Anticholinergic Toxicity: Causes, Symptoms, & Treatment

Many drugs have anticholinergic properties, meaning they inhibit the neurotransmission of acetylcholine in the brain.  Drugs with anticholinergic effects prevent acetylcholine from binding to receptors, resulting in therapeutic effects.  There are three major types of anticholinergic drugs including: antimuscarinics, ganglionic inhibitors, and neuromuscular inhibitors – the majority being antimuscarinic.

Anticholinergic drugs are often administered for the treatment of gastrointestinal disorders, respiratory disorders, insomnia, and even motion-sickness.  Most anticholinergics are sedating and tend to impair cognitive function.  That said, many people find them helpful due to the fact that they are often sedating and reduce stimulation of the central nervous system.

What is anticholinergic toxicity?

Unfortunately a minority of individuals ingest too much of an anticholinergic drug or multiple drugs with anticholinergic properties, and the cumulative anticholinergic effect is poisonous to the body.  Experts have referred to this poisonous effect as anticholinergic toxicity or anticholinergic syndrome.  In some cases the word “toxidrome” is used which represents the combination of “toxicity” and “syndrome.”

Anticholinergic toxicity can occur accidentally or may result from a deliberate poisoning attempt (e.g. overdose).  Due to the fact that anticholinergic drugs don’t produce euphoric or pleasurable effects, they are considered to have a low potential for abuse; hence the reason many are over-the-counter.  That said, some people take illicit drugs (e.g. heroin) laced with anticholinergics, which increases likelihood of toxicity.

Diagnosing Anticholinergic Toxicity

It is relatively difficult to diagnose anticholinergic toxicity unless a professional knows that the poisoned individual specifically ingested an anticholinergic drug.  With knowledge of symptoms and the particular drug ingested, treatment can be administered.  However, in some cases it is more difficult to get a proper diagnosis.  Laboratory screenings may be beneficial to pinpoint a specific diagnosis of anticholinergic toxicity.

What causes anticholinergic toxicity?

The most obvious cause of anticholinergic toxicity is ingesting too much of an anticholinergic agent or multiple anticholinergic agents.  Anticholinergic toxicity is most likely to occur in the elderly taking anticholinergic drugs due to the fact that most already have suboptimal levels of acetylcholine.  In this case, adding a potent anticholinergic to their medication regimen can result in dangerously low levels of acetylcholine.

Anticholinergic agents: There are hundreds of drugs and compounds that elicit anticholinergic effects within the body.  This includes prescription drugs, over-the-counter drugs, and even plants.  If you are ingesting a large amount of a drug with potent anticholinergic effects, you may be setting yourself up for a toxicity.

• Antihistamines: If you’re taking an antihistamine like Benadryl to reduce itchy skin or seasonal allergies, it is important to realize that it acts as an anticholinergic. If you’re taking large amounts of over-the-counter antihistamines, beware of potential toxicity.
• Cold medicines: Various cold medications that you’re taking to treat runny nose, sinus drainage, and congestion exhibit anticholinergic properties.
• Illicit drugs: Certain illicit street drugs like heroin are sometimes cut with large quantities of anticholinergic agents like scopolamine. This can result in a quick toxicity that is difficult to identify.
• Plants: A variety of plants containing the belladonna alkaloid “atropine” elicit anticholinergic effects, which may lead to anticholinergic toxicity.
• Tricyclic antidepressants: This is an older generation of antidepressants that contain a three-ring chemical structure or “tricyclic” bond. Tricyclic antidepressants often elicit significant anticholinergic effects that are believed to play a role in their therapeutic efficacy.
• Sleep aids: Those taking sleep aids such as Doxylamine could result in anticholinergic toxicity, especially if combined with anticholinergic medications.

Other influential factors to consider:

