拉米夫定的少见不良反应

目的了解拉米夫定在临床应用中较少见的不良反应。方法对近年来相关文献资料进行归纳总结。结果与结论拉米夫定少见不良反应有：斑秃、肾结石、YMDD变异、病毒性上呼吸道感染。     

拉米夫定的少见不良反应

拉米夫定(Lamivudine,商品名贺普丁)是新一代核苷类抗病毒药,用于艾滋病和乙型肝炎的治疗,1991年问世,1998年在我国上市,以往认为本品较安全,不良反应较轻,部分患者可出现轻度头痛、恶心、嗜睡、肝区不适、腹泻、乏力等,一般可耐受,但在广泛应用后,仍有一些少见的不良反应发生,现将近年来国内所报道的在应用拉米夫定过程中出现的一些少见不良反应介绍如下:     

拉米夫定治疗慢性乙型病毒性肝炎的新进展

目的:探索拉米夫定治疗慢性乙型病毒性肝炎的机制和优点。方法:总结拉米夫定抑制乙型病毒性肝炎复制的分子机制,研究近年来大量拉米夫定抗病毒治疗的大规模临床研究以深入研究拉米夫定在慢性乙型病毒性肝炎治疗中的特点、优势和安全性。结果:拉米夫定(LMV)具有高效的抗HBV活性,对乙肝病毒有长期稳定的抑制作用,长期应用可引起病毒变异发生,但拉米夫定联合其他抗病毒药物治疗能减少耐药株的产生并增强治疗效果,同时,不良反应少见。结论:拉米夫定治疗慢性乙型病毒性肝炎是安全和有效的。     

拉米夫定治疗期间出现斑秃

拉米夫定(lamivudine)是新一代核苷类抗病毒药,用于艾滋病和乙型肝炎的治疗.1991年问世,1998年在我国上市,现已3年.在既往的临床安全性研究中证实其不良反应轻微,发生率不高,患者耐受性较好.但在广泛的临床应用中,仍有一些少见的不良反应发生,本文报告1例患者在服用拉米夫定过程中发生斑秃,仅供参考.     

拉米夫定的不良反应

拉米夫定是一种脱氧嘧啶核苷类似物,是新一代核苷类抗病毒药。拉米夫定自1991年问世以来, 已在许多国家广泛地用于治疗HIV感染与艾滋病患者。1995年有人发现拉米夫定对乙型肝炎病毒(HBV)DNA有抑制作用。1999年在中国注册上市。拉米夫定在用于乙型肝炎治疗的Ⅱ期Ⅲ期临床研究中取得了较理想的效果。根据有关资料报道其不良反应较轻,发生率也不高,部分患者出现轻度头痛、嗜睡、恶心、肝区不适和疲乏等,但多数病人都能很好地耐受。但在广泛的临床应用中仍有一些少见的不良反应。如:过敏反应,病人出现紫绀、血管神经水肿、哮喘、荨麻疹和低血压。乙肝病人应用拉米夫定停药后,病毒复制仍可恢复,并出现HBV DNA的反跳,有时甚至高于治疗前水平。有人报道12例艾滋病患者在用拉米夫定治疗后引起甲沟炎。也有报道拉米夫定引起脂肪异常分布,水牛背,引起血友病患者出血,引起冻肩,胰肾综合征等。     

拉米夫定治疗乙型肝炎出现耐药及少见不良反应

拉米夫定(lamivudine)是核苷类抗病毒药,具有抑制乙型肝炎病毒(HBV)逆转录酶的作用.该药进入肝细胞内形成三磷酸衍生物,作用于HBV聚合酶,阻止HBV-DNA的合成;可以减少体内的病毒含量,促使HBeAg,抗-HBe血清转换,同时改善肝坏死和肝硬化的作用.目前据国内外多项研究报道,其不良反应发生率低且症状轻微,病人的耐受性较好.1992年以来,经Ⅲ期临床研究和以往的报道证实,在单独使用拉米夫定或联合其它抗病毒药物的过程中,会出现一些少见的不良反应.本文仅讨论在乙型肝炎治疗中出现的耐药现象以及一些少见的不良反应,现综述如下:     

59例拉米夫定药物不良反应分析

目的 探讨拉米夫定不良反应(ADR)的一般规律和特点.方法 对2000～2006年国内医药学术期刊报道的59例拉米夫定不良反应案例进行统计、分析.结果 拉米夫定不良反应多发生于8～45岁男性;临床表现以神经系统反应和肝炎病情加重为主.结论 临床应重视拉米夫定的不良反应,以确保用药安全.     

