bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuraminidase Inhibitors: Zanamivir and Oseltamivir
Authors: McNicholl Ian R , McNicholl Joan Jovero
Published: June 2003

OBJECTIVE:

To review the pharmacology, pharmacokinetics, efficacy, and safety of zanamivir and oseltamivir for the prophylaxis and treatment of influenza.

DATA SOURCES:

A MEDLINE search restricted to English-language journals was conducted (1980–May 2000).

STUDY SELECTION AND DATA EXTRACTION:

All efficacy and safety trials were included if conducted in humans and published in a journal. Abstracts were included if no other data source was available.

DATA SYNTHESIS:

Zanamivir and oseltamivir block influenza neuraminidase and prevent the cleavage of sialic acid residues, thus interfering with progeny virus dispersement within the mucosal secretions and reducing viral infectivity. The neuraminidase trials for prophylaxis and treatment of influenza enrolled predominantly young (mean age 29–37 y), healthy, mostly unvaccinated individuals who were at the lowest risk of influenza and its complications. When zanamivir 10 mg inhaled twice daily or oseltamivir 75 mg orally twice daily were used for treatment, systemic symptoms such as myalgias, fever, and headache were reduced by approximately 0.7–1.5 days. Greater efficacy (symptom reduction by 1.5–2.0 d) was noted in proven cases of influenza infection, in febrile patients, and in patients who received the treatment medication within 30 hours of symptom onset. Clinical efficacy did not increase when doses higher than the treatment dose approved by the Food and Drug Administration were used. When given for prophylaxis, zanamivir 10 mg inhaled once daily or oseltamivir 75 mg orally once daily was used for four to six weeks and achieved protective clinical efficacy for laboratory-confirmed influenza ranging from 67% to 74%, depending on whether culture or serologic tests were performed. The most common adverse effects (usually <5%) included upper respiratory tract symptoms. Patients with asthma or chronic obstructive pulmonary disease who received zanamivir had an increased incidence of a >20% decline in forced expiratory volume in one second or peak expiratory flow rates. Headaches, nausea, and vomiting were more frequent in the oseltamivir groups than in placebo groups. The most common gastrointestinal adverse effects, nausea and vomiting, were reduced to approximately 10% by administering the medication with food.

CONCLUSIONS:

Zanamivir and oseltamivir are more effective in preventing culture-positive influenza or for treatment of culture-positive influenza in febrile (⩾37.8 °C) individuals. Treatment is more effective if initiated within 30 hours of symptom onset in febrile individuals; however, it is difficult to meet these criteria. More realistically, clinical efficacy is closer to 60–70% and, for treatment started within 48 hours for laboratory-confirmed influenza, symptom reduction is approximately 0.7–1.5 days. If used appropriately to minimize the development of resistance, the neuraminidase inhibitors represent a new and unique class of antiinfluenza agents that can potentially reduce the morbidity associated with influenza.
Treatment of Bipolar Depression with Twice-Weekly Fluoxetine: Management of Antidepressant-Induced Mania
Authors: Megna James L , Devitt Patrick J
Published: June 2003

OBJECTIVE:

To report a case of treatment of bipolar depression and management of antidepressant-induced mania with a low-dose fluoxetine regimen.

CASE SUMMARY:

A 59-year-old white woman was admitted involuntarily to a New York State psychiatric center with a diagnosis of bipolar (type I) disorder, mixed, with psychotic features. Initial treatment with lithium, olanzapine, and clonazepam produced a remission of manic and psychotic symptoms. However, the patient remained clinically depressed. Addition of oral fluoxetine 10 mg every morning to her medication regimen was followed 22 days later by the development of a manic state. Reduction of the fluoxetine dosage to 10 mg twice weekly was associated with the attainment of euthymia in 18 days. Thirteen days after the fluoxetine dosage reduction, the patients fluoxetine blood concentration was 20 μg/L and the norfluoxetine concentration was reported as 53 μg/L.

DISCUSSION:

To our knowledge, this is the first published case that describes the association between a low-dose fluoxetine regimen and the evolution of a bipolar affective state from depression to euthymia via manic switching. The temporal synchrony of this switching with initial implementation of fluoxetine 10 mg every morning, followed by a dose reduction to 10 mg twice weekly, suggests that bipolar depressed patients are extremely sensitive to low doses of antidepressants and to incremental changes in these doses. However, it also suggests that they can respond clinically to such treatment. Furthermore, our laboratory data indicate that antidepressant blood concentrations may play a contributory role in maintaining the balance between euthymia and mania in these patients.

CONCLUSIONS:

Manic switching is always a concern when treating a bipolar depressed patient. Utilization of a low-dose antidepressant drug regimen may be a clinically prudent approach in such an individual.
Opioid Antagonists in the Treatment of Opioid-Induced Constipation and Pruritus
Authors: Friedman Jill D , Buono Felicia A Dello
Published: June 2003

OBJECTIVE:

To describe the role of opioid antagonists in the treatment of opioid-induced constipation and pruritus.

DATA SOURCES:

A MEDLINE search was performed (1966–February 2000) for narcotics and opioid antagonists. Results were limited to English-language and clinical trials. Background information was obtained from pharmacology and pharmacotherapy references and review articles. Hand searching of selected bibliographies yielded several references.

