bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of Tacrolimus Absorption in Transplant Patients Receiving Continuous versus Interrupted Enteral Nutritional Feeding
Authors: Murray Michelle , Grogan Tracy A , Lever Jacqueline , Warty Vijay S , Fung John , Venkataramanan Raman
Published: March 2004

OBJECTIVE:

To determine the effect of enteral nutritional feeding on the absorption of tacrolimus administered through a nasoduodenal tube to organ transplant patients.

METHODS:

A nonrandomized, prospective study of tacrolimus absorption was performed in 10 liver or lung transplant patients who received Osmolite enteral nutrition through a nasoduodenal feeding tube. Multiple blood samples were collected just prior to and at 30 minutes, 1, 2, 3, 4, 6, 8, 10, and 12 hours after nasoduodenal administration of tacrolimus on 2 consecutive days, once when tacrolimus was administered along with the continuous enteral feeding and the other time when the enteral feeding was withheld 1 hour prior to and 8 hours after tacrolimus administration, to assess tacrolimus absorption. The whole blood tacrolimus concentrations were measured by the microparticulate enzyme immunoassay method. Pharmacokinetic parameters between the two time periods were compared by using a paired t-test at a significance level of a p value of 0.05 or less.

RESULTS:

The time to reach peak blood concentrations (p = 0.055), dose-normalized trough concentrations (p = 0.617), maximum blood concentrations (p = 0.197), and dose-normalized AUC (p = 0.755) were not significantly different between two study periods.

CONCLUSIONS:

This study demonstrated that simultaneous administration of Osmolite enteral feedings with tacrolimus did not interfere with tacrolimus absorption in transplant patients.
Respiratory Depression following Administration of Intrathecal Bupivacaine to an Opioid-Dependent Patient
Authors: Piquet Catherine Y , Mallaret Michel P , Lemoigne Aude H , Barjhoux Claude E , Danel Vincent C , Vincent Françoise H
Published: March 2004

OBJECTIVE:

To document two cases of respiratory depression in patients receiving morphine once the stimulating effect of pain on respiration was removed by bupivacaine.

CASE SUMMARIES:

Case 1: A 72-year-old 84-kg white man with cancer of the bladder and bone metastases had intense back and leg pain that was treated with intrathecal morphine for 6 months at an increasing dosage up to 10 mg twice daily. The intrathecal route was avoided for 4 days because of a suspected local infection at the site of the intrathecal catheter. During this 4-day period the patient received extended-release morphine and subcutaneous morphine daily. When the intrathecal route was used again, he received an identical dose of morphine plus bupivacaine and epinephrine. Ten minutes after the injection, fatal respiratory distress occurred. Case 2: A 92-year-old white woman was admitted for revascularization of arteritis on her left leg. To treat a painful sacrum and heel bedsores, she received extended-release oral morphine for 8 days. Induction of the intrathecal anesthesia was performed with bupivacaine. After 10 minutes, the patient became subcomatose, with miosis and apnea. Intravenous naloxone restored spontaneous respiration and normal consciousness.

CONCLUSIONS:

Pain is a physiologic antagonist of the respiratory depressant effects of opioid analgesics. By reducing pain stimulation, bupivacaine may make patients more susceptible to opioid respiratory depression. Such situations require titration of bupivacaine and other analgesics as well as increased monitoring of the patient.
Extravasation Injury Associated with Low-Dose Dopamine
Authors: Chen Julie L , O'Shea Marianne
Published: March 2004

OBJECTIVE:

To describe the occurrence of extravasation in two patients receiving low-dose dopamine infusions.

CASE SUMMARY:

Intravenous dopamine was infused peripherally (in the antecubital fossa) to two patients in the cardiac intensive care unit in an attempt to enhance renal blood perfusion and urine output. Dopamine extravasation occurred in both patients while the low dose (<3 μg/kg/min) was infused. Significant local tissue injury was observed in both patients.

DISCUSSION:

Dopamine infusion can cause tissue ischemia or necrosis secondary to vasospasm and extravasation. Most of the case reports in the literature have occurred when relatively high doses of dopamine were infused. Only one reported extravasation-induced injury with low-dose dopamine. Although low-dose dopamine has a vasodilatory effect in selected tissues, high concentrations achieved locally as a result of extravasation can still cause severe vasoconstriction and ischemic tissue injury.

CONCLUSIONS:

Low-dose dopamine therapy should be administered with similar precautions as high-dose dopamine. A central intravenous access should be placed for dopamine infusion whenever possible. If this approach is not feasible, dopamine should be infused only peripherally through a long intravenous catheter into a large vein. A 5-cm angiocatheter that is 20 gauge or larger is recommended for peripheral dopamine infusion in our institution. The infusion site should be inspected frequently for early detection of extravasation, and changed to a central or a peripherally inserted central catheter as soon as possible, especially in patients at high risk for extravasation.
β-Blockers and Depression: The More the Murkier?
Authors: Ried L Douglas , McFarland Bentson H , Johnson Richard E , Brody Kathleen K
Published: March 2004

OBJECTIVE:

To review the literature regarding the purported association between oral ingestion of β-blocker drugs and depressed mood.

DATA SOURCE:

MEDLINE was searched for published articles using the key words propranolol, atenolol, metoprolol, nadolol, timolol, β-blocker, β-adrenergic antagonist, or β-adrenergic blocker in combination with the key words depression, depressive symptomatology, major depressive disorder, or depressed mood from January 1966 through December 1996.

