Cholinesterase inhibitors: Uses, common brands, and safety info

Cholinesterase inhibitors (ChEIs), also known as acetylcholinesterase inhibitors, are medications usually prescribed to treat symptoms of Alzheimer’s disease. However, they can also be used to treat other conditions, such as Parkinson’s disease. These medications help increase levels of acetylcholine, an important neurotransmitter in the body needed for communication between nerve cells, and they are only available with a prescription. 

Continue reading to learn more about cholinesterase inhibitors, how they work, and their possible side effects. 

Other cholinesterase inhibitors

• Cognex (tacrine)

• Bloxiverz (neostigmine)

• Humorsol (demecarium)

• Enlon (edrophonium)

• Mytelase (ambenonium)

• Metrifonate

• Phenserine

What are cholinesterase inhibitors?

Cholinesterase inhibitors are medications used to treat neurodegenerative conditions, such as Alzheimer’s disease and Parkinson’s disease. They are primarily used to treat symptoms of dementia and other signs of cognitive impairment in people with Alzheimer’s disease. Those with dementia often show a decline in cognition, which is characterized by frequent instances of memory loss, confusion, trouble with communication, or problems with organization. 

The three main cholinesterase inhibitors prescribed for Alzheimer’s disease are Aricept (donepezil), Razadyne ER (galantamine), and Exelon (rivastigmine). Depending on the severity of the disease, clinicians may add Namenda (memantine) to the treatment regimen. 

Cholinesterase inhibitors come in several different formulations depending on the medication prescribed. Cholinesterase inhibitors are available as medications that can be administered orally, intravenously (IV), intramuscularly (IM), or transdermally (as a patch). Oral forms of cholinesterase inhibitors are usually administered once or twice a day, depending on which medication is prescribed. 

How do cholinesterase inhibitors work?

Acetylcholine is a primary neurotransmitter, or nerve signal messenger, found at cholinergic receptor sites in the peripheral and central nervous system (CNS). It is involved with many important functions, such as smooth muscle contractions, regulation of blood pressure and heart rate, and the processing of memories and information. While the exact cause of Alzheimer’s disease is unclear, those with Alzheimer’s disease typically have low levels of acetylcholine, which may contribute to symptoms.

As the name suggests, cholinesterase inhibitors work by blocking cholinesterase, an enzyme that breaks down acetylcholine or butyrylcholine. Sometimes known as anticholinesterases, these medications help prevent the breakdown of acetylcholine and increase the amount of acetylcholine available in the body. One meta-analysis compared the effectiveness and tolerability of cholinesterase inhibitors in 41 different clinical trials published by The Lancet and The BMJ, among other journals. Results from this meta-analysis showed that these medications can help improve cognitive function in those with Alzheimer’s disease. 

What are cholinesterase inhibitors used for?

Cholinesterase inhibitors can be used for different purposes other than the treatment of Alzheimer’s disease. They’re often prescribed for a range of different medical uses:

• Dementia disorders

  • Vascular dementia

  • Lewy body dementia

• Alzheimer’s disease

• Parkinson’s disease

• Myasthenia gravis

• Vascular dementia

• Muscle agent effects reversal after surgery

• Anticholinergic drug toxicity

Types of cholinesterase inhibitors

Acetylcholinesterase inhibitors

Acetylcholinesterase is one of two types of cholinesterase enzymes, and it is the primary target of treatment for Alzheimer’s disease. Most cholinesterase inhibitors can block both acetylcholinesterase and butyrylcholinesterase, but some may be more selective for acetylcholinesterase than others. Aricept (donepezil) and Razadyne (galantamine) are examples of selective acetylcholinesterase inhibitors. 

Butyrylcholinesterase inhibitors 

Butyrylcholinesterase is a cholinesterase enzyme that may be increased in severe Alzheimer’s disease. Cognex (tacrine) is an example of a cholinesterase inhibitor that can block both the acetylcholinesterase and butyrylcholinesterase enzyme. However, it has more selectivity for butyrylcholinesterase.  

Competitive, non-competitive, irreversible, and pseudo-irreversible inhibitors 

Cholinesterase inhibitors can be further classified as competitive, non-competitive, irreversible, or pseudo-irreversible inhibitors. These categories of cholinesterase inhibitors refer to how strongly the drug binds to the active site of the cholinesterase enzyme to block it. Donepezil is a mixed competitive and non-competitive inhibitor, galantamine is a competitive inhibitor, organophosphates like sarin and methanesulfonyl fluoride are irreversible inhibitors, and rivastigmine and metrifonate are pseudo-irreversible inhibitors. 

Who can take cholinesterase inhibitors?

Adults

Adult men and women with dementia disorders are often prescribed a cholinesterase inhibitor. Compared to placebo, cholinesterase inhibitors are considered effective in most adults. They are sometimes given with other forms of treatment to treat different neurodegenerative conditions in adults. 

