WRITE A NOTE ON DONEPEZIL ?
A 4 INTRODUCTION
1 Donepezil is marketed under the trade name Aricept, is a medication used in the palliative treatment ofAlzheimer’s disease.
2 Donepezil is used to improve cognition and behavior of people with Alzheimer’s, but does not slow the progression of or cure the disease ( vv imp )
MECHANISM OF ACTION
A ) 1 Donepezil binds and reversibly ( vv imp ) inactivates the cholinesterases, thus inhibiting hydrolysis of acetylcholine - This results in an increased acetylcholine concentrations at cholinergic synapses.
2 The precise mechanism of action of donepezil in patients with Alzheimer’s disease is not fully understood.
3 In addition to its actions as an acetylcholinesterase inhibitor, donepezil has been found to act as a potentagonist of the σ1 receptor (Ki = 14.6 nM), and has been shown to produce specific antiamnestic effects in animals mainly via this action.
B ) Absorption
Bioavailability: 100%
Peak plasma time: 3-4 hr
C ) Distribution
Protein bound: 96%
Vd: 12-16 L/kg
D ) Metabolism
Hepatic P-450 enzymes CYP2D6, CYP3A4 ( v imp )
Metabolites: 4 major metabolites, 2 active
E ) Elimination
Half-life: 70 hr
Total body clearance: 0.13 L/hr/kg
Excretion: Urine (57%), feces (17%)
USES
1 ALZHEIMER DISEASE -
A ) There is no evidence that donepezil or other similar agents alters the course or progression ofAlzheimer’s disease (AD).
B ) a 6 to 12-month controlled studies have shown modest benefits in cognition and/or behavior.
C ) The UK National Institute for Clinical Excellence (NICE) recommends donepezil as an option in the management of mild to moderate Alzheimer’s disease.
D ) The person should, however, be reviewed frequently and if there is no significant benefit it should be stopped.
E ) In 2006 the U.S. Food and Drug Administration also approved donepezil for treatment of mild, moderate and severe dementia in Alzheimer’s disease
F ) it also improves sleep apnea
2 Lewy body dementia
3 Vascular dementia
DOSAGES ( V IMP )
A ) Dosage Forms & Strengths
1 tablet
5mg , 10mg , 23mg
2 tablet, oral disintegrating
5mg , 10mg
B ) Mild to moderate Alzheimer disease
5 mg PO qHS initially, may increase to 10 mg/day after 4-6 weeks if warranted
C ) Moderate to severe Alzheimer disease
5 mg PO qHS initially, may increase to 10 mg qDay after 4-6 weeks; may further increase to 23 mg/day after 3 months if warranted
PRECAUTIONS
1 Donepezil should be used with caution in people with heart disease, cardiac conduction disturbances,chronic obstructive pulmonary disease, asthma, severe cardiac arrhythmias and sick sinus syndrome.
2 People with peptic ulcer disease or taking NSAIDS should use caution because increased risk of gastrointestinal bleeding was noted.
3 Slow heart beat and fainting in people with heart problems were also seen - These symptoms may appear more frequent when initiating treatment or increasing the donepezil dose.
4 Although occurrence of seizures is rare, people who have a predisposition to seizures should be treated with caution.
SIDE EFFECTS
1 Nausea, vomiting
2 diarrhea
3 loss of appetite/weight loss
4 dizziness, drowsiness,weakness
5 trouble sleeping, shakiness (tremor), or muscle cramps may occur as your body adjusts to the drug. These effects usually last 1-3 weeks and then lessen.
If any of these effects persist or worsen, notify your doctor orpharmacist promptly.