深入解析青霉素如何挽救成百上千万人的生命?

2016-09-13 佚名 生物谷

近年来,在发达国家中感染性疾病引发的死亡占到了死亡人数中的绝大多数,而且在发展中国家里,感染性疾病依然是引发大多数人死亡的主要原因。在这样的背景下,英国医生亚历山大?弗莱明(Alexander Fleming)于1928年发明了青霉素(盘尼西林),该抗生素在改变现代人医疗卫生上做出了巨大的贡献,此后人类终于拥有了第一个抵御常见感染性疾病的武器了,从此人类就开始了使用抗生素的时代。

近年来,在发达国家中感染性疾病引发的死亡占到了死亡人数中的绝大多数,而且在发展中国家里,感染性疾病依然是引发大多数人死亡的主要原因。在这样的背景下,英国医生亚历山大?弗莱明(Alexander Fleming)于1928年发明了青霉素(盘尼西林),该抗生素在改变现代人医疗卫生上做出了巨大的贡献,此后人类终于拥有了第一个抵御常见感染性疾病的武器了,从此人类就开始了使用抗生素的时代。

发现

抗生素的偶然发现证明了观察的重要性,弗莱明在研究中发现,青霉菌(mould Penicillium)具有一定的抗菌特性,而且其能够分泌一种物质来杀灭细菌,为此弗莱明给其取名为青霉素,他说的最有名的一句话就是:有时候一个人能发现别人从来没有寻找过的东西(One sometimes finds what one is not looking for)。

很多时候,我们总能从历史的长河中发现一些线索,比如土壤具有能够愈合皮肤和伤口感染的特性,而且在古希腊、印度和俄罗斯,医生们常常使用发霉的膏状药物(药膏)来治疗伤口感染;20世纪40年代早些时候,辉瑞公司和美国农业部北部地区研究实验室就开发了多种方法来扩大青霉素的商业化生产。1945年和1964年研究者均因青霉素的发现以及发展而获得了当年的诺贝尔生理学及医学奖,此后研究者们也对青霉素的理解越来越深入。

青霉素自发现后研究者立马开始研究其对疾病的影响,其通常用于治疗二战时期的伤员,用来降低伤员机体坏疽的风险,而这就放宽了患者进行外科手术的时间,从而挽救了很多人的生命,并且这些伤者也避免了进行切断手术来保命。

青霉素的工作机制

目前有很多种方法能够摧毁细菌,比如通过破坏细菌的保护性外膜结构或者干扰细菌赖以生存或繁殖的内部机制。青霉素能够结合细菌细胞表面的青霉素结合蛋白,从而阻断细菌细胞对其细胞壁的改造,一旦细胞的细胞壁功能减弱,细菌细胞就会开始泄露并且死亡。

青霉素的化学结构

近年来,青霉素逐渐变成了一类药物—青霉素类抗生素,这些抗生素有着共同的化学结构,青霉素类抗生素就属于β-内酰胺抗生素类,β-内酰胺环对于细菌非常必要,其能够将抗生素结合到青霉素受体上。通过青霉素基本结构的修饰,化学家们就能够扩大该类抗生素的范围,包括如今一些经常用于治疗常见感染的抗生素药物等。

如果你现在提起一种抗生素的话,它们很有可能都是来自于青霉素类家族,比如奥纳欣、双氯西林和力百汀等。特治星 ( Tazocin)是青霉素类抗生素的另一个商标,近年来其逐渐被用来治疗院内常见的严重感染,因为该类抗生素能够有效杀灭多种不同的细菌。

耐药性的产生

在过去50年里,由于基于青霉素的抗生素已经被广泛用于治疗多种类型的感染性疾病,而细菌则开始想法设法地对多种抗生素产生耐药性。随着时间变化,细菌会慢慢改变青霉素的靶向受体,降低其效力,同时细菌还会不断产生β内酰胺酶,这些酶类物质能够阻断青霉素的β-内酰胺结构从而抑制青霉素的作用。

到1942年时,金黄色葡萄球菌就已经开始对青霉素产生耐药性了,而如今在全世界范围内,许多开始对青霉素作用敏感的细菌都开始对青霉素产生耐药性了。从另一方面来讲,很多常见的细菌仍然对青霉素比较敏感,而在社区治疗中,青霉素也是最常用的治疗肺炎的抗生素,引发肺炎的是一种常见的肺炎球菌,其对青霉素比较敏感。

利用和价值

青霉素和其相关的抗生素如今依然是人类最常用于治疗一系列胸部感染、咽喉感染以及皮肤和软组织感染的一类抗生素,2014年仅使用药物奥纳欣,澳大利亚的患者就使用了580万个处方的药物;而且使用这些抗生素的决定依赖于患者机体感染性的位点,同时患者往往会出现被耐药性细菌感染的可能性。

不同的青霉素药物价格并不一样,比如青霉素VK(口服青霉素)的价位15澳元,而药物特治星的价格则为70澳元。

药物让你感觉如何?

青霉素和其相关的抗生素往往和危及生命的过敏症,比如过敏性反应直接相关,幸运的是仅在不到0.03%的患者中才会偶然出现这种过敏性反应,由于青霉素被人们广泛使用,因此对于人们而言有效区分严重的过敏症和轻度的副作用就显得尤为重要了。青霉素是一类非常有用的抗生素家族,因此如果其引发的副作用比较轻的话,在医生的指导下进行服药往往显得非常重要,在有些情况下就很有必要对青霉素严重过敏的患者进行脱敏治疗。

青霉素有着广泛的副作用,最常见的副作用就是胃部不适,同时伴随着恶心、腹泻或者皮疹发生,同时也会出现罕见的副作用,包括肝脏和肾脏炎症等。像所有抗生素一样,青霉素也会引发患者感染艰难梭菌,这种细菌会引发严重的腹泻,而这取决于机体肠道正常菌群的改变。

一般来讲,青霉素能够同其它药物组合起来被患者安全使用,尽管如此,偶然情况下青霉素就会修饰特殊药物的水平来影响药物的疗效,比如药物甲氨蝶呤,其是一种用于治疗癌症及自身免疫障碍的特殊药物。(生物谷Bioon.com)

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参考资料:

【1】"One sometimes finds what one is not looking for" (Sir Alexander Fleming): the most important medical discovery of the 20th century.

Acta Paediatr   http://www.ncbi.nlm.nih.gov/pubmed/17187625

【2】History of Antibiotics

【3】The Nobel Prize in Physiology or Medicine 1945

【4】The Nobel Prize in Chemistry 1964

【5】Florey, Howard Walter

【6】Microbiology of Antibiotic Resistance in Staphylococcus aureus

Clin Infect Dis    doi: 10.1086/519474

【7】THE FACTS ABOUT PENICILLIN ALLERGY: A REVIEW

J Adv Pharm Technol Res    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3255391/

【8】Penicillin Allergy and Desensitization in Serious Infections during Pregnancy

NEJM   DOI: 10.1056/NEJM198505093121905

【9】Weekly Dose: penicillin, the mould that saves millions of lives

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    2017-03-03 hongbochen
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    2016-09-15 sunyl09
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    2016-09-14 青龙偃月

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    2016-09-14 青龙偃月

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    2016-09-14 1dd8a7c5m95(暂无匿称)

    学习了,赞一个!!!

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    2016-09-14 1dd8a7c5m95(暂无匿称)

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