Why are anticholinergics problematic?

Anticholinergics have long been linked to impaired cognition and falls risk, but (more recently) have also been linked to increased morbidity and mortality. Anticholinergics may also be a cause of constipation and urinary retention. The table below shows that anticholinergic effects are dose dependent (adapted from reference26). Of note is, however, that there is significant inter-individual variability regarding anticholinergic dose and manifestations of signs and symptoms of toxicity.

Table 4a: Anticholinergic effects

Atropine dose equivalentDigestive tractUrinary tractSkinEyesCardiovascularCNS
10 mgRed, hot, dry+++Mydriasis
+++Blurred vision
+++ Tachycardia
Fast and weak pulse
Ataxia
Agitation
Delirium
Hallucinations
Delusions
Coma
5 mgDecreased gut motilityUrinary retentionHot and dry++Mydriasis++ TachycardiaRestlessness Fatigue Headache
2 mg++ Mouth dryness+Mydriasis
Blurred vision
+ Tachycardia
Palpitations
1 mg+ Mouth dryness ThirstMydriasisTachycardia
0.5 mgMouth drynessAnhidrosis

Drugs with anticholinergic properties continue to be commonly prescribed to older people and those with mental illness, who are particularly susceptible to adverse effects, even at therapeutic doses. A recent study in NHS Tayside26 found that use of anticholinergics among older patients had increased to 24% in 2010, with 7% being classified as carrying a high anticholinergic drug burden.

How to assess and reduce the anticholinergic burden

Not all drugs with anticholinergic properties may individually put patients at risk of severe adverse effects. However, a wide range of commonly used drugs have anticholinergic properties and their effects may accumulate. A scale or table that lists the anticholinergic activity of commonly prescribed drugs can guide clinical decision-making to limit anticholinergic load. One such tool is the Anticholinergic Risk Scale (ARS), which was developed using 500 most prescribed medications.27 They ranked medication with anticholinergic potential on a scale of 0–3 (0. limited or none; 1. moderate; 2. strong; 3. very strong potential) based on information available on the dissociation constant for the muscarinic receptor and rates of anticholinergic adverse effects, i.e. based on in vitro data which may not always reflect in vivo effects.28 The scale may not always reflect in vivo actions however. The ARS has since been modified (subsequently referred to as mARS) to include newer medications with anticholinergic properties that are available in the United Kingdom (see table overleaf).28 Medications with moderate to severe anticholinergic effects according to other scales (Anticholinergic Burden Scale29 and Anticholinergic Drug Scale30) were added to the list. Medications identified as having significant anticholinergic properties in the BNF were also included and medications not available in the UK were excluded. The table overleaf also lists therapeutic alternatives with no or minimal anticholinergic effects.

mARS category 3mARS category 2mARS category 1Guidance
Antidepressants
Amitriptyline
Imipramine

Desipramine
Trimepramine
Nortriptyline
Clomipramine
Sertraline

Trazodone
Mirtazapine
Paroxetine
Lofepramine
Venlafaxine, duloxetine, bupropion and trazadone have low-to-nil systemic anticholinergic activity
Antipsychotics
Thioridazine
Fluphenazine
Perphenazine
Chlorphenamine
Chlorpromazine
Promethazine
Trifluorperazine
Clozapine
Doxepine
Olanzapine
Levomepromazine
Pericyazine
Quetiapine
Risperidone
Haloperidol
Avoid phenothiazines Among atypical antipsychotics, aripiprazole and ziprasidone are the least anticholinergic
Nausea and vertigo
ProchlorperazineMetoclopramideDomperidone (antiemetic) does not penetrate CNS
Urinary antispasmodics
OxybutyninFesoterodine
Flavoxate
Darifenacin
Trospium
Dosulepin
Solifenacin
Tolterodine
Sedatives
Clemastine
Hydroxyzine
Cyproheptadine
Avoid antihistamine sedatives
Antiallergics
Cetirizine
Loratadine
Desloratadine may be an alternative
H2 blockers
CimetidineRanitidinePPIs may be an alternative
Antiparkinson
Procyclidine
Benzatropine
AmantadineLevodopa/Carbidopa
Selegeline
Entacapone
Pramipexole
Others
Atropine
Dicyclomine
Orphenadrine
Tizanidine
Loperamide
Tiotropium
Pseudoephedrine
Baclofen
Propiverine
Methocarbamol
Reboxetine