to plausible changes in both clinical and economic parameters.
Management of End-Stage Renal Disease in Children
Authors: Smith Pamela S
Published: March 2004

OBJECTIVE:

To review the medical literature on management of end-stage renal disease (ESRD) and its complications in the pediatric patient.

DATA SOURCES AND STUDY SELECTION:

MEDLINE searches (1970–1997) of the English-language literature. Clinical trials and reviews of drug therapy management were included, and bibliographies were reviewed for relevant articles.

DATA SYNTHESIS:

Principles of renal replacement therapy in children have been expanded to include maintenance of fluid and electrolyte balance and to manage the complications of ESRD in children. Types of renal replacement and their complications are reviewed. Complications of ESRD are reviewed with emphasis on drug therapy management of anemia of chronic renal failure, growth retardation, and hypertension. A discussion of the use of vitamins and supplements to maintain bone and mineral homeostasis is provided, and specific recommendations for vaccination of children with ESRD are given.

CONCLUSIONS:

Children with end-stage renal failure present a unique challenge to the pharmacist. Renal replacement therapy for children with ESRD involves some form of dialysis and an intensive medication regimen. Complications must be treated with appropriate drug therapy. Drug therapy must be monitored closely for dosage adjustment, clinical response, drug interactions, and toxicity. Patients and families must receive continuous education and follow-up to encourage compliance. The pharmacist must work closely with the healthcare team to optimize drug therapy and improve patient education and compliance.
Ambulatory Management of Chemotherapy-Induced Fever and Neutropenia in Adult Cancer Patients
Authors: Davis Diane D , Raebel Marsha A
Published: March 2004

OBJECTIVE:

To review the literature on the management of low-risk adults with chemotherapy-induced fever and neutropenia (CIFN). Included in the review are methods to identify these patients, management options, and economic impact associated with nontraditional treatment options.

DATA SOURCES:

A MEDLINE and bibliographic search (January 1966–December 1997) for all English-language studies evaluating the identification and treatment of adult, low-risk CIFN patients was completed. Reference lists from identified articles also served as literature sources.

STUDY SELECTION AND DATA EXTRACTION:

All human studies identified from the data sources were evaluated. Pertinent information, excluding pediatric studies, was selected and critically evaluated for discussion.

DATA SYNTHESIS:

Alterations in prominent bacterial isolates in CIFN, newer antibiotic choices, enhanced focus on patient comfort, and cost-containment directives have promoted recent research identifying adult cancer patients with low-risk CIFN. Using this information to select low-risk CIFN patients, several investigators have completed trials using antibiotic therapy applicable to the ambulatory setting. Additionally, some investigators have included the use of an oral outpatient antibiotic regimen. Limited data indicate that this approach is a reasonable treatment option for selected patients.

CONCLUSIONS:

A subset of adult patients with CIFN are at low risk for serious morbidity and mortality when treated with broad-spectrum antibiotics in the ambulatory setting. Managing these patients with this approach requires close patient selection, intense follow-up, data collection, and ongoing evaluation to determine efficacy and patient safety. Currently, ambulatory treatment with oral antibiotics for CIFN is not considered standard of care. Further studies of larger size designed to confirm low-risk patient characteristics and optimal antibiotic selection are required.
Isoniazid-Induced Psychosis
Authors: Alao Adekola O , Yolles Jennifer C
Published: March 2004

OBJECTIVE:

To report a suspected case of isoniazid-induced psychosis in a 31-year-old woman.

CASE SUMMARY:

A 31-year-old white woman without a prior psychiatric history presented with psychotic symptoms suspected to be related to prophylactic treatment with isoniazid after she tested positive to a tuberculin (purified protein derivative) test. The psychotic symptoms resolved partially after isoniazid was discontinued and completely after treatment with olanzapine was begun. The patient remained symptom-free 11 months after discharge from the hospital.

DISCUSSION:

Cases of isoniazid-related psychiatric disorders reported in the literature include psychosis, obsessive–compulsive neurosis, and mania. With the increasing prevalence of tuberculosis in the US, more people are expected to receive treatment for tuberculosis. Pyridoxine deficiency may play a role in the pathogenesis of isoniazid-induced psychosis. Such deficiency states may be detected indirectly by measuring urinary metabolites of tryptophan.

