anticholinergic drugs, risks, adverse effects, hypertension, depression, antihistamines, dementia, diarrhea, anxiety,

Death in a Bottle: Risks of Anticholinergic Drugs

Death in a Bottle: Risks of Anticholinergic Drugs

© 2012 Dr. Dale Peterson &

As I approach my sixty-fifth birthday I’ve been receiving a steady stream of solicitations from companies selling Medicare supplement policies. The benefit that seems to be the most significant factor in the cost of each plan is the “Part D” prescription drug coverage. It’s possible to obtain a supplement with low office visit copays and a reasonable hospital deductible for no additional cost beyond the basic Medicare premium if one foregoes prescription drug coverage. Plans that cover prescription drugs can cost several hundred dollars per month. The plan promoters are quick to point out that those who fail enroll in “Part D” initially will face a financial penalty when (not if) they enroll at a future date.

I have no intention of enrolling in Medicare “Part D” now or in the future. When the program was first introduced I labeled it “government-sponsored euthanasia.” My opinion hasn’t changed over the years; it has been strengthened. A recent study published in the Journal of the American Geriatrics Society is a case in point.

Researchers at the University of East Anglia in the United Kingdom studied 13,400 individuals over the age of sixty-five to determine the effects of anticholinergic drugs on mental health and longevity. To appreciate the significance of the study it is necessary to understand what the term “anticholinergic” means.

Neurotransmitters are substances that facilitate the passage of messages in the brain and the rest of the nervous system. The first to be identified in the early 1900s was acetylcholine. Choline is a B vitamin. It is found in legumes such as soybeans and lentils, egg yolks, dairy products, peanuts, potatoes, cauliflower, tomatoes, bananas, oranges, and whole grains. The richest source of choline is lecithin, which is available as a food supplement.

Acetylcholine receptors are found throughout the body and brain. In the brain acetylcholine is a key factor in learning and memory. In the body it stimulates muscle tissue. Choline and lecithin supplementation is helpful in preventing or slowing the progression of dementia, such as in Alzheimer’s disease. Ginkgo biloba, which has been used to enhance memory, is believed to do so by improving acetylcholine activity.

Anticholinergic drugs interfere with acetylcholine and should therefore be expected to accelerate mental decline. The East Anglia study explored this possibility and found the answer to be a resounding yes.

The use of drugs that have anticholinergic effects is quite common. At the beginning of the study fifty-one percent of the participants were taking a drug suspected of having anticholinergic effects. The study lasted for two years, a relatively short period of time. Nevertheless, there was a significantly greater decline in Mini Mental Status Examination scores in those on the drugs. The death rate of people taking the drugs was over 1 ½ times that of those who were not. The researchers concluded that, “The use of medications with anticholinergic activity increases the cumulative risk of cognitive impairment and mortality.”

The number of drugs that can speed mental decline and death is quite large. They are divided into two groups: those that have proven anticholinergic effects and those that are suspected of having anticholinergic effects. Use of the drugs is rarely necessary, as effective alternatives exist.

First generation antihistamines are one family of drugs with known anticholinergic effects. These are available over-the-counter and are therefore readily available. Some of the most familiar are brompheniramine (Dimetapp), chlorpheniramine (Chlor-Trimeton), clemastine (Tavist), diphenhydramine (Benadryl), dimenhydrinate (Dramamine), meclizine (Antivert or Bonine), hydroxyzine (Atarax or Vistaril), and promethazine (Phenergan). The primary use of these drugs is for management of allergy symptoms such as sneezing or itching, but they are also used for other reasons. Benadryl is commonly recommended as a sleep aid for elderly patients. Dimenhydrinate and hydroxyzine are used to reduce motion sickness or nausea. .

Allergy symptoms can be managed by newer antihistamines such as loratidine (Claritin) or cetirizine (Allegra). In many instances herbal substances such as stinging nettle will bring relief as effectively as the drugs in question without causing any adverse effects.

An excellent alternative for symptoms of motion sickness or nausea is ginger. Fresh ginger or ginger capsules can be used, but even ginger ale can provide enough ginger to be of benefit. Another anticholinergic medication that is commonly prescribed for management of motion sickness is scopolamine (Scopace or Transderm Scop). Sea bands, which are worn on the wrists, can effectively prevent motion sickness and eliminate the need for medication.

Hydroxyzine (Atarax or Vistaril) are often recommended to relief anxiety. Other anti-anxiety medications such as alprazolam (Xanax), clorazepate (Tranxene), and diazepam (Valium) also produce anticholinergic effects. B vitamins can be as effective as hydroxyzine in the management of anxiety and work even more effectively if combined with calmative herbs such as valerian and hops. I have seen excellent results from a product called Serenity, which is a B vitamin/herbal combination. Serenity is also a good alternative to Benadryl for helping with sleep issues.