DATA SYNTHESIS:

Findings regarding the association are equivocal. Plausible explanations include study design, case definition, and confounding disease states. Most of the evidence supporting an association has used case series and case reports. Findings from cross-sectional observational studies and case–control studies are equivocal. Case definition and measurement instruments may partially explain these inconsistencies. Studies using a diagnosis of depression generally do not support the relationship. Trials using depressive symptoms are about evenly split, but they have generally enrolled a small number of patients and have questionable statistical power. Studies defining antidepressant prescriptions dispensed as a marker for depression generally support the association. Evidence exists both for and against the hypothesis that lipophilic β-blockers cause more depression than do hydrophilic β-blockers.

CONCLUSIONS:

β-Blockers may have been unjustly associated with depression and their use avoided for that reason. Future studies into the association between depression and β-blocker use should evaluate whether the association is affected by case definition and study design characteristics, including disease, dose–response, bias, measurement error, or ability to precisely measure the length of the exposure.
Concomitant Prescribing of Tranquilizers and Hypnotics among Patients Receiving Antidepressant Prescriptions
Authors: Bingefors Kerstin , Isacson Dag GL
Published: March 2004

OBJECTIVE:

To evaluate concomitant prescribing of tranquilizers and hypnotics in antidepressant treatment with particular focus on the relationship to drug class in patients prescribed antidepressant treatment for depressive disorders.

DESIGN AND METHODS:

Repeated cross-sectional surveys of Swedish physicians in ambulatory care from 1991 to 1996, including specialty practices. The participation rate was 65–70%.

RESULTS:

Tranquilizers and hypnotics were prescribed in 36.1% of the visits in which the intention was to treat depression. Concomitant prescribing increased with the patient's age for all antidepressant drug classes. Women received more concomitant prescriptions than men when treated with nonselective monoamine-reuptake inhibitors (NSMRI), mainly tricyclic compounds. Psychiatrists prescribed more concomitant tranquilizers and hypnotics than other physicians, and general practitioners fewer, when treating depression with selective serotonin-reuptake inhibitors (SSRIs), mainly citalopram. A logistic regression model showed that the risk for concomitant prescribing was higher when an NSMRI was prescribed than with other antidepressants.

CONCLUSIONS:

Concomitant prescribing of tranquilizers and hypnotics was common among antidepressant-treated patients. The most plausible reasons for the high rate of concomitant prescribing were the symptoms of the depression itself and/or the common comorbidity with anxiety disorders seen in this group of patients. The results of this study indicate that the concern about increased tranquilizer and hypnotic use among patients treated with SSRIs suggested in other studies seems to be unfounded in Sweden.
Stability of Mycophenolate Mofetil as an Extemporaneous Suspension
Authors: Venkataramanan Raman , McCombs Jacqueline R , Zuckerman Sheila , McGhee Bill , Pisupati Jaya , Dice James E
Published: March 2004

OBJECTIVE:

To evaluate the physical and chemical stability of a suspension of mycophenolate mofetil (MMF) prepared in the hospital from commercially available MMF capsules.

METHODS:

Suspensions of MMF were prepared at room temperature and stored at 5, 25, 37, and 45 °C over a period of 50 to 210 days. The contents of MMF and its degradation product, mycophenolic acid, in the suspension were measured at various time points by HPLC.

RESULTS:

MMF suspensions were stable (as determined by the presence of ≥90% of the labeled amount) at 45 °C for at least 11 days, at 37 °C for at least 28 days, at 25 °C for at least 28 days, and at 5 °C for at least 210 days. The suspension was also physically stable at 5 °C during the entire test period.

CONCLUSIONS:

The compounded MMF suspension was stable for at least 11 days at all the temperatures studied and for as long as 210 days at 5 °C. This formulation appears to be clinically acceptable and provides a convenient dosage form for pediatric patients and for adults during the early postoperative period.
Glucosamine Sulfate for Osteoarthritis
Authors: da Camara Carlos C , Dowless Gregory V
Published: March 2004

OBJECTIVE:

To characterize the usefulness of glucosamine sulfate in the treatment of patients with osteoarthritis (OA).

DATA SOURCES AND STUDY SELECTION:

Pertinent citations were identified via a MEDLINE search (January 1975–March 1997). Only trials available in the English language involving human subjects, OA, and glucosamine sulfate were selected for review.

DATA SYNTHESIS:

OA is the most common form of arthritis and represents a major cause of morbidity and disability in the elderly. The main symptom of OA is pain and most of the commonly prescribed medications (e.g, acetaminophen, nonsteroidal antiinflammatory drugs) have been targeted at relieving the pain. Some of these medications have serious adverse effects and do not necessarily change the natural course of the disease. Glucosamine sulfate, a nutritional supplement, has recently emerged as an alternative treatment option for patients with OA. The beneficial effects of this chondroprotective agent have been reported to reverse or at least stop the progression of the disease without inducing serious adverse effects. Limited data from short-term human trials suggest that glucosamine sulfate administered orally, intravenously, intramuscularly, and intraarticularly may produce a gradual and progressive reduction in joint pain and tenderness, as well as improved range of motion and walking speed. Results of the trials have also shown that glucosamine has produced consistent benefits (>50% overall improvement in symptom scores) in patients with OA and that, in some cases, it may be equal or superior to ibuprofen in controlling symptoms.

