To Use Aricept or Not?

Cholinergic Activity Makes the Brain Go Round…
In Alzheimer’s dementia there is a lack of the neurotransmitter acetylcholine. We give patients Aricept, and two other medications, because they increase the bioavailability of acetylcholine in the brain.  Think of acetylcholine as the “gasoline” of your brain’s engine, by giving more gas to it, the brain can think more clearly, faster and better.  Thus, Aricept is a “proacetylcholinergic” (or pro-cholinergic for short).   It’s like giving Prozac (a proserotonergic drug) to a depressed person, in order to boost serotonin in the body and give more gas to the emotional system, to improve mood. Or, it's like giving Sinemet as a prodopaminergic drug to Parkinson’s patients, to boost their motor system’s activity.

Acetylcholine is a neurotransmitter that transmits nerve impulses in both the central and peripheral nervous system; i.e., your brain/spine and the rest of your nervous system.  This includes the parasympathetic nervous system; i.e., an involuntary system that let’s us automatically breath, digest and control our bowels without thinking, etc.  A fairly common side effect of taking Aricept is lower GI distress and diarrhea, as increasing acetylcholine activates the bowel and enhances peristalsis, sometimes causing overactivity and mild bowel distress.

What is Anticholinergic Activity?
I often do home visits to see if my senior patients are taking any “anticholinergic” prescribed drugs, herbs or over-the-counter (OTC) remedies, before recommending to a PCP that they put a dementia patient on Aricept.  Otherwise, why bother as the Aricept would conflict with the anticholinergic? And, many anticholinergic drugs are OTC supplements and remedies, never reported to doctors. These are drugs and need to be reviewed. So I often, with permission, wander about the house looking in the medicine chest or by the bed side table to see what sleeping OTC drugs (soporifics), antihistamines, etc. are being used.  These are the things patients rarely remember to tell their doctors, thinking they are "just" like vitamins and safe. If you think that, then you have not yet read the section on supplements, here.

So exactly what is the problem with using anticholinergic medications? Well anticholinergic side-effects include: fuzzing of the mind and constipation (the opposite of procholinergic medications); urinary retention (but, urinary incontinence while sleeping); sedation; dry eyes, mouth and nose; and, reduced skin heat dissipation and lessened sensitivity to itchiness.  It also can cause warm, blotchy or reddened skin so there is a cost to this.  Side effects include increased intraoccular pressure–not good if you have glaucoma.  Anticholinergics interfere with the parasympathetic nervous system's control smooth muscle function, thus they seem to quiet so-called “overactive” bladder, or stomach activity associated with nausea.  It reduces nerve transmission efficiency, and in the vagus nerve this reduces bowel motility causing constipation.  They cause pupil dilation which is why your eye doctor uses solutions of Bella Donna to put drops in your eyes so as to enlargen your pupils to better look inside your eyes.  In fact, the name Bella Donna (beautiful woman) was given to the drug atropine when Italian Renaissance painters discovered that applying it to the eyes of their subjects enhanced their eyes in their portraits.  Other side-effects include double vision, which is why you are dizzy after visiting your eye doctor.  They increase heart rate and stop sweating.  Overall, they are not good–but, the pharmaceutical and trade medicine manufacturers realized they could sell anticholinergics to address annoying problems like allergies, insomnia, bladder leaking, etc. The problem is you can't selectively just treat one issue as you get all the side effects, and the confusion and fall risk they induce in elders has been a major cause of psychiatric distress and falls in recent years.

OK, What Anticholinergic Drugs I should Avoid?
Well, there are many. Consider just the OTC drugs that contain Benadryl (diphenhydramine) like; Advil-PM, Tylenol-PM, Nytol, Excedrin PM, Doans PM, Aleve PM, ZzzQuil, Pain Relief PM, Motrin PM, Advil PM, Ibuprofen PM, Bayer PM, Alka-Seltzer PM; doxylamine (Unisom); or, doxepin (Sinequan, Deptran, Silenor) which are used to induce drowsiness and treat pain/headache.  Diabetic Tussin Night Time Cold & Flu, Theraflu Nighttime Severe Cold & Cough, Suphedrine PE Severe Cold, Contact Day and Night Cold and Flu, Contact Day and Night Allergy, Sedated Sinus Nighttime Plus Pain, Tylenol Allergy Complete NightTime, Endal CD, Airacof, Hydro-DP, Endal HD, Tussinate, Alahist LQ, Delsym Children’s Night Time Cough & Cold are used used to treat cold/flu/cough symptoms because they dry out the mucous membranes; i.e., cause dry eyes-mouth-nose syndrome. And, they are used to reduce skin itching with Allegra Cooling Relief Anti-Itch, and many more Benadryl containing creams and salves.  Or the are used for allergies, like; Ala-Hist, Ala-Hist D, Dytan-AT, D-Tann AT, Unit-Tann CS, D-Tann CD, Benylin Muti-Symptom, Acted Allergy Day/Night, Benadryl Childrens Allergy and Sinus.  And, these are just some of the anticholinergics that are based on just one (1) drug, Benadryl, and they are marketed everywhere. Whole sections of Stop & Shop are dedicated just to these types of drugs.

