How are drugs developed to target specific areas (pain/allergies/disease). How do you translate scientific body knowledge into a drug that targets that area. And how do scientists determine cross reactions to other drugs or conditions. Do they have to test every combo?
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To be clear, you’re Eli 5-ing a doctoral degree:
[Pharmacy](https://en.m.wikipedia.org/wiki/Pharmacy) is the clinical health science that links medical science with chemistry and it is charged with the discovery, production, disposal, safe and effective use, and control of medications and drugs. The practice of pharmacy requires excellent knowledge of drugs, their mechanism of action, side effects, interactions, mobility and toxicity. At the same time, it requires knowledge of treatment and understanding of the pathological process. Some specialties of pharmacists, such as that of clinical pharmacists, require other skills, e.g. knowledge about the acquisition and evaluation of physical and laboratory data.
“Designing” drugs is kind of new. Historically, we found chemicals that did something interesting, then we made chemical modifications to it, or looked for ones with similar shapes and experimented to see if they did something.
Today, we still do that, but we also do things like work out what causes pains or disease and try to make drugs specifically shaped to fit some other molecule, or chemically react with it. A lot of biology involves sort of lock-and-key type situations where a particular shape fits into a protein or something, and some shape change or chemical reaction is the result.
Most drugs are still not “targeted”. They mostly get put into the body until they bump into something they happen to interact with, usually by circulating in the blood. Ideally, a drug only interacts with one thing that causes a problem, and hopefully the body doesn’t break it down into smaller molecules that do something undesirable. This is hard, and some drugs can make people sick because it affects things in addition to the one it is supposed to.
However, a great deal of research is being put into how to get drugs to focus on specific tissues or types of calls (like cancer cells). This frequently involves looking for features that are unique to particular groups of cells and finding away to attach to the drug something that will stick to those cell-specific features (like proteins). This is very hard.
If you take something like ibuprofen, you swallow it, the pill dissolves, it’s absorbed into your blood like nutrients from food, and it swishes around your insides by way of your blood like millions of others molecules. When it happens to brush up against a particular protein involved in inflammation, it gets wedged in it and prevents it from furthering the inflammation.
Drugs generally are not designed to target a specific area. This is often the source of drug side effects – the drug target causes disease in one tissue or scenario, but is important for healthy function elsewhere, and the drug does not discriminate.
There are a couple of ways to define cross-reactions:
1. The most common cross-reactions with other drugs are caused by inhibiting the breakdown of the other drugs you’re taking. All drugs become harmful if taken at too high a dose, and the dose one takes on a daily basis is selected to achieve a balance of the amount coming in with the amount that is exiting the body. Some drugs will interfere with the mechanism by which another drug is eliminated, causing it to accumulate to abnormal levels. However, we understand most of the mechanisms through which drugs are eliminated, and we can test to see if a new drug interferes with those mechanisms – this allows us to predict cross reactions (e.g., if Drug X is eliminated by mechanism X, and Drug Y slows down mechanism X, you would expect Drug Y to cause excess accumulation of Drug X).
2. The less desirable mechanism is to see the cross-reactions in the real world in patients. When enough people have taken a drug, you can use anonymized medical records to determine if they have better or worse long-term outcomes (e.g., likelihood of dying from a disease). You can similarly see if there is an unexpected rise in health problems when two drugs are combined. Of course, this means bad things have happened to people, so the objective is to identify and remove these risks before the drug goes to people, or at least a broad population (hence the need for rigorous clinical trials before approving a new drug)
One of the key parts of interactions is understanding how the drug is absorbed, broken down or excreted by the body. Knowing what liver enzyme, how it’s absorbed into the bloodstream, or whether it’s actively excreted by the kidneys or in the bowel, will give a string hint as to which other foods or drugs are known to inhibit, compete with, or enable those reactions. For instance, grapefruit juice inhibits a liver enzyme that breaks down many blood pressure drugs, which can lead to an overdose; many foods inhibit some drugs getting into the bloodstream so you’re assured to take it long before or after eating.
I’ll try to explain with an example: Benadryl is for allergies and is in a class of drugs called antihistamines. They are called this because they block the substance, histamine, from doing its thing in the body that causes symptoms like itching, runny nose and sneezing.
Say you’re allergic to cats. You get cat dander in your eyes which your body recognizes as a threat. Histamine starts flowing and triggering this type of response/symptoms. You take Benadryl and the drug gets absorbed and starts traveling all over the body. In most places, you won’t feel any difference but you’ll feel relief where the histamine is causing you the most discomfort. Same thing with seasonal allergies and it’s the same response and same way the drug helps.