CONCLUSIONS:

Clinicians should be aware of this adverse effect of isoniazid and that it may present with a broad clinical picture.
Minocycline-Associated Tooth Staining
Authors: Dodd Melanie A , Dole Ernest J , Troutman William G , Bennahum David A
Published: March 2004

OBJECTIVE:

To describe a case of tooth discoloration in an adult after minocycline treatment for arthritis.

CASE SUMMARY:

A 68-year-old white woman presented with blue–black staining of her lower anterior teeth after 4 months of minocycline therapy for arthritis. Her other medications are not known to cause discoloration of teeth. While the patient continued taking minocycline, her dentist was not able to remove the discoloration. Within 1 month after discontinuation of the minocycline, the dentist was able to remove the discoloration entirely.

DISCUSSION:

Minocycline, a synthetic derivative of tetracycline, has been shown to cause abnormal pigmentation of the skin, thyroid gland, nails, bone, sclera, and conjunctiva in adults. It also has been shown to cause tooth discoloration in a few patients. This case is unusual in that the tooth discoloration disappeared after discontinuing minocycline therapy.

CONCLUSIONS:

This complication of minocycline is more commonly thought of in the pediatric population. However, clinicians need to be aware of this adverse drug reaction, as this agent may be used increasingly in the treatment of adults with arthritis.
Pill Count, Self-Report, and Pharmacy Claims Data to Measure Medication Adherence in the Elderly
Authors: Grymonpre Ruby E , Didur Cathy D , Montgomery Patrick R , Sitar Daniel S
Published: March 2004

OBJECTIVE:

To compare medication adherence calculated from four different data sources including a pill count and self-report obtained during a home medication history, as well as calculations based on refill frequency derived from a provincial prescription claims database (manual and electronic).

DESIGN:

Baseline medication adherence was collected as part of a prospective, randomized, controlled study. Mean medication adherence results obtained from the four data sources were compared using repeated-measures ANOVA followed by a Tukey's multiple range test.

SETTING:

A pharmacy consultation service located at an interdisciplinary wellness center for noninstitutionalized elderly.

PATIENTS:

65 years or older, noninstitutionalized, taking one or more prescribed or nonprescribed medications. Clients would either present to the wellness center or be referred by the Provincial Home Care program.

RESULTS:

When calculated from self-report or manual or electronic prescription claims data, mean percent adherence by drug was high and not statistically different (95.8% ± 17.1%, 107.6% ± 40.3%, and 94.6% ± 24.0%, respectively), whereas the pill count adherence was significantly lower at 74.0% ± 41.5% (p < 0.0001).

CONCLUSIONS:

An unexpected finding was that the pill count technique used in this study of elderly clients using chronic, repeat medications appeared to underestimate medication adherence. Numerous other limitations of pill count, self-report, and a province-wide prescription claims database in estimating medication adherence are presented. When using medication adherence as a process measure, the researcher and practitioner should be aware of the limitations unique to the data source they choose, and interpret data cautiously.
Medication Use in Residential Care Facilities for the Elderly
Authors: Williams Bradley R , Nichol Michael B , Lowe Beverly , Yoon Peter S , McCombs Jeffrey S , Margolies Jane
Published: March 2004

OBJECTIVE:

To describe medication use by residents of residential care facilities for the elderly (RCFEs).

DESIGN:

A cross-sectional survey of medication use.

SETTING:

Licensed, private RCFEs recruited from a roster of all licensed RCFEs in the Los Angeles area.

SUBJECTS:

Residents who were ≥60 years of age and whose medications were centrally stored in the facility.

MEASURES:

Age, gender, race, health insurance coverage, dietary restrictions, ambulation status, medical diagnoses, and medication profile.

RESULTS:

A total of 818 residents were surveyed. Residents were primarily white women who were >80 years. The average number of medications per resident was five; 94% of the sample took at least one medication. Cardiovascular drugs, central nervous system drugs, analgesics, diuretics, and potassium supplements were most commonly used. Use of multiple drugs within a therapeutic class was also common, with means ranging from 1.46 to 1.81 per resident for the most commonly prescribed classes. Diagnoses supporting the use of many medications were not documented in the residents' health records.