The issue is you can’t just get the desired nighttime sedation, without also getting other side effects, meaning you'll have to get up in the middle of the night with a dry mouth for a drink of water. And, given the slowed metabolism of a senior’s liver, these drugs stay in the system for many more hours.  Consider, every bottle of Benadryl says in its warnings “Don’t drive or operate machinery while taking this medication.”  And, that is for 20-30 year olds!

There are other first generation antihistamines which are also highly anticholinergic, like brompheniramine, or chorpheniramine on which many OTC remedies are based like Chlor-Trimeton so the list above represents a tiny fraction of the OTC drugs on the market, and those are just for allergy relief.  You can can take dimenhydrinate (Dramamine) or scopolamine to reduce nausea.  Brand name drugs are also marketed because of desirable anticholinergic effects.  For example; 25+ years ago Ditropan or Detrol (oxybutynin or tolterodine) were marketed to induce urinary retention in people who “leak” a bit, as most of us do as we get older.  Second generation anticholinergics included Enablex, Vesicare and Sanctura (darifencacin, solifenacin and trospium) approved in 2004 and Toviaz (fesoterodine) approved in 2008 may cause less anticholinergic effects, and thus less cognitive compromise.  There is a nonanticholinergic medications for urinary frequency–Mybetriq or mirabegron. Second generation antihistamines like Claritin, loratadine, Allegra or fexofenadine and Zyrtec or cetirizine, but they tend to be more expensive brand name drugs, or still under patent requiring a prescription. Care should be even be used with histamine blocking drugs like Tagament, Pepcid, Axid, Prevacid and Zantac (cimetidine, famotidine, nizatadine, lansoprazole and ranitidine) for GERD as while weakly anticholinergic, they can worsen confusion in the elderly.

OK, This Stuff is Everywhere, Can it Get Any Worse?
But wait! It can get worse!! Not only do anticholinergics cause confusion, disorientation, memory and attention problems, irritability, jerking at night, and irritability–especially in seniors–they also appear to actually increase dementia risk.  A large scale study found this true for anticholinergics even at low dose if used daily for 3 years or more, like: diphenhydramine (Benadryl), chorpheniramine (Chlor-Trimeton) 4 mg; urine control oxybutynin (Ditropan), tolterodine (Detrol) 5 mg; sleep aides doxepin (Sinequan), amitriptyline (Elavil) 10 mg, etc.  This doesn’t surprise this writer, as he has seen cases of anticholinergic poisoning, and physostigmine (a powerful pro-acetylchoinergic) can be used as an antidote.  Other mildly proacetylcholinergic substances include nicotine and caffeine.  The anticholinergic effects of chemicals have formed the basis of many of our most popular insecticides (they disrupt the nervous system of bugs leading to death), and even represent the basic chemistry of nerve gas and toxins, like Sarin gas used in the Japanese subway attacks.

So the point, here, is that if someone has memory or other cognitive problems, we should start by looking at what might be causing confusion (like anticholinergics) before we consider using procholinergics.  Just because you buy in over-the-counter does NOT mean it's save, and with little regulation they are often down right dangerous. So how can you know what is anticholinergic in your medicine chest or on your bedside table?

How Can I Know What's in my Medications & Supplements
The simplest answer is whenever you are prescribed a new drug (especially by a specialist other than your own doctor) and you fill the prescription, when the clerk asks if you have any questions for the pharmacist–say “Yes.”  Pharmacists, geriatricians (doctors who specialize in working with seniors) and mental health providers all rely on the BEERS criteria by the American Geriatric Society (AGS). The AGS offers recommendations, written by interdisciplinary panel of experts in geriatric care, most recently in 2015, of Potentially Inappropriate Medications (PIM) which cause confusion, falls and increased risk of death in seniors. The BEERS criteria actually rates various drugs on how anticholinergic they are.  They use an anticholinergic burden scale (ACB) ratings from 0–3 with 0 being no burden to 3 definitely/highly anticholinergic, there are a number of such risk scales, but the BEERS is by far the most commonly used.  Older drugs like amitriptyline and Benadryl carry a heavy burden, 3 each. Many heart medications are mildly anticholinergic, and are rated at 1.

With the ACB, you can add up what a person is taking and estimate the cumulative risk of side effect severity. For example, a senior might be on two heart medications adding up to an ACB score of 2. If there is atrial fibrillation, using coumadin adds 1 point. Adding Amitriptyline (usually used with gabapentin) for pain, adds 3 points. Then taking a morning Chlor-Trimeton for hay fever adds another 3 points and a soporific like Tylenol PM adds another 3. So a senior with Mild Cognitive Impairment is under a daily anticholinergic burden of 11 points, which could explain episodic confusion and drowsiness. Of course, weakened by a cold the confusion could worsen; especially, if s/he took DayQuil adding another 3 points to an already heavy ACB…