/u/Corpcasimir hit it on the head. Acetaminophen would never make it to market today. The window between "this works" and "this kills you" is so small for that drug that it's scary that you can just buy it over the counter.

Whenever you take a drug, your body has mechanisms that "see" that it's not something your body has produced and is not food/nutrition. It will then take steps to modify that compound chemically to get it out of your body. For Acetaminophen, the majority of is is metabolized to something you can just pee out. A small amount of it is converted to something else though, something reactive and extremely toxic. Get enough Acetaminophen in your body, or even if you just happen to metabolize it more in the "bad" way, and you get this stuff building up. What literally happens is that it physically reacts with the proteins that control energy production in your cells. No way to make cellular energy = cells die. Enough cells die, your organs start to fail. So yeah. Don't take acetaminophen if you have any other option.

Hey there, I work in pharma, specifically in drug discovery for oncology and rare genetic diseases. Essentially, it's a very long and complicated process, and there's not just one way to do it. Every disease area has its own challenges and methodologies. I'll do my best to give a general overview.

First off, you need a target. A target is typically a protein (but not always) that you are going to try to interact with with a small molecule (what you would think of as a drug). The first step is to determine that there is a causal relationship between the target and the disease. In some cases this is easy, in some cases you can at best prove a peripheral relationship, this is usually where multi-drug therapies come in, like in oncology.

Once you have a target and you can prove via experiment that the target causes the disease, you need an assay. An assay is a test, something that a biologist can put a chemical compound into and determine if it's doing what you want to the target. Sometimes that's shutting the target down, sometimes it's activating it, sometimes that's helping it fold, and so on. Whatever activity you need, the assay tells you if it's working or not.

The next thing that you need is chemical matter. Drugs that you put in a pill are not the only drugs though, so the path is a little different for things like vaccines, antibodies, etc. If we're talking about something that you can put in a pill though, the most common way to start finding chemical matter is through something called at High Throughput Screen or a Virtual Screen. A High Throughput Screen (HTS) is where you take a purchased library of very diverse chemical matter and just test it with the assay to see if any of the compounds do what you want them to do. A Virtual Screen is dependent on whether or not you know what the target looks like and can use computers to model in 3D the target and small molecule to better make decisions about what to test with the assay.

If things work out and your HTS or VS give you a "hit", then you start working on hit expansion. You take that small molecule and make a bunch of little changes. This lets you feel out where changes are tolerated and what parts of that small molecule are essential for your activity. This can take a while. Teams routinely make thousands of what we call "analogs" of our starting hits.

Once you start routinely making very potent compounds, that is compounds that you only need a very small amount of to have the desired effects, you start optimizing for the things that make the potential drugs work well within the body. It's not enough to have a compound that engages your target well, it also has to play well with everything that makes you a human. We use a variety of cells and animal models to make sure that the compounds get transported to the parts of the body we need them to get to, that they're not metabolized in nasty ways by your liver (I'm looking at you acetaminophen), and they stay in your body long enough to have the effect that we need. This is what we refer to as "Late Stage Lead Optimization".

The last stages of this part of the process give us what is called a "Human Dose Projection", which is our estimation based on a lot of data, how much compound we need to put into a person to have the desired effect, whatever that may be.

After that, it's on to human trials. We file a LOT of paperwork with the FDA to being the trials and start recruiting for clinical trials. There are four stages of clinical trials, but the first three are the ones that really matter.

Here's the breakdown:

Phase 1: Healthy volunteers. This is how we show that the drug is safe. We dose a small number of participants with very low doses and watch very closely to make sure that we don't have any bad side effects. If it looks safe, we increase the dose towards what we think is the higher end of what we need to have our desired effect. There are exceptions for "healthy" volunteers, in the event that the risk to the patient for side effects may be outweighed by potential benefit. A good example of this is if we have a very sick cancer patient and a drug that may help them live longer or recover, even if the treatment has side effects.

Phase 2: This is the stage where we have to prove statistically that it works and what the optimal dose is. We dose a larger amount of patients, usually exclusively with the disease (instead of "healthy" volunteers) and try to determine the best dose and dosing protocol, for example, does one big pill once a day work better than two medium sized pills? We try to find the best way to treat the disease while still keeping side effects to a minimum.

Phase 3 is the big one. We dose a much larger patient population and have to prove that whatever drug we're proposing is better than the current treatment available on the market. We have to prove that it's safe, tolerated, and effective. Once the trial is completed, all the data goes to the FDA and they make the call on whether or not the drug is approved. If the drug is approved, it goes on the market, and doctors can prescribe it for the disease it's intended to treat.

Phase 4: Once the drug is on the market and available to anyone who needs it, a field called pharmacovigilance kicks in. These are the folks who look for rarer and more severe side effects that you may not have seen in a smaller trial. Any time you go on a medication, have some bad effect, and report it back to your doctor, that will get back to the drug manufacturer. We literally have teams that watch social media, conferences, literature and so on to look for these rare bad effects called "Adverse reactions". If enough of these happen, the FDA can recall a medication or give it what's called a "black box warning".

To specifically address your question about combination of chemicals, that's typically done when there's not one single target that causes the disease. For example, cancer needs a LOT of stuff to go wrong in your cells for the disease to form. In these cases you typically will pair one new drug, with other already approved drugs to try to hit multiple targets at once. It is exceedingly rare that two new drug molecules will be trialled at the same time, since there are so many variables to control for when it comes to safety, side effects and dosing.

If you have any follow up questions, I'm happy to expand on any of this.