CONCLUSIONS:

There is evidence that glucosamine sulfate may provide pain relief, reduce tenderness, and improve mobility in patients with OA. Most of the current data, however, are derived from the European and Asian literature and there are no studies supporting the use of this agent in the US. The studies published to date have been done in small numbers of patients; adequate long-term trials examining the safety, efficacy, and optimal dosage requirements of glucosamine sulfate are lacking. Most of the available clinical data are difficult to interpret due to serious deficiencies in study design. Furthermore, studies evaluating the appropriate place of glucosamine sulfate in the therapeutic armamentarium of OA remain to be done.
Atypical Antipsychotics Part I: Pharmacology, Pharmacokinetics, and Efficacy
Authors: Markowitz John S , Brown Candace S , Moore Thea R
Published: March 2004

OBJECTIVE:

To compare the pharmacology, pharmacokinetics, and efficacy of the newer atypical antipsychotics with those of conventional agents and existing atypical agents.

DATA SOURCES:

Information was retrieved from a MEDLINE English-literature search from July 1986 to June 1998 and by review of references. Indexing terms included neuroleptics, atypical antipsychotics, clozapine, risperidone, olanzapine, sertindole, quetiapine, and ziprasidone.

STUDY SELECTION:

Comparative studies were selected when possible; placebo-controlled studies were included when data were limited on newer atypical antipsychotics.

DATA EXTRACTION:

Emphasis was placed on properly designed clinical trials that assessed dosage, expanded efficacy, enhanced adverse effect profile, and cost.

DATA SYNTHESIS:

Like other atypical antipsychotics, the newer agents have an enhanced 5-hydroxytryptophan/dopaminergic receptors (5-HT2/D2) affinity ratio and undergo extensive biotransformation. Risperidone and olanzapine demonstrate more favorable efficacy/adverse effect ratios than clozapine, sertindole, and conventional antipsychotics in nonrefractory and refractory schizophrenics. Future studies will more clearly define the role of quetiapine and ziprasidone in antipsychotic therapy.

CONCLUSIONS:

Data from controlled trials on efficacy and extrapyramidal side effects support risperidone or olanzapine as first-line agents for the treatment of schizophrenia. Pharmacologic and pharmacokinetic factors do not distinguish between agents sufficiently for drug selection.
Glucosamine
Authors: Barclay Teresa Susanne , Tsourounis Candy , McCart Gary M
Published: March 2004

OBJECTIVE:

To review the pharmacology and pharmacokinetics of glucosamine and critically evaluate currently available literature regarding its safety and efficacy.

DATA SOURCE:

A MEDLINE search was conducted between January 1965 and May 1997. Key words used in the search were osteoarthritis, osteoarthrosis, gonarthrosis, and glucosamine. In addition, references cited in articles obtained from the MEDLINE search were reviewed for additional literature.

STUDY SELECTION AND DATA EXTRACTION:

All articles were considered for inclusion in the review. Articles were excluded from critical evaluation for lack of randomization, lack of a control group, 30 or fewer study participants, inconsistent treatment regimen, incomplete dosing information, or incomplete reporting of results.

DATA SYNTHESIS:

Osteoarthritis affects approximately 12% of the US population; the incidence increases with increasing age. Currently used pharmacologic treatments, including acetaminophen and nonsteroidal antiinflammatory drugs, do not slow or reverse the degenerative process in osteoarthritis. Glucosamine has recently received a great deal of attention from the public as a potential treatment of osteoarthritis, prompting healthcare professionals to investigate its clinical usefulness and potential for adverse effects. The drug has been proposed to stop and possibly reverse the degenerative process in osteoarthritis. Following absorption of an oral dose, glucosamine is incorporated into plasma proteins during first-pass metabolism, resulting in 26% bioavailability. Unbound glucosamine is concentrated in the articular cartilage. Each of the three critically evaluated studies reported a decrease in the symptoms of osteoarthritis (e.g., decreased Lequesne index, decreased pain severity, increased range of motion) for the glucosamine group, which was greater than that obtained in the control group. Flaws in study design, however, prevent the use of these results in modifying current clinical practice. Reported short-term adverse effects include mild gastrointestinal problems, drowsiness, skin reactions, and headache.

CONCLUSIONS:

Improvement in the symptoms of osteoarthritis associated with the use of glucosamine has been observed in clinical trials; however, those trials have flaws in design and data analysis. Further research needs to be conducted before glucosamine can be recommended as a treatment for osteoarthritis.
Probable Diltiazem-Induced Acute Interstitial Nephritis
Authors: Abadín José A , Durán José A , de León José A Pérez
Published: March 2004

OBJECTIVE:

To describe a case of acute interstitial nephritis (AIN) probably related to administration of diltiazem.

CASE SUMMARY:

A 53-year-old white man presented to the hospital experiencing abdominal pain radiating to both renal fossae, as well as dysuria. Diltiazem and atenolol had been prescribed to treat an episode of precordial pain associated with effort. An erythematous maculopapular rash developed approximately 2 hours after administration of a single dose of diltiazem, and acute renal failure, associated with elevated liver function test results, developed 6 days later.

