bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neuropharmacology of St. John's Wort (Hypericum)
Authors: Bennett Dean A , Phun Lisa , Polk Jeffrey F , Voglino Susan A , Zlotnik Vladislau , Raffa Robert B 
Published: March 2004

OBJECTIVE: To review preclinical information related to possible antidepressant mechanism(s) of action of St. John's wort in order to address the issue of whether its purported clinical effectiveness has a rational pharmacologic basis. DATA SOURCES: Primary and review articles were identified by a MEDLINE search (1966–January 1998) and through secondary sources. Many of the original German articles had English abstracts, but where necessary, German articles were translated into English. The results of a new screen of hypericin activity at receptor and uptake sites are summarized. STUDY SELECTION AND DATA EXTRACTION: All of the articles identified from the data sources were evaluated and all information deemed relevant was included in this review. DATA SYNTHESIS: The neuropharmacology of St. John's wort has been examined in only a few studies. A mechanism similar to that of the synthetic antidepressants, such as the selective serotonin-reuptake inhibitors or monoamine oxidase (MAO) inhibitors, might play a role, but other mechanisms are possible. CONCLUSIONS: Hypericum extracts have only weak activity in assays related to mechanisms of the synthetic antidepressants, that is, inhibition of MAO, catechol O-methyltransferase, or serotonin reuptake. It has been postulated that the clinical efficacy of St. John's wort could be attributable to the combined contribution of several mechanisms, each one too weak by itself to account for the overall effect. The recent demonstration of a significant affinity of hypericin for σ receptors presents new possibilities for consideration.
Paradoxical Response to Valproic Acid in a Patient with a Hypothalamic Hamartoma
Authors: Stecker Mark M , Kita Mariko 
Published: March 2004

OBJECTIVE: To report a patient who developed the paradoxical effect of increasing electrical seizure activity and confusion with initiation of valproic acid therapy. CASE SUMMARY: A 25-year-old African-American woman with a hypothalamic hamartoma had an electroencephalogram (EEG) that demonstrated frequent bursts of generalized spike and wave activity. The prevalence of spike and wave activity increased dramatically and the patient became increasingly somnolent as valproic acid was added to carbamazepine and phenobarbital therapy. Her EEG and mental status changes resolved when the valproic acid was discontinued. There was a strong positive correlation between the prevalence of spike and wave activity and the valproic acid concentration, but not between spike and wave activity and the concentrations of carbamazepine or phenobarbital. DISCUSSION: Although this is a complex case, it is clear that the addition of valproic acid produced an increase in spike and wave activity. Possible mechanisms and pathophysiologic significance of this paradoxical effect are discussed in light of the differences between this epileptic syndrome and the primary generalized epilepsies.
Topotecan: A New Topoisomerase I Inhibiting Antineoplastic Agent
Authors: Cersosimo Robert J 
Published: March 2004

OBJECTIVE: To review the pharmacologic, pharmacokinetic, therapeutic, and safety aspects of topotecan, a new antineoplastic agent, and to assess its role in the treatment of cancer. DATA SOURCES: MEDLINE database English language only, January 1990–March 1998; SmithKline Beecham Pharmaceuticals; published articles, books, and abstracts. STUDY SELECTION: Studies in humans with cancer, clinical case reports, open clinical trials, and controlled clinical studies. Efficacy studies were limited primarily to trials with at least 20 evaluable patients. DATA EXTRACTION: Relevant data were extracted only from published reports. Data were obtained from studies in both articles and abstracts. Only articles written in English were reviewed. DATA SYNTHESIS: Topotecan is an effective second- or third-line therapy for patients with advanced ovarian cancer and is comparable to ifosfamide, liposomal doxorubicin, and paclitaxel. Activity in combination with other agents and as a first-line agent is yet to be determined. Limited data indicate activity in small-cell lung cancer, cancers of the breast and uterus, and in nonlymphocytic leukemia. The dose-limiting toxicity is myelosuppression. CONCLUSIONS: Topotecan is an effective second-line agent for patients with unresponsive or relapsed cancer of the ovary. It appears to be similar to other active agents in patients with this disease status. Its ultimate role in ovarian cancer and other neoplasms awaits additional evaluation in combination with other agents and as first-line therapy.
Tiagabine: A Novel Antiepileptic Drug
Authors: Luer Mark S , Rhoney Denise H 
Published: March 2004