CONCLUSIONS:

This RCFE sample was medically frail and took many medications. The frequent use of cardiovascular medication reflected the prevalence of cardiac disease in the elderly. The frequency of psychotropic drug use without a corresponding indication suggested prescribing for symptoms rather than documented medical conditions. Lack of recorded diagnoses limited the ability to evaluate drug therapy. Improved record keeping; periodic medication review; and resident, staff, and prescriber education are necessary to ensure appropriate medication use in this setting.
Comparing the Delivery of Albuterol Metered-Dose Inhaler via an Adapter and Spacer Device in an in vitro Infant Ventilator Lung Model
Authors: Avent Minyon L , Gal Peter , Ransom J Laurence , Brown Yvonne L , Hansen Charles J
Published: March 2004

OBJECTIVE:

To compare the delivery of an albuterol metered-dose inhaler (MDI) (Ventolin) via an Aerochamber (Monaghan) with an inline adapter (Medicomp Straight Swivel) in an in vitro infant lung model.

METHODS:

An in vitro infant lung model was modified to compare the delivery of albuterol MDI 10 inhalations via an Aerochamber with an inline adapter. The adapter and Aerochamber were placed at the endotracheal tube. A 1000 mL intravenous bag filled with 500 mL deionized water was attached to a 3.5 mm endotracheal tube (10 cm length). An Infant Bear Cub ventilator was used at the following settings: positive inspiratory pressure 20 cm H2O, intermittent mandatory ventilation 40 breaths/min, positive end expiratory pressure 4 cm H2O, and inspiratory time 0.5 second. Each device was run at least 10 times and assayed in duplicate by HPLC. An unpaired Student's t-test was used to analyze the statistical significance of the data.

RESULTS:

There was significantly greater delivery of albuterol with the Aerochamber (19.49 ± 7.23 μg; 2.17% ± 0.8%) as compared with an inline adapter (1.0625 ± 1.36 μg; 0.12% ± 0.15%) (p = 0.001).

CONCLUSIONS:

The Aerochamber provides a greater delivery of albuterol metered-dose inhalations to the lung than the inline adapter in an in vitro infant lung model.
Management of SSRI-Induced Sexual Dysfunction
Authors: Woodrum Sharon T , Brown Candace S
Published: March 2004

OBJECTIVE:

To describe the occurrence and management of sexual dysfunction induced by selective serotonin-reuptake inhibitors (SSRIs), to provide an overview of sexual dysfunction, reports of SSRI-induced sexual dysfunction, and management strategies.

DATA SOURCES:

Information was retrieved from a MEDLINE English-literature search from January 1986 to July 1998 and by review of references. Indexing terms included sexual dysfunction, antidepressants, selective serotonergic reuptake inhibitors, fluoxetine, sertraline, paroxetine, fluvoxamine, clomipramine, buspirone, nefazodone, bupropion, cyproheptadine, amantadine, yohimbine, and central nervous system stimulants.

STUDY SELECTION:

There are no controlled studies describing SSRI-induced sexual dysfunction or its management. Twenty-one studies are presented, including 2 open-label studies, 12 case series, and 7 case reports. SSRI-induced sexual dysfunction is described with fluoxetine, paroxetine, sertraline, and fluvoxamine for 3–24 weeks of therapy.

DATA SYNTHESIS:

Data were organized according to the pharmacologic agent used in the management of SSRI dysfunction, target population, SSRI implicated, type of sexual dysfunction, experimental design, and treatment response. Data were extracted from methodology and results sections of reports. Methodologic flaws included failure to account for gender differences, omission of SSRI dose and duration, and use of concomitant drugs.

