What are anticholinergic drugs?
Anticholinergic drugs are a class of medication that works by blocking the action of acetylcholine, a key neurotransmitter in the central and peripheral nervous systems. Acetylcholine is responsible for transmitting signals that regulate various involuntary bodily functions controlled by the parasympathetic nervous system, often called the "rest-and-digest" system. By blocking acetylcholine from binding to its receptors, anticholinergic medications reduce this nervous system activity.
This blocking effect is used therapeutically to treat many different medical conditions, depending on the specific drug and the receptors it targets. However, the same mechanism that provides a therapeutic effect can also cause a range of side effects throughout the body, including dry mouth, blurred vision, and constipation.
The spectrum of anticholinergic medications
Anticholinergic drugs are not a single category but rather a spectrum of medications with varying degrees of anticholinergic properties. Some drugs are primarily prescribed for their anticholinergic effects, while others have it as a secondary, and often unwanted, side effect. The therapeutic uses span multiple fields, from treating neurological disorders to managing gastrointestinal problems.
Medications for Overactive Bladder (OAB)
Many drugs used to treat overactive bladder are strong anticholinergics. They work by relaxing the bladder muscles, reducing the urgency and frequency of urination.
- Oxybutynin (Ditropan)
- Tolterodine (Detrol)
- Solifenacin (Vesicare)
- Darifenacin (Enablex)
- Fesoterodine (Toviaz)
Antihistamines
First-generation antihistamines, commonly used to treat allergies, colds, and insomnia, are a well-known source of anticholinergic activity. The same effect that causes drowsiness is a result of their anticholinergic properties in the central nervous system.
- Diphenhydramine (Benadryl, Advil PM)
- Doxylamine (Unisom)
- Brompheniramine (Dimetapp)
- Dimenhydrinate (Dramamine)
Antidepressants
Several older antidepressants, particularly tricyclic antidepressants (TCAs), have significant anticholinergic effects, which contribute to their side effect profile.
- Amitriptyline (Elavil)
- Imipramine (Tofranil)
- Nortriptyline (Pamelor)
- Doxepin (Silenor)
Medications for Parkinson's Disease
Anticholinergics are some of the oldest drugs used to treat Parkinson's, specifically targeting tremors and rigidity, though newer treatments have become more common due to better side effect profiles.
- Benztropine (Cogentin)
- Trihexyphenidyl (Artane)
Other common medications with anticholinergic effects
- Scopolamine: Used for motion sickness.
- Ipratropium (Atrovent) and Tiotropium (Spiriva): Inhaled medications for asthma and COPD.
- Glycopyrrolate: Used to reduce saliva and excessive sweating.
- Cyclobenzaprine (Flexeril): A muscle relaxant.
- Antipsychotics: Some, like clozapine and olanzapine, also have anticholinergic effects.
Comparison of anticholinergic drugs
The impact and risk profile of anticholinergic medications can vary significantly. The Anticholinergic Burden Scale (ACB) is a tool used by clinicians to quantify the cumulative anticholinergic effects of a patient's total medication regimen.
| Drug Type | Primary Therapeutic Use | Anticholinergic Strength | Notes |
|---|---|---|---|
| Diphenhydramine | Allergies, sleep aid | Strong | Commonly found over-the-counter; CNS penetration causes drowsiness. |
| Oxybutynin | Overactive bladder (OAB) | Moderate to Strong | Older OAB medication with well-known anticholinergic side effects. |
| Tolterodine | Overactive bladder (OAB) | Moderate | Often better tolerated than oxybutynin; ER formulations reduce side effects. |
| Amitriptyline | Depression, nerve pain | Very Strong | A tricyclic antidepressant with a high anticholinergic burden. |
| Benztropine | Parkinson's disease | Very Strong | Used mainly for tremors in younger patients due to high cognitive risk in elderly. |
| Tiotropium | COPD, asthma | Low to Moderate | Inhaled and less systemic effects than oral anticholinergics. |
Risks and side effects
The most common anticholinergic side effects are often described with the mnemonic "can't see, can't pee, can't spit, can't poop," referring to blurred vision, urinary retention, dry mouth, and constipation.
Central nervous system (CNS) effects
- Confusion and Memory Issues: Anticholinergics can impair cognitive function, especially in older individuals.
- Dementia Risk: Long-term use of highly anticholinergic medications has been associated with an increased risk of dementia in older adults, prompting careful consideration by healthcare providers.
- Delirium: In high doses or in vulnerable individuals, anticholinergic toxicity can cause acute delirium.
Peripheral effects
- Dry Mouth (Xerostomia): A very common side effect due to decreased saliva production.
- Blurred Vision: Can be caused by dilation of the pupils (mydriasis).
- Urinary Retention: Difficulty or inability to urinate is a risk, particularly in men with an enlarged prostate.
- Constipation: Reduced gastrointestinal motility can lead to constipation.
- Hyperthermia: Decreased sweating can interfere with the body's ability to cool itself, leading to overheating.
- Tachycardia: An increased heart rate can occur.
Who is at high risk?
The elderly are at the highest risk for adverse effects due to a reduced capacity to tolerate anticholinergic medications and a more permeable blood-brain barrier. Those with existing cognitive issues or dementia are particularly vulnerable to exacerbations of their condition.
Management and alternatives
In many cases, clinicians can manage anticholinergic side effects by adjusting the dose, switching to an alternative medication, or carefully monitoring the patient. For some conditions, alternative drug classes exist that offer similar benefits with fewer anticholinergic effects.
- For overactive bladder, newer beta-3 agonists like mirabegron work differently and have a lower anticholinergic burden, although they can be more expensive. Combination therapy may also be used to maximize efficacy while reducing side effects.
- For allergies, second-generation antihistamines like loratadine and cetirizine are effective and have minimal to no anticholinergic effects.
- For depression, newer classes of antidepressants typically do not have the same level of anticholinergic activity as TCAs.
Conclusion
Numerous drugs are considered to be anticholinergic, spanning a wide array of therapeutic categories, from common OTC sleep aids to prescription medications for complex neurological and urinary conditions. While effective for their intended purposes, their mechanism of action can result in a range of side effects, especially in older adults. The concept of anticholinergic burden highlights the importance of considering the cumulative effects of all medications, emphasizing the need for careful risk assessment by healthcare providers. For patients, being aware of their medication's anticholinergic potential is a key part of maintaining health, especially as they age, and discussing potential alternatives with their doctor is always recommended. For more information, the American Academy of Family Physicians offers guidance on avoiding highly anticholinergic medications in older adults.
