药学的重要性英语论文

Oral Administration 口服给药 For oral administration, the most common route, absorption refers to the transport of drugs across membranes of the epithelial cells in the GI tract. Absorption after oral administration is confounded by differences in luminal pH along the GI tract, surface area per luminal volume, blood perfusion, the presence of bile and mucus, and the nature of epithelial membranes. Acids are absorbed faster in the intestine than in the stomach, apparently contradicting the hypothesis that un-ionized drug more readily crosses membranes. However, the apparent contradiction is explained by the larger surface area and greater permeability of the membranes in the small intestine. 口服是最常用的给药途径，其吸收涉及药物通过胃肠道上皮细胞膜的转运。由于给药时相关环境条件的不同，如胃肠道管腔内pH及单位腔道容积的表面积，组织血流灌注情况，胆汁和粘液的存在以及上皮细胞膜的性质等，口服给药的吸收也有差异。酸性药物在肠中的吸收较胃中快，这显然与非解离药物更易透过细胞膜这一假设相矛盾。然而，这种明显的矛盾却可以从小肠具有很大的表面积和小肠细胞膜具有较大的通透性中得到答案。 The oral mucosa has a thin epithelium and a rich vascularity that favors absorption, but contact is usually too brief, even for drugs in solution, for appreciable absorption to occur. A drug placed between the gums and cheek （buccal administration） or under the tongue （sublingual administration） is retained longer so that absorption is more complete. 口腔粘膜上皮很薄，血管丰富，有利于药物吸收。但是，接触的时间太短暂，即使是溶液剂也来不及等到明显的吸收发生。把一种药物置于齿龈和面颊之间（颊部给药）或置于舌下（舌下给药）则可保留较长时间，使吸收更加完全。 The stomach has a relatively large epithelial surface, but because it has a thick mucous layer and the time that the drug remains there is usually relatively short, absorption is limited. Absorption of virtually all drugs is faster from the small intestine than from the stomach. Therefore, gastric emptying is the rate-limiting step. Food, especially fatty foods, slows gastric emptying （and the rate of drug absorption）, explaining why some drugs should be taken on an empty stomach when a rapid onset of action is desired. Food may enhance the extent of absorption for poorly soluble drugs （eg, griseofulvin）, reduce it for drugs degraded in the stomach （eg, penicillin G）, or have little or no effect. Drugs that affect gastric emptying （eg, parasympatholytic drugs） affect the absorption rate of other drugs. 胃具有相对大的上皮表面，但由于它有较厚的粘液层，而且药物在胃内停留的时间相对较短，吸收也较少。事实上，所有药物在小肠中的吸收速度都要比胃中快。因此，胃排空即是一限速性步骤。食物，特别是脂类食物，延缓胃排空速度（从而也延缓药物吸收速度），这也就是为何某些希望迅速奏效的药物宜空腹服用的原因。食物可增强某些溶解性差的药物（如灰黄霉素）的吸收，减少胃内降解药物（如青霉素G）的吸收，食物以裁缝折吸收或无影响，或影响甚少。影响胃排空的药物（如副交感神经阻断剂）可影响其他药物的吸收速度。 The small intestine has the largest surface area for drug absorption in the GI tract. The intraluminal pH is 4 to 5 in the duodenum but becomes progressively more alkaline, approaching 8 in the lower ileum. GI microflora may inactivate certain drugs, reducing their absorption. Decreased blood flow （eg, in shock） may lower the concentration gradient across the intestinal mucosa and decrease absorption by passive diffusion. （Decreased peripheral blood flow also alters drug distribution and metabolism.） 小肠在胃肠道中具有最大的药物吸收表面积。十二脂肠腔内pH值为4~5，管腔内pH值趋碱性逐渐增强，至回肠下部时pH接近8。胃肠道内的菌丛可使某些药物失活，降低药物的吸收。血流量的减少（如休克病人）可以降低跨肠粘膜的浓度梯度，从而减少被动扩散吸收。（外周血流减少也会改变药物的分布和代谢。 Intestinal transit time can influence drug absorption, particularly for drugs that are absorbed by active transport （eg, B vitamins）, that dissolve slowly （eg, griseofulvin）, or that are too polar （ie, poorly lipid-soluble） to cross membranes readily （eg, many antibiotics）. For such drugs, transit may be too rapid for absorption to be complete. 肠道通过时间肠道通过时间能影响药物吸收，特别是经主动转运吸收的药物（如维生素B）、溶解缓慢的药物（如灰黄霉素），或极性太高（即脂溶性差）难以透过细胞膜的药物（如许多抗生素）。这类药物通过太快，致使吸收不全。 For controlled-release dosage forms, absorption may occur primarily in the large intestine, particularly when drug release continues for > 6 h, the time for transit to the large intestine. 对控释剂型来说，吸收主要在大肠内进行，特别是药物释放时间超过6小时，也就是药物运达大肠的时间。 Absorption from solution: A drug given orally in solution is subjected to numerous GI secretions and, to be absorbed, must survive encounters with low pH and potentially degrading enzymes. Usually, even if a drug is stable in the enteral environment, little of it remains to pass into the large intestine. Drugs with low lipophilicity （ie, low membrane permeability）, such as aminoglycosides, are absorbed slowly from solution in the stomach and small intestine; for such drugs, absorption in the large intestine is expected to be even slower because the surface area is smaller. Consequently, these drugs are not candidates for controlled release. 溶液剂型的吸收药物吸收受到大量胃肠道内分泌液的影响。药物要想被吸收，就必须要在与低pH环境及潜在的降解酶的接触中生存下来。通常，即使某种药物在肠环境中很稳定，但进入大肠的仍然是极少数。低亲脂性（即膜通透性低）药物，如氨基糖苷类，经胃和小肠溶液被缓慢吸收。而在大肠中，因表面积更小，预期吸收更慢。因此，这些药物不宜制成控释剂型。 Absorption from solid forms: Most drugs are given orally as tablets or capsules primarily for convenience, economy, stability, and patient acceptance. These products must disintegrate and dissolve before absorption can occur. Disintegration greatly increases the drug's surface area in contact with GI fluids, thereby promoting drug dissolution and absorption. Disintegrants and other excipients （eg, diluents, lubricants, surfactants, binders, dispersants） are often added during manufacture to facilitate these processes. Surfactants increase the dissolution rate by increasing the wetability, solubility, and dispersibility of the drug. Disintegration of solid forms may be retarded by excessive pressure applied during the tableting procedure or by special coatings applied to protect the tablet from the digestive processes of the gut. Hydrophobic lubricants （eg, magnesium stearate） may bind to the active drug and reduce its bioavailability. 固体剂型的吸收主要是出于方便、经济、药物稳定性、及病人接受性的考虑，大多数药物都以片剂或胶囊剂口服给药。这些制剂必须经过崩解和溶解才能被吸收。崩解大大增加了药物与胃肠液的接触表面积，从而促进药物的溶解和吸收。在制药过程中,为了促进崩解和溶解作用，往往添加一些崩解剂和其他赋形剂（如稀释剂、润滑剂、表面活性剂、粘合剂、分散剂）。表面活性剂通过增加药物的吸湿性、溶解度和分散性来增加其溶解速率。在制片过程中压片压力过大，或为了使药片免受肠道消化作用的影响而使用特殊的包衣，可延缓固体剂型的崩解。忌水性润滑剂（如硬脂酸镁）可与活性药物结合而降低其生物利用度。 Dissolution rate determines the availability of the drug for absorption. When slower than absorption, dissolution becomes the rate-limiting step. Overall absorption can be controlled by manipulating the formulation. For example, reducing the particle size increases the drug's surface area, thus increasing the rate and extent of GI absorption of a drug whose absorption is normally limited by slow dissolution. Dissolution rate is affected by whether the drug is in salt, crystal, or hydrate form. The Na salts of weak acids （eg, barbiturates, salicylates） dissolve faster than their corresponding free acids regardless of the pH of the medium. Certain drugs are polymorphic, existing in amorphous or various crystalline forms. Chloramphenicol palmitate has two forms, but only one sufficiently dissolves and is absorbed to be clinically useful. A hydrate is formed when one or more water molecules combine with a drug molecule in crystal form. The solubility of such a solvate may markedly differ from the nonsolvated form; eg, anhydrous ampicillin has a greater rate of dissolution and absorption than its corresponding trihydrate. 溶解速率溶解速率决定药物吸收时的可用度。当溶解速率低于吸收速率时，溶解就会制约吸收。药物的总体吸收可通过改变配方来加以调控，例如，减小颗粒体积可增加药物的表面积，从而增加那些溶解缓慢吸收受限的药物的胃肠道吸收速率和分量。药物的不同形式，如盐、晶体或水合物等，都可影响溶解速率。不管介质的pH是多少，弱酸的钠盐（如巴比妥酸盐，水杨酸盐）比其相应的游离酸溶解得快。某些药物有多种形态，可以非晶体形或不同晶体形存在。棕榈酸氯霉素有两种存在形态，但只有一种形态能充分溶解吸收，也因而被临床使用。当一个或多个水分子和一个晶体形药物分子相结合时，就构成一种水合物。这种的溶解度可能与非水合物的溶解度有明显的不同。例如，无水氨苄西林的溶解速率和吸收比其它相应水合物的溶解吸收速率都要快得多。

