How Liver and Kidney Changes in Older Adults Affect Medication Safety

When you’re 70, your body doesn’t process medicine the way it did at 30. It’s not about being weak or slow-it’s about biology. Your liver and kidneys, the two main organs that clean drugs out of your blood, change as you age. And those changes can turn a safe dose into a dangerous one. Many older adults end up in the hospital not because they took too much, but because their bodies couldn’t clear the drug like they used to. In fact, 10% of hospital admissions in people over 65 are linked to bad reactions to medications. That’s not rare. That’s predictable.

What Happens to Your Liver as You Age?

Your liver shrinks. By the time you hit 70, it’s lost about 30% of its mass. Blood flow through it drops by nearly 40%. That means drugs move through your liver slower. Some drugs rely on this blood flow to get broken down. These are called flow-limited drugs. Examples include propranolol (for high blood pressure), lidocaine (a local anesthetic), and morphine (for pain). When liver blood flow drops, these drugs stick around longer. Your body can’t clear them fast enough. The result? Higher levels in your blood. More side effects. Dizziness. Confusion. Falls.

Other drugs, called capacity-limited, depend on liver enzymes to break them down. These include diazepam (Valium), theophylline (for asthma), and phenytoin (for seizures). Here’s the good news: the enzymes themselves don’t decline much with age. So these drugs are cleared at about the same rate. But there’s a catch. Many older adults take multiple drugs. One drug can block the enzyme that breaks down another. That’s when things go wrong-even if the enzyme is still working fine.

There’s also something called first-pass metabolism. That’s when a drug gets broken down by the liver before it even enters your bloodstream. As your liver slows down, more of the drug slips through untouched. For drugs like propranolol and verapamil, that means up to 50% more of the drug reaches your blood. A standard dose meant for a 40-year-old can become a toxic dose for a 75-year-old.

Your Kidneys Don’t Work the Same Either

Your kidneys filter your blood. They remove waste-and drugs-through tiny filters called glomeruli. Between age 30 and 80, your glomerular filtration rate (GFR) drops by 30% to 50%. That’s not a small change. It’s massive.

Here’s the problem: doctors often think kidney function is fine because your creatinine level looks normal. But creatinine comes from muscle. As you age, you lose muscle mass. So even if your kidneys are failing, your creatinine stays in the normal range. It’s misleading. That’s why using formulas like Cockcroft-Gault or CKD-EPI to estimate kidney function is critical. You can’t just guess.

Drugs that leave your body mostly through the kidneys need dose adjustments. Think of antibiotics like vancomycin, painkillers like morphine, and diuretics like furosemide. If your kidneys can’t clear them, they build up. Vancomycin can damage your kidneys. Morphine can make you stop breathing. A 78-year-old patient in a 2022 study had their vancomycin dose adjusted based on their real kidney function-and avoided kidney failure. That’s the difference between guessing and measuring.

It’s Not Just One Organ-It’s Both Working Together

Here’s something many don’t realize: your kidneys and liver talk to each other. When your kidneys start to fail, it can slow down liver enzyme activity too. That means even drugs that are supposed to be cleared by the liver might stick around longer. It’s a double hit.

And then there are prodrugs. These are inactive until your liver turns them into the active drug. Perindopril, an ACE inhibitor for blood pressure, is one. If your liver slows down, the conversion happens slower. You might not get the full benefit. Your blood pressure stays high, and your doctor might think the dose isn’t enough-so they increase it. But now you’re getting too much of the active drug. It’s a trap.

What Drugs Are Most Dangerous for Older Adults?

Some drugs are just riskier as you age. The Beers Criteria®-a guide used by doctors worldwide-lists medications to avoid or use with extreme caution in seniors. Here are a few:

• Amitriptyline (an old antidepressant): Causes dizziness, confusion, urinary retention. A 82-year-old woman in Massachusetts ended up in the ER after a standard dose made her fall repeatedly.
• Benzodiazepines (like diazepam or lorazepam): Increase fall risk by 60%. Even short-term use can cause memory loss.
• NSAIDs (ibuprofen, naproxen): Can cause kidney damage, stomach bleeds, and high blood pressure. Older adults are 5x more likely to have a GI bleed from these.
• Anticholinergics (for overactive bladder or allergies): Linked to dementia risk. Drugs like diphenhydramine (Benadryl) are common in OTC sleep aids.
• Acetaminophen (Tylenol): Seems safe, right? But in older adults with reduced liver function, even 3,000 mg a day can cause liver failure. It’s responsible for half of all acute liver failure cases in seniors.

These aren’t just warnings. These are real stories. A Reddit user in the r/geriatrics forum shared how their mother, on a standard dose of amitriptyline, couldn’t stand up without help. The doctor didn’t adjust the dose. It took three weeks and a hospital visit to realize the problem.

How Doctors Should Adjust Dosing

The rule isn’t “take less because you’re old.” It’s “take less because your body doesn’t clear it like it used to.”

Start low, go slow. For most drugs cleared by the liver, doctors should begin with 20-40% of the standard adult dose. For those over 75, reduce even more. For kidney-cleared drugs, calculate your creatinine clearance-not just look at serum creatinine. Use the CKD-EPI formula without race adjustments, as recommended in 2021. That’s more accurate.

Tools like START and STOPP criteria help doctors avoid bad prescriptions. START tells you what drugs you should be on. STOPP tells you what you shouldn’t be on. One study showed using these tools reduced bad drug reactions by 22%.

And don’t forget over-the-counter meds. Seniors often take Tylenol, antacids, sleep aids, or herbal supplements without telling their doctor. But acetaminophen, even in small doses, can overwhelm a tired liver. St. John’s Wort can interfere with blood thinners and antidepressants. These aren’t harmless.

Why Drug Trials Don’t Tell the Whole Story

Most new drugs are tested on people under 65. The FDA’s own data shows only 38% of participants in new drug trials are over 65. That means we’re prescribing drugs to seniors based on data from people who aren’t them.

That’s changing. In 2019, the FDA started requiring drug companies to include older adults in trials and analyze results by age. In 2023, they approved the first software-GeroDose v2.1-that simulates how a drug will behave in an older body based on liver function, kidney function, weight, and other factors. It’s not perfect, but it’s a step forward.

Researchers are also looking at epigenetics-how your genes turn on or off as you age. A 2023 study found 17 specific gene changes linked to how your liver breaks down drugs. That means two 75-year-olds might need completely different doses of the same drug. The future isn’t one-size-fits-all. It’s personalized.

What You Can Do Right Now

If you or a loved one is over 65 and taking more than three medications:

• Ask your doctor: “Is this still necessary?” Many seniors take drugs they no longer need.
• Ask: “What’s the dose based on? My kidneys? My liver?”
• Bring a full list of everything you take-including vitamins, supplements, and OTC meds.
• Ask if you can switch to a safer alternative. For example, gabapentin instead of amitriptyline for nerve pain.
• Get your kidney function checked with a creatinine clearance test-not just a basic blood test.

There’s no magic pill. But there is smart prescribing. And it saves lives.

What’s Next for Senior Medication Safety?

The future is personal. We’re moving away from dosing by age and toward dosing by biology. Blood tests for liver enzymes, kidney function, muscle mass, and even gene activity will help doctors tailor doses to each person-not just the average 70-year-old.

By 2030, experts predict personalized dosing could cut adverse drug reactions in seniors by 35-50%. That’s not a dream. It’s the next step in medicine. And it starts with asking the right questions-before the next prescription is written.