OBJECTIVE: To provide a comprehensive review of tiagabine, including its pharmacology, toxicology, pharmacokinetics, drug interactions, efficacy, adverse effects, and dosing recommendations. DATA SOURCES: A computerized search of the MEDLINE database from 1966 to December 1997 was used to identify publications related to tiagabine and nipecotic acid derivatives. Included in this review was information gathered from scientific meetings. Manufacturer's information was used when there was no primary literature. DATA SYNTHESIS: Tiagabine amplifies γ-aminobutyric acid (GABA) neurotransmission, the predominant inhibitory neurotransmitter in the brain. Its mechanism of action is selective and has shown promise as an antiepileptic drug (AED) in patients with seizures refractory to other pharmaceutical products. Tiagabine exhibits dose-independent absorption, 90–95% bioavailability, high protein binding (96%), metabolism via hepatic cytochrome P450 enzymes (CYP3A subfamily), and displays first-order elimination pharmacokinetics. The mean plasma half-life is 5–8 hours. Concomitant medications that induce hepatic metabolism enhance tiagabine elimination; metabolism is reduced in patients with hepatic dysfunction. Adverse events of tiagabine typically involve the central nervous system, have been mild to moderate in intensity, and also have been transient in nature. CONCLUSIONS: Tiagabine has demonstrated a good safety profile and, while it has not been demonstrated to be superior to other second-line AEDs for partial seizures, its safety and select mechanism of action warrant its further evaluation in the clinical setting. Tiagabine should be a good alternative add-on agent for patients with unsatisfactory seizure control or intolerable adverse effects of traditional therapies; thus, this agent should be made available to these patients.
Reversible Nonthrombocytopenic Palpable Purpura Associated with Metoclopramide
Authors: Goad Jeffery A 
Published: March 2004

OBJECTIVE: To report a case of reversible nonthrombocytopenic palpable purpura associated with metoclopramide. CASE SUMMARY: A 72-year-old white man was admitted for worsening palpable purpura over a two-day period. Two days prior to admission, metoclopramide 10 mg orally three times per day was started for a gastrointestinal condition. Upon admission, all drugs were continued except metoclopramide. Over the next two days, the purpura began to resolve. Platelet count was within normal limits on admission and the patient developed no serious consequences because of the purpura. DISCUSSION: According to the literature, reversible nonthrombocytopenic palpable purpura has not been previously reported with metoclopramide. A search of MEDLINE (1966 to November 1998) and International Pharmaceutical Abstracts (1970 to November 1998) did not reveal a similar case. Although a rechallenge was not tried, this case appears to demonstrate a temporal relationship between the initiation and discontinuation of metoclopramide and the onset and resolution of symptoms. Similar cases of this reaction have been reported with procainamide, which is structurally similar to metoclopramide. CONCLUSIONS: Metoclopramide may cause reversible nonthrombocytopenic vascular-type palpable purpura. Discontinuation of the drug appeared to be responsible for the resolution of symptoms.
Nelfinavir Mesylate: A Protease Inhibitor
Authors: Pai Vinita B , Nahata Milap C 
Published: March 2004