CONCLUSIONS:

The frequency of reports suggests that SSRI-induced dysfunction is a common adverse effect; controlled studies are necessary to determine prevalence. Most reports have occurred with fluoxetine, but this phenomenon may be related to its widespread use. Further study is needed to evaluate baseline sexual function, to define target populations, and to compare SSRIs in inducing sexual dysfunction. Serotonin antagonists and dopamine agonists have been used most often to treat SSRI-induced dysfunction and have generally been effective, but controlled studies are also needed.
Antiinfectives Update: Focus on Treatment and Prevention of Viral and Associated Infections
Authors: McNicholl Ian R , Palmer Shirley M , Ziska David S , Cleary John D
Published: March 2004

OBJECTIVE:

To review the clinically significant antiinfectives approved by the Food and Drug Administration (FDA) since 1996, with an emphasis on agents used for treatment, prevention, or suppression of infection in immunocompromised individuals.

DATA SOURCES:

A MEDLINE search covering November 1994 to March 1998 was conducted to identify all antiinfectives (new medications and old medications with new indications) and the pertinent literature for review. The search was updated in August 1998 and supplemented with an FDA listing of approved drugs to enhance completeness.

STUDY SELECTION:

Clinically relevant studies were selected to highlight specific points about each medication. Preclinical publications were used when sufficient information was not available from clinical trials and this information was needed for clinical practice.

CONCLUSIONS:

Several new and promising antiretroviral agents (stavudine, lamivudine, saquinavir soft-gel capsules, nelfinavir, efavirenz) have been approved, which may allow more options to control HIV viremia. New options for treatment, prevention, and suppression of infections in immunocompromised individuals include azithromycin, cidofovir, famciclovir, valacyclovir, and itraconazole suspension. Liposomal-based amphotericin products may be associated with less toxicity than conventional amphotericin B; however, superior efficacy has not been proven.
Providing Patients with Written Medication Information
Authors: Buck Marcia L
Published: March 2004

OBJECTIVE:

To review the literature and provide recommendations for the development and dissemination of written medication information to patients and their care providers.

DATA SOURCES:

A MEDLINE search (1966–1997) of the English-language literature was performed to identify articles pertaining to the development or use of written medication information. A search of the Internet was conducted by using Yahoo as the guide and “medication information” as the search term. Additional resources were obtained through texts, bibliographies, and catalogs from medical publishers.

DATA EXTRACTION:

Reports documenting the creation and use of written medication information systems were reviewed, as well as studies of readability and reading skills assessment. Examples of materials available for purchase by laypeople and healthcare providers were also examined.

DATA SYNTHESIS:

Current statistics support the widespread availability of written medication information for patients and care providers. The goal set forth by the Food and Drug Administration of having 75% of patients receive written information by the year 2000 appears achievable. However, there are still many issues to address. Content is not standardized, and materials are frequently written at reading levels higher than that of the average patient. The development and use of resources requiring only minimal reading skills and an increase in the availability of materials written in Spanish are needed.

CONCLUSIONS:

Written medication information provides a useful addition to counseling by healthcare professionals. A wide variety of prepared materials is available, as well as resources for those interested in developing tools for a specific patient, population, or setting. Healthcare professionals should be aware of the limitations of some resources. Content and readability must be appropriate for the intended audience for these tools to serve a useful role in patient education.
Potential Interaction Involving Warfarin and Ritonavir
Authors: Knoell Karen R , Young Tammy M , Cousins Elizabeth S
Published: March 2004

OBJECTIVE:

To report an unexpected decrease in warfarin effect following the addition of ritonavir to the medication regimen.

CASE SUMMARY:

A 27-year-old patient with advanced HIV taking warfarin for an inferior vena cava thrombus was started on ritonavir, clarithromycin, and zidovudine. The international normalized ratio (INR) decreased over a period of weeks after the addition of ritonavir, clarithromycin, and zidovudine to the drug therapy regimen. The warfarin dosage was almost doubled in order to maintain a therapeutic INR. Months later, when ritonavir alone was discontinued, the INR rose rapidly and the warfarin dose requirements decreased significantly.

DISCUSSION:

Potential interactions between warfarin and the protease inhibitors are described in the literature. Ritonavir has been shown to be a potent inhibitor of CYP3A4, an enzyme responsible for warfarin metabolism. Potentiation of warfarin effect and subsequent decrease in the warfarin dosage requirement was anticipated following ritonavir administration; however, the opposite occurred. The mechanism of the potential interaction between warfarin and ritonavir is not known, and may represent a complex, multidrug interaction. The paradoxical decrease in the INR is particularly intriguing.

