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

Have you ever taken the same medication as someone else-same dose, same condition-and had a totally different experience? One person feels fine, another gets dizzy, nauseous, or worse? It’s not just bad luck. It’s biology. Medications don’t work the same way for everyone, and the reasons why are deeper than most people realize.

It’s Not Just About the Drug-It’s About You

When a doctor prescribes a pill, they’re not just giving you a chemical. They’re handing you a key that’s supposed to unlock a specific biological lock. But here’s the catch: everyone’s locks are slightly different. Some keys turn smoothly. Others jam. Some even break the lock.

This isn’t theoretical. About 3.6% of people in Europe are hospitalized because of side effects from medications they were taking as directed. In the UK, adverse drug reactions cost the NHS over £770 million every year. And it’s not just expensive-it’s dangerous. Adverse drug reactions are among the top causes of death in the US, ranking fourth after heart disease, cancer, and stroke.

The truth is, most side effects aren’t random. They’re predictable-if you know what to look for. And the biggest predictor? Your genes.

Your Genes Control How Your Body Handles Drugs

Your DNA doesn’t just decide your eye color or height. It controls how fast your liver breaks down medications. That’s where the cytochrome P450 enzymes come in. These are the body’s main drug-processing machines. Three of them-CYP2D6, CYP2C9, and CYP2C19-handle about 80% of all commonly prescribed drugs.

But here’s the problem: these enzymes vary wildly between people. Some people are poor metabolizers. Their bodies process drugs too slowly. A standard dose of a blood thinner like warfarin can build up to toxic levels. Others are ultra-rapid metabolizers. They burn through drugs so fast that the medication never even has a chance to work. For example, about 1-2% of Europeans and up to 29% of Ethiopians are ultra-rapid metabolizers of CYP2D6. That means a standard dose of codeine? It’s useless for pain relief in those people-and could even turn into dangerous levels of morphine.

One study found that 15% of all adverse drug reactions are directly tied to these genetic differences. That’s not a small number. That’s millions of people every year getting sick from drugs meant to help them.

Age, Weight, and Other Hidden Factors

Genes aren’t the whole story. Your body changes as you get older. Older adults have more body fat and less muscle. Fat-soluble drugs like certain antidepressants or sleep aids get stored in fat tissue and linger longer. That means even a normal dose can pile up over time and cause dizziness, confusion, or falls.

Your liver and kidneys also slow down with age. That’s why older patients often need lower doses-even if they’re otherwise healthy. A 70-year-old might need half the dose of a 30-year-old for the same drug.

Then there’s what you’re taking alongside your medication. A common painkiller like ibuprofen can cause stomach bleeding in 1-2% of people. But if you’re also on a steroid or have a certain gene variant, that risk jumps to 15-30%. Combine that with alcohol, or another drug like warfarin, and you’re playing Russian roulette with your digestive system.

Even something as simple as a cold or the flu can change how your body handles drugs. Inflammation from an infection can shut down your liver’s drug-processing enzymes by 20-50%. That means a drug you’ve taken safely for years might suddenly become dangerous.

Real Cases: When Genetics Save Lives

There’s a 68-year-old woman from Minnesota who kept having dangerous bleeding episodes on warfarin. Her INR levels kept spiking above 10-normal is 2-3. Doctors couldn’t figure it out. She wasn’t eating differently. She wasn’t drinking alcohol. She was following instructions perfectly.

Then she got tested. Turns out, she had two copies of the CYP2C9*3 variant. She was a poor metabolizer. Her body couldn’t break down warfarin at all. Once her dose was cut by 60%, her INR stabilized. She stopped bleeding. She went from being a frequent hospital patient to living normally.

In cancer treatment, the difference is even clearer. Kids with leukemia who get mercaptopurine often suffer severe toxicity. But when doctors test for a specific gene variant (TPMT), they can cut the dose before side effects start. At St. Jude Children’s Research Hospital, this simple test reduced severe side effects from 25% to just 12%.

And it’s not just cancer. In asthma, about 15% of patients have a genetic variant that makes them respond dramatically better to leukotriene modifiers like zafirlukast. For them, these drugs cut symptoms by 45%. But for the other 85%? They get no benefit-and pay $250 to $300 a month for nothing.

Why Isn’t Everyone Getting Tested?

If this is so clear, why aren’t all doctors ordering genetic tests before prescribing?

The answer? It’s not because the science is weak. It’s because the system hasn’t caught up.

The FDA has included pharmacogenomic info in the labels of over 300 drugs. For 44 of them, they even give specific dosing recommendations based on genes. But only 18% of US insurers cover genetic testing for drugs. Most doctors haven’t been trained to interpret the results. Only 32% of major hospitals have systems in place to alert them when a patient’s genes suggest a problem.

A 2023 survey found that 68% of physicians feel unprepared to use genetic data. That’s not because they’re lazy. It’s because they were never taught how. Pharmacogenomics isn’t in most medical school curriculums. And interpreting a genetic report takes 15-20 hours of training-time most doctors don’t have.

Plus, there’s the cost. Five years ago, a full pharmacogenomic panel cost $2,000. Today, it’s around $250. That’s a huge drop. But even at $250, many patients and providers still see it as optional-not essential.

The Future Is Already Here

The tide is turning. In January 2024, Medicare started covering pharmacogenomic testing for 17 high-risk medications. The FDA approved the first point-of-care CYP2C19 test in 2023-it gives results in 60 minutes. That means a cardiologist can test a patient for clopidogrel resistance right in the office and switch them to a better drug before they leave.

In oncology, 65% of hospitals now use pharmacogenomics routinely. In psychiatry, it’s 42%. But in primary care? Only 18%. That’s where most prescriptions start-and where most side effects happen.

The next big leap? Polygenic risk scores. Instead of looking at one gene, scientists are now combining hundreds of genetic markers to predict how someone will respond to a drug. Early studies show this approach is 40-60% more accurate than single-gene tests.

The goal isn’t to eliminate all side effects. That’s impossible. But we can eliminate the ones that are preventable. The ones caused by a simple mismatch between a drug and a person’s biology.

What You Can Do Today

You don’t need to wait for your doctor to order a test. If you’ve had unexpected side effects from a medication-especially if you’ve had them more than once-ask about pharmacogenomics.

Keep a record: What drug? What side effect? When did it start? Did anyone else in your family have a bad reaction? That information is valuable.

If you’re on multiple medications-especially if you’re over 65-talk to your pharmacist. Pharmacists spend 2-3 hours a week on pharmacogenomic cases. They’re often the best people to ask.

And if you’re prescribed a drug with known genetic risks-like warfarin, clopidogrel, or certain antidepressants-ask: “Is there a genetic test that could help determine the right dose for me?”

It’s not about being special. It’s about being smart. Your body isn’t broken. It’s just different. And now, we have the tools to match the medicine to the person-not the other way around.