DISCUSSION:

To the best of our knowledge, this is the third reported case of acute renal failure believed to be induced by diltiazem. In all cases, there was an obvious temporal relationship between administration of diltiazem and the onset of acute renal failure. Previous reports failed to discuss a probable pathogenic mechanism. AIN is the most likely etiology of acute renal failure in our patient. Favorable resolution with no relapse, the presence of the skin rash, and the liver sequelae suggest a common immunoallergic mechanism.

CONCLUSIONS:

Healthcare professionals should consider diltiazem-induced AIN in the differential diagnosis of a patient taking diltiazem who develops acute renal failure.
Hepatitis during Chloroguanide Prophylaxis
Authors: Oostweegel Lonneke MM , Beijnen Jos H , Mulder Jan Willem
Published: March 2004

OBJECTIVE:

To describe a case of severe hepatitis that we attribute to the use of chloroguanide.

CASE SUMMARY:

A patient was admitted with fever and jaundice. This man had recently returned from Indonesia and was still using chloroguanide 200 mg once daily for 6 weeks. Evaluation of the liver function test results was consistent with cholestatic liver disease (alkaline phosphatase 158 U/L, aspartate aminotransferase 33 U/L, alanine aminotransferase 58 U/L increasing up to 183 U/L, γ-glutamyl transferase 96 U/L). This condition was thought to be caused by chloroguanide. A biopsy of the liver indicated drug-induced hepatitis.

DISCUSSION:

To our knowledge, this is the first report in the literature of cholestatic hepatitis associated with chloroguanide prophylaxis. In our patient, chloroguanide-induced hepatotoxicity can be considered as a combined allergic and idiosyncratic manifestation.

CONCLUSIONS:

This case shows that it is possible to develop drug-induced hepatitis with considerable morbidity while taking chloroguanide prophylaxis.
Treatment and Prophylaxis of Disseminated Mycobacterium Avium Complex in HIV-Infected Individuals
Authors: Faris Melissa A , Raasch Ralph H , Hopfer Roy L , Butts John D
Published: March 2004

OBJECTIVE:

To review the pathophysiology, epidemiology, treatment, and prophylaxis of disseminated Mycobacterium avium complex (MAC) infection in HIV-infected individuals.

DATA SOURCES:

A MEDLINE (January 1966–July 1997) and AIDSLINE (January 1980–July 1997) search of basic science articles pertinent to the MAC infection in HIV-infected patients.

STUDY SELECTION AND DATA EXTRACTION:

All articles were considered for possible inclusion in the review. Pertinent information, as judged by the authors, was selected for discussion.

DATA SYNTHESIS:

The organism, epidemiology, and pathophysiology of disseminated MAC are discussed for background. A review of clinical trials for the treatment and prophylaxis of disseminated MAC are presented, along with unresolved issues concerning these topics.

CONCLUSIONS:

The incidence of disseminated MAC has increased dramatically with the AIDS epidemic. The infection can lead to increased morbidity and mortality in HIV-infected patients. Treatment regimens for patients with a positive culture for MAC from a sterile site should include two or more drugs, including clarithromycin. Prophylaxis against disseminated MAC should be considered for patients with a CD4 cell count of less than 50/mm3.
Information Contents of Drug Advertisements: An Indian Experience
Authors: Lal Avtar
Published: March 2004

OBJECTIVE:

To critically analyze the drug information contained in Indian pharmaceutical advertisements.

DESIGN:

Analysis of pharmaceutical advertisements supplied by drug representatives (DRs) to prescribers from July 1, 1995, to June 30, 1996.

SETTING:

A university-affiliated urban teaching hospital in India.

PARTICIPANTS:

585 pharmaceutical ad pamphlets.

MAIN OUTCOME MEASURES:

The ads supplied by DRs to physicians in different clinical departments of the hospital were collected. These were distributed to different systems/categories and a special reference to fixed-dose drug combinations was given. The drug information contained in these ads was evaluated by using a checklist, framed by incorporating the World Health Organization ethical guidelines for medicinal drug promotion and some relevant items from other studies.

RESULTS:

The most frequently occurring ads were for antimicrobial agents. The ads on fixed-dose drug combinations constituted 37.9% of the total. More than 85% of the ads mentioned the generic name, brand name, contents, and pharmaceutical dosage forms, as well as the name and address of the company. The information concerning adverse effects, precautions, contraindications, warnings, major interactions, ingredients known to cause problems, pharmacology, drug overdose, references, drug storage, and cost was present in less than 40% of these ads.

CONCLUSIONS:

There has been inadequate information in pharmaceutical ads supplied by DRs to the physicians in India. The current scenario could be improved by formulating some definite legislative guidelines for the minimum level of information to be included in pharmaceutical ads and adhering to that legislation.
Leukocytoclastic Vasculitis Associated with Clarithromycin
Authors: Gavura Scott R , Nusinowitz Sidney
Published: March 2004

OBJECTIVE:

To report a possible case of leukocytoclastic vasculitis associated with clarithromycin therapy.

CASE SUMMARY:

An 83-year-old white woman was prescribed clarithromycin for pneumonia. Six days after her initial presentation, she developed lesions on her palms. Clarithromycin was discontinued at that time. The following day she developed purpuric eccymotic nonblanching lesions that primarily appeared on the lower extremities, buttocks, and abdomen. Colonoscopy revealed generalized erythema and edema of the bowel mucosa. Gastroscopy revealed duodenitis and gastritis, but no bleeding or ulceration. Skin biopsy of the lesions was compatible with leukocytoclastic vasculitis. Renal function was not affected, although hematuria was noted. All symptoms resolved after drug withdrawal and a short course of corticosteroids.

