药学专业英语

1、 Inflammation, Tissue Damage and RepairWhen living tissues are injured, a series of changes, which may last for hours, days, or weeks, occurs in and around the area of injury. This response to injury is known as inflammation. The injury is abnormal but the bodys reaction, inflammation, is a normal,

2、if complex, physiological reaction -the only one possible in the circumstances of that particular injury. This reactive nature of inflammation was first recognized by John Hunter (1794), who, after his studies of war wounds, concluded: “Inflammation is itself not to be considered as a disease, but a

3、s a salutary operation consequent either to some violence or some disease”. The purpose of inflammation is to localize and eliminate the causative agent, limit tissue injury, and restore tissue to normality. The inflammatory response is usually beneficial, indeed it is essential in combating most in

4、fections and in limiting the harmful effects of many toxic agents. However it is not always of benefit. There are many situations when destruction of tissue or other untoward effects are due not to the damaging agent but to one or other aspect of the bodys response to injury. For example in acute in

5、flammation of the larynx, there may be sufficient inflammatory swelling to obstruct the airway and cause death from asphyxia. Inflammation is best considered not as a single process but as a collection of distinct processes, each of which may have evolved for defence against injury, but each of whic

6、h has also potentially deleterious effects. Inflammation can be divided into two types: acute and chronic. The division of inflammation is based according to the time course and cellular components involved. These categories are not mutually exclusive, and some overlap exists. Acute inflammation is

7、the immediate and early response to an injurious agent and affects the vascular and connective tissue adjacent to the injured cells. There are three major components in the process of acute inflammation: increased blood flow (vasodilation), increased vascular permeability (exudation) and egress of w

8、hite blood cells into the injured tissue (emigration). These three components are coordinated and interrelated by numerous chemical mediators produced or released at the site of injury. Vasodilatation. Vasodilatation occurs directly after injury. Normally blood flow to the capillary bed is limited b

9、y the precapillary sphincter. In acute inflammation, a phase of vasodilatation occurs when the arterioles and precapillary sphincters relax. This results increased blood flow to the injured area and increased hydrostatic pressure. But blood soon flow slowly, because a concomitant increase in vascula

10、r permeability and loss of plasma water raises the viscosity of the blood. In the slowly moving blood, the pattern of flow changes. Red cells tend to clump in the centre of the vessel lumen and leucocytes assume a more peripheral position near the vessel wall. This margination of leucocytes is an im

11、portant initial step in the emigration process. If flow becomes very slow, the blood may clot and form a thrombus.Exudation. This is the increased passage of fluid and solutes, notably proteins, through the vessel wall. The mechanisms leading to increased vascular permeability are complex and incomp

12、letely understood. They include endothelial cell contraction or damage, the effects of mediators, local haemodynamic forces and the osmotic effects of proteins escaping into interstitial tissue. The leak of protein is roughly in proportion to their molecular size. Albumin is in the greastest amount,

13、 but if vascular permeability is extensive, large amounts fibrinogen may leak out. Exudation is an important local defence mechanism. The increase in interstitial fluid dilutes toxins, and proteins such as globulins are effective in neutralizing agents like bacteria. This increased fluid is sometime

14、s called inflammatory oedema or simply oedema.Emigration. Emigration of white blood cells, principally neutrophils and monocytes, is also an important defence mechanism. These are phagocytic cells which engulf and digest foreign particulate matter such as bacteria and debris of dead cells. The emigr

15、ation of leucocytes is an active process which occurs in two stages. The cells stick to the endothelial surface and then actively migrate through the gaps between the endothelial cells and into the tissue spaces.Acute inflammation is the first step in a dynamic response to injury. The sequelae depen

16、d on the nature and extent of injury. Resolution means the complete restoration of normal condition after the cause of the acute inflammation is removed. This occurs when there is minimal cell death and tissue damage, rapid elimination of the causal agent, and local condition favouring the removal o

17、f fluid and debris by lymphatics and by phagocytosis.Some types of inflammatory reaction are of much longer duration than those so far described, persisting for weeks or months after the initial injury. Any prolonged inflammation in termed chronic, the term referring solely to the duration of the in

18、flammatory process.There are two main types of chronic inflammation: chronic supervening on acute and chronic developing slowly with no initial acute phase.Chronic inflammation supervening on acute is almost always suppurative in type and presents as a persistent discharge of pus from an abscess whi

