How do anticholinergic (Anticholinergic) medications work?

From the Guidelines

Anticholinergic medications work by blocking the neurotransmitter acetylcholine from binding to its receptors in the body, thereby preventing the normal action of acetylcholine in both the central and peripheral nervous systems. These drugs competitively inhibit muscarinic acetylcholine receptors, which can reduce secretions, relax smooth muscle in organs, and dilate the pupils. Common anticholinergics include atropine, scopolamine, glycopyrrolate, ipratropium, and oxybutynin. When administered, these medications can reduce secretions, such as saliva, sweat, and bronchial secretions, and relax smooth muscle in organs like the bladder and gastrointestinal tract.

Mechanism of Action

The mechanism of action of anticholinergic medications involves the blockade of muscarinic acetylcholine receptors, which are responsible for various physiological functions, including secretion, smooth muscle contraction, and heart rate regulation. By blocking these receptors, anticholinergic medications can produce a range of effects, including:

• Reduced secretions, such as dry mouth and decreased sweating
• Relaxation of smooth muscle, leading to decreased muscle contractions in the bladder and gastrointestinal tract
• Dilation of the pupils, which can affect vision

Clinical Uses

Anticholinergic medications have several clinical uses, including:

• Treatment of respiratory conditions, such as chronic obstructive pulmonary disease (COPD) and asthma, where ipratropium can help bronchodilation by blocking acetylcholine-induced bronchoconstriction 1
• Treatment of overactive bladder, where oxybutynin can reduce bladder muscle contractions
• Treatment of gastrointestinal disorders, such as irritable bowel syndrome, where anticholinergic medications can help relax smooth muscle and reduce muscle contractions

Side Effects

The side effects of anticholinergic medications are directly related to their mechanism of action and can include:

• Dry mouth
• Constipation
• Urinary retention
• Blurred vision
• Confusion, especially in elderly patients These effects occur because acetylcholine normally stimulates secretions and smooth muscle contractions throughout the body, and blocking this action produces the opposite physiological response. According to a study published in 2021, older antihistamines, muscle relaxants, and overactive bladder agents with strong anticholinergic effects are usually poorly tolerated in aged patients and can result in negative effects on vision, urination, constipation, and cognition 1.

Special Considerations

In elderly patients, anticholinergic medications can have significant adverse effects, including cognitive decline, functional impairment, and increased risk of falls and hospitalizations 1. Therefore, it is essential to use these medications with caution and to monitor patients closely for potential side effects. A study published in 2015 noted that tertiary-amine tricyclic antidepressants (TCAs) are associated with significant adverse anticholinergic effects and are considered a potentially inappropriate medication in the American Geriatric Society’s Beers Criteria 1.

From the FDA Drug Label

Scopolamine, a belladonna alkaloid, is an anticholinergic. Scopolamine acts: i) as a competitive inhibitor at postganglionic muscarinic receptor sites of the parasympathetic nervous system, and ii) on smooth muscles that respond to acetylcholine but lack cholinergic innervation It has been suggested that scopolamine acts in the central nervous system (CNS) by blocking cholinergic transmission from the vestibular nuclei to higher centers in the CNS and from the reticular formation to the vomiting center Scopolamine can inhibit the secretion of saliva and sweat, decrease gastrointestinal secretions and motility, cause drowsiness, dilate the pupils, increase heart rate, and depress motor function.

Anticholinergic medications, such as scopolamine, work by:

• Competitively inhibiting muscarinic receptor sites in the parasympathetic nervous system
• Blocking cholinergic transmission in the central nervous system (CNS)
• Inhibiting smooth muscle responses to acetylcholine Key effects of anticholinergic medications include:
• Inhibiting secretion of saliva and sweat
• Decreasing gastrointestinal secretions and motility
• Causing drowsiness
• Dilating pupils
• Increasing heart rate
• Depressing motor function 2

From the Research

Mechanism of Action

• Anticholinergic medications work by blocking the action of acetylcholine, a neurotransmitter in the central and peripheral nervous system, at muscarinic receptors 3, 4.
• They are competitive antagonists of acetylcholine muscarinic (M-) receptors, which modulate the central nervous system (CNS) 4.
• The blockade of muscarinic receptors results in a decrease in the parasympathetic tone, leading to various effects such as increased heart rate, decreased gastrointestinal motility, and decreased secretions 3, 5.

Pharmacokinetics

• Anticholinergic medications, such as atropine, scopolamine, and glycopyrrolate, have different pharmacokinetic properties 3, 5.
• They have a fast onset of action after intravenous administration, with a rapid disappearance from the circulation 3, 5.
• The elimination phase half-lives of these medications vary from 1 to 4 hours, with significant differences in their metabolism and renal excretion 3.

Clinical Effects

• Anticholinergic medications have various clinical effects, including cardiovascular, peripheral muscarinic, and CNS effects 3, 4.
• They are used clinically to treat vomiting, nausea, and bradycardia, as well as alongside other anesthetics to avoid vagal inhibition 4.
• They can also evoke potent psychotropic effects, including characteristic delirium-like states with hallucinations, altered mood, and cognitive deficits 4.

Therapeutic Uses

• Anticholinergic medications are used in the treatment of various conditions, including Alzheimer's disease, where they increase the availability of acetylcholine at synapses in the brain 6, 7.
• Cholinesterase inhibitors, such as acetylcholinesterase inhibitors, are used to treat Alzheimer's disease, and they work by preventing the degradation of acetylcholine, thereby increasing its availability at synapses 6, 7.