Alzept 5mg

Indications

• Alzheimer's disease
• Dementia associated with Alzheimer's type

Dosage

Children: null

Adults: Initial dose: 5 mg once daily. After 4 to 6 weeks, may increase to 10 mg once daily. Maximum dose: 10 mg once daily.

Mechanism of action

Donepezil selectively and reversibly inhibits acetylcholinesterase, an enzyme that breaks down acetylcholine in the brain. This inhibition enhances cholinergic transmission, which is crucial for cognitive functions. Additionally, donepezil may oppose glutamate-induced excitatory transmission via NMDA receptor downregulation, regulate amyloid proteins, and inhibit inflammatory signaling pathways, contributing to its neuroprotective effects.

Pharmacodynamics

By inhibiting acetylcholinesterase, donepezil improves cognitive and behavioral signs and symptoms of Alzheimer's disease, which can include apathy, aggression, confusion, and psychotic features. The drug's action on cholinergic pathways is linked to its efficacy in managing the cognitive decline seen in Alzheimer's patients.

Pharmacokinetics

Donepezil is well absorbed from the gastrointestinal tract, with peak plasma concentrations occurring approximately 3 to 4 hours after administration. The drug is extensively metabolized in the liver, primarily through cytochrome P450 isoenzymes, and has a half-life of approximately 70 hours, allowing for once-daily dosing. It is excreted mainly as metabolites in urine, with a small percentage eliminated unchanged.

Adverse effects

• Nausea
• Diarrhea
• Insomnia
• Muscle cramps
• Fatigue
• Anorexia
• Bradycardia
• Syncope

Interactions

• mitotane+donepezil: Unknown (decreases exposure)
• rifampicin+donepezil: Unknown (decreases exposure)

Precautions

• Use with caution in patients with a history of asthma or obstructive pulmonary disease due to potential bronchoconstriction.
• Caution is advised in patients with bradycardia or other conduction abnormalities.
• Monitor for gastrointestinal bleeding in patients at risk.

Pregnancy

There are no adequate and well-controlled studies in pregnant women. Donepezil should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Donepezil is excreted in human milk. Caution should be exercised when administering to a nursing woman.

Storage

Store at room temperature, away from moisture and heat. Keep out of reach of children.

Formulations

• Tablets: 5 mg, 10 mg, 23 mg
• Oral solution: 1 mg/mL

Indications

• Alzheimer's disease
• Dementia related to Alzheimer's disease (mild to moderate)

Dosage

Children: Donepezil hydrochloride is not recommended for use in children. Refer to the BNF for Children for further guidance.

Adults: The usual starting dose for adults is 5 mg once daily, which may be increased to 10 mg once daily after four to six weeks, depending on tolerability and clinical response.

Mechanism of action

Donepezil acts by inhibiting the activity of acetylcholinesterase, an enzyme responsible for the breakdown of acetylcholine in the synaptic cleft. By preventing acetylcholine degradation, donepezil increases the concentration of this neurotransmitter, thereby enhancing cholinergic transmission and improving synaptic communication in the brain regions involved in memory and cognition.

Pharmacodynamics

The pharmacodynamic effects of donepezil include improved cognitive function, particularly in memory, attention, and language skills, as well as potential benefits in behavioral symptoms associated with dementia. The drug's efficacy is linked to its ability to increase cholinergic activity, which is crucial for cognitive processes that are impaired in Alzheimer's disease. Clinical studies have shown that donepezil can lead to modest improvements in cognitive function and overall clinical status.

Pharmacokinetics

Donepezil is well absorbed after oral administration, with peak plasma concentrations typically reached within 3 to 4 hours. It has a prolonged half-life of approximately 70 hours, allowing for once-daily dosing. The drug undergoes hepatic metabolism primarily via the cytochrome P450 system (CYP2D6 and CYP3A4), and its elimination is mainly via urine. Special caution is advised in cases of hepatic impairment, as it may increase exposure to the drug.

