How donepezil works
Donepezil is an anti-dementia drug. The most common form of dementia is Alzheimer’s disease. In this disease, nerve cells (neurons) in the brain gradually die. In most cases, a large number of neurons have already died before the first symptoms appear and the disease is discovered.
To communicate with other neurons, a nerve cell can secrete messenger substances (neurotransmitters). These transmit their signal by docking at special docking sites (receptors) in the membrane of neighboring nerve cells.
One of the most important nerve messengers involved in memory, retentiveness and recall is acetylcholine. Like the other neurotransmitters, it acts by docking to its receptors in the membrane of other nerve cells. Acetylcholine is then cleaved by an enzyme (acetylcholinesterase) into acetate and choline, which no longer act at the receptors, terminating the signal. The two cleavage products are reabsorbed into the first nerve cell, linked, and can then be released again as needed.
To alleviate the symptoms of Alzheimer’s disease and improve memory performance, donepezil is used as a selective inhibitor of the enzyme acetylcholinesterase. In other words, it inhibits the enzyme so that acetylcholine remains longer on the receptors of downstream neurons – its signal becomes stronger, so to speak.
Despite the loss of brain cells, the remaining nerve cells can therefore still communicate with normal intensity, which improves the memory and retentiveness of Alzheimer’s patients. This makes it possible to delay the time when a patient needs care.
Clinical studies of donepezil use in Alzheimer’s disease confirm stabilization of cognitive performance (human functions related to perception, learning, remembering, thinking and knowing) over a period of at least six months.
Absorption, degradation and excretion
After ingestion as a tablet, donepezil enters the blood via the intestine and from there crosses the blood-brain barrier into the central nervous system. There it exerts its effect.
When is donepezil used?
Donepezil is approved for the symptomatic treatment of mild to moderate Alzheimer’s dementia.
Off-label, it is also used as a palliative drug for severe Alzheimer’s dementia.
It must be taken continuously to maintain its effect. The effect is dose-dependent, which is why the highest tolerated dosage is targeted.
How donepezil is used
The active ingredient is taken as a salt (donepezil hydrochloride), in the form of tablets or melting tablets (dissolve in seconds in the mouth). Treatment is usually started with five milligrams of donepezil once daily.
After one month, the doctor will assess whether the dosage is sufficient or needs to be increased to ten milligrams of donepezil daily. Higher dosages are not recommended.
Therapy should only be given if the patient is in a nursing facility or has a caregiver who monitors the patient’s use of donepezil.
What are the side effects of donepezil?
More than ten percent of those treated complain of diarrhea, nausea, and headache. These side effects occur mainly when the dose is increased too quickly.
Other common side effects of donepezil include loss of appetite, aggressive behavior, agitation, dizziness, insomnia, vomiting, indigestion, skin rashes, muscle cramps, incontinence, and fatigue.
One in one hundred to one thousand patients may also experience seizures, slowed heartbeat, and gastrointestinal bleeding as side effects.
What should be considered when taking donepezil?
Contraindications
Donepezil should not be taken in case of known hypersensitivity to the active substance.
Drug interactions
Since donepezil is mainly broken down in the liver by two different enzymes (cytochrome P450 2D6 and 3A4) that also break down other active ingredients, interactions may occur if these agents are given in combination.
Some active ingredients cause more enzymes to be produced in the liver, which then break down donepezil more quickly. This reduces its effectiveness. This is caused, for example, by anticonvulsants and epilepsy agents (such as phenytoin, carbamazepine, oxcarbazepine), the anesthetic phenobarbital, and also some foods (such as ginger, garlic, licorice).
Patients with respiratory diseases such as asthma or COPD should take donepezil with caution, as the risk of acute exacerbation may increase.
If non-steroidal anti-inflammatory drugs (NSAIDs such as ASA, ibuprofen, diclofenac) are taken regularly in addition to donepezil, the risk of gastrointestinal bleeding may increase.
Age restriction
Use of donepezil is not recommended in children and adolescents under 18 years of age. Similarly, adult patients with severe hepatic impairment should not take donepezil due to lack of experience.
Pregnancy and Lactation
Pregnant and breastfeeding women should not take donepezil because no studies are available on its safety or effectiveness.
To receive medication with donepezil
How long has donepezil been known?
The development of donepezil began in Japan in 1983. The active ingredient received its first approval in the U.S. in 1996. Generics containing the active ingredient donepezil have been on the market since 2010.
