药源性血液病(一)

药物所致血液学反应常见,约占药物不良反应(ADR)总数的10%。比例虽不高,但病情多严重,死亡率可高达32.5%,占药物引起相关死亡的40%。1药源性血液病(DHD)的类型1.1预期性反应药物血液浓度过高或用药总量过大,对任何人均可引起剂量相关性反应,占药物不良反应总数的70%～80%,如治疗肿瘤的细胞毒药物。药物血液浓度过高可由用药量过大或药物在体内的代谢、排出障碍所至。少数药物在常规有效剂量下,也不可避免的出现某些反应。1.2非预期性反应此类药物不良反应仅发生在少数敏感个体上,约占ADR总数的20%～30%。又分为:1.2.1超敏感性与药物的药…     

药源性血液病(5)

药源性白细胞减少症(D-LP)和粒细胞缺乏症(D-AGC)1白细胞减少症和粒细胞缺乏症概念外周血白细胞(WBC)低于4ⅹ109/L时称为白细胞减少症(Leucopenia)。白细胞以中性粒细胞为主,中性粒细胞绝对计数(ANC)成人低于2ⅹ109/L,儿童低于1.5ⅹ109/L者称为粒细胞减少症(Neutropenia)。人的粒细胞数受多种因素影响,除遗传、环境因素外,尚可因病人的年龄、活动状态而不同。当ANC低于0.5ⅹ109/L时称为粒细胞缺乏症(Agranulocytosis)。引起粒细胞减少的病因很多,药源性粒细胞减少症是指特定药物通过不同机制引起ANC选择性减少或缺乏的病症。2病…     

药源性血液病(6)

药源性出血性疾病1药物相关性血管性紫癜许多药物可通过几种途径改变血管壁的通透性引起紫癜。如通过免疫机制,产生特异性抗血管抗体或免疫复合物,或通过对血管壁的直接损伤等。表现为四肢瘀点或瘀斑,罕见其他部位出血。停药后,紫癜大多很快消退,但应避免再用此种药物。可引起血管性紫癜的相关药物有:①解热镇痛药:水杨酸钠,阿司匹林,吲哚美辛,非那西丁等;②催眠镇静药:巴比妥类,水合氯醛,甲丙氨酯,氯丙嗪等;③抗感染药:青霉素,氯霉素,磺胺类,对氨水杨酸钠,异烟肼,奎宁,枸橼酸哌嗪;④利尿剂:氯噻嗪类,呋塞米;⑤内分泌系统药:氯磺丙脲、甲苯…     

药源性血液病(3)

药源性溶血性贫血(DHA)在药物引起的血液学不良反应中,DHA相对少见。据WHO药物不良反应国际监督调查研究中心估计,DHA占主要药源性血液系统不良反应的10%。1总论1.1发病机制及分类(表1)1.1.1药物氧化性溶血多为急性溶血。见于遗传性红细胞酶缺乏和某些血红蛋白分子病。患者红细胞对特定药物或其代谢产物的氧化性应激极为敏感,易至功能损伤,红细胞寿命缩短。人每天约有3%的血红蛋白转变为Met-Hb,持续产生少量活性氧。所以说红细胞是活性氧的最佳发源地,又是活性氧发病学分类缺陷部位疾病名药物氧化性溶血遗传性酶缺乏磷酸戊糖旁路GSH…     

药源性血液病(4)

药源性巨幼细胞性贫血(DMA ) 凡能 直接或间 接影响细胞 DNA 合成酶系 统的药 物 , 均 有 可 能 引 起 红 细 胞 巨 幼 变 : 由 于 细 胞DNA 复制 障碍 ,细胞 核不 能正 常发 育 成熟 , 核分裂 受 阻 ,造 成 核 发 育 晚于 胞 浆 。 此 种 异 常 不 但 影响 红 细 胞, 也 影 响 粒 细胞 、 巨 核 细 胞 及 一 切 更 新型 细 胞 ,包 括 消 化 道 黏膜 上 皮 细 胞 。 巨 幼 细 胞 性贫 血 患 者的 骨 髓 增 生 明显 活 跃 , 幼 稚 细 胞 红 系 巨幼 变 , 粒系 巨 型 变 , 巨核 细 胞 核 分 叶 过 多 ; 外 周血 全 血 细胞 减 少 , 贫 血…     

药源性血液病

药物引起的血液病比较少见,但比较严重,发生后其死亡率比较高.与其它药物不良反应(ADR)一样,药物引起的血液ADR被分为A型和B型两类:常见的A型反应有细胞毒剂和免疫抑制剂对骨髓的抑制反应.A型反应是可预测的,经过适当的控制可以限制其危害性.因此,我们主要讨论药物引起的不可预测的B型血液ADR.     