Contra-indications

• Frontotemporal dementia
• Cognitive impairment caused by multiple sclerosis
• Known history of persistent bradycardia (heart rate less than 60 beats per minute)
• Heart block
• Recurrent unexplained syncope
• Concurrent treatment with drugs that reduce heart rate

Adverse effects

• Nausea
• Diarrhea
• Insomnia
• Muscle cramps
• Fatigue
• Aggression
• Agitation
• Anorexia
• Skin reactions
• Dizziness

Interactions

• Anticholinesterases
• Centrally acting drugs that may exacerbate cognitive effects

Precautions

• Caution in patients with hepatic impairment
• Caution in patients with a history of seizures
• Monitor for worsening of motor symptoms in patients with Parkinson's disease dementia
• Regular review of antipsychotic medication

Pregnancy

Donepezil should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus. Limited data is available.

Breast-feeding

Donepezil is excreted in human milk; breastfeeding is not recommended during treatment.

Storage

Store at room temperature, away from moisture and direct sunlight. Keep out of reach of children.

Formulations

• Oral tablets
• Orodispersible tablets

Mechanism of action

The commonly accepted cholinergic hypothesis proposes that a portion of the cognitive and behavioral decline associated with Alzheimer's are the result of decreased cholinergic transmission in the central nervous system. Donepezil selectively and reversibly inhibits the acetylcholinesterase enzyme, which normally breaks down acetylcholine. The main pharmacological actions of this drug are believed to occur as the result of this enzyme inhibition, enhancing cholinergic transmission, which relieves the symptoms of Alzheimer's dementia. In addition to the above, other mechanisms of action of donepezil are possible, including the opposition of glutamate-induced excitatory transmission via downregulation of NMDA receptors and the regulation of amyloid proteins, which have demonstrated significant effects on the disease process of Alzheimer's. Other possible targets for donepezil may also include the inhibition various inflammatory signaling pathways, exerting neuroprotective effects. Donepezil hydrochloride, a piperidine derivative, is a centrally active, reversible inhibitor of acetylcholinesterase. The drug is structurally unrelated to other anticholinesterase agents (eg, tacrine, physostigmine). The precise mechanism(s) of action of donepezil in patients with dementia of the Alzheimer's type (Alzheimer's disease) has not been fully elucidated. The drug is an anticholinesterase agent that binds reversibly with and inactivates cholinesterases (eg, acetylcholinesterase), thus inhibiting hydrolysis of acetylcholine. As a result, the concentration of acetylcholine increases at cholinergic synapses. In vitro data and data in animals indicate that the anticholinesterase activity of donepezil is relatively specific for acetylcholinesterase in the brain compared with butyrylcholinesterase inhibition in peripheral tissues. A deficiency of acetylcholine caused by selective loss of cholinergic neurons in the cerebral cortex, nucleus basalis, and hippocampus is recognized as one of the early pathophysiologic features of Alzheimer's disease associated with memory loss and cognitive deficits. Because the resultant cortical deficiency of this neurotransmitter is believed to account for some of the clinical manifestations of mild to moderate dementia, enhancement of cholinergic function with an anticholinesterase agent, such as tacrine or donepezil, is one of the pharmacologic approaches to treatment. Because widespread degeneration of multiple central neuronal systems eventually occurs in patients with Alzheimer's disease, potentially beneficial effects of anticholinesterase agents theoretically would diminish as the disease process advances and fewer cholinergic neurons remain functioning. Current theories on the pathogenesis of the cognitive signs and symptoms of Alzheimer's Disease attribute some of them to a deficiency of cholinergic neurotransmission. Donepezil hydrochloride 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. There is no evidence that donepezil alters the course of the underlying dementing process. For more Mechanism of Action (Complete) data for Donepezil (6 total), please visit the HSDB record page.

Pharmacodynamics

By inhibiting the acetylcholinesterase enzyme, donepezil improves the cognitive and behavioral signs and symptoms of Alzheimer's Disease, which may include apathy, aggression, confusion, and psychosis.