安理申ARICEPT(多奈哌齐)

ARICEPT(Donepezil)

 

Donepezil, sold as the trade name Aricept among others, is a medication used to treat Alzheimer's disease.[1] It appears to result in a small benefit in mental function and ability to function.[2] Use, however, has not been shown to change the progression of the disease.[3] Treatment should be stopped if no benefit is seen.[4] It is taken by mouth.[1]

 

Common side effects include nausea, trouble sleeping, aggression, diarrhea, feeling tired, and muscle cramps.[1][4] Serious side effects may include heart arrythmias, urinary retention, and seizures.[1] Donepezil is a centrally acting reversible acetylcholinesterase inhibitor.[1]

 

Donepezil was approved for medical use in the United States in 1996.[1] It is available as a generic medication.[4] In the United Kingdom a typical months supply costs the NHS about £8.44 as of 2019.[4] The wholesale cost of this amount in the United States is about US$1.38. [5] In 2016 it was the 98th most prescribed medication in the United States with more than 7 million prescriptions.[6]

 

Medical uses

Alzheimer's disease

There is no evidence that donepezil or other similar agents alters the course or progression of Alzheimer's disease. 6 to 12-month controlled studies have shown modest benefits in cognition or behavior.[7] The UK National Institute for Clinical Excellence (NICE) recommends donepezil as an option in the management of mild to moderate Alzheimer's disease.[8] The person should, however, be reviewed frequently and if there is no significant benefit it should be stopped.[8] In 2006 the U.S. Food and Drug Administration also approved donepezil for treatment of mild, moderate and severe dementia in Alzheimer's disease.[9]

 

Adverse effects

 

In clinical trials the most common adverse events leading to discontinuation were nausea, diarrhea, and vomiting.[10][11] Other side effects included difficulty sleeping, muscle cramps and loss of appetite. Most side effects were observed in patients taking the 23 mg dose compared to 10 mg or lower doses. Side effects improved with continued use.[12]

Precautions

Donepezil should be used with caution in people with heart disease, cardiac conduction disturbances, chronic obstructive pulmonary disease, asthma, severe cardiac arrhythmiasand sick sinus syndrome.[12]

 

People with peptic ulcer disease or taking NSAIDS should use caution because increased risk of gastrointestinal bleeding was noted.[12] Slow heart beat and fainting in people with heart problems were also seen. These symptoms may appear more frequent when initiating treatment or increasing the donepezil dose. Although occurrence of seizures is rare, people who have a predisposition to seizures should be treated with caution.[12]

 

Mechanism of action

 

Donepezil binds and reversibly inactivates the cholinesterases, thus inhibiting hydrolysis of acetylcholine. This increases acetylcholine concentrations at cholinergic synapses.

The precise mechanism of action of donepezil in patients with Alzheimer's disease is not fully understood. Certainly Alzheimer's disease involves a substantial loss of the elements of the cholinergic system and it is generally accepted that the symptoms of Alzheimer’s disease are related to this cholinergic deficit, particularly in the cerebral cortex and other areas of the brain.[13][14] It is noted that the hippocampal formation plays an important role in the processes of control of attention, memory and learning. Just the severity of the loss of cholinergic neurons of the central nervous system (CNS) has been found to correlate with the severity of cognitive impairment.

 

In addition to its actions as an acetylcholinesterase inhibitor, donepezil has been found to act as a potent agonist of the σ1 receptor (Ki = 14.6 nM), and has been shown to produce specific antiamnestic effects in animals mainly via this action.[15]