STUDY SELECTION AND DATA EXTRACTION:

Studies were reviewed that examined the use of naloxone, naltrexone, and methylnaltrexone for opioid-related constipation and pruritus. Selected citations included various clinical trials and case series.

DATA SYNTHESIS:

Opioid agents are used for cancer and nonmalignant pain. Peripheral opioid receptor stimulation due to endogenous (i.e., endorphins) or exogenous (i.e., morphine) stimulants may result in negative adverse effects, including constipation and pruritus. Adjuvant agents, such as laxatives and antihistamines, are often used to treat these adverse effects, but are themselves associated with adverse effects and are sometimes ineffective. Opioid antagonists have demonstrated reversal of peripheral opioid receptor stimulation. Clinical trials show adequate maintenance of pain control, as well as decreases in opioid-induced constipation and pruritus.

CONCLUSIONS:

Opioid antagonists offer a therapeutic alternative to conventional adjuvant agents, with the risk of loss of analgesia at higher doses. Methylnaltrexone offers the advantage of peripheral action only, therefore not reversing analgesia. Results are promising; however, larger clinical trials are necessary before opioid antagonists become the standard of care for opioid-induced constipation and pruritus.
Etanercept in Juvenile Rheumatoid Arthritis
Authors: Johnson Carrie J , Reilly Kathleen M , Murray Kim M
Published: June 2003

OBJECTIVE:

To review the classification, pathophysiology, safety, and efficacy of treatment options for juvenile rheumatoid arthritis (JRA). Etanercept, the agent most recently approved by the Food and Drug Administration for use in JRA, is featured.

DATA SOURCES:

Articles were identified from a search of the MEDLINE database (1966 to January 2000) and through secondary sources. Meeting abstracts and posters were also evaluated.

STUDY SELECTION AND DATA EXTRACTION:

Articles identified and retrieved from data sources were evaluated and, if determined to be relevant, were included in this review.

DATA SYNTHESIS:

JRA represents a major cause of functional disability in children. In contrast to traditional therapeutic agents for JRA, which act through generalized antiinflammatory activity or generalized immunosuppression, new therapeutic modalities have been developed that target specific molecules involved in the pathophysiology of JRA. Etanercept inhibits the activity of tumor necrosis factor and lymphotoxin-α. In a clinical trial of patients with polyarticular-course JRA, etanercept-treated patients experienced less pain and swelling in their joints, decreased incidence of disease activity, less frequent flare, and a longer time to flare than patients receiving placebo. Treatment with etanercept was generally well-tolerated.

CONCLUSIONS:

Etanercept represents an exciting new therapeutic option for the treatment of JRA. The positioning of etanercept among other therapeutic options for JRA will be more clearly established as additional safety and efficacy data are made available.
Beneficial Effects of Statins in Coronary Artery Disease — Beyond Lowering Cholesterol
Authors: Sotiriou Christopher G , Cheng Judy WM
Published: June 2003

OBJECTIVE:

To review the benefits of statins in coronary artery disease management beyond their cholesterol-lowering effects.

DATA SOURCES:

A MEDLINE search (1966–May 2000) was conducted using the following terms: lovastatin, pravastatin, simvastatin, atorvastatin, fluvastatin, cerivastatin, endothelium, plaque stabilization, antithrombotic effects.

STUDY SELECTION:

English-language human studies and case reports.

DATA EXTRACTION:

Studies published demonstrating other mechanisms of statins' clinical beneficial effects were evaluated and reviewed.

DATA SYNTHESIS:

The understanding of the pharmacologic effects of statins has led to the realization that the benefits of these agents extend beyond simply lowering cholesterol. These properties include beneficial effects on vessel endothelial tissue; decreased low-density lipoprotein oxidation and inflammation; ability to stabilize atherosclerotic plaques and perhaps promote regression; proliferative effects on smooth-muscle growths, possibly strengthening atherosclerotic plaques; antithrombotic effects by inhibiting platelet aggregation and stimulation of fibrinolytic factors; and improvement of blood viscosity and flow. With these actions, statins may benefit the situation of long-term atherosclerotic plaque formation and the setting of acute coronary syndrome.

CONCLUSIONS:

Further large-scale studies are needed to determine the clinical importance and validity of these postulated beneficial effects of statins.
Seizure Possibly Associated with Fluvoxamine
Authors: Kim Kye Y , Craig Janet M , Hawley Joanne M
Published: June 2003

OBJECTIVE:

To inform clinicians of the possibility that seizures due to therapeutic doses of fluvoxamine may not be as rare as previously considered.

CASE SUMMARY:

A 49-year-old white man with schizoaffective disorder and a past history of seizures secondary to head trauma had been seizure-free for approximately 10 years. Fluvoxamine therapy was begun due to increasing obsessive—compulsive behavior. Despite receiving anticonvulsants for his mood disorder, the patient had a breakthrough seizure. There were no underlying medical conditions that might have induced this seizure. No further seizures occurred after he was placed on a higher dosage of the anticonvulsants. The obsessive—compulsive behavior improved considerably as a result of fluvoxamine treatment.

DISCUSSION:

The patient presented here developed a seizure with a therapeutic dosage of fluvoxamine; seizures associated with this agent have occurred more often with overdose. Multiple factors such as a prior history of seizures, head trauma, and concurrent treatment with other psychotropic agents are considered in this case report.

