bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phenytoin/Isradipine Interaction Causing Severe Neurologic Toxicity
Authors: Cachat Francois , Tufro Alda 
Published: June 2003

OBJECTIVE: To report a young man on phenytoin who developed acute neurologic symptoms after isradipine was introduced to his treatment regimen and discuss the possible causes of this drug interaction. CASE SUMMARY: A 21-year-old white man, with propionic acidemia and seizures treated with phenytoin and carbamazepine, was started on isradipine for essential hypertension. Soon thereafter, he developed acute and severe lethargy, ataxia, dysarthria, and weakness that resolved once isradipine was withheld. Phenytoin concentrations were within normal limits or elevated, despite sequential reductions of phenytoin dosage, during concomitant isradipine administration. DISCUSSION: Isradipine is a known inhibitor of the CYP450 isoenzyme family. Although the daily dose of phenytoin was decreased significantly, phenytoin blood concentrations remained high, suggesting a pharmacokinetic interaction. Previously, the patient had never had neurologic symptoms associated with increased phenytoin concentrations. This also indicates a likely pharmacodynamic interaction between phenytoin and the calcium-channel blocker. Both phenytoin and isradipine have been shown to bind to calcium channels and to inhibit calcium entry into the cells. Binding of isradipine to the brain has been described in humans and animals, and calcium-channel blockers have been shown to cause potentiation of anticonvulsant action of phenytoin. CONCLUSIONS: Acute pharmacokinetic and pharmacodynamic interactions between phenytoin and isradipine were probably responsible for the lethargy, dysarthria, ataxia, and weakness our patient developed. The combination of phenytoin and calcium-channel blockers should be used with caution.
Aspirin Resistance
Authors: Howard Patricia A 
Published: June 2003

OBJECTIVE: To review the literature addressing the problem of aspirin resistance in patients with vascular disease. DATA SOURCES: A MEDLINE search (1966–February 2002) was performed. Key search terms included aspirin, resistance, resistant, failure, tolerance, and nonresponder. English-language studies were identified as well as pertinent references from these articles. DATA SYNTHESIS: Aspirin resistance has been reported in patients with cardiovascular, cerebrovascular, and peripheral vascular disease. Because of differences in the definition of resistance, variations in detection methods, and a lack of controlled trials, the true significance of the problem remains unknown. Multiple mechanisms for resistance have been proposed, including increased reactivity to platelet aggregating factors, genetic polymorphism, and alternate pathways for thromboxane synthesis. The studies to date have failed to demonstrate consistent relationships between aspirin's platelet-inhibiting effects, the impact of dosage escalation, and clinical outcomes. CONCLUSIONS: For many patients, aspirin is an effective antithrombotic agent. However, patients taking aspirin may demonstrate highly variable responses to in vitro tests for platelet aggregation and may experience breakthrough thromboembolic events. Although this phenomenon has been termed aspirin resistance, the lack of a uniform definition or agreement on diagnostic criteria precludes definitive recommendations at this time. In addition, strategies are needed to identify patients at risk for aspirin resistance who might benefit from alternative or combined antiplatelet therapy.
Current and Emerging Therapy for Primary Pulmonary Hypertension
Authors: Pass Steven E , Dusing Michelle L 
Published: June 2003

OBJECTIVE: To review the epidemiology, pathophysiology, clinical symptoms, and diagnostic workup of primary pulmonary hypertension (PPH) and to discuss the available data on the current and emerging therapies being used to treat this disorder. DATA SOURCES: Primary and review articles were identified with a MEDLINE search (1966–December 2001) and through secondary sources. STUDY SELECTION AND DATA EXTRACTION: All articles identified from the data sources were evaluated and all information deemed relevant was included in this review. DATA SYNTHESIS: In the absence of a definable cause, PPH is a disorder classified by a progressive increase in pulmonary vascular resistance and mean pulmonary artery pressure. A relatively rare condition, PPH has an annual incidence of 1–2 cases per million people, slightly higher in women than men. The prognosis is poor, with a mean survival time of 2.8 years after diagnosis if untreated. Vasoconstriction, vascular remodeling, and thrombosis are hallmarks of the disease process. Anticoagulation and vasodilators are the most commonly employed treatment options, showing benefits in clinical outcomes, hemodynamic parameters, and mortality. Several new vasodilators are being evaluated for the treatment of PPH. Bosentan was recently approved as the first oral agent for the treatment of PPH. Iloprost, treprostinil, and beraprost are investigational agents in Phase III studies. CONCLUSIONS: Until additional studies and experience with these agents become available, calcium-channel blockers (CCBs) remain the first option for therapy. For patients not responding to CCBs, therapeutic options will now include epoprostenol and bosentan. Since there are no comparison trials between these 2 agents, therapeutic decisions should be based on patient-specific concerns. Clinical data and experience support the use of epoprostenol; however, in patients at risk or considered unsuitable candidates, bosentan may become a preferred option. Additional studies are warranted to address the potential therapeutic benefits of combination therapy and long-term benefits of agents to treat PPH.
Sialorrhea — Therapeutic Drug Options
Authors: Tscheng Dorothy Z 
Published: June 2003

