Anticholinergic Side Effects
Anticholinergic burden scale
Anticholinergic Burden Scale (Risk of CNS impairment/dementia) – “mad as a hatter”
Anticholinergic load should be minimized with older adults. Dose should be taken into consideration when estimating risk.
When we refer to “anticholinergic”, we actually mean antimuscarinic. We’re talking about blocking the action of the neurotransmitter acetylcholine at muscarinic receptors, not at nicotinic receptors. All five muscarinic receptor subtypes—M1, M2, M3, M4, and M5—are present in various locations throughout the brain. Anticholinergic side effects are especially problematic for older adults. Ongoing use of strong anticholinergic medication can increase the risk of dementia by 50%.
Tacky (tachycardia) Auntie Choli is...
“Dry as a bone”
❖ Constipation (risk of ileus, bowel rupture)
❖ Urinary retention
❖ Decreased sweating; flushing—“Red as a beet”
❖ Dry mouth (risk of sublingual adenitis)
❖ Dry nasal mucus membranes
❖ Dry eyes
❖ Inhibition of lactation
“Mad as a hatter”
❖ Confusion, memory problems
❖ 50% increased risk of developing dementia
❖ Delirium with visual hallucinations
“Blind as a bat”
❖ Cycloplegia (loss of accommodation)—lens cannot focus on near objects
❖ Photophobia due to mydriasis (dilated pupils)
❖ Increased intraocular pressure; contraindicated in
angle-closure glaucoma (unless already treated by laser iridotomy)
Anticholinergic drugs
Anticholinergic (antimuscarinic) agents block muscarinic acetylcholine receptors. Atropine is the strongest anticholinergic. They are used to treat:
❖ Parkinsonism, EPS – benztropine (Cogentin), trihexyphenidyl (Artane), diphenhydramine (Benadryl) are given for dystonic reactions
❖ Overactive bladder (OAB) – oxybutynin (Ditropan), tolterodine (Detrol), etc decrease premature detrusor contractions
❖ Irritable bowel syndrome (IBS) – dicyclomine (Bentyl) and hyoscyamine (Levsin) slow GI transit time
❖ To decrease secretions and spasms of rhinorrhea, hypersalivation, hyperhidrosis, diarrhea, peptic ulcers, biliary colic, and renal colic
❖ Vertigo and motion sickness – meclizine (Antivert), scopolamine (Transderm Scōp)
❖ Asthma and COPD – inhaled ipratropium (Atrovent) works as a bronchodilator
❖ Bradycardia – injections of atropine increase heart rate; In cardiac arrest, atropine is given to reverse asystole and severe bradycardia.
❖ Cycloplegia – Atropine eye drops are used to paralyze the accommodation reflex and produce mydriasis (pupil dilation) for procedures
❖ Nerve agent poisoning – Atropine is used to counteract poisoning by agents that block the action of acetylcholinesterase, e.g., pesticides
Anticholinergics should not be routinely coadministered with high potency antipsychotics. Although some psychiatrists automatically add
benztropine to haloperidol, this is not recommended, at least for long-term use. Anticholinergics do not prevent, but rather increase risk of tardive dyskinesia. Also, anticholinergics exacerbate the underlying cognitive impairment in patients with schizophrenia.
Anticholinergic Cognitive Effects
The elderly are especially susceptible to cognitive side effects of anticholinergic (antimuscarinic) medications. These “mad as a hatter” cognitive impairments may include:
❖ Memory problems
❖ Increased risk of developing dementia
❖ Delirium
Delirium is an acute confusional state that develops over a short period of time, typically hours to days. It tends to fluctuate from hour to hour. Classically, delirium is worse in the evening, a phenomenon colloquially referred to as “sundowning”. Delirium involves impaired attention and disorientation. Visual hallucinations are common in the delirious state (as opposed to psychosis, which is more likely to manifest as auditory hallucinations). Medications that can contribute to delirium in elderly patients are listed below as 2 to 3 points on the anticholinergic burden scale. Most episodes of delirium are multifactorial, brought about by a combination of medications (anticholinergics, opioids, benzodiazepines, corticosteroids) and medical conditions. Delirium is very common among medically hospitalized elderly patients.
Treatment of acute delirium traditionally included a short-term course of an antipsychotic, one with minimal anticholinergic properties. There is controversy over whether antipsychotics are actually beneficial for delirium.
Antipsychotics scoring 0 or 1 points on the anticholinergic burden scale are reasonable choices for management of delirium. For acute agitation associated with delirium, IM ziprasidone (Geodon) is a suitable choice. Benzodiazepine use should be minimized, unless the delirium is caused by withdrawal from benzodiazepines or alcohol (delirium tremens).
The anticholinergics that impair cognition:
❖ Block the M1 muscarinic receptor subtype
❖ Get past the blood brain barrier (BBB) by
– being a small molecule
– being lipid soluble (i.e., lipophilic, not hydrophilic)
– having a neutral charge
– not being a P-gp substrate
P-glycoprotein (P-gp) is an efflux transporter that pumps substances out of the CNS, back into systemic circulation. P-gp works as a component of the BBB, preventing the accumulation of certain drugs (P-gp substrates) in the brain.
