Donepezil
A reversible acetylcholinesterase inhibitor that eases the symptoms of Alzheimer's dementia, from mild to severe stages.
Drug card
- How it works
- Blocking acetylcholinesterase so more acetylcholine stays in the brain
- Used for
- Alzheimer's dementia, mild to severe
- Dementia with Lewy bodies or Parkinson's disease
- Known for
- Nausea, vomiting and diarrhea
- Slow heart rate, heart block or fainting
Study it as a flashcard, and it comes back before you forget it.
Mechanism of action
How does donepezil work?
A piperidine derivative that reversibly inhibits acetylcholinesterase, so acetylcholine lasts longer and cholinergic signaling in the brain improves; it does not change the course of the disease. The liver clears it through CYP2D6, CYP3A4 and glucuronidation, and its elimination half-life is about 70 hours.
Like other cholinesterase inhibitors for dementia: These drugs enter the brain and inhibit acetylcholinesterase, the enzyme that breaks down acetylcholine, so more acetylcholine stays at the synapses of the cholinergic neurons that still work in Alzheimer's or Parkinson's dementia. Memory and thinking improve for a time, but the disease is not slowed and the benefit fades as neurons are lost. Extra acetylcholine in the gut and heart causes the main side effects.
Uses
What is donepezil used for?
- Alzheimer's dementia, mild to severe
- Dementia with Lewy bodies or Parkinson's disease
Side effects
Side effects of donepezil
- Nausea, vomiting and diarrheaKnown for
- Slow heart rate, heart block or faintingKnown forSerious
- Insomnia and abnormal dreams
- Muscle cramps
- Loss of appetite and weight loss
- Headache and dizziness
- QT prolongation and torsade de pointesSerious
- Stomach ulcers and bleedingSerious
- SeizuresSerious
- Difficulty passing urine
- Neuroleptic malignant syndrome (rare)Serious
- Hepatitis (rare)Serious
Known for marks what an exam expects you to know it for.
Watch for
Cautions and what sets it apart
- It exaggerates the muscle relaxation of suxamethonium during anesthesia.
- Conduction disease or heart-slowing drugs such as beta blockers and digoxin raise the risk of bradycardia and fainting.
- A past ulcer or NSAID use raises the risk of stomach bleeding; care in asthma or COPD.
- Ketoconazole and quinidine slow its breakdown; inducers such as rifampicin, phenytoin and carbamazepine speed it.
Good to know: It inhibits acetylcholinesterase only, unlike rivastigmine, and is the one licensed in the US for severe as well as mild to moderate Alzheimer's disease.
Remember it
A way to remember it
More acetylcholine: a slower heart and a busier gut.
Outside the brain the extra acetylcholine slows the heart (bradycardia, heart block, fainting) and stirs the gut (nausea, vomiting, diarrhea), the two side effects these drugs are known for.
Written for biofideX
Its class
Cholinesterase inhibitors for dementia
Other cholinesterase inhibitors for dementia with a card:
Easily mixed up with anticholinesterases, NMDA receptor antagonists and antimuscarinics.
Sources
Checked against
Written for biofideX in plain words, after checking these references:
For learning pharmacology, not for treatment decisions: no doses are given, and a prescriber, pharmacist or the product's own label is the word on any one patient. Spotted a mistake? Tell us and we'll correct it.
Parkinson's, dementia and migraine
Donepezil is one of 9 drugs practiced together here: their classes, how they work, what they treat and what they're known for.
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