CONCLUSIONS:

Despite the relatively safe and benign adverse effect profile of the selective serotonin-reuptake inhibitors such as fluvoxamine, clinicians should be cautious about seizures as an adverse effect, especially when the patient has even a remote history of seizure or head trauma.
Neuroleptic Malignant Syndrome during a Change from Haloperidol to Risperidone
Authors: Reeves Roy R , Mack James E , Torres Rafael A
Published: June 2003

OBJECTIVE:

To report a case of neuroleptic malignant syndrome (NMS) in a patient whose therapy was being switched from haloperidol to risperidone.

CASE REPORT:

A 57-year-old African-American man, treated for schizophrenia with haloperidol for several years, developed NMS within 48 hours of the addition of low doses of risperidone and mirtazapine to his regimen. Symptoms, which included fever, generalized rigidity, and altered mental status, resolved after discontinuation of psychotropics, supportive management, and several weeks of treatment with bromocriptine and dantrolene. He was subsequently treated with olanzapine without adverse effects.

DISCUSSION:

Several cases of NMS have been reported with risperidone, but none under these circumstances. NMS most likely occurred in this patient as a result of the additive dopamine2 receptor blocking of haloperidol and risperidone. Sympathetic hyperactivity secondary to mirtazapine may also have been a contributing factor. If NMS may be induced by the simultaneous use of older, high-potency antipsychotics and newer, atypical antipsychotics such as risperidone, switching patients from older to newer antipsychotics may at × be difficult, since completely stopping one antipsychotic before starting the second may place patients at risk for psychotic relapse.

CONCLUSIONS:

Clinicians should closely monitor patients receiving both haloperidol and risperidone or combinations of similar medications.
Postpartum Alopecia
Authors: Eastham John H
Published: June 2003

OBJECTIVE:

To determine whether there are effective treatments for postpartum alopecia.

DATA SOURCES:

Clinical literature identified through MEDLINE (January 1966–May 2000), EMBASE (June 1980–March 2000), and International Pharmaceutical Abstracts(January 1970–March 2000). Key search terms included alopecia, puerperium, and postpartum.

DATA SYNTHESIS:

Postpartum alopecia is a diffuse shedding of scalp hair that can begin two to five months following parturition. Few articles examine the treatment of this condition. Treatments in the form of thyroid supplementation, topical progesterone and estradiol lotions, and an oral contraceptive have been studied. All available studies on this subject have significant limitations, such as small sample size, absence of a control group, or subjective measurement of treatment response. Nondrug therapy for a related type of hair loss has been recommended and includes education about hair cycles and reassurance to minimize anxiety.

CONCLUSIONS:

From the available studies, no specific treatment has been studied well enough with sufficient treatment response to justify recommendation or to be termed effective.
Impact of an Intravenous Fluconazole Restriction Policy on Patient Outcomes
Authors: Burkiewicz Jill S , Kostiuk Karen A , Jacobs Richard A , Guglielmo B Joseph
Published: June 2003

OBJECTIVE:

To evaluate both the economic and clinical impact of an intravenous fluconazole restriction policy in a university teaching hospital.

METHODS:

Intravenous fluconazole was restricted to patients unable to take oral medications due to significant nausea or to patients whose oral intake was restricted. A retrospective chart review and computerized record review was conducted in patients receiving intravenous or oral fluconazole from January 1 to June 30, 1997, and again from January 1 to June 30, 1998, after implementation of the policy.

RESULTS:

Six-month institutional expenditures for intravenous fluconazole decreased following policy implementation, from $81 900 to $45 400, an estimated annual institutional savings of $73 000. A 47% reduction in the number of patients treated with intravenous fluconazole was observed over the six-month period after policy implementation. During this time, the rate of successful clinical outcomes for documented or suspected disseminated Candida albicansinfection or febrile neutropenia remained the same (66.6% prepolicy and 65.9% postpolicy; p = 0.95). Similarly, the number of deaths in patients receiving fluconazole remained unchanged (p = 0.31).

CONCLUSIONS:

A restriction policy for intravenous fluconazole results in significant cost savings, with no significant decrease in successful outcomes or change in mortality.
Alternate-Day Dosing of HMG-CoA Reductase Inhibitors for Cholesterol Reduction
Authors: Metz Charity A , Lucas Kristy H
Published: June 2003

OBJECTIVE:

Assess efficacy, safety, and cost of alternate-day dosing with 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (HRIs).

DATA:

International Pharmaceutical Abstracts and MEDLINE (English-language clinical trials, 1966–April 2000) were searched.

DATA SYNTHESIS:

Established efficacy of HRIs is based on daily administration. Many patients who could benefit from these agents are unable to afford them; therefore, alternate-day dosing may be a solution for reducing expense without decreasing therapy benefits. Studies addressing alternate-day HRI therapy are evaluated to determine the usefulness of this option for cholesterol reduction.

CONCLUSIONS:

Although limited studies imply a trend toward benefit with alternate-day HRI therapy, large, controlled, randomized trials are needed before making this a standard recommendation.
Anticoagulation Therapy for Radiation-Induced Myelopathy
Authors: Liu Chin Y , Yim Barbara T , Wozniak Antoninette J
Published: June 2003

OBJECTIVE:

To report the use of heparin and enoxaparin for radiation-induced myelopathy.

