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Why are anticholinergics problematic?

Why are anticholinergics problematic?

Anticholinergics have long been recognised as causing symptoms such as dry mouth, constipation and urinary retention. Exposure to anticholinergic agents has also been linked to impaired cognition and physical decline. There may also be an association with falls, and increased mortality and cardiovascular events. The table below shows that anticholinergic effects are dose dependent (adapted from reference1). Of note is, however, that there is significant inter-individual variability regarding anticholinergic dose and manifestations of signs and symptoms of toxicity, which is why it is essential to understand the patient’s perspective.

1Sumukadas D, McMurdo MET, Mangoni AA, Guthrie B. Temporal trends in anticholinergic medication prescription in older people: repeated cross-sectional analysis of population prescribing data. Age and Ageing 2014 July 1, 2014;43(4):515-21.

Table 3a: Anticholinergic effects

Atropine dose equivalent

Digestive tract

Urinary tract

Skin

Eyes

Cardiovascular

CNS

10 mg

Red, hot, dry

+++Mydriasis

+++Blurred vision

+++ Tachycardia

Fast and weak pulse

Ataxia

Agitation

Delirium

Hallucinations

Delusions

Coma

5 mg

Decreased gut motility

Urinary retention

Hot and dry

++Mydriasis

++ Tachycardia

Restlessness

Fatigue

Headache

2 mg

++ Mouth dryness

+Mydriasis

Blurred vision

+ Tachycardia

Palpitations

1 mg

+ Mouth dryness

Thirst

Mydriasis

Tachycardia

0.5 mg

Mouth dryness

Anhidrosis

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.

Anticholinergic burden principles:

  • Anticholinergic effect of individual drugs vary greatly between individual patients
  • Anticholinergic effect of multiple drugs are accumulative
  • The comparative degree of anticholinergic drugs are based partly on clinical evidence and partly on pharmacological theory

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 when used in combination, effects may accumulate. Reducing the anticholinergic burden may result in improvements in short term memory, confusion, behaviours and delirium.

A scale or table that assigns a cumulative anticholinergic score to a patient’s prescribed medication can be used to assess Anticholinergic Burden. A number of these scoring systems are available. While this approach is valid, the overall aim is to reduce overall anticholinergic exposure as much as possible. The table below is intended to be a guide as to which areas anticholinergic burden is likely to be the highest.

Table 3B Reducing Anticholinergic Exposure

Notes

This is a developing area with many disagreements between different sources. Some of this table is based on incomplete or poor evidence, or on expert opinion.. The anticholinergic effects of drugs may become better understood with time.

Some of these therapeutic areas are highly specialised (for example Parkinson’s disease and would require expert advice before considering a change

As noted here less anticholinergic alternatives often have other concerns. If an anticholinergic agent must be used, consider reducing the dose.

 

AVOID IF POSSIBLE

Highly anticholinergic drugs

CAUTION

Drugs with some anticholinergic activity

Alternatives and general notes

Antidepressants

Tricyclic antidepressants

SSRIs*

Mirtazapine

 

Venlafaxine, trazodone and duloxetine have low anticholinergic activity

 

*SSRIs, Sertraline best choice. Avoid paroxetine

Antipsychotics

Fluphenazine

Chlorpromazine

Clozapine

Doxepin

Levomepromazine

Olanzapine

Quetiapine

Risperidone

Haloperidol

Aripiprazole is an acceptable choice

Trifluoperazine and perphenazine have unknown activity (conflicting data)

Nausea and vertigo

 

Prochlorperazine

Metoclopramide has unknown activity (conflicting data). However, carries specific caution regarding parkinsonian and cognitive side effects. (See MHRA Alert regarding long term use)

Domperidone does not usually penetrate the CNS, but caution is required for QT prolongation

Nausea treatments all cause potential problems. Keep courses as short as possible

 

Urinary antispasmodics

Oxybutynin

Tolterodine

Fesoterodine

Flavoxate

Darifenacin

Solifenacin

Propiverine

Dosulepin

Mirabegron has no recorded anticholinergic activity and may be an option.