Let’s talk briefly about side effects. If you’ve ever taken Benadryl, like most people you’ll notice it makes you tired. This is because the drug gets everywhere in your body including the brain. It blocks histamine there, too, but the effect is much different. In the brain, histamine keeps you alert and you’re blocking its effect there so you get tired.
Finally, drug to drug interactions. We get our information for interactions from a couple main sources. One is when it happens in real life. Another is when you expect an interaction to happen because we know the way drugs work in the body. This is even harder to explain but let’s give one example. Many interactions happen because of how the body processes drugs. There are substances in the liver that break down many drugs to keep them from being active for a long time or prepare them for being eliminated from the body. Sometimes when one of these substances is acting on drug A, that drug can either make the substance break down drug B faster or slower. If it breaks down drug B slower, more of drug B will still be in the body causing its effects. If it breaks down drug B faster, you may not get all the desired effects you’re looking for from drug B because it’s getting broken down too quickly.
Targeted drug therapies are way too complicated to explain and there are many ways that are being developed every day, it seems. (Source: am PharmD)
Drugs are chemicals that bind to a specific molecular target and usually block that target from doing the bad thing it was doing. The premise of a good drug is that it is specific and selective- meaning it binds very well to the thing you want it to, and not to anything else. This is easiest to accomplish when the target belongs to a different organism, like a bacteria or virus, and more difficult to do when it needs to bind to a target on a cell in the body. As the science gets better, we can replace older less specific drugs – think chemotherapy which targets rapidly dividing cells like cancer cells, but also other “normal” cells to a lesser extent, thus making you very sick, and is now being replaced with drugs that recognize specific molecules that cancer cells will have that normal cells do not, or immunotherapy, which elicit that immune system to recognize a cancer target and destroy it.
Most drugs target molecules called enzymes – which control a single interaction in the cell. Once you determine the enzyme that you need to inhibit, you can then chemically refine the drug to improve its selectivity so that it does not bind to other similar enzymes. For instance, aspirin inhibits the Cox2 enzyme, but it also inhibits the Cox1 enzyme. Ibuprofen and other newer NSAIDs target Cox2 and bind much less to Cox1 so they are more selective. They don’t inhibit Cox1 controlled blood clotting or stomach neutralization nearly as much as aspirin does, while still relieving inflammation from Cox2.
Most large pharmaceutical companies have multiple divisions, the basic chemistry and biology research to discover new drugs and refine them (R&D), up scaling production and modifying the format of the drug to be efficiently available and active biologically (Formulations and Pharmacokinetics) and testing in animals and humans for proper dosing, effectiveness and safety (Clinical Development). Smaller companies will do part of the soup to nuts, and partner with other companies to accomplish the rest. Clinical trials are extensive and very, very expensive (think hundreds of millions of dollars).
There are ways to determine many drug interactions just based on mechanisms of action, as well as how the drug is metabolized by the liver. The reason many prescriptions are labeled to to warn you not to eat grapefruit has to do with the fact that grapefruit has a big effect on the way the liver handles things, and it will cause an unwanted blood level of the drug. Most interactions are easy to predict, but others may not be, and will be added as the drug goes through clinical trials. The last stage of clinical development can last years, even after the drug is approved for general use, and if unexpected interactions crop up, they will be added to the database of the drug.
There is much, much more to it but I gave it my best shot!
The simple answer is: We test with animals or people and see the effects. Many medications are actually side effects found when testing a new drug. For example, Viagra’s properties were discovered by accident when using it during a study to treat heart conditions and patients reported boners several days after taking it. If you read the pamphlets that are included in some brand-name medications they use wording such as “It is believed that component-x has an anti-inflammatory action on the xxxxx” which can be translated to “We are not totally sure”. With the existing knowledge you can create new drugs combining drugs with known effects on the body either directly or at a molecule level and hope for the best. Only around 6:/. of drugs make it to market due to unforseen side effects, in other words 94:/. fail.
certain cells have certain ‘receptors’ those receptors either cause a reaction or communicate something to the cell(make more cells, release fluid, absorb sugars)
while biological chemistry only recently got to a point where they could actually design drugs, most of the time is an observed effect of some odd chemical that is then refined into a usable drug.
typically it’s on accident, then used for what it can be used for.
yes basically they have to test combinations as drug interactions can be extremely dangerous.
Hey, so all throughout your body are receptors (locks) drugs work by binding (key) to these locks, which can trigger the receptors to stop doing an action or start an action. Drugs (keys) are being designed to be more exact so they only fit into one similar type of lock rather than multiple types. I work in mental health, when you are given an antidepressant (key), it can act on multiple types of receptors (locks), like dopamine, serotonin, epinephrine receptors. Science is starting to give us the ability to refine the drug so it only will target the dopamine receptor and leave the other ones alone.
lol did you just ask to have all of pharmacology explained to you on reddit?
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