拉米夫定不良反应分析

目的:探讨拉米夫定不良反应的一般规律和特点。方法:对1999年～2005年国内医药学术期刊报道的43例拉米夫定不良反应案例进行统计、分析。结果:拉米夫定不良反应多发生于8a～45a男性;发生时间无规律性;临床表现以神经系统反应和肝炎病情加重为主。结论:临床应重视拉米夫定的不良反应,以确保用药安全。     

拉米夫定的不良反应和安全性评价

目的：评估拉米夫定临床用药的安全性。方法：对1999～2003年国内报道的拉米夫定的不良反应进行整理归纳和分析。结果：拉米夫定的不良反应分布范围较广，临床表现为变态反应、神经系统反应、血液系统反应、泌尿生殖系统反应、对肝功能的影响及其它反应等，其中以锥体外系反应发生率最高，尤以青少年最易发生。结论：临床应注意拉米夫定的不良反应，坚持合理用药。     

国家食品药品监督管理局提醒高度关注拉米夫定和替比夫定引起的横纹肌溶解

<正>2010年07月22日发布日前,国家药品不良反应监测中心发布《第30期药品不良反应信息通报》表示,拉米夫定和替比夫定可引起横纹肌溶解的严重不良反应。横纹肌溶解是拉米夫定和替比夫定已知的不良反应。虽然这2种产品的说明书已明确了此类不良反应,但鉴于该不良反应的及时发现、诊断和治疗将有利于患者的预后,国家食品药品监督管理局再次提醒广大医务工作者、药品生产企业和公众,警惕拉米夫定和替比夫定引起横纹肌溶解的风险。     

Side-effects of drugs in epileptic patients

Drug therapy in patients suffering from various forms of epilepsy aims at the administration of such dosages of antiepileptic drugs as to produce significant reduction of seizures without the occurrence of serious side-effects. To assess these side-effects 75 patients (48 males, 27 females) with epilepsy, attending an out-patient clinic were studied prospectively and data were collected regarding diagnosis, drug use and side-effects. Primarily generalized epilepsy and partial complex epilepsy with secondary generalization are the most prevailing categories. 69% (52) Of the patients are treated with monotherapy, with carbamazepine as the drug most frequently prescribed (30/52). Side-effects were scored after examining and questioning the patient with the help of a standard questionnaire. A distinction was made between groups of side-effects, being systemic, anamnestic, dermatological, neurological or miscellaneous. Also, haematological and biochemical changes were looked for. In the monotherapy group 26/52 (50%) of the patients showed side-effects (23 patients with 1, 2 with 2, 1 with 3 side-effects), and in the polytherapy group 15/23 (65%) (8 patients with 1, 7 with 2 side-effects). Adverse drug reactions were hardly related to the plasma concentration category. Between 50–60% of the patients at sub-therapeutic and low-therapeutic plasma levels complained of side-effects. No clear relationship between the clinical efficacy and the side-effects could be established. The clinical custom, among others, to titrate the dose according to the disappearance or appearance of side-effects seems open for discussion.     

Risk factors in the development of adverse reactions to N-acetylcysteine in patients with paracetamol poisoning

AIMS: To identify risk factors in the development of side-effects to N-acetylcysteine (NAC) in patients with paracetamol poisoning. METHODS: A retrospective study was carried out based upon the hospital charts of 529 consecutive patients admitted with paracetamol poisoning, all treated with NAC, at the Department of Hepatology, Copenhagen University Hospital (the tertiary care centre of liver disease in Denmark). RESULTS: Forty-five patients (8.5%; 95% confidence intervals (CI) 6.4, 11%) developed side-effects to NAC and 18 patients (3.4%; 95% CI 2.1, 5.4%) developed systemic side-effects. Asthmatics were 2.9 times (95% CI 2.1, 4.7) more likely to develop side-effects (Chi-square: P = 0.004). Side-effects were of similar severity in asthmatics and nonasthmatics. A history of medical allergy was not a risk factor. Serum paracetamol was lower in patients with side-effects than in those without (Mann-Whitney: P = 0.00006). CONCLUSIONS: Asthma must be considered a risk factor in the development of side-effects to NAC. However, the side-effects are easily managed and there is no reason to withhold NAC from any patient with paracetamol poisoning. Paracetamol itself seems to offer some protection against the development of side-effects to NAC.     