It is essential to ensure that medication is effective and stop if not.

Sedatives

 

 

Zolpidem and zopiclone no anticholinergic activity but falls risk

Avoid sedative antihistamines

Non-drug measures are preferred

Antihistamines

Chlorphenamine

Promethazine

Hydroxyzine

Clemastine

Cyproheptadine

Cetirizine

Loratadine

Fexofenadine

 

Consider locally acting products for hayfever symptoms

If taken for seasonal conditions check this is happening

H2-receptor antagonists

 

Ranitidine

Cimetidine

PPIs have no anticholinergic burden. Prescribe at the lowest dose to control symptoms

Omeprazole or pantoprazole may be preferred over lansoprazole. Caution with increased risk of Clostridium difficile infection

Drugs used in Parkinson’s Disease

Procyclidine

Trixehiphenidyl (benzhexol)

Orphenadrine

 

Amantadine

Bromocriptine

 

Entacapone may have a small potential for anticholinergic activity.

 

Co-careldopa, pramipexole, ropinirole and selegiline have no significant anticholinergic activity

 

Spasticity

Tizanidine

Baclofen

Diazepam

Methocarbamol

 

Analgesia

 

Opiates*

Paracetamol and NSAIDs are not thought to have anticholinergic activity.

Gabapentin has minimal anticholinergic activity

Others

Atropine

Hyoscine

Propantheline

Dicycloverine

Ipratropium

Loperamide

Carbamazepine

Theophylline

Lithium

Furosemide and digoxin have unknown anticholinergic activity.

The following have no or negligible anticholinergic activity:

Corticosteroids, statins, beta-blockers, ACE inhibitors, calcium channel blockers, triptans, valproate, phenytoin, phenobarbitone, topiramate.

Notes: This is a developing area with disagreements between different sources. Some of this table is based on incomplete or poor evidence, or on expert opinion. The anticholinergic effects of drugs may become better understood with time. Some of these therapeutic areas are highly specialised (for example Parkinson’s disease) and would require expert advice before considering a change. As noted here less anticholinergic alternatives often have other concerns. If an anticholinergic agent must be used, consider reducing the dose.

References

Duran C.E., Azermai M., Stichele RHV. Systematic review of anticholinergic risk scales in older adults. Eur J Clin Pharmacol 2013 July 2013;69(7):1485-1496.

Nishtala P.S., Salahudeen M.S., Hilmer SN. Anticholinergics: theoretical and clinical overview. Expert Opinion on Drug Safety 2016 02 Jun 2016;15(6):753-768.

Bishara D., Harwood D., Sauer J., Taylor DM. Anticholinergic effect on cognition (AEC) of drugs commonly used in older people. Int J Geriatr Psychiatry 2017 June 2017;32(6):650-656.

Chew ML, Mulsant BH, Pollock BG, Lehman ME, Greenspan A, Mahmoud RA, et al. Anticholinergic activity of 107 medications commonly used by older adults. J Am Geriatr Soc 2008 Jul;56(7):1333-1341.

Ehrt U, Broich K, Larsen JP, Ballard C, Aarsland D. Use of drugs with anticholinergic effect and impact on cognition in Parkinson's disease: a cohort study. Journal of Neurology, Neurosurgery & Psychiatry 2010 Feb;81(2):160-165.

Rudolph JL, Salow MJ, Angelini MC, McGlinchey RE. The anticholinergic risk scale and anticholinergic adverse effects in older persons. Arch Intern Med 2008 Mar 10;168(5):508-513.

Sittironnarit G, Ames D, Bush AI, Faux N, Flicker L, Foster J, et al. Effects of anticholinergic drugs on cognitive function in older Australians: results from the AIBL study. Dementia & Geriatric Cognitive Disorders 2011;31(3):173-178.