CASE SUMMARY:

A 46-year-old white woman with presumed metastatic lung cancer presented with worsening numbness and weakness of both legs. The neurooncology service was consulted and determined that the symptoms were consistent with radiation-induced myelopathy. The patient briefly responded to steroid treatment. A trial of intravenous heparin therapy was initiated by the primary team and managed by the clinical pharmacy services. Her symptoms improved when heparin was begun. She was able to walk and was subsequently discharged home on enoxaparin.

DISCUSSION:

Spinal cord injury is one of the known adverse effects of radiation. The onset of symptoms can be acute or delayed. The clinical signs and symptoms of delayed neurologic injury are related to the narrowing and occlusion of the vessel lumen, ischemia, edema, and cell death in the surrounding nervous tissue. Treatment often consists of corticosteroids and/or hyperbaric oxygen; however, the outcomes are often disappointing. In addition to the inhibition of serum protein—mediated coagulation, heparin inactivates or prevents the release of mediators of vascular injury, inflammation, permeability, and edema. Therefore, patients with radiation-induced spinal cord injury may benefit from anticoagulant therapy.

CONCLUSIONS:

Heparin and/or enoxaparin may be considered as potential treatments for patients with radiation-induced myelopathy.
Serum Concentrations of Cefuroxime after Continuous Infusion in Coronary Bypass Graft Patients
Authors: Pass Steven E , Miyagawa Clyde I , Healy Daniel P , Ivey Tom D
Published: June 2003

OBJECTIVE:

To describe the serum concentrations of continuous infusion of cefuroxime for postsurgical prophylaxis of sternal wound infection in patients undergoing coronary artery bypass graft (CABG), and to assess the incidence of sternal wound infection in this population.

METHODS:

This was a prospective, noncomparative trial involving 54 patients undergoing elective CABG surgery. All patients enrolled in the study received cefuroxime 1.5 g as a single intravenous dose 30 minutes preoperatively, followed by a continuous infusion of 3 g every 24 hours until removal of all central venous catheters.

RESULTS:

Of the 53 evaluable patients, the mean steady-state cefuroxime serum concentration was 21.6 ± 14.2 μg/mL (range 6.56–59.5). No patient developed a sternal wound infection. The mean treatment duration was 2.58 ± 2.13 days (range 1–13). The median hospital and intensive care unit lengths of stay were six days and 46 hours, respectively. The average antibiotic cost per day was $32.76.

CONCLUSIONS:

These preliminary results of continuous infusion of cefuroxime 3 g/d for prophylaxis of sternal wound infections in CABG patients indicate that serum concentrations are highly variable, but reliably above the minimum inhibitory concentration for the common anticipated pathogens in this setting. Further comparative trials in a larger number of patients are necessary before this mode of administration can be routinely advocated for prophylaxis.
Common Prescriptions in Ambulatory Care in Lebanon
Authors: Hamadeh Ghassan N , Dickerson Lori M , Saab Bassem R , Major Stella C
Published: June 2003

OBJECTIVE:

To describe prescribing practices of family physicians in a staff model health maintenance organization at a university health center in Lebanon and estimate costs of such practices for common diseases.

METHODS:

All prescriptions issued between July 1, 1997, and June 30, 1998, were prospectively collected. The diagnoses made by physicians at each encounter were recorded, and the total price of medications prescribed was calculated. The core prescribing indicators as defined by the World Health Organization and the mean annual prescription price per person for the 25 most common diagnoses were calculated.

RESULTS:

Prescribing occurred in 27.1% of encounters, with a mean of 1.6 medications per encounter; 17.5% of all prescriptions included an antibiotic. Generic drugs and essential drugs each accounted for 2.9% of all medications. Approximately 50% of the consultations for either respiratory or ear infections resulted in a prescription. Cervical spine syndromes and lipid metabolism disorders cost most among recorded diagnoses, with mean annual prescription prices per person of US $2016 and $1128, respectively.

CONCLUSIONS:

The low rate of generic and essential drug prescribing, as well as the frequency of prescribing in respiratory infections, highlight the need for initiatives to help rationalize prescribing in primary care in Lebanon. Together with the diagnostic categories incurring high cost per person, these issues can be part of physician education or treatment guideline development. These measures may aid the government in its subsidy of primary health care centers.
Rhabdomyolysis Secondary to a Drug Interaction between Simvastatin and Clarithromycin
Authors: Lee Audrey J , Maddix Daniel S
Published: June 2003

OBJECTIVE:

To report a case of rhabdomyolysis resulting from concomitant use of clarithromycin and simvastatin.

CASE SUMMARY:

A 64-year-old African-American man was admitted to the hospital for worsening renal failure, elevated creatine phosphokinase, diffuse muscle pain, and severe muscle weakness. About three weeks prior to admission, the patient was started on clarithromycin for sinusitis. The patient had been receiving simvastatin for approximately six months. He was treated aggressively with intravenous hydration, sodium bicarbonate, and hemodialysis. A muscle biopsy revealed necrotizing myopathy secondary to a toxin. The patient continued to receive intermittent hemodialysis until his death from infectious complications that occurred three months after admission. There were several factors that could have increased his risk for developing rhabdomyolysis, including chronic renal failure.

DISCUSSION:

Clarithromycin is a potent inhibitor of CYP3A4, the major enzyme responsible for simvastatin metabolism. The concomitant administration of macrolide antibiotics and other hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have resulted in previous reports of rhabdomyolysis. Other factors may increase the risk of this drug interaction, including the administration of other medications that are associated with myopathy, underlying renal insufficiency, and administration of high doses of HMG-CoA reductase inhibitors.

