Anticholinergic Adverse Effects

Acetylcholine is a neurotransmitter that transfers signals between cells to regulate the body’s functioning. With a particular role in the regulation of movement, thought and emotions, acetylcholine acts through two types of receptors: muscarinic and nicotinic . Muscarinic receptors function in the peripheral and central nervous system and are present in various organs of the body, while nicotinic receptors function in the central nervous system and neuromuscular junction.

Anticholinergic drugs act by blocking both types of receptors and are useful to treat respiratory disorders, such as chronic obstructive pulmonary disease (COPD), asthma, overactive bladder, urinary incontinence, cardiovascular diseases, Parkinson’s disease, and as antispasmodics or muscle relaxants.​ In In the United Kingdom, the proportion of patients per month prescribed at least one medication with anticholinergic properties increased from 6.1% to 16.7% between 1989 and 2000 and to 18.6% between 1989 and 2016. This It may be due, at least in part, to increased prescription rates of antidepressants and medications for urinary incontinence and overactive bladder.

Indications for anticholinergic medication.

There are more than 600 medications with anticholinergic properties, including:

• Those that are prescribed mainly for their anticholinergic effect.
• Those that are prescribed mainly for other reasons.

Regardless of the primary indication, all patients prescribed medications with anticholinergic properties are vulnerable to anticholinergic side effects. The use of these medications is highest among three particularly vulnerable patient groups: older people, people with learning disabilities, and people with mental health problems .

For many people within these vulnerable groups, the medication may be prescribed for clinical indications other than the primary diagnosis. For example, anticholinergic medications are prescribed to more than half of patients with Parkinson’s disease for clinical indications other than parkinsonism.

Anticholinergic load and pathophysiology.

Anticholinergic drugs act on muscarinic acetylcholine receptors. There are five subtypes of muscarinic receptors: M1, M2, M3, M4 and M5. Anticholinergics block acetylcholine by binding to these receptor sites and competitively blocking the effects of parasympathetic nervous activity on the nervous system, as well as those that affect smooth muscle function in the digestive and urinary systems.

Many patients tend to take several medications with anticholinergic properties at the same time. This concomitant use increases the risk of side effects. The cumulative effect of taking one or more medications with anticholinergic activity is called anticholinergic load (ACB). Common side effects related to ACB are listed below. They can be the cause of significant morbidity and mortality:

• Dizziness
• Blurry vision
• Increased risk of falls
• Urinary retention
• Constipation
• Dry mouth
• Nausea
• Incrise of cardiac frecuency
• Dry eyes
• Narrow angle glaucoma
• Sedation
• Vascular events
• Cognitive impairment
• Delirium
• Dementia

Anticholinergic burden ( ACB) is particularly pronounced in the vulnerable patient groups mentioned above. For example, patients with mental health problems, such as psychosis, often experience a cascade of prescriptions. First, they are treated with antipsychotic medications , many of which have inherent anticholinergic properties, and if they develop extrapyramidal side effects due to the antipsychotic, they are also prescribed anticholinergics, thus creating a cumulative effect.

Adults with intellectual disabilities are also at increased risk for very high ACB due to polypharmacy of multiple classes of medications.​ An example would be those with intellectual disabilities, challenging behavior, and co-occurring mental health conditions, such as depression or psychosis. These patients are often prescribed antipsychotics, antidepressants, and/or mood stabilizers in combination, many of which have anticholinergic properties. Additionally, many of these patients develop extrapyramidal side effects from the use of antipsychotic medications and are then prescribed more anticholinergic medications to combat them.

Any over-the-counter medication with anticholinergic effects (for example, antihistamines) could make this worse. In general, anticholinergic prescribing appears to begin early in this population and continues for several years.

Cognitive impairment is another aspect of CBA that has been studied extensively. Due to sedation and delirium as a result of ACB, the risk of adverse outcomes, including falls and hospitalization, increases with increasing exposure to anticholinergics. Cumulative use of strong anticholinergics is associated with an increased risk of dementia.

