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陕西医学杂志 2007年第5期36卷 599-601页

作者：顾琴李岩汤继宏胡斯明王浙东苏州大学附属儿童医院神经科苏州215003

目的:观察小剂量托吡酯添加治疗儿童Tourette综合征的疗效,探索合理的有效剂量及副作用。方法:将53例Tourette综合征患儿分为两组,一组为氟哌啶醇单药治疗组,另一组为氟哌啶醇添加托吡酯治疗组。两组治疗6个月进行观察。结果:32例Toure... 详细信息

目的:观察小剂量托吡酯添加治疗儿童Tourette综合征的疗效,探索合理的有效剂量及副作用。方法:将53例Tourette综合征患儿分为两组,一组为氟哌啶醇单药治疗组,另一组为氟哌啶醇添加托吡酯治疗组。两组治疗6个月进行观察。结果:32例Tourette综合征患儿用氟哌啶醇治疗的有效率为78.1%,但不良反应较多,出现嗜睡、肌张力增高等,很难改善。在减少氟哌啶醇剂量、添加托吡酯小剂量后,疗效明显增加(90.5%),耐受性强,副作用明显减少。结论:添加小剂量托吡酯辅佐氟哌啶醇治疗小儿Tourette综合征的方法可成为目前较好的选择。

关键词：行为障碍/诊断行为障碍/药物疗法酯类/治疗应用哌啶类/治疗应用

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The use of insulin secretagogues in the treatment of type 2 diabetes

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PRIMARY CARE 1999年第4期26卷 895-+页

作者： Luna, B Hughes, ATD Feinglos, MN Campbell Univ Dept Internal Med & Infect Dis Sch Pharm Buies Creek NC 27506 USA

Secretatogues are a class of agents that achieve their hypoglycemic effects through stimulating insulin release. They include the sulfonylureas, repaglinide, and the investigational agent glucagonlike peptide. The secretagogue agents have been studied extensively as monotherapy and in conjunction with other classes of oral agents, including alpha-glucosidase inhibitors, bijuanides, and thiazolidinediones, for the treatment of type 2 diabetes. This article reviews the pharmacodynamic and pharmacokinetic differences of the secretagogues, as well as the most recent clinical trials. Such information should be helpful when deciding which agent or agents will yield the best glycemic control for an individual patient.

关键词：阿卡波糖/治疗应用氨甲酸酯类/治疗应用色满类/治疗应用糖尿病 2型/药物疗法药物疗法联合胰高血糖素/治疗应用胰高血糖素样肽1 降血糖药/药理学降血糖药/治疗应用二甲双胍/治疗应用肽碎片/治疗应用哌啶类/治疗应用蛋白质前体/治疗应用危险因素磺酰脲化合物/药理学磺酰脲化合物/治疗应用噻唑类/治疗应用噻唑烷二酮类人类

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Relative contributions of a single-admission 12-lead electrocardiogram and early 24-hour continuous electrocardiographic monitoring for early risk stratification in patients with unstable coronary artery disease

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AMERICAN JOURNAL OF CARDIOLOGY 1999年第5期83卷 667-674页

作者： Holmvang, L Andersen, K Dellborg, M Clemmensen, P Wagner, G Grande, P Abrahamsson, P Univ Copenhagen Hosp Rigshosp DK-2100 Copenhagen Denmark Ostra Univ Hosp Gothenburg Sweden Duke Univ Med Ctr Durham NC USA

Patients with unstable coronary syndromes are a heterogeneous group with varying degrees of ischemia and prognosis. The present study compares the prognostic value of a standard electrocardiogram (ECG) obtained at admission to the hospital with the information from 24-hour continuous electrocardiographic monitoring obtained immediately after admission. The admission ECGs and 24 hours of vectorcardiographic (VCG) monitoring from 308 patients admitted with unstable coronary artery disease were analyzed centrally regarding standard electrocardiographic ST-T changes, ST-vector magnitude (ST-VM), and ST change vector magnitude episodes. End points were death, acute myocardial infarction, and refractory angina pectoris within a 30-day follow-up period. ST-VM episodes (greater than or equal to 50 mu V for greater than or equal to 1 minute) during VCG monitoring was the only independent predictor of death or acute myocardial infarction by multivariate analysis. ST-VM episodes during vectorcardiography was associated with a relative risk of 12.7 for having a cardiac event, hypertension was associated with a relative risk of 1.7, and ST depression on the admission ECG was associated with a relative risk of 5.7. Patients with ST depression at admission had an event rate (death or acute myocardial infarction) of 17% at 30-day follow-up. Patients without ST depression could further be risk stratified by 24 hours of VCG monitoring into a subgroup with ST-VM episodes at similar (8%) risk and a subgroup without ST-VM episodes at low (1%) risk (p = 0.00005). Continuous VCG monitoring provides important information for evaluating patients with unstable coronary artery disease, It is recommended that patients not initially estimated at high risk based on the admission ECG are referred for 24 hours of VCG monitoring for further risk stratification. (C)1999 by Excerpta Medica, Inc.