Seniors

As noted in prevalence studies from the Alzheimer’s Association, Alzheimer’s disease is a condition that primarily affects older adults. As a result, cholinesterase inhibitors are often prescribed in older adults to treat dementia. The average age of people enrolled in clinical trials evaluating the use of Aricept is 73. Still, caregivers should monitor older adults for possible adverse effects from cholinesterase inhibitors.

The American Geriatrics Society recommends regular follow-up visits for older adults who use cholinesterase inhibitors in order to evaluate how well the medication is working and to identify any adverse effects. 

Children 

Cholinesterase inhibitors are not approved by the Food and Drug Administration (FDA) or recommended for use in children. However, in some situations, cholinesterase inhibitors may be prescribed off-label for different purposes. Clinical studies have found that certain cholinesterase inhibitors may be useful for alleviating symptoms in children with ADHD and improving REM sleep in children with autism. 

Are cholinesterase inhibitors safe?

Cholinesterase inhibitors are generally safe and effective, according to clinical controlled trials. However, the use of cholinesterase inhibitors can lead to high levels of acetylcholine. These medications can cause side effects involving the parasympathetic nervous system, such as stomach upset, increased salivation and tearing, increased urination, slow heartbeat, diarrhea, and low blood pressure. 

Recalls

No current recalls are available.

Restrictions

Those with heart conduction diseases or low heart rate may need to avoid cholinesterase inhibitors. These medications can increase the risk of low heart rate and heart conduction problems, which could lead to an increased risk of fainting or falls. Patients with low blood pressure, or hypotension, may also need to avoid cholinesterase inhibitors due to an increased risk of low blood pressure.

Patients with stomach ulcers or those taking nonsteroidal anti-inflammatory drugs (NSAIDs) should avoid cholinesterase inhibitors because of an increased risk of bleeding with cholinesterase inhibitors. Those with urinary retention problems should also avoid taking cholinesterase inhibitors since these drugs can cause urinary incontinence as a side effect. 

Symptoms of asthma and chronic obstructive pulmonary disease (COPD) may be worsened with the use of cholinesterase inhibitors. These medications can increase acetylcholine, which plays a role in bronchial secretions and constriction of the bronchial tubes. 

Cholinesterase inhibitors can increase the risk of seizures in certain individuals. Patients with a history of seizures may need to use caution while taking a cholinesterase inhibitor. 

Cholinesterase inhibitors should not be used in those with a history of allergic reactions to any cholinesterase inhibitor in the past.

Consult your prescribing healthcare provider for other possible warnings and restrictions before starting treatment with a cholinesterase inhibitor. A doctor who specializes in neurology or pharmacology can help determine whether a cholinesterase inhibitor would be appropriate for you. 

Are cholinesterase inhibitors controlled substances?

No, cholinesterase inhibitors are not controlled substances.

Common cholinesterase inhibitors side effects

The most common side effects of cholinesterase inhibitors include:

• Nausea

• Vomiting

• Diarrhea

• Dizziness

• Cramps

• Headache

• Fatigue

• Insomnia

• Abnormal dreams

• Decreased appetite

• Weight loss

• Increased urination

Most cholinesterase inhibitors are generally well tolerated with mild side effects. Side effects may be lessened through the use of different dosing techniques, such as lowering the dose of the medication (with a doctor’s approval) or administering the medication with meals. The timing of drug administration may also influence the development of side effects. Taking donepezil in the morning instead of at night may decrease the risk of abnormal dreams. 

Severe side effects and adverse events typically develop as a result of toxicity, or taking doses that are higher than normal. Serious side effects can include severe nausea and vomiting, gastrointestinal bleeding, and respiratory depression. Involuntary muscle movements or paralysis are other signs of toxicity. Immediate medical attention is necessary to reverse the effects of toxicity from cholinesterase inhibitors. 

Adverse effects may also occur as a result of drug interactions. Consult a healthcare provider to determine thge risk of drug interactions, depending on other drugs you may be taking. Tell your doctor if you’re taking other medications that have cholinergic or anticholinergic effects. You should also tell your doctor about any prescription medications, over-the-counter medications, and herbal supplements you may be taking. 

How much do cholinesterase inhibitors cost?

Cholinesterase inhibitors are generally covered by most Medicare and insurance plans. These medications are typically available in both a brand name and generic version, the latter of which is often the cheaper alternative. The total cost for your cholinesterase inhibitor prescription will depend on the drug and dosage prescribed, as well as the quantity supplied. 

For those without insurance, other savings options such as manufacturer coupons and patient assistance programs may be available to lower the cost of cholinesterase inhibitors. SingleCare also provides a prescription discount savings card that may reduce the cost of cholinesterase inhibitors, or other prescription medications, whether you’re insured or uninsured.