OBJECTIVE: To review the clinical pharmacology, pharmacokinetics, efficacy, adverse effects, drug interactions, and dosage guidelines of nelfinavir mesylate. DATA SOURCE: A MEDLINE search restricted to English-language literature from January 1966 to February 1998 and an extensive review of journals was conducted to prepare this article. MeSH headings included protease inhibitors, nelfinavir mesylate, and AG1343. Abstracts presented at meetings and data submitted to the Food and Drug Administration (FDA) were also reviewed. DATA EXTRACTION: The data on efficacy, pharmacokinetics, adverse effects, and drug interactions were obtained from in vitro studies, as well as open-label and controlled trials. DATA SYNTHESIS: Nelfinavir inhibits HIV protease enzyme resulting in formation of immature and noninfectious virions. In combination with nucleoside reverse transcriptase inhibitors, nelfinavir is effective in reducing the viral load below the quantifiable limit (<500 copies/mL) and increasing the mean CD4+ cell count. This antiviral effect is sustained at least over 21 months. The bioavailability of nelfinavir ranges from 20% to 80%, and it increases when nelfinavir is administered with food. Following multiple dosing of nelfinavir 750 mg three times daily, maximum concentration at steady-state was 3–4 μg/mL and minimum concentration was 1–3 μg/mL. The elimination half-life for nelfinavir ranges from three to five hours. Nelfinavir is primarily metabolized in the liver by the cytochrome P450 isoenzymes and excreted in the feces. Current dosing recommendations are 750 mg three times daily for adults and adolescents and 20–30 mg/kg/dose three times daily for children aged 2–13 years. Studies of twice-daily regimens in adults are being conducted and are promising. Use of nelfinavir as salvage therapy is also being studied. Some of the commonly reported adverse events of nelfinavir are diarrhea, nausea, vomiting, and abdominal pain. CONCLUSIONS: Despite the limited published data, the FDA has approved nelfinavir in combination therapy for the treatment of HIV infection. The choice of antiretroviral (ARV) regimens should be made based on the risk of disease progression as indicated by HIV RNA concentrations and CD4+ cell counts, patients' previous ARV experiences and responses, concomitant drug therapy, compliance history, underlying disease states, and adverse reaction history.
Ibutilide: An Antiarrhythmic Agent for the Treatment of Atrial Fibrillation or Flutter
Authors: Howard Patricia A 
Published: March 2004

OBJECTIVE: To discuss the clinical pharmacology of the antiarrhythmic drug ibutilide in patients with atrial fibrillation (AF) or atrial flutter (AFl). DATA SOURCES: A MEDLINE search (January 1983–December 1997) was used to identify pertinent English-language articles on ibutilide. Key search terms included ibutilide, AF, AFl, cardioversion, and sinus rhythm. The MEDLINE search was supplemented by references included in the bibliographies of comprehensive review articles and studies. STUDY SELECTION: Studies and review articles describing the chemistry, pharmacology, and pharmacokinetics of ibutilide were selected. All abstracts and published clinical trials evaluating the efficacy and safety were reviewed. DATA EXTRACTION: Pertinent information on the pharmacology and mechanism of action of ibutilide was summarized. Data were extracted from the clinical trials describing trial design, patient population, interventions, methods of evaluation, outcomes, and statistical significance. DATA SYNTHESIS: Ibutilide is a Vaughan–Williams class III antiarrhythmic agent approved for intravenous use for the rapid termination of recent-onset AF or AFl. The drug is extensively metabolized by the liver, has a volume of distribution of 11–15 L/kg, is 40% protein bound, and has an elimination half-life of 6 hours (range 2–12). Data from two placebo-controlled trials demonstrated the efficacy of ibutilide for converting AF or AFl of short duration (≤90 d) to normal sinus rhythm. A third placebo-controlled trial demonstrated efficacy in patients who developed AF or AFl following cardiac surgery. Comparative trials with procainamide and sotalol have shown at least similar and perhaps superior efficacy with ibutilide. There are no comparative trials with other antiarrhythmic drugs or with direct current cardioversion (DCC). In 586 clinical trial patients receiving ibutilide, the most significant adverse effect was the development of torsade de pointes in 25 patients (4.3%) including 10 cases (1.7%) in which the rhythm was sustained. All cases of torsade de pointes were terminated electrically and none resulted in death or severe morbidity. No prospective cost-effectiveness studies are available; however, results from two decision models suggest that ibutilide may have advantages over other drugs and first-line electrical cardioversion. CONCLUSIONS: Ibutilide appears to be an effective alternative method for rapid conversion of recent-onset AF or AFl. The drug may be particularly useful in patients who have undergone recent cardiac surgery or those who are not ideal candidates for DCC. Although studies suggest that the risk of proarrhythmia and in particular torsade de pointes is relatively low, caution is advised until additional experience is gained in clinical practice.
Torsade De Pointes Induced by Cisapride/Clarithromycin Interaction
Authors: Piquette Rosemary K 
Published: March 2004