An investigation of the alpha1A-adrenergic receptor gene and antipsychotic-induced side-effects

Antipsychotic treatment is hampered by the induction of side-effects such as tardive dyskinesia (TD), weight gain, sedation and extrapyramidal side-effects (EPS). Identification of the factors related to their development would facilitate their avoidance and the improvement of antipsychotic treatment. It has been hypothesised that genetic variants in drug targeted receptors may contribute to the development of side-effects. In this study, we have investigated the possible influence of genetic variants (-563-C/T, -4155-G/C and -4884-A/G) of the alpha(1A)-adrenergic receptor, an important target of atypical antipsychotic drugs, and development of side-effects after antipsychotic medication in a sample of N = 427 US Caucasian patients. We found several marginal associations (p < 0.05) between alpha(1A)-adrenergic genetic variants and antipsychotic-induced side-effects which did not reach statistical significance after corrections for multiple analyses. These results do not support a major role of alpha(1A)-adrenergic genetic variants in obesity and other side-effects observed after prolonged treatment with antipsychotic medications.     

Self-reported side-effects of anti-retroviral treatment among IDUs: a 7-year longitudinal study (APROCO-COPILOTE COHORT ANRS CO-8)

The introduction of potent anti-retroviral treatment (ART) has transformed HIV disease into a chronic condition with the prospect, for the patient, of strict adherence to effective but life-long treatments. Within this framework, a major issue that can negatively affect adherence is the side-effects of the treatment. To date, studies documenting how individuals HIV-infected through drug injection (IDUs) experience ART-related side effects are sparse. Longitudinal data collected from the APROCO-COPILOTE cohort have been used to compare the experience of ART-related side-effects who have been HIV-infected via injecting drug use and non-IDU patients. A 20-item list was used to collect self-reported side-effects over a 7-year follow up period. Of 922 patients, 15% were IDUs. At any given visit, IDUs reported a significantly higher number of side-effects and had approximately twice the risk of reporting any side effect than non-IDUs. Most commonly reported side-effects were dry skin, fatigue, vomiting, bone troubles, insomnia. After adjustment for social conditions, depressive symptoms, use of sleeping pills and time since HIV diagnosis, IDUs reported experiencing significantly more side-effects than non-IDUs. Whether or not this is related to sensitivity to pain or to other comorbidities is difficult to establish. Further research is needed to understand how substitution treatment can mediate the relationship between exposure to opioids and side-effects. Providing appropriate care to reduce side-effects, thereby increasing adherence to ART in this population, remains a major challenge especially in those countries scaling up ART. Incorporating symptom management and improving access to analgesic medications within a model of comprehensive care for HIV-infected IDUs, could reduce the impact of drug-related and HIV-related harms and induce better long-term treatment outcomes and quality of life.     

Comparison of methods to detect side-effect on clinical application of chloranolol,a beta-adrenergic receptor inhibitor

Summary The incidence of side-effects on administration of chloranolol (Tobanum^®), a beta-adrenergic receptor blocking drug, to 2066 patients with hypertension, angina pectoris or arrhythmias was measured by three different methods. In 600 patients in an efficacy trial (Group 1) both spontaneously reported complaints and objective signs were tabulated. A side effect — directed method, utilising a questionnaire containing a list of possible side-effects was also used, with the questionnaire being completed by the physician. 35 questions referred to anticipated and other side-effects. The trial was performed in two groups: in 537 patients a placebo was also given (Group 2), and in another set of 929 patients (Group 3) the questionnaire inquiry was performed uncontrolled, without placebo. All three groups were comparable in their distribution of sexes, ages and diagnoses, the mean daily dose of chloranolol its use alone or in combination, and in a similar duration of treatment. 55% of all patients received chloranolol therapy for a period of more than 3 months. The ratio of in- and outpatients was 1:5. The side-effect incidence was independent of the age and sex of the patients and of the dose of chloranolol. The incidence was also unaffected whether chloranolol was used alone or in combination. The number of side-effects differed markedly between the three groups, their ratio was 1:10:24 in Groups 1, 2 and 3. Two-thirds of the side-effects subsided spontaneously within 1 month of their onset. The duration of the side-effects varied according to their character: cardiorespiratory side-effects were of the shortest duration and those affecting the central nervous system were the most enduring. The appreciable differences in incidence could be attributed to the methods of collection of the data. It has been stated that placebo controlled trials using a detailed questionnaire are the most suitable for estimating the incidence of side-effects; recording side-effects spontaneously reported by patients are insufficiently sensitive, and uncontrolled trials using a questionnaire have been shown to be too sensitive. The revealed incidence of side effects leading to interruption of treatment is less affected by the method chosen. In 100 patients (4.8%) therapy had to be suspended because of the side-effects of chloranolol (Group 1: 1%, Group 2: 6.20%, Group 3: 6.6%). Comparison of the incidence of cessation of therapy due to side-effects did not show an appreciable difference between the various beta-adrenergic receptor blocking agents, including chloranolol.     

