Donepezil Disease Interactions

Due to their pharmacological action, cholinesterase inhibitors can have a vagotonic effect on the sinoatrial and atrioventricular nodes producing bradycardia or heart block. Therapy with cholinesterase inhibitors should be administered cautiously in patients with preexisting bradycardia or underlying cardiac conduction abnormalities. Syncopal episodes have been reported in patients with and without cardiac abnormalities. Atropine may be used to reverse bradycardia produced by cholinesterase inhibitors.

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Cholinesterase inhibitors inhibit the hydrolysis of acetylcholine. The enhanced effect of acetylcholine produces constriction of the bronchi, increased bronchial secretions, and bronchospasm. Therapy with cholinesterase inhibitors should be administered cautiously in patients with respiratory dysfunction, history of asthma or obstructive pulmonary disease. Monitoring respiratory function during dosage initiation and adjustment is recommended. Use of atropine along with discontinuation of the cholinesterase inhibitor may be required for serious respiratory distress. Neostigmine may produce more severe muscarinic side effects than does pyridostigmine and ambenonium. However, the duration of action is longest for ambenonium and shortest for edrophonium. Echothiophate iodide ophthalmic may be systemically absorbed and cautious use is recommended in these patients.

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The use of cholinesterase inhibitors has been associated with a constriction of coronary arteries. Therapy with cholinesterase inhibitors should be administered cautiously in patients with coronary artery disease.

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Cholinesterase inhibitors should be used with caution in patients with parkinsonism. Some of these drugs might be contraindicated in these patients (refer to specific prescribing information). Symptoms of Parkinson's disease may be exacerbated with the increase in cholinergic activity. Caregivers and patients should be advised.

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The use of cholinesterase inhibitors is associated with an increase in gastric acid secretion and gastric contractions. Therapy with cholinesterase inhibitors should be administered cautiously in patients with peptic ulcer disease.

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Cholinesterase inhibitors have been associated with convulsions and tremor. Therapy with cholinesterase inhibitors should be administered cautiously in patients with seizure disorders.

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Many of the manifestations of hyperthyroidism may be exacerbated by increased levels of acetylcholine produced by cholinesterase inhibitors. Therapy with cholinesterase inhibitors should be administered cautiously to patients with hyperthyroidism. Monitoring of thyroid levels is recommended.

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Donepezil is extensively metabolized by the liver (CYP450-2D6/3A4) to two active and various minor forms. The clearance of donepezil was decreased 20% in patients with stable alcoholic cirrhosis compared to healthy patients. Care should be exercised when using donepezil in patients with liver disease.

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