OBJECTIVE: To highlight a case of torsade de pointes ventricular arrhythmia induced by the concomitant use of cisapride and clarithromycin. CASE SUMMARY: A 77-year-old white woman was admitted to the hospital with a diagnosis of pneumonia and exacerbation of congestive heart failure. In addition to her usual medications, which included cisapride, the patient was prescribed trimethoprim/sulfamethoxazole and clarithromycin for pneumonia. Within 48 hours, the patient had documented episodes of symptomatic torsade de pointes arrhythmia, which eventually responded to therapy. Both cisapride and clarithromycin were discontinued, and the patient did not have any recurring episodes during a 32-month follow-up. DISCUSSION: Cisapride has been implicated in causing adverse cardiac events, including torsade de pointes arrhythmia. In most cases, the patients had preexisting risk factors for torsade de pointes and/or were receiving other medications known to inhibit the hepatic CYP3A4 enzyme system and the metabolism of cisapride. There is evidence that clarithromycin, a relatively new macrolide antibiotic, also inhibits the isoenzyme CYP3A4. The resulting accumulation of cisapride caused by concomitant clarithromycin therapy was believed to have been the cause of the torsade de pointes arrhythmia in this patient. CONCLUSIONS: Concomitant use of cisapride and clarithromycin may cause torsade de pointes arrhythmia.
Pill-Induced Esophagitis Caused by Oral Rifampin
Authors: Smith Steve J , Lee Audrey J , Maddix Daniel S , Chow Albert W 
Published: March 2004

OBJECTIVE: To report a case of pill-induced esophagitis caused by oral rifampin. DATA SOURCES: English-language references identified via a MEDLINE search from January 1966 to May 1998 and a bibliographic review of pertinent articles. DATA SYNTHESIS: A large number of oral medications have been reported to cause pill-induced esophagitis. This case represents the second report attributed to rifampin. A 70-year-old white man receiving vancomycin, gentamicin, and oral rifampin for treatment of Staphylococcus epidermidis prosthetic valve endocarditis reported dysphagia immediately after swallowing a rifampin capsule on the fourth day of therapy. The following day, fiberoptic laryngoscopy and esophagoscopy demonstrated a red capsule partially embedded in the neopharynx. A day later, upper esophageal obstruction consistent with edema related to pill-induced esophagitis was identified by barium swallow. Following the procedure, the patient was placed on total parenteral nutrition and took nothing by mouth. Sixteen days after first reporting dysphagia, he was placed on a full liquid diet. Several factors may have increased the patient's risk for pill-induced esophagitis, including age, bedridden state, gastroesophageal reflux disease, simultaneous administration of several medications, and neopharyngeal stricture. CONCLUSIONS: Oral rifampin may cause esophagitis. Healthcare providers should be alert to the possibility of pill-induced esophagitis in susceptible patients. Patients with predisposing factors for the development of pill-induced esophagitis should be educated about proper swallowing of oral medications.
INR Elevation Associated with Diarrhea in a Patient Receiving Warfarin
Authors: Smith Joseph K , Aljazairi Abdulrazaq , Fuller Stephen H 
Published: March 2004

