1. Donepezil

2. Donepezil Generic name: Donepezil. Brand name: Aricept. Chemistry: Donepezil hydrochloride is a piperidine derivative. It is a white crystalline powder with a molecular weight of 425.96. Preparation: 5 and 10 mg tablets. Storage: tablets should be stored at room temperature. Dosing: Donepezil is generally taken once daily at night prior to retiring. Its absorption is not affected by food.

3. Chemical Structure of Donepezil

4. Pharmacokinetics: 1- Donpezil hydrochloride is a selective, reversible and non- competitive acetylcholinesterase inhibitor with a relatively high central versus peripheral specificity. 2- Has extensive extravascular distribution. 3- Highly bound to plasma proteins (95.6%). 4- Given orally, absorbed from the gastrointestinal tract at a moderate rate. Peak concentration occurring approximately 4 hours after drug administration.

5. Pharmacokinetics: 5- Slow clearance from plasma by microsomal hepatic enzymes. 6- Undergoes significant first pass metabolism following oral administration. 7- Long half-life of approximately 70 hours. 8- 80% of the administered drug is excreted in the urine as unchanged drug, glucoronidated metabolite and hydrolysis product. 9- Feacal elimination accounts for the remaining 20%.

6. Mechanism of action: AD is characterized by deficits in memory and cognition that are associated with significant losses of presynaptic cholinergic function in the brain. Donepezil enhances cholinergic transmission by reducing the enzymatic degradation of acetylcholine. Donepezil is 1200 times more selective for acetylcholinesterase rather than butylcholinesterase.

7. Pharmacological effects: 1- It improved cognitive and global function in patients with mild to moderate AD. 2- It produces no clinically significant changes in laboratory parameters, including liver function. 3- There is no need to modify the dose in the elderly or in patients with hepatic or renal failure.

8. Therapeutic uses: 1- Donepezil gives a short-term improvement in cognitive function but does not appear to alter the underlying disease process. 2- Causes a 3-6 month delay in disease progression. 3- Symptomatic improvement of memory, cognition, mood and behavior.

9. Drug interactions: 1- Concurrent administration of donepezil with digoxin would not alter the pharmacokinetic of digoxin. 2- No pharmacodynamic or pharmacokinetic interactions occur between donepezil and warfarin. 3- The concurrent administration of donepezil and ketoconazole produce no change in ketoconazole plasma concentrations, but did result in increase plasma concentrations of donepezil. 4- Donepezil does not alter the pharmacokinetics of sustained-release theophylline.

10. Adverse effects: 1- Urinary incontinence. 2- Convulsions. 3- Behavioral worsening. 4- Diarrhea and vomiting. 5- No clinically significant affects on vital signs, hematology or clinical biochemistry tests. 6- Not associated with hepatotoxicity.

11. Contraindications: Not contraindicated in pregnancy, lactation, hepatic or renal impairment.

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