19、ch has ruptured or been drained surgically. Suppurative inflammation is usually caused by infection with pyogenic bacteria such as staphylococcus aureus and streptococcus pyogenes. There are two types of suppurative inflammation: superficial, e.g. a boil, and deep-seated, e.g. an abscess within a ho

20、llow viscus such the gall bladder.Chronic developing slowly with no initial acute phase. This type of response occurs after many types of injury. The injury may be physical, chemical, such as the response to talc or asbestos, or may result from poor local circulation. Certain micro-organisms, includ

21、ing those that cause tuberculosis and syphilis, characteristically induce chronic inflammation. In still other types of chronic inflammation, including rheumatoid arthritis and ulcerative colitis, the cause is not known but disturbances of immune mechanisms are believed to play an important aetiolog

22、ical role. 炎症，组织损伤和修复 当活组织受损时，损伤区及其周围会发生一系列的变化，这些变化可持续数小时、数天或数周。这种对损伤的反应被称为炎症。损伤是异常的，而机体的反应炎症，则是正常的，即使它是复杂的生理反应，但仍然是在特有损伤下唯一可能的反应。首先认识炎症反应本质的是John Hunter(1794),他通过战伤的研究之后得出这样的结论：“炎症本身不应被看作是一种疾病而应看作是某种暴力或疾病所引起的有益的反应”。炎症的目的就是聚集在致病因子区并消除它，降低组织损害，使组织恢复正常。炎症反应常常是有益的，在对抗大多数感染及限制许多毒性因子的有害影响中，它的确是不可缺少的。然而炎症

23、不是总有益的，许多情况下，组织的破坏或其他不良反应不是由于损害因子的作用，而是由于机体对损害所产生的这方面或那方面的反应。例如喉部急性炎症时，可能会发生严重的炎性肿胀而阻塞气道，并导致因窒息而死亡。最好不要把炎症看作一个单一的过程，而应把它视为一系列不同的过程，每一过程可有对抗损伤的防御作用，但也可能潜在着有害作用。炎症可分为两种类型：急性炎症和慢性炎症。这种分类是根据时间周期和细胞内容物来划分的。这些分类不是绝对的，可以互相交叉。急性炎症是机体对有害因子的即时和早期反应，影响着与受损细胞邻接的血管及结缔组织。急性炎症过程有三大组成部分：血流加快（血管舒张），血管渗透性增高（渗出）及白细胞外出

24、到受损组织内（白细胞游出）。损伤处产生或释放许多化学介质，使这三个部分彼此协调、互相联系。血管舒张 损伤后立即发生。正常情况下血液流到毛细血管床要受到毛细血管前括约肌的限制。在急性炎症时，由于小动脉和毛细血管前括约肌的舒张导致血管扩张。从而加速了血流到达损伤部位，增加流体静力压。但随之而来的血管通透性增加和血浆水分丧失，使血液粘稠度增高，使得血液流速不久就减慢。在缓慢流动的血液中，血液成分分布发生改变：红细胞趋向群集于血管腔的中央，而白细胞则出现于靠近血管壁的周边地带。这种白细胞靠边是白细胞游出过程的重要起始阶段。如果血流非常缓慢，血液可能凝结成块并形成血栓。渗出 渗出是指通过血管壁的液体和溶

25、质，特别是蛋白质增加。血管壁通透性增加的机制是复杂的，而且尚未完全为人们所了解。渗出机制包括内皮细胞的收缩或损伤、介质的作用、局部血液动力学及蛋白质逸出到组织间质中的渗透作用。蛋白质的漏出量大致上与其分子大小成正比，白蛋白渗出量最大，但是如果血管通透性显著增强，则大量纤维蛋白原就会渗出。渗出是一种重要的局部防御机制。组织间液增加可稀释毒素，蛋白质（如球蛋白）能有效地中和像细菌一类的因子。这种液体增加，有时称之为炎性水肿或简称水肿。白细胞游出 白细胞游出主要为中性粒细胞和单核细胞，也是一种重要的防御机制。这些细胞是能吞没及消化外来微粒物质（如细菌和坏死细胞的碎屑）的吞噬细胞。白细胞游出是一种主动

