April 2019 By PsychDB.com

Donepezil

Donepezil (Tradename: Aricept) is an acetylcholinesterase inhibitor and cognitive-enhancing medication. It is used in the treatment of dementias and neurodegenerative disorders.

Acetylcholinesterase inhibitors, including donepezil, rivastigmine, and galantamine all inhibit acetylcholinesterase. The break down of acetylcholine is prevented by the drug binding and reversibly inactivating cholinesterases. This inhibits the hydrolysis of acetylcholine. As a result, acetylcholine levels increase in the brain, which may optimize function of remaining intact cholinergic neurons. This is thought to improve memory and cognitive function. However, treatment does not alter the underlying course of the disease. The increase in acetylcholine also occurs in other organ systems innervated by cholinergic neurons, and leads to the side effects in this medication class as well.

Acetylcholinesterase inhibitors are indicated in:

Acetylcholinesterase inhibitors should be discontinued if the dementia progresses to a stage where there would be no clinically meaningful benefit from continuing therapy. If discontinuing, the dose should always be slowly tapered, and the patient should be monitored for 1-3 months for any signs of cognitive/functional decline. If this decline is seen, then the medication should be restarted.

  • Start at 5mg PO qHS
    • Give 4–6 weeks for time to adjust to the medication. This prevents the frequent side effects associated with starting at higher doses.
    • The maximum dosage for patients is 10 mg PO daily (mild to moderate Alzheimer’s disease)

Formulation

  • Comes in 5 mg, 10 mg, and 23 mg tablets
    • Also comes in 5-mg and 10-mg orally disintegrating tablets

A baseline ECG (to rule out any conduction abnormalities), heart rate, weight, and blood pressure should be obtained prior to starting an acetylcholinesterase inhibitor.

  • Can cause dizziness and drowsiness, especially during initiation of therapy
  • At lower doses, can cause nausea, diarrhea, vomiting, insomnia, fatigue, muscle cramps, loss of appetite, and weight loss, and bradycardia
    • These side effects will usually resolve on its own
    • Discontinue if bradycardia develops or there is a significant conduction abnormality (i.e. - more than a first degree heart block)
  • At higher doses, side effects include headaches, dizziness, drowsiness, blurred vision, urinary frequency and incontinence
  • Can aggravate asthma and other breathing problems
  • Can increase the risk of seizures
  • Make sure to warn patients of possible GI side effects!
  • Anticholinergic drugs (e.g. - atropine, benztropine) may be less effective when combined with an acetylcholinesterase inhibitor. The cholinergic action of acetylcholinesterase inhibitors (an agonist) opposes the anticholinergic action (antagonists) of these medications. Anticholinergic drugs can also decrease the cholinergic action of acetylcholinesterase inhibitor, reducing its efficacy.
  • Beta-blockers (e.g. - propranolol, atenolol, timolol) combined with acetylcholinesterase inhibitors can increase the risk of bradycardia, heart block, and syncope.

Relative

  • Weight loss
    • Lower-weight patients should be closely monitored for vomiting, diarrhea, and loss of appetite. This applies to especially frail, elderly women, who tend to be more frequently affected
  • Upcoming surgeries
    • Acetylcholinesterase inhibitors can interact with muscle-relaxing anesthesias such as succinylcholine
  • Anti-arrhythmic medications
  • History of gastric ulcers or regular NSAID (aspirin, ibuprofen, and naproxen)
    • Should be monitored for signs and symptoms of ulcers and gastrointestinal bleeding
  • Significant alcohol use can induce depressant effects, reduce the efficacy, and intensify the side effects of acetylcholinesterase inhibitors

Absolute

  • Bradycardia (<50bpm) or AV block
  • Severe asthma and COPD, because the increase in acetylcholine activity can cause worsening respiratory function. (Remember that anticholinergics are frequently used as bronchodilators in the management of asthma/COPD!)
  • Severe hepatic or renal failure
  • Obstructive Urinary Disease
  • Seizures
  • Donepezil should be stored in a light-resistant container, away from heat and moisture. Heat and moisture may precipitate breakdown of donepezil