Surfactants may affect drug dissolution in an unpredictable fashion. Low concentrations of surfactants lower the surface tension and increase the rate of drug dissolution, whereas higher concentrations of surfactants tend to form micelles with the drug and thus decrease the dissolution rate.表面活性剂可以影响药物溶出是一种不可预测的方式，低浓度的表面活性剂降低表面张力和提高溶出率，然而高浓度的表面活性剂趋于与药物形成胶团，因此降低药物溶出速率。Introduction of Nucleic acidsNucleic acids are polyanionic molecules of high molecular weight. These polymers are composed of sequence of subunits or nucleotides so that the whole is usually termed a polynucleotide. The nucleic acids are of two main varieties, ribonucleic (RNA) and deoxyribonucleic (DNA). DNA is found primarily in the chromatin to the cell nucleus, whereas 90% of RNA is present in the cell cytoplasm and 10% in the nucleolus. The two classes of nucleic acids are distinguished primary on basis of the five-carbon atom sugar of pentose present. Two general kinds of bases are found in all nucleic acids. One type is a derivative of the parent compound purine. Principle examples are guanine and adenine. The second class of bases found in all nucleic acid is derived from the parent compound pyrimidine. 介绍核酸核酸是超高分子量聚阴离子分子。这些聚合物组成，亚基或核苷酸，使整个通常称为多核苷酸序列。核酸有两种，主要品种核糖核酸（RNA）和脱氧核糖核酸（DNA）的。 DNA是主要存在于细胞核内的染色质，而90％的RNA在细胞质现在和10％的核仁。核酸类的两个主要的区别在于对目前的五个戊糖碳原子的糖基础。一般两个种基地发现，在所有核酸。一类是母体化合物嘌呤的衍生物。原理是鸟嘌呤和腺嘌呤的例子。在所有发现核酸碱基第二类是来自母体化合物嘧啶。

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