26、地过程，有两个阶段：白细胞黏附于内皮的表面，然后从内皮细胞间裂隙主动地移行进入组织间隙。急性炎症是机体对损伤动态反应的起始阶段，其结局取决于损伤的性质和程度。消散指急性炎症的原因除去后，炎区完全恢复正常状态。当细胞死亡和组织损伤很轻微，致炎因子迅速被消除，局部情况有利于液体和碎屑通过淋巴管及吞噬作用清除时，炎症就可消散。某些类型的炎症反应，自开始损伤后持续数周或数月，比上面描述的炎症反应所持续的时间长得多，任何持续很长时间的炎症称为慢性炎症，慢性一词仅指炎症过程的持续。慢性炎症有两个主要类型：即由急性炎症演变为慢性型和开始没有急性期的缓慢发展型。由急性演变而来的慢性炎症几乎均为化脓性炎症，脓液

27、从已溃破的或外科引流的脓肿处持续排除。化脓性炎症通常由化脓菌感染引起，如金黄色葡萄球菌。它有两种类型：表面化脓型（如疖）和积脓刑（如脓液积蓄在胆囊那样的空腔中）。无急性期的慢性炎症。这种炎症反应发生于许多类型损伤之后，损伤可以是物理的、化学的（如对滑石粉或石棉的反应），或是局部血液循环不良所致。某些微生物（包括引起结核病和梅毒的微生物）特别能引起慢性炎症。还有一些慢性炎症（包括类风湿性关节炎和溃疡性结肠炎）的原因尚不明确，但认为免疫机能紊乱起着重要的病因学作用。Medicinal Chemistry Early advances in medicinal chemistry were conc

28、erned principally with the estimation, isolation, structural determination, and synthesis of medicinal agents of natural origin. A second major area was the synthesis of simplified fragments of complex drug molecules. In this phase of its development medicinal chemistry was almost indistinguishable

29、from organic chemistry. The golden age(1940-1960) in the discovery of medicinals by these empirical strategies came to an end concomitant with the thalidomide tragedy. An arid middle age marked by pessimism in drug synthesis in both industrial and academic quarters ensued because of the combined dif

30、ficulties of toxicity, carcinogenicity, and teratogenicity , and the relatively low return from random synthesis. It is characteristic of historical trends, however, that transitions to a new era are obscured and difficult to identify. In medicinal chemistry the doldrums in new drug development are

31、actually yesterdays news, even though the renaissance that has begun is still not widely recognized. Underlying this new age is a foundation that includes the explosive development of molecular biology since 1960, the advances in physical chemistry and physical organic chemistry made possible by hig

32、h-speed computer and new, powerful analytic methods including various types of chromatography, radioimmunoassay, mass spectrometry, X-ray crystallography, and nuclear magnetic resonance spectroscopy. Such newly refined techniques will bring to us an understanding of drug metabolism and its relations

33、hip to drug toxicity, carcinogenicity, teratogenicity, and mutagenicity that will make it possible to minimize or eliminate these hazards. We already know that untoward reactions often caused by reactive metabolites, and we are gaining an understanding of the chemical and biological factors involved

34、 in the production of such substances. In the study of receptors, the combined power of physical chemistry, physical organic chemistry, bioorganic chemistry, and the techniques of quantitative drug design have given such results as the histamine-H2 blockers, a sophisticated antimetabolite and enzyme

35、 inhibitor theory, and a detailed understanding of structure-activity relationships in hormones. Again, the elucidation of the opiate receptor and the finding of endogenous opiate-like substances promise to revolutionize the development of analgesic agents. Work on immuno-stimulatory and immuno-supp

36、ressive agents is dramatically altering our helplessness in the face of viral diseases and immune system disorders such as arthritis.药物化学药化早期的发展被认为主要是源于天然的药剂的预测、分离、结构测定以及合成。第二个主要发展阶段是合成复杂的药物分子的简单片段。这些经验式策略的药物发现黄金时段（1940-1960）随着反应停悲剧的出现而结束。随后跟来的是一个以工业界与学术界对药物合成的悲观为标志的枯燥的中期。因为有致毒、致癌、致畸和因为随意合成而相对低回报的双重