OBJECTIVE: To review the efficacy and safety of various drug treatments for sialorrhea. Pharmacotherapy for drug-induced sialorrhea is not addressed. DATA SOURCES: Clinical studies were identified using PubMed (1966–October 2001). Key search terms included sialorrhea and drug therapy. DATA SYNTHESIS: Sialorrhea is a social and physical detriment to patients. Drug treatment, although not necessarily the treatment of choice for all patients, can offer some symptom relief. CONCLUSIONS: Literature has documented that benztropine, glycopyrrolate, and scopolamine can reduce the incidence of sialorrhea. Although the literature evaluating the therapeutic options has limitations (e.g., small sample size, inconsistent outcome measurements), glycopyrrolate may have an advantage over the other agents due to fewer adverse effects.
Patient-Specific Factors Predictive of Warfarin Dosage Requirements
Authors: Absher Randall K , Moore M Elisabeth , Parker Mary H 
Published: June 2003

OBJECTIVE: To identify patient-specific factors predictive of maintenance warfarin dosage requirements >5 mg/d. METHODS: One hundred forty-six adults taking warfarin were identified from a community hospital and an outpatient anticoagulation clinic. Patient demographics and data on warfarin doses, laboratory results, and medication use were obtained by abstracting patient records. Estimates of vitamin K intake were obtained using a questionnaire and structured interview. Multiple logistic regression was used to identify patient characteristics independently predictive of warfarin maintenance requirements >5 mg/d. An assessment tool for estimating an individual patient's likelihood of requiring warfarin maintenance doses >5 mg/d was derived from the logistic regression model and was assessed in both the study cohort and a separate historical validation cohort of 125 patients. RESULTS: Five factors were independently associated with warfarin requirements >5 mg/d: age <55 years, male gender, African American ethnicity, vitamin K intake >400 μg/d, and body weight ≥91 kg. The assessment tool derived from these factors correctly classified semiquantitative warfarin requirements as non—high-dose in 84 of 93 study cohort patients and 71 of 78 validation cohort patients, and correctly classified requirements as high-dose in 10 of 13 study cohort patients and 11 of 15 validation cohort patients. CONCLUSIONS: African American ethnicity is a newly identified predictor of warfarin requirements >5 mg/d and is independent of dietary vitamin K intake. An assessment tool incorporating this and other predictors can estimate a patient's likelihood of requiring such dosages.
Eplerenone — A Novel Selective Aldosterone Blocker
Authors: Zillich Alan J , Carter Barry L 
Published: June 2003

