Anticholinergic Effects of Antihistamines: Dry Mouth, Constipation, Urinary Issues

Most people reach for antihistamines when allergies hit - runny nose, itchy eyes, sneezing. But what they don’t realize is that many of these common medications are doing more than blocking histamine. They’re also quietly shutting down a key part of your nervous system. This is called the anticholinergic effect, and it’s behind the dry mouth, constipation, and trouble urinating that so many users report - especially those over 65.

Why Do Antihistamines Cause These Side Effects?

Not all antihistamines are the same. There are two main types: first-generation and second-generation. The first-generation ones - like diphenhydramine (Benadryl), chlorpheniramine, and promethazine - were developed in the 1940s. They were designed to block histamine, sure, but they also accidentally bind tightly to muscarinic receptors, which are part of your parasympathetic nervous system. That system controls things like saliva production, gut movement, and bladder emptying.

When these drugs block acetylcholine from activating those receptors, your body doesn’t get the signal to do its normal job. Salivary glands stop making enough saliva → dry mouth. The muscles in your intestines slow down → constipation. Your bladder can’t contract properly → urinary retention. It’s not a coincidence - it’s pharmacology.

Second-generation antihistamines like cetirizine (Zyrtec), loratadine (Claritin), and fexofenadine (Allegra) were made later to fix this. They’re engineered to stay out of your brain and avoid muscarinic receptors. That’s why they’re much less likely to cause these side effects. At standard doses, their anticholinergic activity is practically zero.

How Bad Are These Side Effects Really?

The numbers tell a clear story. In clinical studies, about 28% of people taking diphenhydramine report dry mouth. That’s nearly 3 in 10. With cetirizine? Only 4%. Constipation hits 15-20% of first-gen users, but under 5% with second-gen. For urinary issues, especially in older men with prostate problems, the risk jumps to 5-8% with diphenhydramine - and drops to under 1% with newer options.

These aren’t just minor annoyances. Dry mouth increases your risk of cavities and gum disease. Constipation can lead to bowel obstructions if ignored. Urinary retention? That’s a medical emergency. One study found that 31% of men with moderate to severe prostate symptoms developed acute urinary retention within 48 hours of taking diphenhydramine.

And it gets worse. Long-term use of first-generation antihistamines is linked to a 54% higher risk of dementia over seven years, according to a major study published in JAMA Internal Medicine. The more you take - and the longer you take it - the higher the risk. Diphenhydramine has the highest possible score (3.0) on the anticholinergic cognitive burden scale. That’s the same level as some antidepressants and bladder medications known to harm cognition.

Who’s Most at Risk?

It’s not just older adults - though they’re the most vulnerable. People over 65 are more sensitive to anticholinergic drugs because their bodies clear them slower and their brains have fewer cholinergic neurons to begin with. But it’s not just age. If you have:

• Enlarged prostate (BPH)
• Chronic constipation or IBS
• Glaucoma
• Heart rhythm problems
• Cognitive decline or dementia

- you should avoid first-generation antihistamines entirely. The American Geriatrics Society’s Beers Criteria lists them as “potentially inappropriate medications” for seniors. The European Academy of Allergy and Clinical Immunology says to avoid them completely in patients over 65.

Even if you’re younger, if you’re taking other meds - like antidepressants, painkillers, or motion sickness pills - you’re stacking anticholinergic effects. That’s dangerous. The liver metabolizes these drugs using the same enzymes (CYP2D6, CYP3A4), so combining them can spike blood levels and make side effects worse.

What About the Ones You Can Buy Over the Counter?

First-generation antihistamines are still everywhere. You’ll find diphenhydramine in sleep aids, cold medicines, and allergy tablets. It’s cheap - a bottle of 24 tablets costs $4-6. That’s why people keep buying them. But they’re also the most likely to cause problems.

Look at the label. If it says “PM,” “Nighttime,” or “for sleep,” it’s probably diphenhydramine or doxylamine. These aren’t sleep aids - they’re sedating anticholinergics. And they’re not safe for regular use. The American Academy of Neurology warns that even seven days in a row increases fall risk by 34% in older adults.

Second-generation antihistamines cost more - $12-18 for the same number of doses - but they’re worth it. They don’t make you foggy. They don’t dry out your mouth. They don’t leave you stuck on the toilet. And they last 24 hours, so you only need one pill a day.

What Should You Do Instead?

If you’re currently taking diphenhydramine for allergies or sleep, here’s what to do:

1. Switch to a second-generation option. Cetirizine, loratadine, or fexofenadine are all available over the counter and just as effective for allergies.
2. Check all your meds. Look at your cold medicine, sleep aid, and even stomach remedies. Many contain hidden anticholinergics.
3. Don’t use them for sleep. If you need help sleeping, try melatonin, good sleep hygiene, or talk to your doctor. Antihistamines aren’t safe long-term sleep aids.
4. Use alternatives for dry mouth. Sugar-free gum with xylitol boosts saliva by 40-60% within minutes. Drink water. Avoid caffeine and alcohol - they make it worse.
5. Prevent constipation. If you must take a first-gen antihistamine, take a daily dose of polyethylene glycol (17g). It cuts constipation risk from 18% to 5%.
6. Speak up if you have trouble urinating. Don’t assume it’s just aging. Tell your doctor immediately if you feel like you can’t empty your bladder. It could be an emergency.

Why Is This Still a Problem?

Despite all the evidence, first-generation antihistamines are still sold everywhere. Why? Because they’re cheap, and because people don’t know the risks. Only 28% of patients recognize dry mouth as a side effect of medication - most think they’re just dehydrated.

Hospitals are catching on. Mayo Clinic removed diphenhydramine from its inpatient formulary in 2022 because of too many cases of delirium. Medicare now requires special justification before prescribing these drugs to seniors. The FDA added a dementia warning to diphenhydramine labels in 2021.

The future is clear: second-generation antihistamines are the standard. New drugs like olopatadine nasal spray show no anticholinergic activity at all. Researchers are even developing H4 receptor blockers that target allergies without touching any other system.

Bottom Line

Antihistamines aren’t all created equal. First-generation ones like Benadryl may stop your sneezes, but they come with a hidden cost - dry mouth, constipation, urinary problems, and even long-term brain damage. These aren’t rare side effects. They’re common, predictable, and avoidable.

If you’re over 50, have prostate issues, or take other medications, skip the old-school antihistamines. Choose cetirizine, loratadine, or fexofenadine. They work just as well - without the side effects. Your mouth, your gut, your bladder, and your brain will thank you.