Definition and Overview
Cholinesterase inhibitors are drugs that inhibit acetylcholinesterase, an enzyme that decomposes acetylcholine at synapses. When the enzyme is inhibited, acetylcholine stays in the synaptic gap longer, enhancing cholinergic neurotransmission.
In Alzheimer's disease, cholinergic neurons involved in memory and learning are lost, resulting in a lack of acetylcholine. This drug relieves cognitive symptoms by prolonging the action time of insufficient acetylcholine. Since it cannot prevent the loss of nerve cells themselves or eliminate the root cause of the disease, it is a symptomatic treatment that slows the progression and controls the symptoms.
type
donepezil
Donepezil selectively inhibits acetylcholinesterase and has a long half-life, so it is taken once a day. It is used in mild to moderate as well as severe Alzheimer's disease.
Rivastigmine
Rivastigmine inhibits both acetylcholinesterase and butyrylcholinesterase. There are oral pills and patch pills, and the patch pill helps reduce gastrointestinal side effects. It is also used for Parkinson's disease and dementia.
Galantamine
Galantamine has the action of controlling nicotinic receptors while inhibiting acetylcholinesterase. It is a sustained-release formulation and can be taken once a day.
The cognitive improvement effects and side effects of the three drugs are generally similar, and no clear superiority or inferiority was identified in direct comparison.
Indications
The main indication is mild to moderate Alzheimer's disease. In dementia with Lewy bodies, rivastigmine has been reported to be effective in treating hallucinations and cognitive fluctuations, and rivastigmine is approved for dementia in Parkinson's disease. Before prescribing, establish a diagnosis of the cause of cognitive decline and evaluate concomitant diseases such as cardiac conduction disorder, peptic ulcer, and asthma.
effect
In a meta-analysis combining several randomized controlled trials, cholinesterase inhibitors showed moderate improvement in cognitive scores (ADAS-cog, etc.) and maintenance of overall function compared to placebo. A Cochrane review analyzing donepezil also reported better results than placebo in cognition, daily function, and overall clinical impression across mild to severe Alzheimer's disease.
The size of the effect is modest and varies greatly from person to person. In some patients, the rate of cognitive decline slows and performance of daily activities is maintained for a certain period of time, while in others, the response is minimal. The effect is symptomatic and is maintained during drug use and does not stop the progression of the disease itself.
side effects
The most common side effects are gastrointestinal symptoms caused by cholinergic stimulation, such as nausea, vomiting, diarrhea, decreased appetite, and weight loss. You can increase the dose slowly, step by step, and reduce the frequency by taking it with meals.
Cardiovascular bradycardia, atrioventricular conduction disturbances, and subsequent dizziness and syncope may occur, so caution is required in patients with sinus node dysfunction or conduction disturbances. In addition, insomnia, vivid dreams, muscle cramps, urinary incontinence or frequent urination have been reported. If you have a history of peptic ulcer disease, asthma, or chronic obstructive pulmonary disease, evaluation is necessary as cholinergic effects may worsen the condition.
Precautions when using
When starting treatment, start with a low dose and gradually increase the dose while observing side effects. Regularly evaluate heart rate and cognitive and functional status, and decide whether to continue treatment based on the balance of benefits and side effects. Cognitive function can quickly deteriorate if stopped arbitrarily, so consult a specialist for adjustments.