The Solution to Extreme Side Effects is in Your Genes
How pharmacogenetics will help us prevent extreme drug side effects by individualizing treatment
1 in 250 Americans goes to the hospital emergency ward because of extreme drug side effects.
Wouldn’t it be great if no one had to go to the ER for something as solvable as side effects? We would save more space for people with life-threatening conditions, rather than people who got the wrong drug.
Now finally, our long-awaited saviour is here! The name of it is Personalized Medicine.
You must be thinking — Wait.. 😕 what? What is this long fancy sounding name?
The thing is; all of us have a unique set of DNA. This is why not all widespread treatments will work for every one of us. Even our diseases can range from severe to mild.
This problem is exactly what Personalized Medicine aims to solve; group people into categories, and create specific treatments that would work for them.
Overview
This concept of Personalized Medicine still stands with allocating drugs to individuals.
The effect drugs have on people differs from their DNA and lifestyle. For example, some people get huge rashes or even hives from vaccines while others like myself don’t feel a thing.
But the thing is… How do we know how people will react to drugs
I gotchu don’t worry 😉.
The steps to solving this ⬇️:
- Differentiate people into groups (by genetics or biodata)
- Look at how the body interacts with the drug
- Find how well the drug works
And this right here is the Pharmacogenomics (pharma = medical drugs, genomics = your genetics) 😎!
Differentiating people into groups
Ok, I see… sounds simple. But how do we do this?
Since the issue at hand here is how people react to drugs, we can assume that:
Similar genetically composed people will have similar reactions to drugs.
Now let’s learn about how to differentiate people!
Genome sequencing
Let’s say you’re writing an essay on a play. Wouldn’t you need to read the whole play to write the essay?
I am going with this because DNA is just too small to study off of, WE NEED THE FULL code! And the full code is the genome 🧬.
The genome is the complete set of code that makes up YOU!
Well — how do we find this amazing code?
Here are the steps:
- Get the genome from someone’s body, and cut it up into extra-small bits
- Make copies of each piece (using enzymes)
- Mix copies of the 4 main DNA parts (A, T, G, C) and with enzymes
- Fold the copies you made (and remember what they are!) with the small bits of the genome
- Now the DNA bits will automatically rearrange with their matching pair in the genome (A’s go to the T’s, and the C’s go to the G’s)
- Since they match, you can read the order of the genome bit by reading it reversely (ex. ‘A’ DNA bit = ‘T’ Genome bit)
- Take snapshots of each sequence, and record the order (of the small bits)
- Combine the sequences you found
- Now you have a sequenced Genome!
Now, what do we do with this genome?
→ Within the Genome we can look for genetic variations; mutations in the natural sequence.
For example, let’s say you have this DNA code: CTGATGCT. A mutation of this would be CT_ATGCT, where a part of the code is deleted.
Genetic mutations can lead to:
- Greater risk for adverse side effects of drugs
- Need for a higher dose of the drug
- No benefit from drugs
- Need for a longer set of treatments
How the drug interacts within the body
Now onto how drugs work in the body.
So, when a drug enters the body, it has many forms of interaction, 4 steps that show the effects it has:
- Absorption
- Distribution
- Metabolization
- Elimination
These four steps are a part of the body’s pharmacokinetics, the study of how the body interacts with drugs. To be exact, what the body does to the drug.
Pharmacokinetics is the study of what the drug goes under through the body’s system
This is how it works:
You eat the drug
Through this, your body absorbs the drug through 3 types of processes, which all depend on the type of drug you take.
These three processes are:
→ Passive Diffusion (for water-based or lipid-based drugs)
→ Facilitated Diffusion (if the membrane is larger)
→ Active Transport (needs more assistance in moving through the membrane)
Some more factors that can affect this process are the pH, surface area and blood flow. These can take either more or less time to absorb in the body.
The drug goes everywhere in your body
After this, the drug is distributed to places in your body. How this distributes depends on many factors:
→ your blood flow (eg. low blood pressure takes longer to distribute)
→ capillary permeability (eg. some places in your body take less time for the drug to go through!)
→ plasma and tissue binding (eg. tissue takes more time since it is thicker)
The drug turns into something else (spooky)
Once the drug passes through the liver, with the help of enzymes, it metabolizes into a new substance.
For example, when you eat Tylenol, most of it remains intact until the liver stage. Here, it breaks down with the help of cytochrome P450 and N-acetyl-p-benzoquinone imine(NAPQI) into the simple substances sulphate and glucuronide.