CONCLUSIONS:

Frequent, careful monitoring of warfarin is recommended when ritonavir therapy is initiated or discontinued in a patient taking warfarin. The potential for either an increase or decrease in the INR should be anticipated.
Irinotecan: A New Antineoplastic Agent for the Management of Colorectal Cancer
Authors: Cersosimo Robert J
Published: March 2004

OBJECTIVE:

To review the pharmacologic, pharmacokinetic, therapeutic, and safety aspects of irinotecan, a new antineoplastic agent, and to assess its role in the treatment of colorectal and lung cancer.

DATA SOURCES:

English-language articles from the MEDLINE database, January 1990–March 1998; Pharmacia & Upjohn Company; published articles and meeting abstracts.

STUDY SELECTION:

Studies in humans with cancer, clinical case reports, and open clinical studies were reviewed. Efficacy studies were limited to trials with at least 20 evaluable patients.

DATA EXTRACTION:

Relevant data were extracted from published reports and abstracts.

DATA SYNTHESIS:

Irinotecan is an effective agent for the treatment of advanced colorectal cancer. It demonstrates significant activity as a first-line agent and in patients with disease that is refractory to fluorouracil-containing regimens. Activity against lung cancer has also been demonstrated. Limited data indicate activity against cancers of the ovary, cervix, stomach, and in non-Hodgkin's lymphomas. Major toxicity consists of myelosuppression and diarrhea.

CONCLUSIONS:

Irinotecan is a useful addition to the antineoplastic drug family and offers significant efficacy for treatment of patients with fluorouracil-refractory colorectal cancer.
Reteplase: A New Thrombolytic for the Treatment of Acute Myocardial Infarction
Authors: Wooster Melissa B , Luzier Aileen B
Published: March 2004

OBJECTIVE:

To summarize the published data on reteplase, the most recent thrombolytic agent approved by the Food and Drug Administration for use in the management of acute myocardial infarction in adults.

DATA SOURCES:

Published data on reteplase identified by MEDLINE searches (January 1985–June 1997), as well as other pertinent literature.

DATA SYNTHESIS:

Reteplase is a new thrombolytic agent derived from human tissue plasminogen activator. Its mechanism of action is similar to that of alteplase, but it differs in pharmacokinetic and pharmacodynamic properties. Certain structural changes contribute to differences in pharmacokinetic properties such as a prolonged half-life (15 min), which allows it to be administered as two 10-MU bolus injections. Reteplase has been shown to have fibrin specificity similar to that of alteplase, but with a lower binding affinity for fibrin. This enables reteplase to bind to the thrombus repeatedly and increases its fibrinolytic potential. In clinical trials, reteplase demonstrated more rapid and complete coronary patency compared with alteplase, without a significant increase in clinical adverse events. However, the improvement in coronary artery patency with reteplase versus alteplase did not result in a reduction in mortality in the GUSTO III trial.

CONCLUSIONS:

Despite evidence that use of reteplase results in an improved coronary artery patency rate versus accelerated infusion alteplase, an improvement in mortality rate with reteplase was not shown. Reteplase may have an advantage over alteplase due to a more rapid and simpler dosing regimen, but the significance of this difference is yet to be determined.
Miconazole Oral Gel Enhances Acenocoumarol Anticoagulant Activity: A Report of Three Cases
Authors: Ortín Miguel , Olalla José Ignacio , Muruzábal María José , Peralta Francisco Galo , Gutiérrez María Angeles
Published: March 2004

OBJECTIVE:

To describe three cases of interaction between miconazole oral gel and acenocoumarol, manifested as an increase in the international normalized ratio (INR).

CASE SUMMARIES:

Three patients (62-year-old woman, 89-year-old woman, 43-year-old man) following oral antithrombotic treatment with acenocoumarol for different pathologies were diagnosed with oral candidiasis and started miconazole oral gel. In all cases, the previous INR values were repeatedly within the therapeutic range. The following routine monitoring of the antithrombotic therapy showed a marked increase in anticoagulant activity in all cases, which returned to the therapeutic range after miconazole was withdrawn. None of the patients needed substantial changes in their habitual dosages of acenocoumarol in subsequent measurements of the INR to stay within the therapeutic range.