OBJECTIVE: To review the pharmacology, pharmacokinetics, clinical efficacy, and safety of eplerenone, a new selective aldosterone blocker. DATA SOURCES: Primary literature and review articles were obtained via MEDLINE search (1966–April 2002). Additional studies and abstracts were identified from the bibliographies of reviewed literature. STUDY SELECTION AND DATA EXTRACTION: Studies and review articles related to eplerenone, aldosterone, aldosterone antagonist, and spironolactone were reviewed. Data pertinent to this article were included. DATA SYNTHESIS: Eplerenone is a selective aldosterone blocker. Recent data have demonstrated the deleterious effects of aldosterone in several chronic disease states including hypertension and heart failure. Animal studies using eplerenone have shown a positive role for aldosterone antagonism in the treatment of hypertension, heart failure, myocardial infarction, renal disease, and atherosclerosis. In humans, eplerenone appears to be effective for the treatment of hypertension. An ongoing study will examine the effect of eplerenone for heart failure. To date, the incidence of adverse effects with eplerenone has been slightly lower than with spironolactone. CONCLUSIONS: Eplerenone appears to be a promising drug in a new class of agents called selective aldosterone blockers. The drug may be approved for treatment of hypertension in 2002. Additional studies are ongoing that may provide information on other clinical uses for this medication.
Rhabdomyolysis Associated with Gemfibrozil—Colchicine Therapy
Authors: Atmaca Hulusi , Sayarlıoğlu Hayriye , Külah Eyüp , Demircan Nejat , Akpolat Tekin 
Published: June 2003

OBJECTIVE: To report a case of rhabdomyolysis possibly due to combination therapy with colchicine and gemfibrozil. CASE SUMMARY: A 40-year-old man with amyloidosis and hepatitis B virus—related chronic liver disease was admitted to the university hospital because of fatigue, lack of appetite, dark brownish urine, and myalgia for 2 weeks. The patient was receiving colchicine and gemfibrozil. Elevations of serum creatine kinase, lactate dehydrogenase, and aspartate aminotransferase concentrations with myalgia were compatible with the diagnosis of rhabdomyolysis. DISCUSSION: To our knowledge, myopathy and rhabdomyolysis due to a combination of colchicine and gemfibrozil therapy have not been previously reported. Preexisting mild renal failure, hepatitis B—related chronic liver disease, and amyloidosis may be contributing risk factors for the development of rhabdomyolysis in this patient. An objective causality assessment revealed that the adverse drug event was possible. CONCLUSIONS: Patients receiving combination therapy with colchicine and gemfibrozil, especially those with renal and hepatic dysfunction, should be monitored for rhabdomyolysis, and concomitant colchicine and gemfibrozil therapy should be considered in the differential diagnosis of rhabdomyolysis.
Fluvastatin-Induced Rhabdomyolysis
Authors: Modi Jitu R , Cratty Michael S 
Published: June 2003

OBJECTIVE: To demonstrate a case of rhabdomyolysis with acute renal failure in a patient receiving fluvastatin and to present evidence that this was an adverse drug reaction to fluvastatin. CASE SUMMARY: A 51-year-old white man with a past medical history significant for hyperlipidemia treated with fluvastatin presented with malaise, myalgias, nausea, and lumbar back pain. The patient had azotemia with elevated creatine kinase (CK), lactate dehydrogenase, and transaminases. He developed hematuria and proteinuria. Laboratory results demonstrated a normal antinuclear antibody, rheumatoid factor, angiotensin-converting enzyme, antineutrophil cytoplasmic antibody, and thyroid-stimulating hormone. Cytomegalovirus and Epstein-Barr virus titers were negative for recent infection. There were no signs of systemic infection; the white blood cell count was normal and blood and urine cultures were negative. Renal ultrasound showed hyperechoic renal cortices with no obstruction. The discontinuation of fluvastatin and hemodialysis led to a rapid decrease in CK and improvement in symptoms. DISCUSSION: Hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have the potential to cause rhabdomyolysis. However, fluvastatin is rarely associated with rhabdomyolysis when compared to other statins. Differences in biochemical and pharmacokinetic properties between fluvastatin and other HMG-CoA reductase inhibitors may be important in the development of rhabdomyolysis. CONCLUSIONS: Fluvastatin was the precipitating factor causing rhabdomyolysis in this case report. This patient had no other findings to suggest infection or other disorder inducing rhabdomyolysis. An objective causality assessment revealed that the adverse drug reaction was probable as determined by the Naranjo probability scale. Fluvastatin has the potential to cause serious adverse effects. Therefore, a heightened awareness by the patient and physician for potential signs of myopathy is recommended.
Single-Patient Drug Trial Methodology for Allergic Rhinitis
Authors: Reitberg Donald P , Rio Eve Del , Weiss Sidney L , Rebell Gerbert , Zaias Nardo 
Published: June 2003