A number of antidepressants have strong anticholinergic effects. Some include amitriptyline (Elavil), amoxapine (Asendin), bupropion (Wellbutrin), clomipramine (Anafranil), desipramine (Norpramin), doxepin (Sinequan), fluoxetine (Prozac), fluvoxamine (Luvox), imipramine (Tofranil), nortriptyline (Pamelor), paroxetine (Paxil), sertraline (Zoloft), trazadone (Desyrel), and trimipramine (Surmontil). Antidepressants are frequently prescribed to elderly patients without considering the possibility that the depressive symptoms are due to a medication or underlying disease process.

Commonly prescribed medications such as beta blockers, anti-anxiety agents, and over-the-counter acid suppressants such as ranitidine or cimetidine (Zantac or Tagamet) can cause depression and should be discontinued before antidepressant drugs are prescribed. Many older people have unrecognized thyroid deficiency that can give a picture of depression.

Antidepressants are frequently prescribed unnecessarily to people who are going through a normal grieving process. Because many of the drugs have a strong sedative effect, they are commonly prescribed for management of insomnia.

Depression can be managed effectively with 5-HTP (5-hydroxytryptophan), which the body can use to manufacture the neurotransmitter serotonin. 5-HTP can also be used as a sleep aid. It is one of the components in Sleep Well a formulation I developed several years ago to help restore a normal sleep pattern.

Antidepressants are also used to augment the effects of pain-relievers. Since narcotic pain relievers including codeine, fentanyl, and morphine produce anticholinergic effects, as do cortisone-like drugs such as hydrocortisone and prednisone, combining these drugs significantly increases the risk of serious adverse effects. Systemic enzymes such as Panzymes, Wobenzym, or Vitalzym can bring significant improvement in pain syndromes negating the need to use potentially dangerous drug combinations..

Antipsychotic drugs produce anticholinergic effects. Once limited to use in conditions characterized by hallucinations or violent behavior, antipsychotics are being prescribed with increasing frequency to people with diagnoses of depression and bipolar disorder. Some antipsychotic medications are chlorpromazine (Anafanil), clozapine (Clozaril), haloperidol (Haldol) olanzapine (Zyprexa), perphenazine (Trilafon), quetiapine (Seroquel), respiridone (Risperdal), thioridazine (Mellaril), and trifluoperazine (Stelazine). There may be no good alternative treatment if a person is truly psychotic, but the use of these drugs for other conditions should be seriously questioned.

Antispasmotic medications also place people at increased risk of mental decline or death. These drugs prevent contraction of smooth muscles and are prescribed for symptomatic relief of intestinal cramping or to decrease the frequency of urination. Commonly prescribed antispasmotics are alverine (Spasmonal), atropine, darifenacin (Enablex), dicyclomine (Bentyl), flavoxate (Urispas), hyoscyamine (Anaspaz, Cystospaz, & Levsin), propantheline (Pro-Banthine), and toxlterodine (Detrol). None of these drugs address the underlying cause of abdominal cramping or urinary frequency. Attention should be directed to identifying and correcting the condition causing the symptom, which will eliminate the need for symptomatic treatment.

Skeletal muscle relaxants can also produce anticholinergic effects. Cyclobenzaprine (Flexeril), methocarbamol (Robaxin), and orphenadrine (Norflex) are the most likely to do so. Supplementation of magnesium, which is the body’s natural muscle relaxant, can often improve muscle cramping without the use of medications. A typical amount is 400 – 600 mg. of magnesium citrate or magnesium aspartate two or three times daily.

A few drugs are specifically prescribed for their anticholinergic effect. They are primarily used to improve symptoms of Parkinson’s disease. These are amantadine (Symmetrel), benztropine (Cogentin), and trihexyphenidyl (Artane). Amantadine has also been used as a treatment for influenza.

Efforts should be made to control the symptoms of Parkinson’s disease without resorting to anticholinergic agents. Carbidopa-levodopa (Sinemet) is preferable as it serves as raw material for the manufacture of the neurotransmitter dopamine in the brain. Dopamine deficiencies are believed to be the primary cause of Parkinson’s symptoms. Individuals who find that they are prone to periods during which the medication is less effective can benefit from the use of the herb mucuna pruriens, as it has levodopa and can often be better titrated to control symptoms than Sinemet alone.

Influenza is better controlled by extracts that coat viruses and prevent them from injecting their genetic material into living cells. Two brand names are Sambucol and Immunity Take Care.

Diuretics such as hydrochlorothiazide (HCTZ), chlorthalidone, furosemide (Lasix), and triamterene are commonly prescribed for issues for which excellent alternatives exist. Many physicians continue to prescribe diuretics as initial treatment of high blood pressure even though medications that do not possess anticholinergic effects are readily available. I frequently see people who are taking diuretics for swelling caused not by heart or kidney failure, but by weakness of veins in the lower extremities. Elevation of the feet, use of supportive hose in situations where the feet cannot be elevated, and supplementation of herbs such as gotu kola or horse chestnut that strengthen veins are more effective than diuretics in dealing with this condition.