DISCUSSION:

We report three cases in which a possible interaction between miconazole oral gel and acenocoumarol is suggested by the chronological relationship between the introduction of miconazole and an increase in the INR. Miconazole exerts its fungistatic action by inhibiting some isoenzymes of the fungal cytochrome P450 system. Oral mucosa inflammation (as in oral candidiasis) may enhance its transmucosal absorption. In this setting, cytochrome P450 isoenzymes belonging to the host may be inhibited too. This mechanism provides an explanation for different interactions observed with miconazole oral gel.

CONCLUSIONS:

Miconazole oral gel enhances acenocoumarol anticoagulant activity. Although we did not observe major bleeding complications, we suggest the use of other families of antifungal drugs, such as nystatin, to treat oral candidiasis in patients taking acenocoumarol.
The Use of Oral Vasopressors in the Management of Autonomic Dysfunction and Orthostatic Hypotension
Authors: Wittbrodt Eric T , Kovalick Lawrence J
Published: March 2004

OBJECTIVE:

To describe a patient with hypotension secondary to autonomic dysfunction who was successfully treated with oral vasopressors.

CASE SUMMARY:

A 76-year-old African-American man with a history of cerebrovascular accident with right hemiparesis 30 years prior to admission was admitted from another hospital four days after a new posterior inferior cerebellar artery occlusion and poor distal flow as manifested by weakness and hypotension. This was treated with intravenous fluids and dopamine. The dopamine was weaned and changed to phenylephrine to maintain systolic blood pressure >80 mm Hg. Fludrocortisone 0.3 mg orally once daily was initiated; pressure support garments were used for the management of orthostatic hypotension. Ephedrine 25 mg po tid was added and titrated up to 50 mg po tid. Yohimbine 5.4 mg po every eight hours was added due to continued dependence on phenylephrine to maintain adequate blood pressure. Yohimbine was titrated up to 10.8 mg po tid in an unsuccessful effort to wean the patient from phenylephrine. Fludrocortisone was decreased to 0.1 mg po tid and the phenylephrine was tapered off. The patient developed a pan-sensitive Escherichia coli urinary tract infection that was treated with oral trimethoprim/sulfamethoxazole. Over the subsequent days, an 80% left subclavian stenosis was detected; yohimbine and pressure support garments were discontinued. Subsequently, oral ephedrine was tapered off over two days, and fludrocortisone was tapered to 0.1 mg po bid. The patient was transferred in a stable normotensive condition to an inpatient rehabilitation unit. The fludrocortisone was later discontinued with no further hypotension or orthostatic symptoms.

DISCUSSION:

In this case, orthostatic hypotension associated with autonomic dysfunction was successfully managed with a combination of intravenous vasopressors and hydration, pressure support garments, oral mineralocorticoids, and oral vasopressors. Oral vasopressors and mineralocorticoids are effective treatment options in the management of the vasopressor-dependent patient. In our patient the adverse effects were tolerable. After continued therapy, the oral vasopressors were withdrawn without a return of orthostatic symptoms.

CONCLUSIONS:

Orthostatic hypotension due to autonomic dysfunction may be successfully managed with combination oral therapy after initial treatment with intravenous vasopressors as evidenced by the absence of orthostasis.
An Overview of Levodopa in the Management of Restless Legs Syndrome in a Dialysis Population: Pharmacokinetics, Clinical Trials, and Complications of Therapy
Authors: Janzen Laverne , Rich Jay A , Vercaigne Lavern M
Published: March 2004

OBJECTIVE:

To review published literature investigating the efficacy and safety of levodopa in the management of restless legs syndrome (RLS), with emphasis on the hemodialysis population.

DATA SOURCES:

An English-language literature search using MEDLINE was conducted from 1966 to 1997 (key terms: restless legs syndrome, levodopa, hemodialysis). The bibliographies of all identified published articles were reviewed and cross-referenced to ensure that all possible references were identified.

STUDY SELECTION AND DATA EXTRACTION:

All identified human studies investigating the use of levodopa for the management of RLS in uremic and nonuremic patients were analyzed.

