Why Medications Affect People Differently: The Real Science Behind Drug Side Effects

Have you ever taken the same medication as someone else and had a completely different experience? One person feels fine, another ends up in the hospital. It’s not just bad luck. It’s biology. The reason some people get sick from a drug while others don’t has everything to do with how their body is built - down to their genes.

It’s Not Just the Drug - It’s You

Medications don’t work the same way for everyone. That’s not a myth. It’s science. A drug meant to lower blood pressure might make one person dizzy, while another feels nothing at all. An antibiotic could cause a rash in one person and work perfectly in another. These aren’t rare oddities. They’re the norm.

The World Health Organization defines an adverse drug reaction as any harmful, unintended response to a medicine taken at normal doses. In the U.S., these reactions are the fourth leading cause of death. In Europe, 3.6% of hospital admissions are directly linked to them. And in Australia, the cost of managing these reactions runs into hundreds of millions annually. The problem isn’t that drugs are unsafe - it’s that we treat them like they’re one-size-fits-all.

Your Genes Are the Key

Your DNA holds the blueprint for how your body handles drugs. The most important players are enzymes in your liver, especially the cytochrome P450 family - CYP2D6, CYP2C9, and CYP2C19. These enzymes break down over 70% of all prescription medications. But not everyone has the same versions of these enzymes.

Some people are poor metabolizers. Their bodies break down drugs too slowly. That means the drug builds up, increasing the risk of side effects. About 5 to 10% of Caucasians are poor metabolizers of CYP2D6. If they take a common antidepressant like amitriptyline, they can end up with toxic levels in their blood - even on a normal dose.

Others are ultra-rapid metabolizers. Their bodies clear drugs too fast. For them, standard doses might not work at all. In some populations, like Ethiopians, up to 29% are ultra-rapid metabolizers of CYP2D6. A standard dose of codeine? It turns into morphine too quickly, causing dangerous breathing problems in children - a tragedy that led to FDA warnings in 2013.

And then there’s warfarin, the blood thinner. Two people on the same dose can have wildly different outcomes. One stays stable, the other bleeds internally. Why? Because of two genes: CYP2C9 and VKORC1. Together, they explain 30 to 50% of why warfarin doses vary so much. When doctors test for these variants, patients reach safe levels faster - and have 31% fewer major bleeds.

It’s Not Just Genes - Age, Diet, and Other Drugs Matter Too

Your genes aren’t the whole story. Your age, what you eat, and other medications you take all change how drugs behave in your body.

As you get older, your body changes. Fat increases. Liver and kidney function slow down. That means fat-soluble drugs like diazepam or antidepressants stick around longer. An 80-year-old might need half the dose of a 30-year-old for the same effect.

Then there’s diet. Grapefruit juice? It blocks an enzyme called CYP3A4. That can cause statins like simvastatin to build up to dangerous levels. One glass can turn a safe dose into a toxic one.

And drug interactions? They’re a silent killer. Take amiodarone - a heart rhythm drug - and warfarin together. Amiodarone shuts down the enzyme that clears warfarin. That can boost warfarin levels by 100 to 300%. The result? A spike in INR, internal bleeding, emergency rooms.

Even inflammation from a cold or flu can lower enzyme activity by 20 to 50%. So a drug that worked fine last week might suddenly cause side effects because your body is fighting an infection.

Pharmacogenomics: The Future Is Here - But Not Everywhere

This is where pharmacogenomics comes in. It’s the science of using your genes to choose the right drug and dose. The FDA now includes pharmacogenomic info on the labels of over 300 drugs. For 44 of them, they give specific dosing recommendations based on genetics.

At St. Jude Children’s Research Hospital, testing for a gene called TPMT before giving mercaptopurine to kids with leukemia cut severe side effects from 25% to just 12%. That’s life-changing.

And it’s not just cancer. In psychiatry, testing for CYP2D6 and CYP2C19 helps doctors pick antidepressants that won’t make patients worse. In cardiology, testing for CYP2C19 before giving clopidogrel (a common heart drug) identifies patients who won’t benefit from it at all - about 2 to 15% of people. These patients need a different drug, not a higher dose.

But here’s the problem: most doctors still don’t test. Only 18% of U.S. insurers cover it. Two-thirds of physicians say they don’t feel trained to use genetic results. And hospitals? Only 32% have systems that alert doctors when a patient’s genetics suggest a dangerous interaction.

It’s not that the science is missing. It’s that the system hasn’t caught up.

Why Some People Waste Money on Drugs That Don’t Work

This isn’t just about safety. It’s about money.

Take zafirlukast, a drug for asthma. It costs $250 to $300 a month. But only about 5% of asthma patients have a specific gene variant - the 5-LO polymorphism - that makes it work. The rest? They pay hundreds a month for no benefit. That’s billions wasted every year.

Same with leukotriene modifiers. A 2022 Mayo Clinic study found that patients who got genetic testing had 32% fewer ER visits and 26% shorter hospital stays. But without testing, doctors are guessing. And guessing costs lives - and money.

What’s Changing - And What’s Still Broken

The good news? Things are moving. In January 2024, Medicare started covering pharmacogenomic testing for 17 high-risk drugs. The cost of genetic panels has dropped from $2,000 in 2015 to under $250 today. The FDA approved the first point-of-care CYP2C19 test in 2023 - results in 60 minutes. The EU now requires pharmacogenomic data in all new clinical trials.

But the biggest barrier isn’t science. It’s access. Genetic testing is still mostly available in big hospitals and academic centers. Rural clinics, community pharmacies, and low-income patients? They’re left out. And even when testing is done, results often sit in a file, unread by the doctor who prescribed the drug.

And here’s the hard truth: genes aren’t the whole picture. Most drug responses involve hundreds of small genetic changes, not just one. Single-gene tests explain maybe 15% of side effects. The rest? We’re still figuring it out.

What You Can Do Right Now

You don’t need a genetics degree to protect yourself.

• If you’ve had a bad reaction to a drug, tell your doctor - and write it down. Include the drug, the side effect, and when it happened.
• Ask if your meds are on the FDA’s pharmacogenomic list. You can search it online - it’s public.
• If you’re on multiple drugs (especially if you’re over 65), ask about possible interactions. Many side effects aren’t from one drug - they’re from the mix.
• If you’re considering a new drug, ask: “Is there a genetic test that could help decide if this is right for me?”
• Keep a list of all your meds - including supplements and over-the-counter drugs. Bring it to every appointment.

There’s no magic pill. But knowing your body’s unique response to drugs is the closest thing.