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

Have you ever taken the same medication as someone else-maybe a friend or family member-and had a totally different experience? One person feels fine, while another ends up in the ER with dizziness, nausea, or worse? It’s not just bad luck. It’s biology. Medications don’t work the same way for everyone, and the reasons go far beyond whether you took it with food or forgot to drink water.

Genes Are the Hidden Switches

Your genes control how your body handles drugs. Think of them like tiny switches that determine whether a drug gets broken down quickly, slowly, or not at all. The most important players are enzymes in your liver, especially the cytochrome P450 family-CYP2D6, CYP2C9, and CYP2C19. These enzymes are responsible for metabolizing more than 70% of commonly prescribed drugs.

Some people have gene variants that make these enzymes work too fast-called ultra-rapid metabolizers. They clear drugs so quickly that the medication never reaches effective levels. Others are poor metabolizers. Their enzymes barely work, so drugs build up in their system and cause toxicity. About 5-10% of Caucasians are poor metabolizers of CYP2D6. In some African and Middle Eastern populations, ultra-rapid metabolizers make up nearly 30% of the population.

This isn’t theoretical. Take clopidogrel, a blood thinner given after heart attacks. About 2-15% of people carry a CYP2C19 variant that prevents the drug from activating. These patients get no protection from clots-yet they’re still prescribed the same dose as everyone else. That’s why some people have heart attacks even while taking their meds.

Warfarin, another blood thinner, is even clearer. Two genes-CYP2C9 and VKORC1-explain 30-50% of why people need wildly different doses. One person might need 5 mg a day. Another needs 15 mg. Without genetic testing, doctors guess. And guessing with warfarin can lead to dangerous bleeding or clots. Studies show that when doctors use genetic data to start warfarin dosing, patients reach the right level 27% faster and have 31% fewer major bleeds.

Age, Body Type, and What You Eat

Genes aren’t the whole story. Your body changes as you age. Older adults have more body fat and less muscle. Fat-soluble drugs like diazepam or amitriptyline get stored in fat tissue and released slowly, leading to prolonged effects. That’s why a 70-year-old on the same dose as a 30-year-old might feel groggy for days.

Your liver and kidneys also slow down with age. These organs clear drugs from your body. When they’re less efficient, drugs stick around longer. That’s why seniors are 3-5 times more likely to be hospitalized for side effects than younger adults.

Even what you eat matters. Grapefruit juice blocks an enzyme called CYP3A4. If you’re on statins like simvastatin or blood pressure meds like felodipine, drinking grapefruit juice can cause drug levels to spike-sometimes dangerously. A single glass can have effects that last 72 hours.

And then there’s inflammation. If you have an infection, arthritis, or even a bad cold, your body releases chemicals that shut down liver enzymes. That means drugs you normally handle fine might suddenly build up. A common painkiller like ibuprofen, which you’ve taken without issue for years, can suddenly cause stomach bleeding if you’re fighting off a virus.

Drug Interactions: When Medications Fight Each Other

Most people don’t take just one drug. The average American over 65 takes five or more prescriptions. That’s a recipe for disaster. One drug can block the enzyme another drug needs to be broken down. The result? Toxic buildup.

Take amiodarone, a heart rhythm drug. It shuts down CYP2C9-the same enzyme that breaks down warfarin. When taken together, warfarin levels can jump 100-300%. That’s not a small change. It means your INR (a measure of blood clotting) could soar past 10. Normal is 2-3. Above 4, you’re at high risk of internal bleeding. This combination has sent hundreds of patients to the ER each year.

Even over-the-counter meds can cause trouble. St. John’s wort, a popular herbal remedy for depression, speeds up the breakdown of many drugs-including birth control pills, antidepressants, and some cancer treatments. People think herbal means safe. It doesn’t. It just means unregulated.

Pharmacogenomics: The Future Is Here, But It’s Not Everywhere

There’s a solution: pharmacogenomics. It’s the science of using your genes to guide drug choices. The FDA has added pharmacogenomic info to the labels of over 300 drugs. For 44 of them, they give specific dosing advice based on genetics.

In pediatric oncology, doctors at St. Jude’s started testing kids for TPMT gene variants before giving mercaptopurine, a leukemia drug. Without testing, 25% of kids had life-threatening toxicity. After testing, that dropped to 12%. That’s a 52% reduction in severe side effects.

At the Mayo Clinic, a 10,000-patient study found that those who got genetic testing before starting meds had 32% fewer ER visits and 26% shorter hospital stays. The savings? Around $1,200-$1,800 per patient per year.

So why isn’t everyone getting tested?

Because it’s still not standard. Only 18% of U.S. insurers cover it fully. Most doctors haven’t been trained to read the reports. Only 32% of hospitals have systems that automatically flag dangerous gene-drug combinations in electronic records. And many physicians still think genetic testing is too expensive-though the cost has dropped from $2,000 in 2015 to about $250 today.

Medicare started covering pharmacogenomic testing for 17 high-risk drugs in January 2024. That’s a big step. But coverage still doesn’t include most common prescriptions like antidepressants, statins, or painkillers.

What You Can Do Right Now

You don’t need to wait for your doctor to order a test. Here’s what you can do today:

• Know your meds. Write down every pill, supplement, and OTC drug you take. Include doses and why you take them.
• Ask about interactions. When a new drug is prescribed, ask: “Could this interact with anything I’m already taking?”
• Speak up about side effects. If you feel weird after starting a new medication-dizzy, nauseous, unusually tired-don’t brush it off. Report it. Even if it seems minor.
• Check for genetic testing. If you’ve had bad reactions to multiple drugs, or if a medication didn’t work at all, ask your doctor about pharmacogenomic testing. It’s especially useful for antidepressants, blood thinners, pain meds, and statins.

Some companies offer direct-to-consumer tests that include pharmacogenomic results. But be careful. Not all are clinically validated. Look for tests that are FDA-recognized or recommended by major medical groups like the American College of Medical Genetics.

The Big Picture

Adverse drug reactions are the fourth leading cause of death in the U.S. That’s more than car accidents or Alzheimer’s. And most of them are preventable.

Right now, we treat everyone the same. We give the same dose of a drug to a 90-pound woman and a 250-pound man. We give the same pill to a 25-year-old athlete and a 75-year-old with kidney disease. We assume genetics don’t matter. But they do.

The future of medicine isn’t one-size-fits-all. It’s one-size-fits-you. Genetic testing, smarter prescribing, and better monitoring are making that possible. The tools are here. The data is clear. What’s missing is the will to use them.

If you’ve ever been told, “This drug should work for you,” and it didn’t-or made you sick-you weren’t wrong. The system was.