DATA SOURCES:

Searches were performed on MEDLINE, Embase, International Pharmaceutical Abstracts, and major adverse drug reaction databases to identify reports and articles discussing clarithromycin- and macrolide-induced leukocytoclastic vasculitis.

DISCUSSION:

Leukocytoclastic vasculitis is one category of drug hypersensitivity reactions characterized by distinctive patterns of perivascular inflammation. The case described here is consistent with the diagnosis of leukocytoclastic vasculitis, and is similar to the other single published case report associated with clarithromycin.

CONCLUSIONS:

Leukocytoclastic vasculitis induced by clarithromycin is a rare but serious potential adverse effect.
Syncopal Episodes Associated with Cisapride and Concurrent Drugs
Authors: Gray Vanessa Seals
Published: March 2004

OBJECTIVE:

To report a case of QT prolongation and syncopal episodes resulting from concomitant use of cisapride and agents known to inhibit its metabolism.

CASE SUMMARY:

A 53-year-old white woman was involved in two motor vehicle accidents on the same day after experiencing syncopal episodes. Cardiac and neurologic evaluations were negative; the syncopal episodes were attributed to QT prolongation associated with the concomitant use of cisapride and agents known to inhibit its metabolism.

DISCUSSION:

This is the first case published in the English-language literature describing QT prolongation resulting from the concomitant use of cisapride and agents known to inhibit its metabolism. Clarithromycin inhibits CYP3A4, the isoenzyme responsible for the metabolism of cisapride. Concomitant administration of cisapride with agents known to inhibit CYP3A4 (i.e., azole antifungals, erythromycin, clarithromycin) may result in elevated cisapride concentrations. Elevated cisapride concentrations have been associated with QT prolongation, syncopal episodes, and cardiac dysrhythmias.

CONCLUSIONS:

Acquired QT prolongation is a well-recognized adverse effect of several drugs. Recognition of newer drugs and drug combinations that place patients at risk for this potentially fatal adverse event is imperative for appropriate monitoring and prevention.
Ticlopidine-Induced Phenytoin Toxicity
Authors: Klaassen Spencer L
Published: March 2004

OBJECTIVE:

To report a probable case of ticlopidine-induced phenytoin toxicity.

CASE SUMMARY:

A 72-year-old man suddenly developed combative behavior, refused to leave his room, stopped eating, and began falling to the floor 6 weeks after being given ticlopidine. The total phenytoin concentration was measured at 43.6 μg/mL; the dosage of phenytoin was decreased and the symptoms later resolved. After ticlopidine was discontinued, the patient was rechallenged with the same dose of phenytoin without symptoms of toxicity.

DISCUSSION:

Possible mechanisms of the drug interaction are discussed with emphasis on cytochrome P450 metabolism.

CONCLUSIONS:

Clinicians should be aware of this potentially serious drug interaction and either avoid the phenytoin–ticlopidine combination, or monitor closely for phenytoin toxicity.
Pharmacokinetics and Pharmacodynamics of Intravenous and Oral Azithromycin: Enhanced Tissue Activity and Minimal Drug Interactions
Authors: Rapp Robert P
Published: March 2004

OBJECTIVE:

To review the pharmacokinetics and pharmacodynamics of oral and intravenous azithromycin compared with other macrolide antibiotics, and to evaluate these differences and their relation to clinical effectiveness.

DATA SOURCE:

A MEDLINE search (1966–May 1998) was performed to identify applicable English-language clinical, animal, and microbiologic studies pertaining to pharmacokinetic and pharmacodynamic parameters.

STUDY SELECTION:

Relevant studies concerning microbiology, pharmacokinetics, tissue concentrations, pharmacodynamics, and the clinical effects of these parameters were selected.

DATA SYNTHESIS:

The structural modification that distinguishes the azalide antibiotics from the macrolide antibiotics is responsible for the pharmacokinetic and pharmacodynamic behavior of azithromycin, resulting in the high and sustained tissue and intracellular concentrations seen with this agent. Drug delivery to the site of infection by phagocytes and fibroblasts is the hallmark of azithromycin's tissue-directed pharmacodynamics, allowing for convenient once-daily, 5-day regimens for most infections that respond to oral therapy and 7–10 days for more serious infections requiring initial intravenous therapy. Metabolism is via hepatic pathways other than cytochrome P450, thus minimizing the risk of drug interactions.

CONCLUSIONS:

Compared with other macrolide antibiotics, the unique pharmacokinetic and pharmacodynamic features of azithromycin offer the potential for improved efficacy and safety from drug interactions. These attributes, combined with its once-daily dosing schedule, make azithromycin suitable for the treatment of many types of bacterial infection.
Selective Serotonin-Reuptake Inhibitor–Induced Movement Disorders
Authors: Gerber Patricia E , Lynd Larry D
Published: March 2004

OBJECTIVE:

To compile and evaluate all available data suggesting an association between selective serotonin-reuptake inhibitor (SSRI) administration and the occurrence of movement disorders, and to characterize these reactions in terms of onset, duration, treatment and outcome, and potential predisposing factors.