CONCLUSIONS:

Macrolide antibiotics inhibit the metabolism of HMG-CoA reductase inhibitors that are metabolized by CYP3A4 (i.e., atorvastatin, cerivastatin, lovastatin, simvastatin). This interaction may result in myopathy and rhabdomyolysis, particularly in patients with renal insufficiency or those who are concurrently taking medications associated with myopathy.
Metformin in an HIV-Infected Patient with Protease Inhibitor—Induced Diabetic Ketoacidosis
Authors: Hughes Christine A , Taylor Geoffrey D
Published: June 2003

OBJECTIVE:

To describe a case of diabetes mellitus and diabetic ketoacidosis in a patient receiving protease inhibitor therapy and to describe the patient's response to treatment with metformin.

CASE SUMMARY:

A 49-year-old HIV-positive white man who was receiving indinavir, stavudine, and lamivudine for more than two years presented with shortness of breath and significant weight loss over the previous month. On admission, he had a pH of 7.11 and PaCO2 of 12.9 mm Hg. Laboratory investigations revealed glucose 420 mg/dL, a total carbon dioxide 5 mEq/L, and anion gap of 32. β-Hydroxybutyrate was 5.9 mmol/L (normal value <0.4 mmol/L). Urine was highly positive for glucose and ketones. The patient was given intravenous fluids and an insulin infusion was started. Five days later, he was discharged on 60 units of insulin per day. Following discharge, efavirenz was substituted for indinavir. Metformin was added and six months following discharge the patient's blood glucose was well controlled with 36 units of insulin per day.

DISCUSSION:

New-onset diabetes mellitus has been reported in HIV-infected patients receiving protease inhibitors. To date, diabetic ketoacidosis has been an infrequent acute complication. The mechanism by which protease inhibitors cause diabetes is unclear; however, studies have noted insulin resistance and increased proinsulin. Metformin increases the sensitivity of peripheral tissues to insulin and appeared to be useful in this patient. However, further clinical research is needed.

CONCLUSIONS:

Monitoring glucose concentrations in HIV-positive patients receiving protease inhibitors is important to prevent the development of acute complications, including diabetic ketoacidosis. We recommend that these patients have their fasting serum glucose concentration measured at baseline, with follow-up every three months. The role of metformin and the thiazolidinedione antidiabetic agents in the management of protease inhibitor—induced diabetes requires further study.
Delirium following a Switch from Cimetidine to Famotidine
Authors: Yuan Rey-Yue , Kao Chiung-Rey , Sheu Jau-Jiuan , Chen Chi-Hsun , Ho Chun-Sum
Published: June 2003

OBJECTIVE:

To describe a patient who developed delirium when switched from cimetidine to famotidine.

CASE SUMMARY:

An 84-year-old Taiwanese woman was hospitalized for tarry stools. Her past medical history revealed only a decrease in renal function. She tolerated both oral and intravenous cimetidine therapy with a daily dose of 400–900 mg intermittently for 20 years. On hospital days 1–3, cimetidine 300 mg was injected intravenously every eight hours without difficulty. Considering the possible existence of a cimetidine-resistant bleeding ulcer, famotidine 20 mg was given twice daily orally on hospital days 4–7 and then injected intravenously. Six days after being switched from cimetidine to famotidine, the woman's mental status deteriorated. A series of clinical tests revealed no apparent causative factors. Famotidine was then suspected as a probable cause of her delirium. Discontinuation of the drug resulted in rapid resolution of the patient's delirious status.

DISCUSSION:

Famotidine crosses the blood—brain barrier less easily than cimetidine and was taken for a much shorter period in this patient. Thus, we propose that the occurrence of delirium in this patient was associated with famotidine, but not cimetidine, and was idiosyncratic rather than dose related. Furthermore, this case involved an elderly patient with compromised renal function who developed delirium in response to intravenous, but not oral, administration of famotidine. These factors seem to increase the risk for famotidine-induced delirium.

CONCLUSIONS:

Clinicians should be aware of the possible occurrence of delirium following a switch from one histamine2-receptor antagonist to another. In rare instances, patients switched to famotidine from cimetidine may experience delirium, particularly elderly patients with poor renal function who receive intravenous famotidine.
Converting Patients from Brand-Name Clozapine to Generic Clozapine
Authors: Sajbel Terrie A , Carter Gary W , Wiley Roy B
Published: June 2003

OBJECTIVE:

To evaluate safety and dosage requirements when patients taking brand-name clozapine (Clozaril, Novartis Pharmaceuticals) are converted to generic clozapine (Zenith Goldline).

METHODS:

In November 1999, patients at Colorado Mental Health Institute at Pueblo taking Clozaril were changed to generic clozapine. Seventeen patients had been prescribed Clozaril for three years and were included in the study. Drug dosage, white blood cell (WBC) count values, and adverse drug reaction reports were compared. Data regarding patients on the brand-name product were evaluated retrospectively for the months of November, December, January, and February during the years 1996/1997, 1997/1998, and 1998/1999. These data were compared with those from the same patients after switching to generic clozapine for the same months in 1999/2000. A one-year comparison of brand-name (1998/1999) with generic drug (1999/2000) was also performed. Statistical analysis included a standard t-test comparing WBC values and a Brown—Forsythe test for comparing dosages.