药源性肾损害(二)

7肾功能损害时药物应用原则肾功能损害时应用药物的常规剂量,可因肾脏对这些药物的代谢和排泄障碍使其在血液和组织中蓄积达到中毒水平,促使肾功能进一步减损。这种药物的中毒表现可被患者原有疾病的症状所掩盖,不易引起医生重视。因此,肾功能不全者必须根据以下原则综合考虑。7.1用药需有明确适应证。7.2根据内生肌酐清除率正确判断肾功能状态。7.3熟悉所用药物如药物的代谢方式、排泄途径、有效血药浓度、肾毒性大小以及透析对该种药物的清除能力。同样有效的几种抗生素中,应选用肾毒性较低者,避免使用长效药物。7.4根据药物的清除速率调…     

药源性肾损害(一)

肾脏是体内药物代谢和排泄的重要器官。随着多种抗生素等化学药物和中药的广泛应用或滥用,药源性肾脏损害屡见不鲜。由于许多药物在常规剂量时即可发生有害且非预期的反应,又由于某些药物所致的肾损害多缺乏特征性的临床表现以及肾脏具有巨大的储备能力,因而药物性肾损害不易及早发现。所以,提高对药物肾毒性的认识,正确合理地用药,尽量避免毒副作用及减少药源性肾损害的发生率是临床医生的职责。1药物的肾脏转运大多数药物吸收后,需经肾小球滤过,近端小管分泌、远端小管重吸收和小管上皮细胞降解等代谢过程排出体外。在这一过程中,肾脏对这…     

药源性锥体外系反应综述(附2例报告)

药物具有两重性，既可以治疗疾病。解除痛苦，也可能引起不良反应。自2003年6月～2004年11月，我们遇到2例在病情治疗过程中常用量给药后发生锥体外系症状的病例，经查阅有关文献，现综述药源性锥体外系反应如下并附2例报告。     

药源性神经系统疾病(一)

药源性疾病为药物引起的疾病,是药物不良作用产生的后果。药源性疾病古来有之,并且时有发生,已成为全球主要疾病之一。在美国,它位于心脏病、癌病、肺病之后,成为第4～6位导致死亡的疾病。药源性疾病涉及到人体多系统,神经系统的药源疾病为其常见之一。1997年仅在英国药源性神经系统疾病的发生率已达18%。药物对神经系统的危害是多方面的,既可危及中枢神经,也可侵犯周围神经,有神经症状,也有精神病样发作,其损害程度可能是短暂可逆的,也可能长期不可逆的器质性病变。因此,及时发现、诊治和预防药源性神经系统疾病在临床治疗上具有十分重要的…     

Drug-induced Malabsorption

Abstract

1. The history and relevance of drug-induced malabsorption are reviewed.

2. The tests used to assess intestinal structure and function in man are briefly described.

3. Neomycin, the most potent cause of drug-induced malabsorption, is reviewed in detail. It disturbs small bowel histology, impairs the absorption of actively absorbed substances normally measured in function tests and lowers the serum cholesterol.

4. Each test of intestine absorption is considered separately and the drugs which modify them are discussed. Where possible, the mechanisms of action are described.     

Drug-induced vasculitis

Therapeutic agents from virtually every pharmacological class have been implicated in the development of drug-induced vasculitis. Clinical manifestations range from small vessel hypersensitivity vasculitis and leukocytoclastic vasculitis to clinical syndromes indistinguishable from classical systemic forms of vasculitis such as Wegener’s granulomatosis, polyarteritis nodosa and Churg–Strauss syndrome (CSS). The exact pathogenic mechanisms involved remain to be elucidated; but both cell-mediated and humoral immunity appear to play important roles. Affected individuals may present with cutaneous involvement alone or life-threatening systemic involvement, which may result in severe and sometimes fatal illness. Since clinical presentation as well as serological and pathological parameters is identical to idiopathic forms of vasculitis, a high index of suspicion is necessary to accurately and expeditiously diagnose drug-induced vasculitis. Withdrawal of the offending agent alone is often sufficient to induce prompt resolution of clinical manifestations, obviating the need for systemic corticosteroids or more powerful forms of immunosuppression.     