37、困难。然而这就是历史发展的特征，即转到新的纪元是模糊的和难以分辨的。在药物化学里新药开发的不活跃时期事实上已经是昨天的事，尽管当时文艺复兴已经开始，但还未被广泛认知。在这样一个新时期的基础上，建立了一个包括自1960年以来分子生物学爆炸性的发展和由于高速计算机及新的有力的分析方式（各种类型的色谱分析、放射性免疫鉴别、质谱、X光射线、核磁共振）而使物理化学、物理有机化学的进展成为可能。这些最新的精良技术使我们知道了药物代谢和它跟致毒、致癌、致畸和致突变之间的关系，这也使将这些危害降至最低或消除。我们已经知道不良反应经常由起反作用的物质引起，同时我们也得知化学与生物因素都影响着这些物质的产生。在受

38、体学的研究中，物理化学、物理有机化学、生物有机化学和药物定量设计技术的结合力产生了如下结果：H2组胺阻断剂，复杂的抗代谢物，酶抑制剂理论和激素构效关系的详细理解。再有，对阿片受体的解释与内源性阿片样物质的发明保证了止痛剂开发的革命。对免疫增强和免疫抑制的研究戏剧性改变了我们以往面对病毒疾病和免疫系统疾病（如关节炎）毫无办法的状况。PharmacologyIntroduction to Pharmacology: ReceptorsPharmacology is concerned with all facets of the interaction of chemicals with biol

39、ogical systems. When such interactions are applied to the cure or amelioration of disease, the chemicals are usually called drugs.Most drugs produce effects by combing with biological receptors. The chemical bonds that form between drug molecule and receptor are usually reversible. The ease with whi

40、ch drug and receptor interact is influenced by the degree of complementarity of their respective three-dimensional structures. For this reason, minor chemical modification of a drug may produce profound changes in its pharmacological activity.Pharmacology is a hybrid science. It freely draws upon th

41、e intellectual resources of all the basic medical sciences and contributes to every aspect of clinical medicine. It is appropriate, therefore, that the concept of receptors, a central theorem of pharmacology, should have arisen from the work of John Newport Langley, a physiologist, and Paul Ehrlich,

42、 a polymath best remembered for his work in immunology and in the chemotherapy of syphilis.While still an undergraduate in the department of physiology at Cambridge University, Langley studied the antagonism by atropine of the contractile effects of pilocarpine on smooth muscle. Based upon his exper

43、iments with isolated nerve-muscle preparations, he concluded that the drugs did not act directly on the nerve endings or on the muscle. He observed that nicotine causes contraction of muscle whether or not the muscle is innervated. Furthermore, curare, a drug then commonly thought to act upon nerve

44、endings, blocks the effects when stimulated electrically. Langley concluded that nicotine and curare must combine with something that is neither nerve nor muscle; in 1905 he called it “receptive substance”.The subject of Ehrlichs M.D. thesis in 1878 was the histological utility of certain vital dyes

45、. Impressed by the specificity with which dyes interact with tissues, he postulated that a drug can have a therapeutic effect only if it has “the right sort of affinity”. However, his first application of this idea was to immunology rather than to pharmacology. In his side-chain theory, Ehrlich sugg

46、ested that there is binding between toxins and antitoxins via chemically specific functional groups. Later he expanded this idea to include chemoreceptors located in parasites; these receptors could serve as targets for chemically aimed “magic bullets”. Despite the appeal that such ideas have for mo

47、dern pharmacologists, Ehrlich long resisted the application of his theory to drug-tissue interactions in general. There was simply too great a conceptual gap between the firm binding of an arsenical poison to a trypanosome and the evanescent effects of many drugs. But the passage of time, the accumu

48、lation of date, and in particular, a careful consideration of Langleys experiments eventually caused Ehrlichs “doubts to disappear and made the existence of chemoreceptors seem probable”.Today receptors theory serves as a unifying concept for the explanation of the effects of chemicals on biological

49、 systems, whether these chemicals be of exogenous (pharmacological) or endogenous (physiological) origin. A modern statement of the receptor theorem is that of Goldstein, Aronow, and Kalman: in general, a drug produces a particular effect by combining chemically with some specific molecular constitu

50、ent (receptor) of the biological system upon which it acts. The function of the receptor molecule in the biological system is thereby modified to produce a measurable effect.In searching for chemicals that would kill trypanosomes, Ehrlich discovered that arsanilic acid was quite effective. When inje