RESULTS:

There were no differences between the values obtained for the brand-name and generic products. WBC counts for the three-year data resulted in a p value of 0.9992. There was no difference when comparing the samples one year prior to switching and after the switch (p = 0.9991). There was no difference in dosages at three years or one year (p = 0.9999 and p = 0.9993, respectively). No adverse events were noted with the generic product.

CONCLUSIONS:

No differences were found between the brand-name and generic clozapine groups with regard to WBC count, dosage, and adverse events. The conversion to the generic product is projected to save the pharmacy $90 000 annually.
Probable Colchicine-Induced Neutropenia Not Related to Intentional Overdose
Authors: Dixon Amy J , Wall Geoffrey C
Published: June 2003

OBJECTIVE:

To report a case of neutropenia caused by colchicine not associated with intentional overdose or with preceding severe gastrointestinal symptoms.

CASE SUMMARY:

A 68-year-old white man was admitted to the hospital with intractable pain from an acute attack of gout. The patient was treated with standard doses of oral colchicine for several days. He experienced mild loose stools, but no severe diarrhea or nausea during treatment. The patient then developed severe neutropenia, with an absolute neutrophil count of 240 cells/mm3. His white blood cell count returned to normal after discontinuing colchicine and administering filgrastim.

DISCUSSION:

Although colchicine is commonly associated with neutropenia in cases of intentional or accidental overdose, the patient developed this adverse effect after being treated with doses commonly used for the acute treatment of gout. In addition, this patient had taken low-dose colchicine for many years without experiencing hematologic adverse effects.

CONCLUSIONS:

Colchicine is often an attractive alternative to nonsteroidal antiinflammatory agents for the treatment of gout, especially in patients at risk for renal impairment or gastropathy. Our case illustrates that colchicine treatment can cause hematologic adverse effects; the clinician should monitor cell counts in patients receiving this agent, especially at the higher doses used for acute treatment of gout.
NSAID Impairment of Orthodontic Tooth Movement
Authors: Walker J Bryan , Buring Shauna M
Published: June 2003

OBJECTIVE:

To evaluate the impairment of orthodontic tooth movement caused by nonsteroidal antiinflammatory drugs (NSAIDs).

DATA SOURCES:

Biomedical literature accessed through MEDLINE (1966–January 2000), EMBASE (1980–January 2000), and International Pharmaceutical Abstracts(1970–January 2000). Key search terms included NSAIDs, orthodontics, and tooth movement.

DATA SYNTHESIS:

Orthodontic dentistry applies mechanical force to generate tooth movement. Since prostaglandins are mediators of tooth movement, it is reasonable to expect that prostaglandin inhibitors, such as NSAIDs, inhibit or delay tooth movement. An evaluation of studies measuring the extent of NSAID impairment on tooth movement was undertaken.

CONCLUSIONS:

Results from animal studies have shown that NSAIDs can impair the tooth movement process. Until long-term human data are obtained, acetaminophen remains an appropriate alternative to NSAIDs for treating orthodontic-associated pain.
Pharmacists' Preferences for Continuing Education and Certificate Programs
Authors: Scott Virginia (Ginger) G , Amonkar Mayur M , Madhavan S Suresh
Published: June 2003

OBJECTIVE:

To conduct an assessment of the needs and interests of West Virginia pharmacists with respect to continuing education (CE) and certificate programs (CP) versus a nontraditional PharmD program (NTP).

METHODS:

A cross-sectional study was conducted. The survey was mailed to 2800 West Virginia University School of Pharmacy alumni and West Virginia licensed pharmacists. The survey collected data pertaining to pharmacists' perceptions for the needs of CE, CP, and the NTP program; the optimal structuring of these programs; and the demographics of participants.

RESULTS:

A 24% (674) usable response rate was achieved from two mailings. Respondents were asked to address all areas of interest: approximately 75% showed interest in enrolling in CE, 45% in CP, and 40% in the NTP program. Interest levels varied across demographic and practice characteristics. Seven methods of instruction were evaluated by pharmacists, with live lectures being the most preferred for both CE and CP. Interest for specific content areas and topics for CE workshops and CP were identified. The type and amount of employer support and willingness to pay for enrollment in the two types of programs were obtained. Markets' needs for CE and CP were identified for five typical pharmacists' profiles (e.g., staff pharmacists in community practice).

CONCLUSIONS:

Results can be used by CE providers to develop CE and CP programs of most interest to pharmacists and target them to appropriate demographic segments in order to be cost-effective.
Seizure Induced by Ropivacaine
Authors: Bisschop Dorothée Y , Alardo Jean-Pierre , Razgallah Brahim , Just Bernard Y , Germain Marie-Laure Y , Millart Hervé G , Trenque Thierry C
Published: June 2003

OBJECTIVE:

To report development of a seizure after administration of ropivacaine.

CASE SUMMARY:

A 26-year-old woman was scheduled for a cesarean section because of a stagnation of the uterine neck dilatation after 4.5 hours. After peridural administration of 279 mg of ropivacaine (total dose) over five hours, she presented with oculogyric movements and slurred speech that preceded convulsions of the face and of the upper limbs.

DISCUSSION:

Convulsions are well-known complications of local anesthetics. Ropivacaine, a relatively new agent, is considered safer for the central nervous system. Currently, there are only four published reports that implicate ropivacaine as being associated with convulsions. The likelihood that ropivacaine caused the seizure in our patient was possible based on the Naranjo probability scale.