奥氮平合并阿立哌唑治疗老年痴呆躁狂发作的疗效观察

目的总结奥氮平与阿立哌唑联合应用治疗老年痴呆躁狂发作的疗效及耐受性与安全性。方法收集笔者所在医院2009年1月～2011年6月收治的老年痴呆躁狂发作患者42例,随机分为阿立哌唑组、奥氮平组及阿立哌唑与奥氮平联合组,各14例,治疗8周后观察评定3组患者的治疗效果及不良反应。结果联合用药组在总有效率及不良反应方面均明显优于其他两组,其他组间比较差异无统计学意义。结论奥氮平与阿立哌唑联合应用治疗老年痴呆躁狂发作疗效明显,不良反应少,值得在临床推广应用。     

盐酸氟西汀治疗抑郁症临床对照研究

目的：比较盐酸氟西汀和阿米替林治疗抑郁症的疗效和不良反应。方法：采用HAMD、HAMA和TESS量表及临床疗效评定标准分别评定疗效及副反应。结果：盐酸氟西汀与阿米替林治疗抑郁症均有良好效果。结论：盐酸氟西汀治疗抑郁症,疗效与阿米替林相当,副反应轻微,患者依从性较好。     

Satiation and Sensory Deprivation Combined in Smoking Therapy: Some Case Studies and Unexpected Side-Effects

Two promising techniques for smoking reduction, sensory deprivation and stimulus satiation, were applied in combination to five smokers. All were successful initially in achieving abstinence and four ultimately in maintaining abstinence.

The issue of possible side-effects is worth considering. Quitting per se and both satiation and sensory deprivation may be stressful and as a result may potentially produce negative side-effects. The observation of positive side-effects in these cases balances this possibility to some extent.     

Why there is a need for pharmacovigilance

Not everything is known about a medicine when it receives its licence for marketing. The merits of a new drug, balancing its beneficial and its untoward effects, become only established after sufficient experience has been gained from its use in real practice. Part of the reason for this is that our extensive phase III clinical trials fail to detect some side-effects. Why is this so? Three groups of reasons may be envisaged, namely (1) our trials lack the power to detect rare side-effects; (2) some side-effects do not occur in the context of clinical trials; (3) some side-effects, though common enough, fully or partly escape detection due to lack of suitable detection techniques. The following presents a closer look at these three mechanisms.     

Determination of receptors that mediate opiate side effects in the mouse.

The effects of mu and kappa-opiate receptor agonists were studied in a variety of tests in the mouse designed to correspond to clinical side-effects in man. These included sedation, decrease in pupil diameter, Straub tail, decrease in body temperature, decrease in respiratory rate and inhibition of gut propulsion. The mu-receptor agonists tested produced opiate side-effects in the mouse at doses between 2.4 and 34 times higher than their antinociceptive doses in the abdominal constriction test. Their ranked orders of potency in producing these effects were very similar to their order of antinociceptive potency. In contrast, the kappa-receptor agonists only produced opiate side-effects at doses between 29 and greater than 2500 times higher than their antinociceptive doses. There was no correlation between the potency ratios in these tests and in the abdominal constriction test. It is concluded that mu-receptor agonists may produce both their antinociceptive effects and opiate side-effects by interacting with the mu-receptor. The kappa-receptor agonists have previously been shown to produce antinociception via the kappa-receptor, but the opiate-like side-effects which appear with some of the drugs at much higher doses are probably due either to interaction with the mu-receptor or to some other non-specific action.