Anticholinergic effects of mast cell medications

When I came back from Seattle in 2012 with an amotile colon, my GI mast cell specialist had a lot to say about it.  I had not yet had motility studies or biopsies.  “I’ve seen this before,” he told me.  “Your colon is probably not moving as much from your mast cell disease as from all the medication you take to treat it.  But you can never go off those,” he quickly added, as if there were any doubt.  “You will be on those for life.”

I worked in pharmacy for several years and so was overly familiar with the side effects of most common medications.  A lot of medications were anticholinergic and caused a similar subset of far reaching side effects.  I went through my list of meds in my head and realized that the majority of them had anticholinergic activity.  My colon was inflamed and damaged, and I was taking a handful of medications every day that slowed down GI motility.  It was pretty much a recipe for a colostomy.

An anticholinergic medication is so called because it blocks the molecule acetylcholine from transmitting nerve signals in the central and peripheral nervous systems.  Specifically, anticholinergics interfere with the body sending parasympathetic nerve signals.  The parasympathetic system is responsible for the involuntary movement of some of the body’s smooth muscles.  These include the smooth muscles in the GI tract, the urinary tract and the lungs. 

Blocking acetylcholine is not always the intended function of an anticholinergic drug, but can instead be a side effect.  High doses of anticholinergics can have a lot of side effects, including loss of coordination, dry mouth, dry throat, dilation of pupils, increase in body temperature, rapid heart rate, blurry vision, double vision, urinary retention, diminished GI motility, and others. 

Anticholinergics can also affect the central nervous system, causing respiratory depression, confusion, memory problems, inability to concentrate, slurred speech, myoclonic jerking, visual disturbances and sensory hallucinations.  In some patients, especially the elderly, they can cause orthostatic hypotension, where blood pressure drops when moving to a standing position.

Anticholinergic medications are generally classified as either antimuscarinic (bind to muscarinic acetylcholine receptors) or antinicotonic (nicotinic acetylcholine receptors.)  Most medications are antimuscarinic. 

A lot of antihistamines are well known for their anticholinergic activity, to the extent that this has been well studied.  One study identified the following hierarchy of anticholinergic activity in the body:

Cyproheptadine (periactin) > promethazine (Phenergan) > desloratadine (Clarinex) > loratadine (Claritin) > diphenhydramine (Benadryl)

Regarding common mast cell medications:

Clemastine, doxepin, doxylamine, ipratropium, hydroxyzine and meclizine are known to have anticholinergic activity.

Alprazolam, diazepam, ranitidine, prednisone and hydrocortisone may have anticholinergic activity. 

Of note, cetirizine (Zyrtec) and fexofenadine (Allegra) have no quantifiable anticholinergic activity.  This makes them good choices for people who take a lot of other anticholinergics.

Some people report alleviation of anticholinergic side effects, especially GI side effects, when they smoke cigarettes.  Nicotine is known to counteract anticholinergics by binding to nicotinimic acetylcholine receptors. As an interesting side note, nicotine is known to clinically improve patients with ulcerative colitis.  The reason for this is not clear, and may include anticholinergic activity or modulation of any number of immune activities.  Caffeine also reduces some side effects from anticholinergics by increasing acetylcholine activity.

When you have mast cell disease, it is easy to attribute all new symptoms to the disease, but I have often found that they are caused by medications.  If possible, new medications should be started one at a time and tapered up to therapeutic dose so that any side effects or reactions are apparent.