关键词：心绞痛/病因学心绞痛不稳定型/并发症心绞痛不稳定型/病理生理学抗凝药/投药和剂量抗凝药/治疗应用抗凝血酶类/投药和剂量抗凝血酶类/治疗应用冠心病/并发症冠心病/病理生理学心电描记术心电描记术便携式随访研究甘氨酸/投药和剂量甘氨酸/类似物和衍生物甘氨酸/治疗应用肝素/投药和剂量肝素/治疗应用高血压/并发症多元分析心肌梗死/病因学心肌梗死/预防和控制心肌缺血/病因学心肌缺血/预防和控制病人入院哌啶类/投药和剂量哌啶类/治疗应用预后复发危险性评估危险因素存活率向量心电描记术老年人女(雌)性人类男(雄)性

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TREATMENT OF VARIANT ANGINA-PECTORIS WITH PERHEXILENE MALEATE

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CHEST 1979年第2期75卷 152-156页

作者： RAABE, DS UNIV VERMONT COLL MED BURLINGTON VT 05401 USA

Patients (3) with variant angina pectoris resistant to therapy with nitrates and propranolol were treated with perhexiline maleate. Two patients had normal coronary arteries with documented coronary artery spasm, and the 3rd patient had a fixed coronary artery obstruction. In all 3 patients, attacks of variant angina pectoris disappeared following institution of therapy with perhexiline maleate. When the dose of this drug was decreased to 100 mg/day or less, symptoms reappeared in all patients. Reinstitution of therapeutic doses of perhexiline maleate again resulted in complete control of symptoms. Perhexiline maleate is a useful agent for the treatment of variant angina pectoris.

关键词：心绞痛/药物疗法心绞痛变异型/药物疗法冠状血管造影术药物评价心电描记术硝酸甘油/治疗应用哌克昔林/投药和剂量哌克昔林/治疗应用哌啶类/治疗应用女(雌)性人类男(雄)性中年人

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Defining meaningful change in Alzheimer's disease trials: The donepezil experience

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JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY 1999年第1期12卷 39-48页

作者： McLendon, BM Doraiswamy, PM Duke Univ Med Ctr Dept Pharm Drug Informat Serv Durham NC 27710 USA Duke Univ Med Ctr Dept Psychiat Clin Trials Unit Durham NC 27710 USA

Regulatory guidelines in the US and Europe generally require that a drug specifically indicated for treating Alzheimer's disease (AD) must demonstrate an effect upon the core manifestations of dementia. Progressive cognitive and functional losses are the cardinal features of AD. In the US, current guidelines require that new AD treatments show effectiveness on performance-based measures of cognition and on clinician-rated global assessments. Improvement in function is also emphasized in the European guidelines. The primary instruments that have been used to evaluate changes in cognition and global function in most recent AD trials are the cognitive subscale of the Alzheimer's Disease Assessment Scale and a version of the Clinician's Interview Based Impression of Change, respectively. The results from three pivotal trials investigating the acetylcholinesterase inhibitor, donepezil, are used to demonstrate the way in which these tools are used, how to interpret the data they provide, and to determine their overall value in ascertaining efficacy in clinical practice.