RESULTS:

The prevalence of RLS is 20–40% in patients with end-stage renal disease (ESRD) and approximately 5% in the general population. Although the benefits of levodopa/(carbidopa/ benserazide) in reducing the signs and symptoms of RLS are documented in nonuremic patients, evidence in patients with ESRD is less readily available. Three small (<30 subjects) clinical trials in uremic patients provide preliminary evidence for the usefulness of levodopa/(carbidopa/benserazide) in this population.

CONCLUSIONS:

In general, the small amount of published literature supports the empirical use of levodopa/carbidopa as a safe and effective therapy to manage the distressing symptoms of RLS in a hemodialysis population. We also report personal observations over a 4-year period in our hemodialysis unit that support levodopa as an effective first-line therapy. We have averted suicidal ideation in two patients and frequently modified symptoms of severe sleep deprivation. The dose of levodopa/carbidopa must be individually titrated to each patient's symptomatology, and morning rebound and afternoon augmentation should be monitored.
Neuropharmacology of St. John's Wort (Hypericum)
Authors: Bennett Dean A , Phun Lisa , Polk Jeffrey F , Voglino Susan A , Zlotnik Vladislau , Raffa Robert B
Published: March 2004

OBJECTIVE:

To review preclinical information related to possible antidepressant mechanism(s) of action of St. John's wort in order to address the issue of whether its purported clinical effectiveness has a rational pharmacologic basis.

DATA SOURCES:

Primary and review articles were identified by a MEDLINE search (1966–January 1998) and through secondary sources. Many of the original German articles had English abstracts, but where necessary, German articles were translated into English. The results of a new screen of hypericin activity at receptor and uptake sites are summarized.

STUDY SELECTION AND DATA EXTRACTION:

All of the articles identified from the data sources were evaluated and all information deemed relevant was included in this review.

DATA SYNTHESIS:

The neuropharmacology of St. John's wort has been examined in only a few studies. A mechanism similar to that of the synthetic antidepressants, such as the selective serotonin-reuptake inhibitors or monoamine oxidase (MAO) inhibitors, might play a role, but other mechanisms are possible.

CONCLUSIONS:

Hypericum extracts have only weak activity in assays related to mechanisms of the synthetic antidepressants, that is, inhibition of MAO, catechol O-methyltransferase, or serotonin reuptake. It has been postulated that the clinical efficacy of St. John's wort could be attributable to the combined contribution of several mechanisms, each one too weak by itself to account for the overall effect. The recent demonstration of a significant affinity of hypericin for σ receptors presents new possibilities for consideration.
Paradoxical Response to Valproic Acid in a Patient with a Hypothalamic Hamartoma
Authors: Stecker Mark M , Kita Mariko
Published: March 2004

OBJECTIVE:

To report a patient who developed the paradoxical effect of increasing electrical seizure activity and confusion with initiation of valproic acid therapy.

CASE SUMMARY:

A 25-year-old African-American woman with a hypothalamic hamartoma had an electroencephalogram (EEG) that demonstrated frequent bursts of generalized spike and wave activity. The prevalence of spike and wave activity increased dramatically and the patient became increasingly somnolent as valproic acid was added to carbamazepine and phenobarbital therapy. Her EEG and mental status changes resolved when the valproic acid was discontinued. There was a strong positive correlation between the prevalence of spike and wave activity and the valproic acid concentration, but not between spike and wave activity and the concentrations of carbamazepine or phenobarbital.

DISCUSSION:

Although this is a complex case, it is clear that the addition of valproic acid produced an increase in spike and wave activity. Possible mechanisms and pathophysiologic significance of this paradoxical effect are discussed in light of the differences between this epileptic syndrome and the primary generalized epilepsies.
Topotecan: A New Topoisomerase I Inhibiting Antineoplastic Agent
Authors: Cersosimo Robert J
Published: March 2004

OBJECTIVE:

To review the pharmacologic, pharmacokinetic, therapeutic, and safety aspects of topotecan, a new antineoplastic agent, and to assess its role in the treatment of cancer.

DATA SOURCES:

MEDLINE database English language only, January 1990–March 1998; SmithKline Beecham Pharmaceuticals; published articles, books, and abstracts.