• Age: The age of the person may be a highly deterministic factor in regards to experiencing anticholinergic toxicity. The brains of elderly individuals tend to decline in performance and most have subpar levels of extracellular acetylcholine.  This means that when ingesting an anticholinergic, the elderly may be at a greater risk for experiencing toxicity.
• Baseline acetylcholine levels: A person’s baseline level of acetylcholine may be indicative of whether they are likely to experience toxicity. Those with abnormally low baseline levels of acetylcholine or those that have depleted acetylcholine levels may be more likely to experience toxicity.
• Dosage: Some people may be taking a high dose of an anticholinergic drug without realizing that it’s too much for their nervous system to handle. This is especially common among the elderly and/or those with low baseline levels of acetylcholine.  In some cases, the dosage needs to be scaled back to get the therapeutic effect without toxicity.
• Illicit drug use: An individual using illicit drugs may get a batch that was tainted with an anticholinergic agent like scopolamine. This is common among heroin users – getting a batch of heroin “cut” with scopolamine, resulting in toxicity and delirium.
• Multiple anticholinergics: Taking a combination of antichonlinergic drugs may result in a synergistic effect, meaning that the anticholinergic effect is amplified to a greater extent. Those taking multiple anticholinergics should proceed with caution to avoid toxicity.
• Overdose: If a person attempted an overdose with an anticholinergic drug or multiple anticholinergics, it is obvious that they are likely to experience toxicity. An attempted overdose with anticholinergics virtually guarantees an acute toxicity.

Anticholinergic Toxicity Symptoms

Those that experience anticholinergic toxicity will exhibit a variety of symptoms.  In nearly all cases, the specific symptoms will be a result of the drug(s) ingested, dosage, and the individual.  Keep in mind that the number of symptoms experienced as well as severity will be subject to individual variation.

• Amnesia: Those experiencing anticholinergic toxicity often exhibit amnesia as a symptom. The amnesia may be severe to the extent that they cannot remember who they are, what they’ve done, and may seem extremely disoriented.  Not only is acute amnesia a symptom of toxicity, but long-term usage of anticholinergics has been linked to dementia.
• Confusion: It is common for an individual experiencing anticholinergic toxicity to appear confused.  They may lack momentary awareness, appear as if they don’t know how to interact with others, and they appear confused.  The confusion is coupled with memory impairment and disorientation, resulting in a “drugged” appearance.
• Constipation: Those taking large amounts of anticholinergics may experience constipation.  Being unable to pass a bowel movement can be frustrating and may result in secondary symptoms such as a stomach ache.  In addition to frustration associated with being unable to pass a bowel movement, urinary retention may also be prevalent.
• Disorientation: A person with this form of toxicity will appear delirious and completely disoriented.  Although most anticholinergic substances won’t trigger euphoric emotions, they will make a person appear spaced out or completely lost.  From the disorientation, it should be relatively obvious to an observer that the person is “drugged” and poisoned.
• Dry skin: Those that experience anticholinergic toxicity may end up with very dry skin.  While dry skin alone is not usually indicative of a serious medical issue, dry skin accompanied by other symptoms on this list may be a sign of anticholinergic syndrome.
• Emotional dysregulation: Some individuals experiencing anticholinergic toxicity may have a difficult time coping with their emotions.  Their emotional state may be unpredictable and somewhat influenced by other properties of the drugs that were ingested.
• Fever: Body temperature may increase upon ingestion of anticholinergic substances.  This means that the anticholinergic effect is potentially toxic to the individual.  If you develop a fever, especially with some of these other symptoms, it may be a sign to seek immediate medical attention.
• Flushing of skin: In addition to developing extremely dry skin, from the perspective of others, the skin may appear to be completely flushed.  This means that a person’s skin will become abnormally red in certain areas.
• Heart rate increase: An increase in heart rate is common among those experiencing toxicity from anticholinergic drugs.  If your heart rate skyrockets upon ingestion of a particular drug, it is something that needs to be medically supervised.  In some cases of anticholinergic toxicity, a person’s heart rate increase may lead to other serious problems.
• High blood pressure: It is known that blood pressure may also increase during anticholinergic toxicity.  If blood pressure becomes abnormally high, this could lead to additional medical problems.
• Muscle jerking: Many people will notice involuntary jerking of various muscles as well as ataxia or a lack of voluntary coordination.  If muscle jerks are observed in combination with these other symptoms, and anticholinergic drugs have been ingested, there’s a good chance of toxicity.
• Poor judgment: A person’s judgment becomes impaired as a result of the excess anticholinergic activity.  They may be unable to hold a conversation, let alone make a smart decision.
• Pupil dilation: When ingested in large doses, anticholinergic agents lead to pupil dilation.  If someone’s pupils appear abnormally large and they’re also displaying many other prominent symptoms, anticholinergic toxicity may be the culprit.
• Reduced bowel sounds: Another sign of toxicity is that of reduced bowel sounds or inaudible sounds from the abdominal region.  Bowel sounds are most commonly associated with digestion of food and bowel movements.  Those ingesting toxic amounts of anticholinergics may discover that they lack bowel sounds.
• Slurred speech: It may be difficult for an individual with anticholinergic toxicity to formulate a sentence or speak clearly.  They may appear cognitively impaired and have a difficult time speaking.  Their speech is sometimes slurred, making it seem as if they are drunk and/or drugged.
• Tremors: Many people will exhibit tremors as a result of the anticholinergic poisoning.  Their entire body or various parts may appear to shake uncontrollably.
• Urinary retention: In addition to constipation, many people find that they are unable to completely empty their bladder.  This excess urinary retention is considered “acute” but can be highly uncomfortable for the individual.