关键词：阿尔茨海默病/诊断阿尔茨海默病/药物疗法阿尔茨海默病/心理学胆碱酯酶抑制剂/治疗应用认知障碍/诊断疾病恶化剂量效应关系药物茚满类/治疗应用神经心理学测验哌啶类/治疗应用疾病严重程度指数治疗结果老年人人类

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Electropharmacological characterization of cardiac repolarization in German shepherd dogs with an inherited syndrome of sudden death:: Abnormal response to potassium channel blockers

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JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 2000年第3期36卷 939-947页

作者： Mérot, J Probst, V Debailleul, M Gerlach, U Moise, NS Le Marec, H Charpentier, F INSERM U533 Nantes France Ecole Vet Nantes Lab Med Nantes France Cornell Univ Coll Vet Med Dept Clin Sci Ithaca NY 14853 USA Hoechst Marion Roussel Frankfurt Germany

Objectives This study sought to determine whether abnormal ventricular repolarization is implicated in cardiac arrhythmias of German shepherd dogs with inherited sudden death. Background Moise et al. (9) have identified German shepherd dogs that display pause-dependent lethal ventricular arrhythmias. Methods Ventricular repolarization was studied both in vivo using electrocardiogram recordings on conscious dogs and in vitro with a standard microelectrode technique performed on endomyocardial biopsies and Purkinje fibers. Pharmacological manipulation was used to evaluate the role of potassium channels. Results In control conditions, electrocardiogram parameters were similar in both groups of dogs, except for the PR interval (18% longer in affected dogs, p < 0.05). Injection of d,1-sotalol (2 mg/kg) prolonged QT interval more in affected dogs (+14%, n = 9) than it did in unaffected dogs (+ 6%, n = 6, p < 0.05) and increased the severity of arrhythmias in affected dogs. In vitro, in control conditions, action potential duration (APD(90)) of endomyocardial biopsies and Purkinje fibers were significantly longer in affected dogs (respectively 209 +/- 3 ms, n = 30 and 352 +/- 15 ms, n = 17) than they were in unaffected dogs (197 +/- 4 ms, n = 25 and 300 +/- 9 ms, n = 30) at a pacing cycle length (PCL) of 1,000 ms. This difference increased with PCL. The kinetics of adaptation of APD(90) to a change in PCL was faster in affected dogs. D,1-sotalol (10(-5) and 10(-4)M) increased APD(90) in both groups of dogs, but this increase was greater in affected dogs, with the occurrence of triggered activity on Purkinje fibers. E-4031 (10(-7) and 10(-6) M), an I-Kr-blocker, increased APD(90) similarly in both groups of dogs. Chromanol 293B (10(-6) and 10(-5)M), an I-Ks-blocker, increased significantly APD(90) in unaffected dogs but had no effect in affected dogs. Conclusions These results support the hypothesis of an abnormal cardiac repolarization in affected dogs. The effects of 293B

关键词：抗心律失常药/治疗应用心律失常心性/药物疗法心律失常心性/遗传学心律失常心性/病理生理学心律失常心性/兽医学色满类/治疗应用猝死心脏/兽医学狗疾病/药物疗法狗疾病/遗传学狗疾病/病理生理学心电描记术心内膜/药物作用心内膜/病理学心内膜/病理生理学心脏/药物作用心脏/病理生理学心肌/病理学哌啶类/治疗应用钾通道阻滞剂浦肯野纤维/病理生理学吡啶类/治疗应用参考值索他洛尔/治疗应用磺胺类/治疗应用动物狗

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The role of positron emission tomography in the drug development of M100907, a putative antipsychotic with a novel mechanism of action

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JOURNAL OF CLINICAL PHARMACOLOGY 1999年第Sup1期39卷 17S-24S页

作者： Offord, SJ Wong, DF Nyberg, S Hoechst Marion Roussel Inc Global Mkt Bridgewater NJ 08807 USA Johns Hopkins Med Inst Dept Radiol Div Nucl Med Baltimore MD 21205 USA Karolinska Inst Dept Clin Neurosci Psychiat Sect Stockholm Sweden