METHODOLOGY:

Reports of movement disorders were identified by conducting a comprehensive literature search that included tertiary adverse drug reaction resources, MEDLINE, EmBASE, Biological Abstracts, Current Contents, Reactions, ClinAlert, and International Pharmaceutical Abstracts. In addition, reports were solicited from the Canadian proprietary manufacturers of SSRIs, and from the Therapeutic Products Program of Health Canada. Each case was then classified according to the description of the movement disorder, based on predefined diagnostic criteria.

RESULTS:

A total of 127 published reports of SSRI-induced movement disorders were identified involving akathisia (n = 30), dystonia (19), dyskinesia (12), tardive dyskinesia (6), parkinsonism (25), and 15 cases of mixed disorders. Ten isolated cases of bruxism were identified. Ten additional reports could not be classified. Manufacturers of SSRIs provided 49 reports of akathisia, 44 of dystonia, 208 of dyskinesia, 76 of tardive dyskinesia, 516 of parkinsonism, and 60 of bruxism. Treatment strategies included discontinuation of the SSRI; dosage reduction; or the addition of a benzodiazepine, β-blocker, or anticholinergic agent.

CONCLUSIONS:

SSRI use appears to be associated with the development of movement disorders, as either a direct result of the drug or exacerbation of an underlying condition. Predisposing factors may include the use of neuroleptics, existing neurologic diagnoses, or preexisting movement disorders. Clinicians should be cognizant of the potential for these reactions, as prompt recognition and management is essential in preventing potentially significant patient morbidity.
Statistical Graphics in Pharmacokinetics and Pharmacodynamics: A Tutorial
Authors: Ette Ene I
Published: March 2004

OBJECTIVE:

To discuss the use of statistical graphics in the analysis of pharmacokinetics and pharmacodynamics data.

METHODS:

Information on graphic techniques and their application was retrieved from a MEDLINE search (January 1980–March 1997) of the English-language literature and bibliographic reviews of review articles and books. Data used to generate plots were extracted from some new drug applications submitted to the Food and Drug Administration and by simulation.

DATA SYNTHESIS:

In carrying out data analysis, we should look at data in several ways, construct a number of plots, and do several analyses, letting the results of each step suggest the next. The information from a plot should be relevant to the goals of the analysis. Thus, in choosing a graphic method, it is necessary to match the capabilities of the method to the need in the context of the application. For example, if linear relationships among variables in a set of multidimensional data are relevant, scatter plots such as the pairs plot with smoothing is likely to be more informative than other graphic methods. It is necessary to recognize what kinds of perceived structure are attributable to the data, and what kinds are artifacts of the display technique itself when using graphs for data analysis.

CONCLUSIONS:

Graphic techniques enable the data analyst to explore data thoroughly, look for patterns and relationships, confirm or disprove the expected, and discover new phenomena. An important element of statistical graphic techniques is flexibility, both in tailoring the analysis to the structure of the data and in responding to patterns that successive steps of analysis uncover. Statistical graphics can and should be used to enhance numeric statistical analyses.
Impact of Zidovudine Plus Lamivudine or Zalcitabine on Health-Related Quality of Life
Authors: Scott-Lennox Jane A , Mills Rose J , Burt Melinda S
Published: March 2004

OBJECTIVE:

To assess the impact of treatment with zidovudine plus lamivudine or zalcitabine on health-related quality of life (HRQOL) in patients with HIV.

DESIGN:

HRQOL assessments were conducted as part of a double-blind, randomized, 24-week (extended to 52 wk) efficacy and safety study. The Medical Outcomes Study HIV Health Survey (MOS-HIV), which assesses 10 physical and psychological domains of HRQOL, was self-administered by patients at baseline and at weeks 16, 32, 52, or at treatment discontinuation.

SETTING:

Twenty-one outpatient centers in the US, Canada, and Puerto Rico.

PATIENTS:

The study enrolled 254 HIV-positive patients (CD4+ 100–300 cells/mm3); 206 patients completed the MOS-HIV at baseline and at least once during treatment. Post hoc analyses stratified patients into two subgroups: AIDS (CD4+ <200 cells/mm3) and non-AIDS (CD4+ ≥200 cells/mm3).

INTERVENTIONS:

Patients received zidovudine 200 mg three times daily plus one of the following: lamivudine 150 mg twice daily, lamivudine 300 mg twice daily, or zalcitabine 0.75 mg three times daily.

MAIN OUTCOME MEASURE:

Change in MOS-HIV scores from baseline to last completed questionnaire.

RESULTS:

Following an average of 36 weeks of treatment, there were statistically significant differences across treatment groups in mean change scores on the physical functioning, role functioning, and vitality scales, with stable or increased (improved) scores in the zidovudine plus lamivudine 150 mg group and decreased scores in the zidovudine plus zalcitabine and zidovudine plus lamivudine 300 mg groups for most scales. Post hoc analyses found that in the non-AIDS subgroup, only the zidovudine plus lamivudine 150 mg group had increases in mean MOS-HIV scores (on 8 of 10 scales); in the AIDS subgroup, all but two MOS-HIV scores (in the zidovudine plus zalcitabine group) decreased in all three treatment groups.

