Anticholinergic Medicines

This guide on prescribing anticholinergic medicines is tailored for doctors, pharmacists and other healthcare professionals.

Table of Contents

Mechanism of Action
Clinical Indications of Antimuscarinic Medicines
Medicines Exhibiting Anticholinergic Effects
Adverse Effects
Prescribing Anticholinergic Medicines for Special Populations
Anticholinergic Burden
Clinical Considerations

Mechanism of Action

Anticholinergic medicines bind competitively to cholinergic receptors, which can be either muscarinic or nicotinic, thereby inhibiting the effects of the neurotransmitter acetylcholine and other cholinergic substances in both the central and peripheral nervous systems. Cholinergic receptors are classified into muscarinic cholinergic receptors and nicotinic cholinergic receptors.

Anticholinergic medications that target the muscarinic receptors are referred to as antimuscarinic drugs. In contrast, those that act on the nicotinic receptors are termed antinicotinic drugs and encompass two main categories: ganglionic blockers and neuromuscular blockers.

There are five subtypes of muscarinic receptors, detailed below with their main locations.

M1 – CNS, gastric glands, autonomic ganglia
M2 – Heart, CNS
M3 – Smooth muscles (e.g. bladder, airways, eyes, gut), exocrine glands, blood vessels
M4 – CNS
M5 – CNS

Regarding nicotinic receptors, there are three main receptor subtypes, which are detailed below along with their main synaptic location.

Muscle type – Skeletal neuromuscular junction
Ganglion type – Autonomic ganglia
CNS Type – Many brain regions

Clinical Indications of Antimuscarinic Medicines

Irritable bowel syndrome
Nausea
Motion sickness
Asthma
COPD
Parkinson’s disease
Overactive bladder
Urinary incontinence
Used during ophthalmic examinations
Psychosis
Bradycardia

Medicines Exhibiting Anticholinergic Effects

Listed below are examples of drugs that have anticholinergic properties:

Anti-arrhythmic Drugs

Procainamide
Disopyramide

Antihistamines

Chlorphenamine
Diphenhydramine
Cyproheptadine
Hydroxyzine
Promethazine
Cyclizine
Doxylamine
Cinnarizine
Buclizine
Cyproheptadine

Antidepressants

Amitriptyline
Dosulepin
Doxepin
Clomipramine
Imipramine
Nortriptyline
Doxepin
Imipramine
Nortriptyline
Paroxetine

Antipsychotics

Chlorpromazine
Trifluorperazine
Clozapine
Olanzapine
Quetiapine
Levomepromazine

Bronchodilators

Ipratropium
Tiotropium

Drugs for urinary frequency, enuresis and incontinence

Flavoxate
Fesoterodine
Oxybutynin
Solifenacin
Tolterodine
Darifenacin
Trospium
Propiverine

Antiparkinson

Trihexyphenidyl (benzhexol)
Orphenadrine
Amantadine

Mydriatics and Cycloplegics

Atropine
Cyclopentolate
Tropicamide
Homatropine

Antiemetics

Hyoscine hydrobromide
Prochlorperazine

Antispasmodics

Dicycloverine
Hyoscine butylbromide
Propantheline

Skeletal Muscle Relaxants

Methocarbamol

Antidiarrhoeals

Diphenoxylate

Adverse Effects

Medicines that have anticholinergic properties may have the potential to cause adverse anticholinergic effects. Listed below are some examples of these adverse effects and side effects:

Dry mouth
Thirst
Difficulty in swallowing
Constipation
Paralytic ileus
Nausea or vomiting
Gastro-oesophageal reflux disease
Dyspepsia
Tachycardia
Arrhythmias
Urinary retention
Difficulty in urinating
Dilated pupils
Blurred vision
Dry eyes
Photophobia
Exacerbation or precipitation of acute angle-closure glaucoma
Decreased sweating
Drowsiness or sedation
Dizziness
Hallucinations
Deliriums
Restlessness
Irritability
Nervousness
Slurred speech
Impaired concentration
Confusion
Memory impairment
Falls

Prescribing Anticholinergic Medicines for Special Populations

The following are at increased risk of experiencing adverse effects from anticholinergic medicines

Older/frail people
People with long-term multiple health conditions taking anticholinergic medicines
People with Alzheimer’s disease/dementia
People taking multiple medications (polypharmacy) with anticholinergic properties
People whose health condition could be worsened by taking medicines with anticholinergic properties, such as glaucoma, hyperthyroidism, tachyarrhythmia and prostate hypertrophy.
People with renal or liver impairment

Anticholinergic Burden

Many medications can have varying levels of anticholinergic effects, ranging from significant to minimal.

The use of multiple medications that exert anticholinergic effects can lead to a cumulative effect, increasing the risk of adverse effects and is commonly referred to as the anticholinergic burden (ACB).¹

A high anticholinergic burden increases the risk of dementia and cognitive decline, falls and mortality.¹

Several tools can be used to calculate the anticholinergic burden score for a patient and help assess whether they are at risk of adverse outcomes associated with anticholinergic medicines: The anticholinergic burden calculator, the anticholinergic burden calculator and the anticholinergic effect on cognition (AEC) tool. Each of these tools uses a different scoring system or scale to calculate the anticholinergic burden score for a patient.

Clinical Considerations

Assess the patient’s anticholinergic burden by using one of the anticholinergic burden score tools to calculate the patient’s score
Counsel patients and carers on what adverse effects to be aware of and when to seek medical attention
Before prescribing a medication that has anticholinergic properties, evaluate the patient’s current medication regimen, conduct medicines reconciliation and determine the cumulative anticholinergic effects of various drugs, as well as which medications contribute to a higher cumulative anticholinergic effect. Assess these findings and make changes to reduce the patient’s anticholinergic load.
Before prescribing a medication with anticholinergic properties, it is essential to determine whether the patient has any pre-existing conditions that could negatively impact or exacerbate their condition, such as cognitive impairment associated with dementia
Before initiating anticholinergics, consider any non-pharmacological options. If a pharmacological drug does need to be prescribed, consider choosing one with a low anticholinergic antiburden score or a medicine that does not have anticholinergic properties.
For patients on anticholinergics, it is important to regularly review their medications, particularly for older people, frail patients, those at a higher risk of falls, individuals with multiple health conditions or those taking several medications. Evaluate the possibility of deprescribing anticholinergics to improve health outcomes, ensuring to discuss this with the patient.

References

Primary Health Tasmania. A guide to deprescribing anticholinergics. Dec 2022. Accessed via https://www.primaryhealthtas.com.au/wp-content/uploads/2023/03/A-guide-to-deprescribing-anticholinergics.pdf