This substance created after the metabolization stage will differ between different drugs taken in the body.
The drug leaves your system 👉🚪
This is the smallest, and easiest stage to understand, the drug just excretes from the body! All metabolized substances from the previous stage get excreted through the body’s system. This is how substances don’t stay in the body forever.
Overview:
- The drug enters the body
- It then distributes throughout the body
- Metabolizes into another substance (this substance depends on which drug)
- Leaves the body
How do we target cells with drugs?
Contrasting with Pharmacokinetics which deals with how drugs interact with the body’s systems, pharmacodynamics is how the body reacts to drugs. (think of them as opposites!!)
Pharmacokinetics links to this idea of how we have different genetic makeup, and how we react differently to drugs.
There are two types of drugs that can enter your system:
- Agonists: creates a reaction within the body
- Antagonists: reject the action
This action is the signalling molecule in the brain.
Now let me explain.
Here is a cell that creates a brain transmission:
Within the cell, there is a receptor that when it interacts with the signalling molecule, will create a transmission to your brain (will create a response!)
Both the Agonist drugs and Antagonist drugs have different functions, and either block or amplify the signalling molecule.
Agonist drugs:
There are two types of Agonist drug reactions:
→ Direct: drug links to the receptor, and creates a large transmission
→ Indirect: drug amplifies the signalling molecule
Some examples of Agonist drugs are morphine, heroin, fentanyl, methadone, and endorphins *think of any drug that makes someone high
Antagonist drugs:
Within the category of Antagonist drugs, there are two types:
→ Competitive: blocks small amounts of signalling transmission
→ Non-competitive: completely blocks the signalling transmission
Some examples of Antagonist drugs are naltrexone, naloxone, and drugs that block any type of agonist drug’s effects (ex. naloxone is used to treat opioid overdose)
Another factor that affects how the body reacts to drugs is dose response.
Dose-response
Key points ⭐️
→ Depending on the concentration/potency of the drug, the response can vary.
→ Best point of efficacy is when dose and response are at the highest points
Application:
Now here is the thing, since everyone has a different cell, we can assume that everyone has different receptors, and will have a different highest point for dose-response
Consider:
Now, this is how we can link the ideas we learned about earlier, to how we are different as humans. Since we all have different cells, we have different receptors as well.
→ More receptors: more response, needs less dose
→ Fewer receptors: less response, needs a lower dose
Overview:
- Agonist drugs = amplifying signalling molecules
- Antagonist drugs = blocking signalling molecules
- Dose-response depends on the concentration of the drug
- The number of receptors in cells allows drugs to have either a strong or weak response
Application:
Now that you have made it to this point, give yourself a high five! The final step is to apply this information.
So, let us look at how to treat a patient:
- Sequence their genome, and look for mutations that can affect the drug’s effect on the body
- Using this information, compare it with a set of people that have a similar genetic code (CHECK THEIR REACTIONS!!)
- Allocate drugs that follow the person’s pharmacokinetic process (how they digest, how they metabolize, etc.)
- Check for their pharmacodynamic process; reactions to previous drugs, and the quality of receptors (how much drug they need!)
Challenges of Pharmacogenetics:
- It is a long process of trial and error
- We need lots of data on reactions and people’s genomes! There are many privacy concerns about this since it is very personal information
- Need to study each drug in depth
- This is still under-developed and is a relatively new concept in the medical field
But despite the numerous challenges, the importance of this technology outways it by a landslide!
Especially since everyone and their mom takes vaccines regularly, and the sheer number of people who take them is insane. We need to prevent side effects and save lives!
Companies paving the way🌟
- Genetika: Finding the right type of anti-depressant for the specific patient
- Admera Health: Gives reports on the individual’s pharmacogenomics, and susceptibility to diseases
- Genomind: Changing the way mental health is treated, by individualizing it and creating reports based on genomics
- Mydna.life: Medication tests to help find the right drugs based on the person’s genome.
Since we have all the ingredients, all we need is lots and lots of application!!
Check this out!
- The twenty-year-long process of the first genome ever sequenced
- A little bit about psychiatric pharmacogenomics
- History of Pharmacogenomics
- How genetics are important in medicine
- Pharmacokinetics introduction
- Process of pharmacodynamics
Hey! Thanks for reading my article! My name is Anya Ishani Sharma, and I am a grade 11 student interested in biotech, ecology and visual arts! If you loved this article, please feel free to reach out! You can contact me through my email (anya.ishani.sharma@gmail.com), and my Linkedin (click here).
