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Donepezil |
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## indicationFor the palliative treatment of mild to moderate dementia of the Alzheimer's type.## pharmacologyDonepezil is a centrally acting reversible acetyl cholinesterase inhibitor. Its main therapeutic use is in the treatment of Alzheimer's disease where it is used to increase cortical acetylcholine. An early pathophysiological feature of Alzheimer's disease that is associated with memory loss and cognitive deficits is a deficiency of acetylcholine as a result of selective loss of cholinergic neurons in the cerebral cortex, nucleus basalis, and hippocampus. Donepezil is postulated to exert its therapeutic effect by enhancing cholinergic function. This is accomplished by increasing the concentration of acetylcholine through reversible inhibition of its hydrolysis by acetylcholinesterase. If this proposed mechanism of action is correct, donepezil's effect may lessen as the disease progresses and fewer cholinergic neurons remain functionally intact. There is no evidence that donepezil alters the course of the underlying dementing process.## mechanism of actionDonepezil is a piperidine derivative that is a centerally active, reversible inhibitor of acetylcholinesterase. This drug is structurally unrelated to other anticholinesterase agents. Donepezil's proposed mechanism of action involves the reversible inhibition of cholinesterases (eg. acetylcholinesterase), which prevents the hydrolysis of acetycholine, and leads to an increased concentration of acetylcholine at cholinergic synapses. Evidence suggests that the anticholinesterase activity of donepezil is relatively specific for acetylcholinesterase in the brain.## toxicitySymptoms of overdose include severe nausea, vomiting, salivation, sweating, bradycardia, hypotension, respiratory depression, collapse and convulsions. Increasing muscle weakness is a possibility and may result in death if respiratory muscles are involved.## biotransformationDonepezil is metabolized by CYP 450 isoenzymes 2D6 and 3A4 in the liver and also undergoes glucuronidation. The main metabolite, 6-O-desmethyl donepezil, has been reported to inhibit AChE to the same extent as donepezil in vitro.## absorptionDonepezil is well absorbed with a relative oral bioavailability of 100% and reaches peak plasma concentrations in 3 to 4 hours.## half life70 hours## route of eliminationDonepezil is both excreted in the urine intact and extensively metabolized to four major metabolites, two of which are known to be active, and a number of minor metabolites, not all of which have been identified.## drug interactionsAcepromazine: Possible antagonism of actionAceprometazine: Possible antagonism of actionAlverine: Possible antagonism of actionAmantadine: Possible antagonism of actionAmitriptyline: Possible antagonism of actionAmoxapine: Possible antagonism of actionAtropine: Possible antagonism of actionAzatadine: Possible antagonism of actionBenzatropine: Possible antagonism of actionBiperiden: Possible antagonism of actionBrompheniramine: Possible antagonism of actionCarbinoxamine: Possible antagonism of actionChlorpheniramine: Possible antagonism of actionChlorpromazine: Possible antagonism of actionChlorprothixene: Possible antagonism of actionCimetidine: Possible antagonism of actionClemastine: Possible antagonism of actionClidinium: Possible antagonism of actionClomipramine: Possible antagonism of actionClozapine: Possible antagonism of actionCyclizine: Possible antagonism of actionCyclobenzaprine: Possible antagonism of actionCyproheptadine: Possible antagonism of actionDarifenacin: Possible antagonism of actionDesipramine: Possible antagonism of actionDexbrompheniramine: Possible antagonism of actionDicyclomine: Possible antagonism of actionDimenhydrinate: Possible antagonism of actionDiphenhydramine: Possible antagonism of actionDiphenoxylate: Possible antagonism of actionDiphenylpyraline: Possible antagonism of actionDisopyramide: Possible antagonism of actionDoxepin: Possible antagonism of actionDoxylamine: Possible antagonism of actionEthopropazine: Possible antagonism of actionFlavoxate: Possible antagonism of actionFlupenthixol: Possible antagonism of actionGlutethimide: Possible antagonism of actionGlycopyrrolate: Possible antagonism of actionHydroxyzine: Possible antagonism of actionHyoscyamine: Possible antagonism of actionImipramine: Possible antagonism of actionIsocarboxazid: Possible antagonism of actionIsopropamide: Possible antagonism of actionLoxapine: Possible antagonism of actionMaprotiline: Possible antagonism of actionMeclizine: Possible antagonism of actionMeperidine: Possible antagonism of actionMesoridazine: Possible antagonism of actionMethdilazine: Possible antagonism of actionMethotrimeprazine: Possible antagonism of actionMethylscopolamine: Possible antagonism of actionMirtazapine: Possible antagonism of actionMoclobemide: Possible antagonism of actionMolindone: Possible antagonism of actionNortriptyline: Possible antagonism of actionOlanzapine: Possible antagonism of actionOrphenadrine: Possible antagonism of actionOxybutynin: Possible antagonism of actionPerphenazine: Possible antagonism of actionPhenelzine: Possible antagonism of actionPhenindamine: Possible antagonism of actionPimozide: Possible antagonism of actionPipotiazine: Possible antagonism of actionProcainamide: Possible antagonism of actionProchlorperazine: Possible antagonism of actionProcyclidine: Possible antagonism of actionPromazine: Possible antagonism of actionPromethazine: Possible antagonism of actionPropantheline: Possible antagonism of actionPropericiazine: Possible antagonism of actionProtriptyline: Possible antagonism of actionQuetiapine: Possible antagonism of actionQuinidine: Possible antagonism of actionQuinidine barbiturate: Possible antagonism of actionRisperidone: Possible antagonism of actionScopolamine: Possible antagonism of actionSertraline: Possible antagonism of actionSolifenacin: Possible antagonism of actionThioproperazine: Possible antagonism of actionThioridazine: Possible antagonism of actionThiothixene: Possible antagonism of actionTizanidine: Possible antagonism of actionTolterodine: Possible antagonism of actionTranylcypromine: Possible antagonism of actionTrazodone: Possible antagonism of actionTrifluoperazine: Possible antagonism of actionTriflupromazine: Possible antagonism of actionTrihexyphenidyl: Possible antagonism of actionTrimeprazine: Possible antagonism of actionTrimethobenzamide: The therapeutic effects of the anticholinergic, Trimethobenzamide, and/or the acetylcholinesterase inhibitor (central), Donepezil, may be reduced due to antagonism. Monitor therapeutic effects of both agents.Trimipramine: Possible antagonism of actionTripelennamine: Possible antagonism of actionTriprolidine: Possible antagonism of actionTrospium: The therapeutic effects of the anticholinergic, Trospium, and/or the acetylcholinesterase inhibitor (central), Donepezil, may be reduced due to antagonism. Monitor therapeutic effects of both agents.Ziprasidone: Possible antagonism of actionZuclopenthixol: Possible antagonism of action |