CONCLUSIONS:

Clinicians should be aware of the possibility of seizures as an adverse effect of ropivacaine.
Gastrostomy Tube Placement in Nonadherent HIV-Infected Children
Authors: Temple Mary E , Koranyi Katalin I , Nahata Milap C
Published: June 2003

OBJECTIVE:

To determine the benefits of gastrostomy tube (G-tube) placement in HIV-infected children receiving highly active antiretroviral therapy (HAART).

METHODS:

Children who had a G-tube placed due to medication adminsitration difficulties were followed to determine changes in medication adherence and changes in laboratory parameters. Medication adherence and laboratory parameters were reviewed for three months prior to G-tube placement and then were followed for six months after G-tube placement. Viral RNA and CD4+ counts were assessed between the two time periods. Medication adherence was followed by review of pharmacy refill records and pill counts. Parents were surveyed about their opinion regarding the G-tube placement and medication administration in their children.

RESULTS:

Six children had G-tubes placed due to medication administration difficulties. The G-tube was tolerated in all six cases, although one child developed a staphylococcal infection 13 months after G-tube placement. Before G-tube placement, the medication adherence to HAART averaged 47% ± 20% SD, with a range of 15–90%. After G-tube placement, medication adherence improved to 90–100%. All parents were satisfied with the G-tube and all reported shorter medication administration × and fewer behavioral problems. Five of six patients had at least a 2-log10 decrease in viral load, and CD4+ percentages improved by an average of 6.4%.

CONCLUSIONS:

G-tubes were well tolerated by HIV-infected children. Although G-tube placement is not needed in most children with HIV, it may provide an option for parents and children where administration of antiretroviral medication poses extreme difficulty and all other avenues have been exhausted.
Serotonin Syndrome: Early Management with Cyproheptadine
Authors: McDaniel William W
Published: June 2003

OBJECTIVE:

T o report a psychiatric patient who developed serotonin syndrome after a medication overdose and whose marked mydriasis was quickly reversed by administration of cyproheptadine. This phenomenon was confirmed when other cases of serotonin syndrome were studied.

METHOD:

In the index patient as well as in three subsequent cases of serotonin syndrome, pupil diameter, muscle tone, mental status, and vital signs were monitored before and after a test dose of cyproheptadine as medications were discontinued and antiserotonergic therapy begun.

RESULTS:

In each patient, cyproheptadine produced rapid reversal of mydriasis within one hour of the initial dose. Other signs of serotonin syndrome remitted more slowly. As the signs and symptoms of serotonin syndrome remitted and pupils returned to normal size and reactiveness, cyproheptadine therapy seemed to produce mydriasis after each dose. Cessation of therapy after this point did not result in recurrence of symptoms. One patient developed serotonin syndrome twice. Two patients developed serotonin syndrome during treatment with medications that are partial serotonin antagonists (mirtazapine and nefazodone).

CONCLUSIONS:

Rapid reversal of mydriasis in serotonin syndrome by cyproheptadine may serve as a specific suppressive test for the condition, and possibly may add to our understanding of the syndrome. Treatment with cyproheptadine is not thought to abbreviate the illness, but provides symptomatic relief while symptoms persist.
Physicians' Knowledge, Attitudes, and Practice of Pharmacologic Treatment of Hypertension
Authors: Huse Daniel M , Roht Lewis H , Alpert Joseph S , Hartz Stuart C
Published: June 2003

OBJECTIVE:

To explore how well physicians who treat hypertension know the indications and contraindications for particular antihypertensive therapies, and how closely their opinions and practice of hypertension treatment agree with national guidelines.

METHODS:

We surveyed by mail a stratified random sample of 10 000 US cardiologists, internists, and general/family practitioners. This survey explored their knowledge, attitudes, and practices with respect to the treatment of hypertension. Responses were compared with national guidelines and product labeling at the time of the survey. Results were stratified by physician specialty.

RESULTS:

A total of 1023 physicians, or 10.2% of the sample, responded to the survey. Only 37.3% answered all four knowledge questions correctly, including 25.7% of general/family practitioners, 38.3% of internists, and 49.5% of cardiologists (p < 0.001). In their attitudes with respect to evaluating high blood pressure and establishing treatment goals, most respondents agreed with established guidelines. However, when asked how they would treat uncomplicated, mild hypertension, only 23% limited their selection to diuretics and β-blockers in accordance with the guidelines. Cardiologists in particular were more likely than internists or general/family practitioners to choose other drug classes, such as angiotensin-converting enzyme inhibitors or calcium-channel blockers.

CONCLUSIONS:

The results of our survey suggest that national efforts to educate physicians about the increasingly complex armamentarium for hypertension, and to persuade them to base their prescribing on the results of randomized, controlled trials of primary prevention, must be continued.
The Relationship between Preadmission Indicators and Basic Math Skills at a New School of Pharmacy
Authors: Grillo Joseph A , Latif David A , Stolte Scott K
Published: June 2003

OBJECTIVE:

To examine the relationship between preadmission indicators of 49 PharmD students entering their first professional year at a new school of pharmacy and their scores on a Basic Math Skills Test (BMST). A secondary objective was to determine what factors, if any, contributed to the successful completion of the BMST.

