一位制药科学家解释了药物如何知道在体内的去向

StephenW

一位制药科学家解释了药物如何知道在体内的去向
TOM ANCHORDOQUY，对话
2022 年 6 月 18 日

当您服用阿司匹林治疗头痛时，阿司匹林如何知道会到达您的头部并减轻疼痛？

简短的回答是，它没有：分子不能通过身体运输自己，而且它们无法控制它们最终到达的位置。

但是研究人员可以对药物分子进行化学修饰，以确保它们与我们想要它们的地方牢固结合，而与我们不需要的地方结合较弱。

医药产品不仅仅包含直接影响身体的活性药物。药物还包括“非活性成分”或增强稳定性、吸收性、风味和其他对药物发挥作用至关重要的品质的分子。

例如，您吞下的阿司匹林也含有既能防止药片在运输过程中破裂，又能帮助它在体内分解的成分。

作为一名药物科学家，过去 30 年来我一直在研究药物输送。也就是说，开发方法和设计非药物成分，帮助将药物送到需要进入体内的地方。

为了更好地理解不同药物设计背后的思考过程，让我们跟踪一种药物从首次进入人体到最终到达的过程。
药物是如何被人体吸收的

当您吞下一片药片时，它会在药物分子被吸收到您的血液中之前首先溶解在您的胃和肠中。一旦进入血液，它可以在全身循环以进入不同的器官和组织。

药物分子通过与细胞上可以触发特定反应的不同受体结合来影响身体。

即使药物被设计为靶向特定受体以产生所需的效果，也无法阻止它们继续在血液中循环并与可能导致不良副作用的非靶位点结合。

在血液中循环的药物分子也会随着时间的推移而降解，并最终将身体留在尿液中。一个典型的例子是你吃芦笋后尿液可能有强烈的气味，因为你的肾脏清除芦笋酸的速度有多快。同样，多种维生素通常含有核黄素或维生素 B2，当尿液被清除时，它会导致尿液变成亮黄色。

因为药物分子穿过肠壁的效率会因药物的化学性质而异，所以您吞下的一些药物永远不会被吸收并会从粪便中排出。

因为不是所有的药物都被吸收，这就是为什么一些药物，比如那些用于治疗高血压和过敏的药物，会被反复服用，以取代消除的药物分子，并保持血液中足够高的药物水平以维持其作用。身体。
把药物送到正确的地方

与药丸和药片相比，将药物直接注入血液的一种更有效的方法是将其直接注射到静脉中。这样，所有药物都会在全身循环，避免在胃中降解。

许多静脉内给药的药物是“生物制剂”或“生物技术药物”，其中包括来自其他生物体的物质。

其中最常见的是一种称为单克隆抗体的抗癌药物，它是与肿瘤细胞结合并杀死肿瘤细胞的蛋白质。这些药物直接注入静脉，因为您的胃无法区分消化治疗性蛋白质和消化芝士汉堡中的蛋白质。

在其他情况下，需要非常高浓度才能有效的药物，例如用于严重感染的抗生素，只能通过输注来输送。

虽然增加药物浓度可以帮助确保足够的分子与正确的位点结合以产生治疗效果，但它也增加了与非靶位点的结合和副作用的风险。

在正确位置获得高药物浓度的一种方法是将药物涂抹在需要的地方，例如在皮疹上涂抹药膏或使用眼药水治疗过敏。虽然一些药物分子最终会被吸收到血液中，但它们会被稀释到足以到达其他部位的药物量非常低并且不太可能引起副作用。

同样，吸入器将药物直接输送到肺部，避免影响身体其他部位。
患者依从性

最后，所有药物设计的一个关键方面是让患者在正确的时间服用正确数量的药物。

因为对于许多人来说，记住每天服用数次药物很困难，研究人员试图设计药物配方，使它们每天只需服用一次或更少。

同样，药丸、吸入器或鼻腔喷雾剂比需要前往诊所让训练有素的临床医生将其注入您的手臂的输液更方便。
给药的麻烦和成本越低，患者就越有可能在需要时服药。

然而，有时输注或注射是某些药物可以给药的唯一有效方式。

即使所有的科学都足以很好地了解一种疾病以开发一种有效的药物，但通常取决于患者是否让这一切按设计工作。对话

Tom Anchordoquy，科罗拉多大学安舒茨医学校区药物科学教授。

本文根据知识共享许可从 The Conversation 重新发布。 阅读原文。

StephenW

A Pharmaceutical Scientist Explains How Drugs Know Where to Go in The Body
TOM ANCHORDOQUY, THE CONVERSATION
18 JUNE 2022

When you take aspirin for a headache, how does the aspirin know to travel to your head and alleviate the pain?