CONCLUSIONS:

These results suggest that, of the three combination therapies studied, zidovudine plus lamivudine 150 mg was most likely to maintain or improve HRQOL in HIV-positive patients.
Cidofovir in the Treatment of Cytomegaloviral Disease
Authors: Kendle Julie B , Fan-Havard Patty
Published: March 2004

OBJECTIVE:

To review the clinical pharmacology and microbiology of cidofovir in the therapy of cytomegalovirus (CMV) disease.

DATA SOURCES:

Pertinent literature was identified via a MEDLINE search (October 1986–February 1997), and data from abstracts presented at recent scientific meetings were also included; unpublished information was provided by the manufacturer.

STUDY SELECTION:

Antiviral activity data were included if widely accepted methodology was used. All clinical data currently available from human studies were also included.

DATA SYNTHESIS:

Cidofovir is similar to ganciclovir in mechanism of action; however, cidofovir does not require viral enzymes for activation. Although the half-life of cidofovir in plasma is only 2.6 hours, the intracellular half-life may be much longer, allowing efficacy with biweekly maintenance dosing. In vitro, cidofovir appears to be equally or more effective than the other agents currently available for the treatment of CMV. In vivo, cidofovir appears to be effective in delaying the progression of CMV retinitis, although no clinical trials to date have directly compared cidofovir with either ganciclovir or foscarnet. Current intravenous dose recommendations are 5 mg/kg once weekly for two doses (induction), and then 5 mg/kg once every other week (maintenance). Since cidofovir is cleared almost entirely by the kidneys, dosage adjustments must be made in patients with impaired renal function. Disadvantages of cidofovir primarily include its risks of adverse drug reactions, such as nephrotoxicity, which is likely to occur in up to 50% of patients if appropriate preventative measures are not taken. Neutropenia and constitutional reactions to probenecid are also commonly encountered during the course of cidofovir therapy.

CONCLUSIONS:

Cidofovir is the first acyclic phosphonate nucleoside antiviral agent to be approved for general use in the US. In addition to delaying the progression of CMV retinitis, cidofovir may provide some protective benefits to patients at risk for developing the disease and may be active against certain strains of virus resistant to other currently available therapies. Another advantage of cidofovir is its infrequent dosage schedule, which may prove beneficial in patients who are not compliant with daily intravenous dosing regimens. When determining the appropriate treatment for a patient with CMV retinitis, the benefits of using cidofovir must be weighed carefully against the risk of potentially serious adverse effects.
Mibefradil: A New Class of Calcium-Channel Antagonists
Authors: Billups Sarah J , Carter Barry L
Published: March 2004

OBJECTIVE:

To describe the pharmacology, pharmacokinetics, and clinical efficacy of mibefradil compared with other agents used for hypertension and angina.

DATA SOURCES:

A MEDLINE search was performed for the period of January 1980 through September 1997 using the key terms mibefradil or Ro 40–5967. All articles written in English were considered for review.

STUDY SELECTION AND DATA EXTRACTION:

All clinical studies involving mibefradil were evaluated. Preclinical data were included if these data were not adequately represented in clinical (human) studies.

DATA SYNTHESIS:

Mibefradil is the first member of a new class of calcium-channel antagonists (CCAs) that block the T-type calcium channels. A long elimination half-life makes once-daily dosing feasible, and the drug's lack of negative inotropy and reflex tachycardia distinguishes it from other available CCAs. When administered at recommended dosages (50 or 100 mg once daily), mibefradil reduces blood pressure over 24 hours in patients with hypertension, improves exercise capacity, and relieves anginal symptoms in patients with chronic stable angina pectoris.

CONCLUSIONS:

Clinical studies have found that the antihypertensive effects of mibefradil are comparable with those of nifedipine, verapamil, and amlodipine, and more effective than those of diltiazem. These effects result from peripheral vasodilation and a slight reduction in heart rate. Selective vasodilation of the coronary vasculature makes it an effective antianginal agent when used alone or added to β-blocker therapy. Mibefradil demonstrates no significant effects on cardiac contractility, and no adrenergic stimulation resulting in reflex tachycardia. Therefore, it may have some advantages over currently available CCAs, especially in patients with congestive heart failure, although such advantages are unproven in published clinical trials. Ongoing clinical studies, including the Mortality Assessment in Congestive Heart Failure Trial (MACH-1) currently in progress, are needed to clarify mibefradil's place in cardiovascular therapy.
Home Blood Glucose Monitoring
Authors: Foster Shonda A , Goode Jean-Venable “Kelly” R , Small Ralph E
Published: March 2004

OBJECTIVE:

To provide a review of self-monitoring blood glucose including home blood glucose meters and patient education.

DATA SOURCES:

A MEDLINE search (January 1966–January 1998) was conducted to identify original and review articles. Search terms included self-monitoring blood glucose and blood glucose monitoring. Owner's manuals and package inserts were reviewed to determine specific characteristics for each glucose meter.

DATA EXTRACTION:

All current original and review articles about self-monitoring blood glucose and home blood glucose meters were included if they contained information about benefits of self-monitoring blood glucose, technology and performance of blood glucose meters, quality control, selection characteristics of blood glucose meters, and patient education.

DATA SYNTHESIS:

Self-monitoring of blood glucose has become an increasingly vital component of the care of the diabetic patient. Many glucose monitors are available with various features that may be confusing to pharmacists. Pharmacists need to be able to aid patients in the selection of an appropriate glucose meter and provide the education necessary for proper use and follow-up. Patient education is a key component in optimizing the potential benefits of self-monitoring.