Other blood pressure medications also exert anticholinergic effects. Some of these are hydralazine (Apresoline), beta blockers, which are extremely popular among cardiologists, the calcium channel blocker nifedipine (Procardia), and the ACE inhibitor captopril (Capoten). Other calcium channel blockers or ACE inhibitors have not been found to have significant anticholinergic effects and can be used in place of the medications listed. For a comprehensive discussion of the management of high blood pressure see the January 2012 issue of this letter.

Cimetidine (Tagament) and ranitidine (Zantac), which are used for heartburn or other stomach upset and are available over the counter have anticholinergic effects. Famotidine (Pepcid) does not, but it is known to trigger delirium in some people. In nearly all cases, heartburn and indigestion are better managed by increasing the percentage of raw food in the diet and using digestive enzyme supplements than by taking acid reducing medications.

The antidiarrheal medication loperamide (Immodium) is another medication with anticholinergic effects. Antidiarrheal medications should be avoided if the diarrhea is caused by an infection as they will worsen or prolong the condition. Instituting a clear liquid diet will usually allow the diarrhea to subside within 24 to 48 hours. Psyllium husk (Metamucil or Tasty Fiber) can absorb many times its weight in water and so can help bring form to loose stools.

Other drugs with anticholinergic effects include colchicine (used for gout), digoxin (a drug that strengthens the heartbeat), dipyridamole (an antiplatelet drug like aspirin), disopyramide (used to treat irregular heartbeats), isosorbide (to prevent angina), quinidine, theophylline (sometimes used in asthma), and warfarin (to prevent blood clots). The list will continue to grow as new medications are introduced.

My reason for reviewing the drugs that have anticholinergic effects and offering alternatives to their use was a study conclusion that such drugs increase the risk of mental decline and premature death. The study did not look at drug combinations. Given the wide array of medications that have anticholinergic effects it is quite likely that a person may be prescribed two or more of them simultaneously. This would be expected to increase the risks associated with these drugs.

It is important to recognize that while adverse effects are reported for single drugs, almost nothing is known about the effects produced when two or more drugs are taken simultaneously. Each time a drug is added to someone’s regimen they become an experimental subject for the particular combination of drugs they are taking. Carefully consider this whenever a physician decides to add a drug to others you are already taking. The combination of drugs may produce adverse effects that are not listed on any of the individual drug information sheets.

It is my contention that if an individual is taking more than three medications on an ongoing basis, many of the drugs have been prescribed in an attempt to address the adverse effects created by the other medications. In many cases, a better solution would have been to eliminate the drug causing the adverse effect rather than adding another to counter that symptom. It is wise to review medication regimens regularly asking, “Is this drug really necessary at this time?” I often find that the reason for which the drug was originally prescribed no longer exists and that it can and should be discontinued.

Effects of drugs are continually emerging. While I was preparing this article the Journal of Optometry and Vision Science reported that people taking cholesterol-lowering statin drugs are twice as likely to develop cataracts as non-users. The Canadian Medical Association Journal carried an article reporting that the broad-spectrum antibiotics levofloxacin (Levaquin) and moxifloxacin (Avelox) can cause liver injury serious enough to require hospitalization in people over the age of sixty-five.

I point this out to emphasize that medications should never be taken in a cavalier manner. Conditions that require the use of drugs should not be over-treated. Hypertension (high blood pressure) is a case in point. While studies have consistently shown that lowering the diastolic (lower number) blood pressure to less than 80 – 85 mm/Hg results in a greater number of strokes and premature deaths, I frequently see people whose physicians are pleased with diastolic blood pressures of 60 or less. In many cases those individuals are on multiple blood pressure medications. It is not uncommon for me to see someone who is on five or even six blood pressure medications simultaneously.

The results obtained do not justify such intensive treatment. In one study type II diabetics who were treated aggressively to control blood pressure and blood sugar were just as likely to have heart attacks as those who received less intense treatment, but the aggressively treated group had a higher complication rate. In another study, diabetics who were treated with 3 – 4 drugs to lower their systolic (upper number) blood pressure to 120 fared worst that others who were treated with two drugs to bring their systolic pressure below 140.

On average, people in the United States fill prescriptions for twelve drugs each year. In the 1970s the average was seven. One of the factors is direct to consumer pharmaceutical advertising, which was not allowed at that time. Another is the practice of providing pharmaceutical companies detailed information on individual physician prescribing habits, which can then be used to tailor in office sales presentations. Regardless of the cause, the dramatic increase in drug use over the past four decades has only served to diminish the quality of life and increase the incidence of premature death. As Oliver Wendell Holmes, the physician father of the Supreme Court justice by that name, observed over a century ago, “If all the drugs were thrown in the ocean, everyone would be better off . . . except the fish.” There are exceptions, of course, but Holmes’ statement is worth keeping in mind.

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