The short answer is, it doesn't: Molecules can't transport themselves through the body, and they don't have control over where they eventually end up.

But researchers can chemically modify drug molecules to make sure that they bind strongly to the places we want them and weakly to the places we don't.

Pharmaceutical products contain more than just the active drug that directly affects the body. Medications also include "inactive ingredients," or molecules that enhance the stability, absorption, flavor and other qualities that are critical to allowing the drug to do its job.

For example, the aspirin you swallow also has ingredients that both prevent the tablet from fracturing during shipping and help it break apart in your body.

As a pharmaceutical scientist, I've been studying drug delivery for the past 30 years. That is, developing methods and designing nondrug components that help get a medication where it needs to go in the body.

To better understand the thought process behind how different drugs are designed, let's follow a drug from when it first enters the body to where it eventually ends up.
How drugs are absorbed in the body

When you swallow a tablet, it will initially dissolve in your stomach and intestines before the drug molecules are absorbed into your bloodstream. Once in the blood, it can circulate throughout the body to access different organs and tissues.

Drug molecules affect the body by binding to different receptors on cells that can trigger a particular response.

Even though drugs are designed to target specific receptors to produce a desired effect, it is impossible to keep them from continuing to circulate in the blood and binding to nontarget sites that potentially cause unwanted side effects.

Drug molecules circulating in the blood also degrade over time and eventually leave the body in your urine. A classic example is the strong smell your urine might have after you eat asparagus because of how quickly your kidney clears asparagusic acid. Similarly, multivitamins typically contain riboflavin, or vitamin B2, which causes your urine to turn bright yellow when it is cleared.

Because how efficiently drug molecules can cross the intestinal lining can vary depending on the drug's chemical properties, some of the drugs you swallow never get absorbed and are removed in your feces.

Because not all of the drug is absorbed, this is why some medications, like those used to treat high blood pressure and allergies, are taken repeatedly to replace eliminated drug molecules and maintain a high enough level of drug in the blood to sustain its effects on the body.
Getting drugs to the right place

Compared with pills and tablets, a more efficient way of getting a drug into the blood is to inject it directly into a vein. This way, all the drug gets circulated throughout the body and avoids degradation in the stomach.

Many drugs that are given intravenously are "biologics" or "biotechnology drugs," which include substances derived from other organisms.

The most common of these are a type of cancer drug called monoclonal antibodies, proteins that bind to and kill tumor cells. These drugs are injected directly into a vein because your stomach can't tell the difference between digesting a therapeutic protein and digesting the proteins in a cheeseburger.

In other cases, drugs that need very high concentrations to be effective, such as antibiotics for severe infections, can be delivered only through infusion.

While increasing drug concentration can help make sure enough molecules are binding to the correct sites to have a therapeutic effect, it also increases binding to nontarget sites and the risk of side effects.

One way to get a high drug concentration in the right location is to apply the drug right where it's needed, like rubbing an ointment onto a skin rash or using eyedrops for allergies. While some drug molecules will eventually get absorbed into the bloodstream, they will be diluted enough that the amount of drug that reaches other sites is very low and unlikely to cause side effects.

Similarly, an inhaler delivers the drug directly to the lungs and avoids affecting the rest of the body.
Patient compliance

Finally, a key aspect in all drug design is to simply get patients to take medications in the right amounts at the right time.

Because remembering to take a drug several times a day is difficult for many people, researchers try to design drug formulations so they need to be taken only once a day or less.

Similarly, pills, inhalers, or nasal sprays are more convenient than an infusion that requires traveling to a clinic for a trained clinician to inject it into your arm.

The less troublesome and expensive it is to administer a drug, the more likely it is that patients will take their medication when they need it.

However, sometimes infusions or injections are the only effective way that certain drugs can be administered.

Even with all the science that goes into understanding a disease well enough to develop an effective drug, it is often up to the patient to make it all work as designed.The Conversation

Tom Anchordoquy, Professor of Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus.

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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