CONCLUSIONS:

Self-monitoring of blood glucose, if used properly, can have a positive effect by increasing patient involvement in overall diabetes care. Pharmacists are accessible and can teach patients necessary skills that will enhance their ability to self-manage blood glucose.
A Mechanistic Approach to Antiepileptic Drug Interactions
Authors: Anderson Gail D
Published: March 2004

OBJECTIVE:

To describe the primary types of antiepileptic drug (AED) interactions by using a mechanistic approach.

DATA SOURCES:

A literature search was performed using MEDLINE and bibliographies of recent review articles and published abstracts.

DISCUSSION:

AEDs are associated with a wide range of drug interactions, including hepatic enzyme induction and inhibition and protein-binding displacement. Hepatic induction by AEDs affects the metabolism of a limited number of drugs with low therapeutic indices. Anticipation of induction interactions and careful clinical monitoring may alleviate potential problems. Most commonly used AEDs are eliminated through hepatic metabolism catalyzed by the cytochrome P450 (CYP) and uridine diphosphate glucuronosyltransferase (UGT) enzymes. Phenytoin, phenobarbital, and carbamazepine induce CYP and UGT enzymes. Lamotrigine is a weak inducer of UGT. Valproate is a broad-spectrum inhibitor of UGT enzymes, epoxide hydrolase, and CYP2C enzymes. Felbamate induces CYP3A4, but inhibits CYP2C19 substrates. Topiramate inhibits only CYP2C19 substrates. Ethosuximide, gabapentin, tiagabine, and vigabatrin are neither inducers nor inhibitors of drug metabolism. Hepatic enzyme inhibition usually occurs because of competition at the enzyme site. Knowledge of the specific metabolic enzymes involved in the metabolism of AEDs allows clinicians to predict potential interactions.

CONCLUSIONS:

By understanding the mechanisms of drug interactions, the pharmacist can play a key role in patient care by anticipating and preventing AED drug interactions.
Doxorubicin Dosage Guidelines in a Patient with Hyperbilirubinemia of Gilbert's Syndrome
Authors: Cupp Melanie Johns , Higa Gerald M
Published: March 2004

OBJECTIVE:

To reconcile dosage modification guidelines for doxorubicin in a patient with hyperbilirubinemia of Gilbert's syndrome (GS).

CASE SUMMARY:

A 62-year-old white man with concurrent diagnoses of large-cell non-Hodgkin's lymphoma and GS was treated with standard doses of a doxorubicin-containing chemotherapy regimen. No increase of end-organ toxicity was observed during four treatment cycles.

DISCUSSION:

The relative prevalence of GS coupled with the rising incidence of non-Hodgkin's lymphoma increases the probability that both disorders will be present in the same individual. A MEDLINE search (1966 through July 1997) revealed little, and often conflicting, information pertaining to drug metabolism and disposition in GS. In addition, no information has been reported regarding the metabolic fate of doxorubicin in these patients. It is important to emphasize that the lack of enhanced extramedullary toxicity in this patient is not conclusive evidence that the hepatic abnormality of GS had no effect on doxorubicin metabolism.

CONCLUSIONS:

Based on information regarding mechanisms for hepatic clearance, dosage modification of doxorubicin may not be necessary in hyperbilirubinemia of GS.
Cost-Effectiveness Analysis of Abciximab: A Canadian Hospital Perspective
Authors: Zed Peter J , Frighetto Luciana , Sunderji Rubina , Marra Carlo A
Published: March 2004

OBJECTIVE:

To assess the cost-effectiveness of abciximab therapy versus traditional practice in high-risk patients receiving percutaneous transluminal coronary angioplasty (PTCA) from a Canadian hospital perspective.

DESIGN:

A predictive decision analytic model using published clinical and economic evaluations, as well as costs of medical care in Canada.

SUBJECTS:

High-risk PTCA patients as defined by the Evaluation of c7E3 for Prevention of Ischemic Complications trial and the c7E3 Fab Antiplatelet Therapy in Unstable Refractory Angina trial.

INTERVENTIONS:

Two treatment strategies were compared: (1) abciximab 0.25 mg/kg intravenous bolus 10 minutes prior to PTCA followed by abciximab 10 4μg/min intravenous infusion for 12 hours after the procedure, and (2) no abciximab adjunctive therapy at the time of PTCA. Both treatment strategies were combined with intravenous heparin up to 100 units/kg bolus pre-PTCA followed by bolus doses for 1 hour after PTCA per the protocol. Cumulative outcomes were considered up to 6 months after initial PTCA.

RESULTS:

At 6 months, 29% of the patients in the abciximab treatment arm compared with 33% in the no abciximab arm achieved one of the primary events. The most common adverse event experienced was major bleeding at 4% in the abciximab treatment arm versus 1.6% in the no abciximab arm. The average cost per patient for each strategy was $3261 Can ($1 Can = $0.686 US) (abciximab arm) versus $2073 Can (no abciximab arm), resulting in an incremental cost-effectiveness ratio of $29 700 Can per event-free patient. In univariate sensitivity analyses, the only controllable factor that changed the results of the cost-effectiveness outcome was the cost of abciximab.

CONCLUSIONS:

Although the use of abciximab as an adjunct to PTCA results in a reduction in event rates in high-risk patients compared with traditional treatment, there is an increased cost associated with this strategy.