STUDY SELECTION:

Studies in humans with cancer, clinical case reports, open clinical trials, and controlled clinical studies. Efficacy studies were limited primarily to trials with at least 20 evaluable patients.

DATA EXTRACTION:

Relevant data were extracted only from published reports. Data were obtained from studies in both articles and abstracts. Only articles written in English were reviewed.

DATA SYNTHESIS:

Topotecan is an effective second- or third-line therapy for patients with advanced ovarian cancer and is comparable to ifosfamide, liposomal doxorubicin, and paclitaxel. Activity in combination with other agents and as a first-line agent is yet to be determined. Limited data indicate activity in small-cell lung cancer, cancers of the breast and uterus, and in nonlymphocytic leukemia. The dose-limiting toxicity is myelosuppression.

CONCLUSIONS:

Topotecan is an effective second-line agent for patients with unresponsive or relapsed cancer of the ovary. It appears to be similar to other active agents in patients with this disease status. Its ultimate role in ovarian cancer and other neoplasms awaits additional evaluation in combination with other agents and as first-line therapy.
Tiagabine: A Novel Antiepileptic Drug
Authors: Luer Mark S , Rhoney Denise H
Published: March 2004

OBJECTIVE:

To provide a comprehensive review of tiagabine, including its pharmacology, toxicology, pharmacokinetics, drug interactions, efficacy, adverse effects, and dosing recommendations.

DATA SOURCES:

A computerized search of the MEDLINE database from 1966 to December 1997 was used to identify publications related to tiagabine and nipecotic acid derivatives. Included in this review was information gathered from scientific meetings. Manufacturer's information was used when there was no primary literature.

DATA SYNTHESIS:

Tiagabine amplifies γ-aminobutyric acid (GABA) neurotransmission, the predominant inhibitory neurotransmitter in the brain. Its mechanism of action is selective and has shown promise as an antiepileptic drug (AED) in patients with seizures refractory to other pharmaceutical products. Tiagabine exhibits dose-independent absorption, 90–95% bioavailability, high protein binding (96%), metabolism via hepatic cytochrome P450 enzymes (CYP3A subfamily), and displays first-order elimination pharmacokinetics. The mean plasma half-life is 5–8 hours. Concomitant medications that induce hepatic metabolism enhance tiagabine elimination; metabolism is reduced in patients with hepatic dysfunction. Adverse events of tiagabine typically involve the central nervous system, have been mild to moderate in intensity, and also have been transient in nature.

CONCLUSIONS:

Tiagabine has demonstrated a good safety profile and, while it has not been demonstrated to be superior to other second-line AEDs for partial seizures, its safety and select mechanism of action warrant its further evaluation in the clinical setting. Tiagabine should be a good alternative add-on agent for patients with unsatisfactory seizure control or intolerable adverse effects of traditional therapies; thus, this agent should be made available to these patients.
Reversible Nonthrombocytopenic Palpable Purpura Associated with Metoclopramide
Authors: Goad Jeffery A
Published: March 2004

OBJECTIVE:

To report a case of reversible nonthrombocytopenic palpable purpura associated with metoclopramide.

CASE SUMMARY:

A 72-year-old white man was admitted for worsening palpable purpura over a two-day period. Two days prior to admission, metoclopramide 10 mg orally three times per day was started for a gastrointestinal condition. Upon admission, all drugs were continued except metoclopramide. Over the next two days, the purpura began to resolve. Platelet count was within normal limits on admission and the patient developed no serious consequences because of the purpura.

DISCUSSION:

According to the literature, reversible nonthrombocytopenic palpable purpura has not been previously reported with metoclopramide. A search of MEDLINE (1966 to November 1998) and International Pharmaceutical Abstracts (1970 to November 1998) did not reveal a similar case. Although a rechallenge was not tried, this case appears to demonstrate a temporal relationship between the initiation and discontinuation of metoclopramide and the onset and resolution of symptoms. Similar cases of this reaction have been reported with procainamide, which is structurally similar to metoclopramide.

CONCLUSIONS:

Metoclopramide may cause reversible nonthrombocytopenic vascular-type palpable purpura. Discontinuation of the drug appeared to be responsible for the resolution of symptoms.