METHODS:

This cross-sectional investigation used a convenience sample of PharmD students entering the first professional year at a three-year-old, private, southeastern school of pharmacy. All first-year students who took the mandatory BMST, as part of a math mentor pilot program, were eligible for enrollment. The BMST covered nine different competencies and was validated at the grade-8 level. Math test scores, the student's Pharmacy College Admissions Test (PCAT), and other demographic and scholastic information was obtained from the student's application file in a retrospective manner. All identifiers were removed before the data were submitted to the investigators.

RESULTS:

Statistical analysis suggested that two preadmission indicators strongly influenced BMST performance: percentile scores on the quantitative section of the PCAT (PCAT—QP) and whether the student attended a private or public university prior to admission to the pharmacy school. In addition, four factors significantly contributed to successful completion of the BMST: math/science grade point average (MS-GPA), PCAT percentile scores, PCAT—QP percentile scores, and the number of BMST items left blank.

CONCLUSIONS:

A relationship exists between preadmission indicators of PharmD students entering their first professional year and their BMST score. In addition, certain identifiable factors impact BMST scores of first-year PharmD students. Admissions committees may find this useful in identifying students who may need remedial math assistance prior to beginning math-intensive courses such as pharmaceutical calculations and pharmacokinetics.
Treatment of Neuropathic Pain with Venlafaxine
Authors: Sumpton Janice E , Moulin Dwight E
Published: June 2003

OBJECTIVE:

To report a case of successful treatment of neuropathic pain with venlafaxine.

CASE REPORT:

A 39-year-old white woman presented with neuropathic back pain. The patient obtained 50% pain relief with consecutive use of amitriptyline, desipramine, and imipramine. Anticholinergic effects prompted a switch to extended-release venlafaxine 75 mg/d. Pain relief was as effective with this therapy as with the tricyclic antidepressants. The absence of adverse effects allowed the patient to discontinue all laxatives.

DISCUSSION:

Venlafaxine is an antidepressant that inhibits reuptake of norepinephrine and serotonin. This is the major mechanism by which tricyclic antidepressants relieve neuropathic pain. Venlafaxine does not bind to muscarinic-cholinergic, histaminic or α1-adrenergic receptors responsible for the common adverse effects seen with tricyclic antidepressants.

CONCLUSIONS:

This report describes the efficacious use of venlafaxine in the treatment of neuropathic pain. Double-blind, randomized, controlled trials are needed to explore this further.
Subtherapeutic INR Values Associated with a Switch to Generic Warfarin
Authors: Hope Kimberly A , Havrda Dawn E
Published: June 2003

OBJECTIVE:

To discuss the effect on the international normalized ratio (INR) when patients are converted from therapy with Coumadin to generic warfarin.

CASE SUMMARY:

Two cases at a family medicine center anticoagulation clinic in Oklahoma City, OK, in which subtherapeutic INR values occurred after a switch from Coumadin to generic warfarin, while all other variables were kept consistent demonstrate the need for close monitoring of the INR when patients are switched between brands of warfarin.

DISCUSSION:

Warfarin is a narrow therapeutic index drug since small changes in systemic concentration can lead to significant variation in pharmacodynamic response. In March 1997, the Food and Drug Administration (FDA) approved generic warfarin based on the FDA and United States Pharmacopeia (USP) standards. Due to different specifications between Dupont Pharma and the USP, content uniformity may differ between brand and generic forms of warfarin. Limited studies have demonstrated bioequivalence between brand and generic. The two cases presented demonstrate the potential for fluctuations in the INR when switching between generic and brand. Thus, these cases illustrate the need for close monitoring if a change is made.

CONCLUSIONS:

While considered bioequivalent by the FDA, switching between Coumadin and generic warfarin may lead to significant changes in the INR, warranting dose alterations due to different content uniformity specifications between Dupont Pharma and the USP. Patients switching between Coumadin and generic warfarin should have their INR monitored more carefully.
Fluconazole-Induced Torsade de Pointes
Authors: Tholakanahalli Venkatakrishna N , Potti Anil , Hanley James F , Merliss Andrew D
Published: June 2003

OBJECTIVE:

To present a case of fluconazole-associated torsade de pointes (TDP) and discuss fluconazole's role in causing TDP.

CASE SUMMARY:

A 68-year-old white woman with Candida glabrataisolated from a presacral abscess developed TDP eight days after commencing oral fluconazole. The patient had no other risk factors for TDP, including coronary artery disease, cardiomyopathy, congestive heart failure, and electrolyte abnormalities. There was a temporal association between the initiation of fluconazole and TDP. The TDP resolved when fluconazole was discontinued; however, the patient continued to have premature ventricular contractions and nonsustained ventricular tachycardia (NSVT) until six days after drug cessation.

DISCUSSION:

Use of the Naranjo probability scale indicates a probable relationship between the use of fluconazole and the development of TDP. The possible mechanism is depression of rapidly activating delayed rectifier potassium currents. In our patient, there was no other etiology identified that could explain QT prolongation or TDP. The complete disappearance of NSVT and premature ventricular contractions followed by normalization of QT interval after the drug was stopped strongly suggests fluconazole as the etiology.

CONCLUSIONS:

Clinicians should be aware that fluconazole, even at low doses, may cause prolongation of the QT interval, leading to TDP. Serial electrocardiographic monitoring may be considered when fluconazole is administered in patients who are at risk for ventricular arrhythmias.