Note: Other symptoms that an individual experiences along with anticholinergic toxicity are often those related to the specific drug that was ingested.  For example, a tricyclic antidepressant may also affect serotonin levels, norepinephrine, etc. – whereas heroin “cut” with an anticholinergic will result in different secondary drug-specific symptoms.

Anticholinergic Toxicity Treatment

Those dealing with anticholinergic toxicity first need to be properly diagnosed by a medical professional.  Once it is verified that an individual is exhibiting anticholinergic toxicity, typically a drug like Physostigmine is administered.  In some cases benzodiazepines can also be administered with success depending on the patient.

Additionally symptoms will require close supervision from medical professionals to ensure safety of the patient.  Prior to administration of any drug, those with this form of toxicity are usually transported to the emergency room in which toxic substances are removed from the gastrointestinal tract.  In some cases activated charcoal is administered (if within 30 minutes).

Physostigmine Salicylate: This is an acetylcholinesterase inhibitor that functions to reverse anticholinergic toxicity by increasing extracellular levels of the neurotransmitter acetylcholine.  In essence, this substance is counteracting the effects of the anticholinergic drugs that were ingested.  Physostigmine is not only the most common treatment for anticholinergic toxicity, it is the most effective remedy.  It is also administered frequently in life-threatening cases of the condition.

There are a few risks associated with using Physostigmine such as taking too high of a dose, which could then tip the scales to the opposite end of the spectrum, leaving a person to experience cholinergic toxicity.  In some cases, seizures and other unwanted side effects have been documented upon administration of Physostigmine for tricyclic antidepressant overdose.

In a comparison study for treating anticholinergic syndrome, Physostigmine was the most effective at controlling both agitation and reversing delirium.  Additionally there is less of a risk of experiencing further complications with this agent compared to other treatment modalities. Furthermore, this drug is thought to facilitate the quickest recovery time compared to others.

Benzodiazepines: While Physostigmine may be the preferred drug for treating most cases of anticholinergic toxicity, benzodiazepines are sometimes administered to help control symptoms.  Initial treatment with benzodiazepines is less effective in treating agitation and CNS stimulation, and is considered ineffective for treating symptoms of delirium.  Furthermore, benzodiazepines are considered controlled-substances and should be used with caution, especially among individuals with addictive tendencies.

Nootropics: Another potentially effective treatment would be administering various nootropics such as Racetams, Choline, or Alpha-GPC which affect cholinergic activity.  Some speculate that these agents may help offset anticholinergic toxicity due to their mechanisms of action.

Other drugs: In some cases, other drugs may need to be administered if a person attempted an overdose and/or is exhibiting other potentially life-threatening complications.  While the anticholinergic effects can be offset by Physostigmine, the effects of the actual drug that was ingested may require intense medical supervision and administration of other pharmacological agents to restore normative functioning.

• Source: http://www.ncbi.nlm.nih.gov/pubmed/10736125

How common is anticholinergic toxicity?

Anticholinergic toxicity is considered uncommon, with very few actual deaths resulting from the condition.  Based on research from the American Association of Poison Control Centers, there were nearly 20,000 cases of individuals being exposed to anticholinergic agents with approximately 50 very serious cases.  The number of deaths resulting from anticholinergic toxicity is extremely low, with fatalities being significantly less common than in the past.

The decrease in deaths resulting from anticholinergic toxicity is due to an increase in knowledge of anticholinergic toxicity as well as knowledge of best treatment practices.  Emergency medical responders are able to recognize this condition quickly and administer proper treatment agents.

• Source: http://www.ncbi.nlm.nih.gov/pubmed/20028214

Have you ever experienced anticholinergic toxicity?

If you’ve experienced anticholinergic toxicity, feel free to mention what caused it (e.g. drugs, medicines, plants, etc.), the symptoms you developed and how long it lasted.  Did you know you had anticholinergic toxicity or did a medical practitioner tell you that you had it?  In all likelihood, you were treated with Physostigmine, but in the event that other medications were prescribed, feel free to mention them in your comment.

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