OBJECTIVE: To report a case of international normalized ratio (INR) prolongation in a patient receiving warfarin who experienced several episodes of diarrhea. CASE SUMMARY: A 56-year-old white woman, previously controlled on warfarin therapy (INR 2.5–3.5) after aortic valve replacement, experienced six episodes of INR elevation, each associated with an acute bout of diarrhea lasting from one to four days. The patient had not received additional warfarin or new medications (including nonprescription medications and herbal remedies) prior to the episodes. The patient had no obvious signs of bleeding (except bruising on 1 episode) or signs of infection determined through physician evaluation of the patient and her stools. In addition, she had no diagnosis of liver disease or acute or chronic malabsorption. The patient did report that her dietary intake decreased to 25–50% of normal during these episodes of diarrhea, which may result in decreased vitamin K ingestion. DISCUSSION: This is one of the first case reports documenting a trend of INR elevation specifically with episodes of diarrhea. Since most of the common reasons for acute INR elevation have been eliminated, diarrhea with decreased oral intake are the most probable causes for these observed changes in the INR. Several reports suggest that acute diarrhea results in malabsorption of vitamin K, which can predispose patients taking warfarin to INR elevations, but in many of these reports patients had other risk factors for INR elevation. Although the effect of diarrhea on vitamin K absorption and the INR is difficult to quantify, the INR elevation reported here seemed to be directly associated with the duration of each diarrheal episode. CONCLUSIONS: Diarrhea episodes in patients receiving warfarin can result in prolongation of the INR and possible bleeding. Patients who experience diarrhea or decreased oral intake resulting in elevated INRs should have their INRs evaluated more frequently and their warfarin doses adjusted appropriately.
Evaluation of Amlodipine Dosing for Conversion of Nifedipine Extended-Release to Amlodipine in the Treatment of Hypertension
Authors: Yamreudeewong Weeranuj , Halverson Valerie J , Lower Dennis L , Kilpatrick David M , Enlow Ann M , Montopoli George 
Published: March 2004

OBJECTIVE: To evaluate the appropriate dosing of amlodipine when converting patients from nifedipine extended-release (nifedipine ER) to amlodipine in the treatment of hypertension. METHODS: Patients of the Outpatient Clinic of Cheyenne Veterans Affairs Medical Center, Wyoming, receiving nifedipine ER for the management of hypertension (systolic BP or SBP >140 mm Hg and diastolic BP or DBP >90 mm Hg), participated in this study. Nifedipine ER was changed to amlodipine on entry into this study. An inclusion criterion was the BP had to be under control (SBP <140 mm Hg and DBP <90 mm Hg) before the switch. The BP in each study patient was monitored once weekly (once every 2 wk in some patients) for a total of six clinic visits or until BP was under control. Dosing titration of amlodipine was required in 16 of 27 patients after the switch. To assess the adequacy of the conversion, the statistical significance of the difference of the mean BP values before and at the end of the monitoring period was estimated by using the t-test for paired data. RESULTS: Twenty-seven male patients completed this study. BP in all study patients was adequately controlled after nifedipine ER was switched to amlodipine. The SBP and DBP values before and after the switch were similar (SBP: 124 ± 12 vs. 126 ± 9 mm Hg, CI of the mean difference −6.10 to 1.80; DBP: 76 ± 8 vs. 76 ± 7 mm Hg, CI of the mean difference −2.45 to 3.63). Initial amlodipine dose of 5 or 10 mg once daily was used in our study. No serious adverse effects were observed in any of the study patients after the drug switch. CONCLUSIONS: This study indicates the amlodipine dosage of 5 or 10 mg once daily can be used when nifedipine ER is converted to amlodipine in the treatment of hypertension. Dosage titration of amlodipine may be required to obtain adequate control of BP.
Hepatotoxicity Possibly Caused by Amphotericin B
Authors: Gill John , Sprenger Henry R , Ralph Edward D , Sharpe Michael D 
Published: March 2004

OBJECTIVE: To report a case of possible amphotericin B–induced hepatotoxicity in a patient with pulmonary blastomycosis. SUMMARY: A 26-year-old white man with life-threatening pulmonary blastomycosis developed elevation of his liver enzymes after the addition of amphotericin B to his initial itraconazole therapy. The hepatotoxicity resolved rapidly with discontinuation of the amphotericin B, and the blastomycosis was successfully treated with itraconazole alone. DISCUSSION: This case illustrates an unusual occurrence of hepatotoxicity associated with a short course of amphotericin B. Liver biopsy was compatible with drug-induced changes and showed no evidence of blastomycosis. Discontinuation of amphotericin B with no other therapeutic changes resulted in a rapid resolution of hepatotoxicity. A possible adverse drug interaction with itraconazole and amphotericin B is postulated based on the mechanism of action of each drug. CONCLUSIONS: Amphotericin B therapy can be associated with many adverse effects, but reports of hepatotoxicity are rare. Closer monitoring of liver enzymes in patients receiving amphotericin B, especially in combination with potentially hepatotoxic agents, including azole antifungal drugs, would be prudent.