Anticholinergic drugs work by blocking a chemical called acetylcholine, which serves as the chief neurotransmitter of the parasympathetic nervous system. This part of the nervous system, also known as the rest and digest system, governs various bodily functions, including heart rate, blood vessel dilation and smooth muscle contraction.
But according to recent studies, prolonged use of anticholinergic medications has deleterious effects, especially on the brain. British researchers discovered that exposure to certain anticholinergics, such as antidepressants, anticonvulsants and anti-Parkinson drugs, increases the risk of dementia, especially among the elderly.
Their study, which appeared in the journal JAMA Internal Medicine, underscores the need for alternative medications to decrease the risk of severe cognitive impairment among middle-aged and older adults.
Clinical uses of anticholinergic drugs and reported side effects
Acetylcholine receptors can be found in the central nervous system and the peripheral nervous system. These receptors are classified as either nicotinic or muscarinic receptors. While nicotinic receptors are involved in skeletal muscle functions, muscarinic receptors mediate cardiac and smooth muscle functions. Anticholinergic drugs inhibit the action of acetylcholine by binding to these receptors; but unlike acetylcholine, they do not activate these receptors, thus decreasing the activity of the parasympathetic nervous system.
In clinical practice, anticholinergics are often prescribed to decrease nasal and bronchial secretions. They are also used to reduce salivation, sweating, gastric acid production and other secretions associated with allergic and inflammatory diseases. In addition, anticholinergic drugs are smooth muscle relaxants, which is why they're frequently used to prevent nausea and vomiting, and to treat gastrointestinal, urological and respiratory conditions that involve spasms and dysmotility. Anticholinergics are also used to treat bradycardia, or slow heart rate.
But as with any synthetic drug, anticholinergics have many reported side effects. These include anxiety, constipation, headache, hyperthermia, impotence, mouth and eye dryness, palpitations, restlessness, tachycardia (abnormally fast heart rate), urinary retention and visual blurring. There have also been reported instances of agitation and delusion caused by anticholinergics. (Related: If they can’t cure your depression, maybe they can make you forget you have it: Common anticholinergic drugs increase dementia risk by 50 percent.)
Today, some anticholinergic medications are still sold over the counter. The most common of these are first-generation antihistamines and antimuscarinic agents for urinary incontinence. These two types of anticholinergics also happen to be the most frequently used OTC medications by older adults. Besides these, other anticholinergics currently used for treatment include certain antiarrhythmics, antidepressants, antipsychotics, antispasmodics and sleep aids.
Exposure to anticholinergics increases dementia risk
A team of British researchers recently conducted a nested case-control study involving 58,769 patients diagnosed with dementia and 225,574 healthy individuals who matched the patients in terms of age, sex, general practice and calendar time. The goal of the study was to determine if the risk of dementia among people aged 55 and above is associated with the use of different types of anticholinergic medications. These medicines, the researchers noted, are known for their short-term adverse effects on cognition.
After analyzing data, which included the total standardized daily doses of anticholinergic drugs prescribed one to 11 years prior to the diagnosis of dementia and information on prescriptions for 56 anticholinergic drugs, the researchers found statistically significant associations between dementia risk and exposure to anticholinergic antidepressants, anti-Parkinson drugs, antipsychotic drugs, bladder muscarinic and anti-epileptic drugs.
Even after adjusting the exposure windows to three to 13 years or five to 20 years before diagnosis, the researchers obtained similar results. They also noted that the association between anticholinergic use and dementia risk was stronger in patients diagnosed before the age of 80. Based on these findings, the researchers concluded that cumulative exposure to anticholinergic drugs increases the risk of dementia. They recommend that physicians practice caution when prescribing these medications, especially to middle-aged and older adults.
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