Antipsychotic drug development has been a slow process since the discovery of chlorpromazine more than 45 years ago. Researchers identify a large number of potential compounds; screen them for antipsychotic activity in in vitro and animal test models; devise appropriate formulations; perform preclinical phar- macology, pharmacokinetic, and toxicology studies; perform healthy volunteer and then patient clinical studies; and finally negotiate with regulatory agencies for drug approval. In the United States, this process takes an average of 10 to 12 years and costs more than $500 million per approved drug. More recently, the pharmaceutical industry is bene- fiting from a new wave of technologic innovations that have advanced our understanding of the biology of dis- ease processes and increased the efficiency of the research and development process. However, while these new technologies may appear to be expensive, by providing the basis for early go/no-go decisions, tech- nologies such as PET can actually be cost-effective. To ensure that innovative drug research continues, a practical strategy (rational drug design) to evaluate drugs more efficiently in terms of both time and cost (fewer studies with fewer patients) must be developed for each new drug candidate. One of the most important and difficult steps in the drug development process is defining the dose- response relationship. Using M100907 as an example, we demonstrated that mechanism-based research pro- motes cost-effective drug development. The therapeu- tic index of M100907 was defined in phase I single- and multiple-dose tolerability studies. Nuclear imag- ing using PET technology was then used to confirm the mechanism of action of M100907 in the target organ (living human brain) and to target an appropriate dose range and regimen. With these data, clear go/no-go decision points could be established early within the clinical drug development process, and the selection of M100907 doses to carry forward into l

关键词：抗精神病药/治疗应用脑化学/药物作用临床试验(主题) 多巴胺/代谢氟苯类/药理学氟苯类/治疗应用哌啶类/药理学哌啶类/治疗应用精神分裂症/药物疗法血清素拮抗药/药理学血清素拮抗药/治疗应用工艺学制药体层摄影术发射型计算机人类

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CLINICAL INVESTIGATION OF AGENTS WITH PROPHYLACTIC ANTI-ALLERGIC EFFECTS IN BRONCHIAL-ASTHMA

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CLINICAL ALLERGY 1978年第4期8卷 373-382页

作者： CRAPS, L GREENWOOD, C RADIELOVIC, P SANDOZ LTD CLIN MED & BIOL RES CH-4002 BASEL SWITZERLAND

To determine the efficacy of ketotifen as an oral anti-asthmatic agent, experimental and therapeutic long-term trials were carried out. Four models were used in the experimental therapeutic trials and the antihistaminic agent clemastine and disodium cromoglycate were used as comparative substances. Ketotifen provided protection against bronchospasm induced by allergens, histamine and exercise, but not against that induced by acetylcholine. In the therapeutic long-term trials, the efficacy and tolerance of ketotifen were compared with that of clemastine and disodium chromoglycate for a period of 6 mo. In another study ketotifen was administered for 1 yr. Ketotifen proved very effective in decreasing the frequency and duration of asthmatic attacks, concomitant medication could be reduced and the patients improved subjectively. Ketotifen is a safe and effective oral anti-anaphylactic agent for use in the long-term treatment of bronchial asthma.

关键词：乙酰胆碱/药理学气雾剂哮喘/药物疗法氯马斯汀/治疗应用色甘酸钠/治疗应用双盲法用力用力呼气量组胺/药理学超敏反应/药物疗法哌啶类/治疗应用噻吩类/治疗应用肺活量人类

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PERORAL AND PARENTERAL ADMINISTRATION OF LONG-ACTING NEUROLEPTICS - DOUBLE-BLIND-STUDY OF PENFLURIDOL COMPARED TO FLUPENTHIXOL DECANOATE IN TREATMENT OF SCHIZOPHRENIA

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ACTA PSYCHIATRICA SCANDINAVICA 1975年第2期52卷 132-144页

作者： GERLACH, J KRAMP, P KRISTJANSEN, P LAURITSEN, B LUHDORF, K MUNKVAD, I ST HANS HOSP DEPT EDK-4000 ROSKILDEDENMARK ST HANS HOSP DEPT HDK-4000 ROSKILDEDENMARK ST HANS HOSP DEPT ADK-4000 ROSKILDEDENMARK