BACKGROUND: Historically, single-patient trials (SPTs) have been specifically designed for each patient, requiring significant time and effort for execution. There has been no previous attempt to standardize an SPT for routine commercial availability. OBJECTIVE: To validate the use of an SPT method to discriminate effectiveness and adverse events while comparing drugs/doses in patients with allergic rhinitis. DESIGN: Double-blind, randomized, 4 paired—period, multiple-crossover SPT. SETTING: Academic and commercial investigative sites. PATIENTS: Thirty-six patients with allergic rhinitis were evaluated for the most appropriate treatment; 6 of these participated in 2 different SPTs. INTERVENTIONS: Treatment of symptoms of allergic rhinitis by comparing either loratadine with chlorpheniramine maleate or loratadine with placebo in a series of SPTs. MEASUREMENTS: Effectiveness endpoints were selected from a modern, Food and Drug Administration (FDA)-approved new drug application. Expected adverse events were directly solicited; unsolicited events were also recorded. Total signs and symptoms cumulatively included sneezing, runny nose, itchy nose, teary eyes, and itchy eyes. Quality of life was measured by the most bothersome symptom and the patient's global evaluation. RESULTS: Of 42 initiated SPTs, 40 (95%) provided complete data and 1 (2%) provided partial data, resulting in 41 (98%) evaluable tests. Thirty-one evaluable SPTs compared loratadine 10 mg/d with chlorpheniramine maleate 12 mg twice daily, and 10 SPTs compared loratadine 10 mg/d with placebo. Four of 31 SPTs (13%) showed significant superiority for loratadine over chlorpheniramine maleate and 5 of 31 (16%) for chlorpheniramine maleate over loratadine. Twenty-two of 31 (71%) showed parity performance between loratadine and chlorpheniramine maleate. Loratadine was significantly superior to placebo in 3 of 10 trials (30%), consistent with rates found in 3 pivotal group trials used for FDA approval (24%, 17%, and 0%). Sleepiness could be discriminated for loratadine versus placebo and for chlorpheniramine maleate versus loratadine. CONCLUSIONS: The allergic rhinitis SPT proved to be acceptable to patients, feasible to administer, and reproducible. It can statistically discriminate effectiveness and adverse events, serving as a useful, prognostic tool in community practice.
Management of Botulism
Authors: Robinson Renee F , Nahata Milap C 
Published: June 2003

OBJECTIVE To provide a concise review of the presentation and treatment of botulism. DATA SOURCES Searches of MEDLINE (1966–November 2001), tertiary references, and public and government Internet sites were conducted. STUDY SELECTION All articles and additional references from those articles were thoroughly evaluated. DATA SYNTHESIS Clostridium botulinum toxin blocks acetylcholine release in a dose-dependent fashion, resulting in acute symmetric diplopia, dysarthria, dysphonia, dysphagia, and possible neurologic sequelae despite the route of exposure (i.e., food-borne, wound, intestinal, inhalation). Disease secondary to genetically engineered C. botulinum may differ from that of inadvertent exposure. Present treatment is primarily supportive care, respiratory support, rapid decontamination, and antitoxin administration (i.e., trivalent, pentavalent, heptavalent antitoxin). Early initiation of antitoxin limits the extent of paralysis, but does not reverse it. CONCLUSIONS Supportive care and the use of antitoxin have been effective in the treatment of botulism from food-borne, intestinal, and wound exposure. However, the effectiveness of antitoxin in the treatment of inhaled C. botulinum has not been proven.
Fatal Aspiration Pneumonia during Transition from Donepezil to Rivastigmine
Authors: Taylor Amy M , Hoehns James D , Anderson Doris M , Tobert Daren G 
Published: June 2003