51、cted into infected mice, some the blood was completely free of parasites. Unfortunately, the mice died shortly thereafter of arsanilic acid poisoning. Arsanilic acid was not an effective therapeutic agent because it was not selectively toxic to trypanosomes. Albert (1979) provides the following defi

52、nition: a remedy is said to have selectivity when it can influence one kind of living cell without affecting others, even when these cells are close neighbors.In Ehrlichs time and no less so today, it is a goal of pharmacology to discover drugs that are highly selective in their actions. In the cont

53、ext of receptors, a drug may be intended to act upon a single type of receptor, and no others, to produce its therapeutic effect. In some areas of therapeutics, mat goal has been approximated; many antibacterial drugs are remarkably free of effects upon mammalian cells. In other areas, the goal is s

54、till far distant; drugs used in an attempt to kill cancer cells often produce toxicity at unintended sites.If drug and receptor interact via chemical forces, then our understanding of drug-receptor interactions will be limited by our knowledge of the chemical forces involved. At the beginning of thi

55、s century, Ehrlichs reluctance to apply the notion of chemoreceptors to all drug-tissue interactions was in part due to an incomplete knowledge of possible binding forces between drug and receptor. Thus, covalent bonds would readily explain the interaction of arsanilic acid with a trypanosome but wo

56、uld fail to account for the fleeting nature of the interaction between acetylcholine and a muscle. Today, we are reasonably confident that the range of known chemical bonds is adequate to rationalize all known drug-receptor interactions.药理学绪论：受体药理学是全面研究化学物质与生物系统之间相互作用的一门学科。当这种相互作用被用于疾病治疗时，该化学物质即被称为药

57、物。大多数药物通过与生物学受体相结合而产生药效。药物分子与受体之间的化学偶联作用往往是可逆的。它们之间相互作用的难易受各自三维结构互补程度的影响。因此，即使是细微的化学修饰也可能会引起药物药理学活性的重大改变。药理学是一门交叉学科。它最大限度综合了基础医学各学科的理论资源并指导着临床医学的方方面面。因此，受体这一概念作为药理学的核心理论之一，最早由生理学家John Newport 和Paul Ehrlich 提出也就不足为奇了，后者因其在免疫学和化学治疗梅毒上得突出贡献而为人所熟知。早在就读于剑桥大学生理学院（本科）的时候，Langley 就研究了阿托品对毛果芸香碱所引起的平滑肌收缩的拮抗作用

58、。通过对离体神经肌肉的实验研究，他推断药物并不是直接作用于神经末端或肌肉。Langley 注意到，无论肌肉是否受到神经的支配，烟碱都能够使其收缩；而当时普遍认为作用于神经末端的药物箭毒却能够阻断烟碱对于去神经支配的肌肉的作用；最后被箭毒麻痹的肌肉在电刺激下仍然能够产生收缩。根据上述现象，Langley 认为，烟碱和箭毒一定是与神经和肌肉以外的物质产生了结合；并与1905年将其称为“接受物质”。Ehrlich 1878年的学位论文研究了某些活体染料在组织学中的应用。鉴于染料与组织之间作用的特异性，他推论只有当药物具有正确的亲和性时才能产生治疗作用。然而，该理论的首次应用是在免疫学而不是药理学领域

59、。在他的侧链理论中，Ehrlich 提出在毒素和抗毒素之间存在由特异的化学官能团所形成的偶联。随后，他又将定位于寄生虫体内的化学感受器扩充到这一理论中，这些感受器起着化学上所谓“魔力子弹”的靶点的作用。虽然该理论受到了现代药理学家的广泛关注，但是由于砷化物与锥体虫的牢固结合与很多药物转瞬即逝的药效之间存在巨大差异，因此Ehrlich 一直不愿将此理论应用于解释一般的药物组织相互作用。但随着时间的流逝，数据的积累，特别是Langley 周密的实验设计最终打消了Ehrlich 的疑虑从而使化学感受器理论成立。现在，受体理论作为一个统一的概念，用于阐释化学物质对生物系统的作用，无论该化学物质是外源性的（药理学的）还是内源性的（生理学的）。Goldstein Aronow, 和Kalman 就受体理论作了一个现代意义上的阐述：一般而言，药物通过与（受）其作用（影响）的生物系统上的某些特定分子结构（受体）的化学结合而产生特定的作用。即生物系统中受体分子的功