Oral health

The side effects of anticholinergics can often affect oral health. In 2016, the World Dental Federation FDI stated that “oral health is multifaceted and includes the ability to speak, smile, smell, taste, touch, chew, swallow and convey a variety of emotions through facial expressions confidently and without pain.” discomfort and disease of the craniofacial complex.”

There is a significant correlation between anticholinergic load (ACB) and the presence of xerostomia (i.e., dry mouth). Dry mouth is subjectively experienced by the patient as a symptom and can be demonstrated objectively by measuring saliva production. Deutsch and Jay summarize how normal salivary function is essential in speech, digestion, and swallowing . Antimicrobials in saliva prevent cavities and tooth wear. Stimulated saliva has a high serous volume, with higher concentrations of bicarbonate to neutralize acids in the mouth, food, and plaque than resting saliva. High flow volumes improve effective buffering capacity and help eliminate glucose and bacteria.

Anticholinergics alter the stimulation of saliva and reduce salivary flow. Alteration of the protective functions of saliva in the oral cavity causes more oral health problems. A 5% reduction in saliva flow may occur before patients become aware of their oral health problems.

Oral health problems can, in turn, lead to a number of serious health consequences, including diabetes, cardiovascular disease and cancer.​ Therefore, early identification and intervention is important to address these oral side effects. Pharmacists play a vital role in this: they can educate service users about dry mouth and its causes, consequences and management; make referrals to appropriate service providers, such as dentists, dental hygienists, psychiatrists and primary care physicians; supporting hospitals with oral care policies and audits; and direct patients to appropriate dental services upon discharge from the hospital.

Prevention and intervention strategies

Medication reviews by primary care and hospital pharmacists can identify all drugs with potential anticholinergic effects. Additionally, medication optimization may help reduce or eliminate anticholinergic polypharmacy , based on advice from primary care or hospital pharmacists to prescribers. Doctors can also use medications with a lower ACB score and prescribe them only if necessary, especially in high-risk groups. Once anticholinergic drugs are prescribed, pharmacists and doctors should:

• Teach the patient to self-monitor and provide specific advice on how to seek help (e.g., report symptoms of dry mouth to a pharmacist, dentist, GP, treating psychiatrist, etc.).
   
• Ensure regular reviews of effectiveness and monitor side effects.
   
• Address any side effects proactively, including lifestyle changes (such as reducing intake of acidic drinks, alcohol, caffeinated drinks, tobacco and substance abuse, as these can cause poor oral health).
   
• Advise the use of frequent sips of water throughout the day to relieve dry mouth, sugar-free gum to stimulate salivary flow, and the use of oral moisturizing products.
   
• Consider prescribing anticholinergic drugs, if clinically appropriate.​
   
• They may suggest that patients receive regular assessments of their oral health by the dental service; Community or hospital pharmacists can monitor whether this is happening as expected. The dental service will be able to decide whether or not saliva tests are necessary.

Better practices

Careful consideration should be given to whether the patient is in a high-risk group for ACB (e.g., older people, cognitive deficits, intellectual disability, mental health problems). Whenever possible, there should be a careful discussion between the doctor and the patient about the risks and benefits of anticholinergic medication. This may involve summarizing the reasons for prescribing, response to the medication, adherence, side effects, and the patient’s views on continuing the medication. If the patient does not have the capacity to participate in such a discussion, best interest decision-making principles should be followed.

Before deciding to start or continue treatment with a drug with anticholinergic effects, consider the following:

• Have non-pharmacological strategies been optimized?
   
• Has the option of treating the condition with drugs without anticholinergic effect or with lower anticholinergic potential been considered?
   
• Has a review been undertaken to minimize the co-prescribing of other medicines with anticholinergic properties (including over-the-counter medicines such as antihistamines)?
   
• Use the lowest dose of the anticholinergic necessary to control the condition for the shortest time possible.