OBJECTIVE: To report a case of fatal aspiration pneumonia in a patient shortly after initiation of rivastigmine and discontinuation of donepezil, with no washout period between therapies. CASE SUMMARY: An 83-year-old white man presented to the emergency department in respiratory distress (O2 saturation 70%; RR 44 breaths/min) secondary to aspiration. He had started rivastigmine 1.5 mg twice daily that same day. The patient had been previously treated with donepezil 10 mg/d, and there was no washout period. He was intubated due to worsening respiratory status and was transferred to the cardiac care unit. He then became hypotensive and required dopamine and fluid support. Brief bronchoscopy revealed food particles in the lower airways and bile-stained secretions. Intubation was notable for the large amount of secretions. The patient died approximately 27 hours after presentation to the emergency department. Blood and sputum cultures were subsequently positive for Haemophilus influenzae. DISCUSSION: Cholinesterase (ChE) inhibitors approved for treatment of Alzheimer disease are associated with nausea and vomiting in a sizable percentage of patients, ranging from 5% to 31% in clinical trials. Most of these adverse events occur during the initiation/titration phase of therapy. An additive risk of adverse events may be expected with coadministration of ChE inhibitors or cholinergic agents or, potentially, with an inadequate washout period between such agents. Review of MEDLINE (1966–July 2002) and International Pharmaceutical Abstracts (1970–July 2002) failed to identify any previous reports of aspiration with rivastigmine or donepezil. CONCLUSIONS: A washout period should be considered when switching between ChE inhibitors to minimize the risk of vomiting and aspiration.
Effect of Number of Medications on Cardiovascular Therapy Adherence
Authors: Shalansky Stephen J , Levy Adrian R 
Published: June 2003

OBJECTIVE: Increasing regimen complexity is generally assumed to result in lower medication adherence, but there is conflicting evidence. This study determined the relationship between the number of medications dispensed and adherence with chronic cardiovascular regimens. METHODS: A survey was administered to 367 patients who had taken an angiotensin-converting enzyme inhibitor or lipid-lowering medication for at least 3 consecutive months. Information was collected on nonprescription drug use, demographics, adverse effects, and use of adherence aids. Prescription drug use data over the previous 12 months were obtained for each subject from the British Columbia prescription claims database. Adherence for each prescription medication was calculated based on prescription fill dates and number of days supplied. Univariate and multivariate analyses were used to identify predictors of nonadherence (>80%) with cardiovascular medications. RESULTS: Forty-five subjects (12%) were categorized as nonadherent. Nonadherent subjects took fewer regularly scheduled prescription medications per day (4.1 ± 2.7 vs. 5.9 ± 3.4; p = 0.001), fewer pills per day (5.3 ± 3.6 vs. 9.2 ± 7.1; p < 0.001), and had fewer administration × per day (1.8 ± 0.7 vs. 2.4 ± 0.9; p = 0.001). A multivariate logistic regression model adjusting for age, gender, reported adverse effects, reported nonprescription drug use, and use of adherence aids identified fewer regularly scheduled prescription drugs as an independent predictor of nonadherence with chronic cardiovascular medications (OR = 0.85 per medication, 95% CI 0.74 to 0.94; p = 0.01). CONCLUSIONS: Contrary to popular belief, taking fewer medications was associated with lower adherence with chronic cardiovascular regimens.
Clonidine-Induced Hypertension in a Patient with a Spinal Lesion
Authors: Backo Angel L , Clause Steven L , Triller Darren M , Gibbs Karen A 
Published: June 2003

OBJECTIVE: To report a case of possible clonidine-induced hypertension (by Naranjo score) in a patient with a C4 spinal lesion. BACKGROUND: Clonidine is a medication long used to treat hypertension, and it is still used in the treatment of refractory hypertension. Although effective, clonidine use is hindered by adverse effects and its dual mechanism of action. CASE SUMMARY: A 39-year-old white, quadriplegic man with poorly controlled pain displayed many characteristics consistent with autonomic dysfunction (e.g., C4 spinal lesion, orthostatic hypotension, hypertension). The patient was routinely receiving transdermal clonidine and also received transdermal nitroglycerin paste as needed for control of acute hypertensive episodes. On the recommendation of the home healthcare pharmacists, clonidine was discontinued. Since that time, the patient's blood pressure and the use of emergent antihypertensive treatment have decreased significantly (maximum systolic and diastolic BP by ∼50 and 25 mm Hg, respectively). CONCLUSIONS: Many of the characteristics of autonomic dysfunction, such as refractory hypertension, can seem selective for the use of clonidine and, because of its reliance on central α2-activity for its hypotensive effects, clonidine may induce hypertension in patients with autonomic dysfunction. Clonidine should be used with great caution when autonomic dysfunction is suspected.