Drug-induced cholestasis

Drugs may cause several overlapping syndromes of cholestasis, the pathophysiological syndrome resulting from impaired bile flow. These reactions comprise approximately 17% of all hepatic adverse drug reactions (ADRs) and they may be severe. Causes of 'pure' (bland) cholestasis include oestrogens and anabolic steroids; rarer associations are with antimicrobials and NSAIDs. 'Cholestatic hepatitis' is a common drug reaction in which liver injury and inflammation cause significant elevation of serum alanine aminotransferase (ALT) as well as cholestasis. Chlorpromazine and ketoconazole are classic examples, but it is now exemplified by amoxycillin-clavulanate and other oxy-penicillins. Chronic cholestasis results from small bile duct injury leading to the vanishing bile duct syndrome (VBDS), a disorder mimicking primary biliary cirrhosis, or from injury to larger bile ducts causing secondary sclerosing cholangitis. Whilst there is increasing evidence of a genetic predisposition to cholestatic drug reactions, there are currently no pretreatment tests to predict drug safety. Prevention of severe reactions therefore relies on early detection of liver injury and prompt drug withdrawal. Symptomatic management includes relief of pruritus and correction of fat-soluble vitamin deficiency. In small cohort studies, ursodeoxycholic acid (UDCA) arrested progressive cholestasis in two-thirds of cases, but evidence for use of corticosteroids is anecdotal. This review considers diagnosis, pathogenesis, prevention and management of drug-induced cholestasis, with particular reference to frequently- and newly-described causes.     

Drug-induced vasculitis

Therapeutic agents from virtually every pharmacological class have been implicated in the development of drug-induced vasculitis. Clinical manifestations range from small vessel hypersensitivity vasculitis and leukocytoclastic vasculitis to clinical syndromes indistinguishable from classical systemic forms of vasculitis such as Wegener's granulomatosis, polyarteritis nodosa and Churg-Strauss syndrome (CSS). The exact pathogenic mechanisms involved remain to be elucidated; but both cell-mediated and humoral immunity appear to play important roles. Affected individuals may present with cutaneous involvement alone or life-threatening systemic involvement, which may result in severe and sometimes fatal illness. Since clinical presentation as well as serological and pathological parameters is identical to idiopathic forms of vasculitis, a high index of suspicion is necessary to accurately and expeditiously diagnose drug-induced vasculitis. Withdrawal of the offending agent alone is often sufficient to induce prompt resolution of clinical manifestations, obviating the need for systemic corticosteroids or more powerful forms of immunosuppression.     

Drug-induced stuttering

(1) Remember that some drugs can cause stuttering, even if this side effect appears to be rare.     

Drug-induced lupus

Autoantibodies and, less commonly, systemic rheumatic symptoms are associated with treatment with numerous medications and other types of ingested compounds. Distinct syndromes can be distinguished, based on clinical and laboratory features, as well as exposure history. Drug-induced lupus has been reported as a side-effect of long-term therapy with over 40 medications. Its clinical and laboratory features are similar to systemic lupus erythematosus, except that patients fully recover after the offending medication is discontinued. This syndrome differs from typical drug hypersensitivity reactions in that drug-specific T-cells or antibodies are not involved in induction of autoimmunity, it usually requires many months to years of drug exposure, is drug dose-dependent and generally does not result in immune sensitization to the drug. Circumstantial evidence strongly suggests that oxidative metabolites of the parent compound trigger autoimmunity. Several mechanisms for induction of autoimmunity will be discussed, including bystander activation of autoreactive lymphocytes due to drug-specific immunity or to non-specific activation of lymphocytes, direct cytotoxicity with release of autoantigens and disruption of central T-cell tolerance. The latter hypothesis will be supported by a mouse model in which a reactive metabolite of procainamide introduced into the thymus results in lupus-like autoantibody induction. These findings, as well as evidence for thymic function in drug-induced lupus patients, support the concept that abnormalities during T-cell selection in the thymus initiate autoimmunity.