Fifty-six out of 60 schizophrenic patients completed a double-blind study of two long-acting neuroleptics, penfluridol (peroral) and flupenthixol decanoate (parenteral). Half of the patients were on maintenance therapy of flupenthixol prior to the study, the other half on penfluridol. The actual double-blind study (12 weeks) was commenced after a preliminary period of 4 weeks, the patients in the two main groups being randomly divided into two further groups, one continuing the medication unchanged, the other changing to the alternative drug. It was found possible to make a sudden switch from penfluridol to flupenthixol decanoate and vice versa without any significant change in the condition of the patient. The same dosage (in 70% of the patients from 40 to 80 mg) of penfluridol was used per week as was employed for flupenthixol decanoate per fortnight. Changes in the intensity of the symptoms (total Brief Psychiatric Rating Scale (BPRS) score) were moe pronounced in the preliminary period (during unchanged treatment) than on changed medication in the blind period. Both drugs induced approximately the same degree of akathisia, Parkinsonism and autonomic side effects. The practical consequences of equipotent therapeutical effect of a peroral and parenteral long-acting neuroleptic are briefly discussed.

关键词：投药口服迟效制剂药物评价氟哌噻吨/投药和剂量氟哌噻吨/治疗应用注射五氟利多/投药和剂量五氟利多/治疗应用哌啶类/治疗应用安慰剂精神分裂症/药物疗法噻吨类/治疗应用青少年成年人老年人人类男(雄)性中年人

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Clinical evaluation of twice-daily emedastine 0.05% eye drops (Emadine eye drops) versus levocabastine 0.05% eye drops in patients with allergic conjunctivitis

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AMERICAN JOURNAL OF OPHTHALMOLOGY 2001年第6期131卷 691-698页

作者： Verin, P Easty, DL Secchi, A Ciprandi, G Partouche, P Nemeth-Wasmer, G Brancato, R Harrisberg, CJ Estivin-Ebrardt, C Coster, DJ Apel, AJG Coroneo, MT Knorr, M Carmichael, TR Kent-Smith, BT Abrantes, P Leonardi, A Cerqueti, PM Modorati, G Martinez, M Univ Bristol Dept Ophthalmol Bristol BS8 1TH Avon England Univ Padua Dept Ophthalmol Padua Italy Univ Genoa Dept Allergol Genoa Italy Univ Milan Hosp San Raffaele Dept Ophthalmol Milan Italy Flinders Med Ctr Bedford Pk SA Australia Greenslopes Private Hosp Greenslopes Australia Prince Wales Hosp Randwick NSW 2031 Australia Univ Tubingen Hosp Eye Tubingen Germany Olivedale Clin Randburg South Africa Hosp San Jose A Serrano Lisbon Portugal Alcon Res Ltd Ft Worth TX USA

PURPOSE: The efficacy and safety of emedastine 0.05% eye drops (Emadine;Alcon Laboratories, Inc, Fort Worth, Texas), a new H-1 antagonist, were studied in comparison to levocabastine 0.05% eye drops (Livostin;Janssen-Cilag N V, Berchem, Belgium) during a twice-daily treatment schedule for 6 weeks in adult and pediatric patients with seasonal allergic conjunctivitis. METHODS: In a prospective, multicenter, randomized, double-masked, parallel group study, 222 patients with allergic conjunctivitis were randomized (221 received treatment) to either emedastine or levocabastine, instilled twice daily for 6 weeks. Patient diaries were completed four times daily (before the morning and evening instillations, at noon, and in the afternoon), and clinical examinations were conducted at regular intervals. Primary efficacy variables of ocular redness and itching and secondary efficacy variables of chemosis, eyelid swelling, patient diary data, and physician's global assessment were analyzed. RESULTS: Both emedastine and levocabastine produced a statistically significant (P = .0001) reduction in itching and redness within 5 minutes of the first instillation. All signs and symptoms improved progressively over the 6-week treatment period. After 7 days of use, and throughout the remainder of the study, emedastine was statistically superior to levocabastine (P < .006) in preventing and alleviating the signs and symptoms (itching, redness, chemosis, and eyelid swelling) of allergic conjunctivitis. CONCLUSIONS: Emedastine 0.05% eye drops administered twice daily are more efficacious than levocabastine 0.05% eye drops in the prevention and treatment of the signs and symptoms of allergic conjunctivitis in adults and children of 4 years and above. Both emedastine 0.05% eye drops and levocabastine 0.05% eye drops were well tolerated. (Am J Ophthalmol 2001;131:691-698. (C) 2001 by Elsevier Science Inc. All rights reserved.).

关键词：眼药水哌啶类/投药和剂量哌啶类/治疗应用前瞻性研究瘙痒症人类中年人

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