Alzheimer's Disease Flashcards
(34 cards)
Explain the place in therapy of Cholinesterase Inhibitors in Alzheimer’s Disease.
Cholinesterase Inhibitors are used to treat cognitive function and global functioning in all stages of Alzheimer’s, with greater clinical benefit in mild-to-moderate disease.
State the dose of Donepezil for Alzheimer’s Disease.
Initially, 5mg ONCE daily at bedtime. Increase if necessary after at least one month to a maximum of 10mg daily.
Explain the mechanism of Donepezil.
Donepezil selectively and reversibly inhibits the acetylcholinesterase enzyme, which usually breaks down acetylcholine. As a result of the enzyme inhibition, acetylcholine concentrations increase, and cholinergic transmission is enhanced.
Explain the mechanism of Rivastigmine.
Rivastigmine inhibits acetylcholinesterase and butyrylcholinesterase by covalently binding to active sites on these enzymes, blocking their function. As a result, acetylcholine concentration increases, and cholinergic transmission is enhanced.
Explain the mechanism of Galantamine.
Galantamine is a cholinesterase inhibitor with dual mechanisms. It selectively and reversibly binds to cholinesterase, thereby blocking the hydrolytic degradation of acetylcholine and increasing its concentration in the synaptic cleft. Galantamine is also an allosteric potentiator of the alpha-7 nicotinic receptor, facilitating acetylcholine release from pre-synaptic neurons.
Explain how anticholinesterase inhibitors may cause heart block and bradycardia, which medicines to caution and how patients initiated on Donepezil need to be monitored.
Cholinesterase inhibitors increase the concentration of acetylcholine. Acetylcholine binds to muscarinic M2 receptors in cardiac tissue, which opens potassium channels and slows firing in the sinus node.
Patients taking BB, CCB, Digoxin or Amiodarone should be cautioned.
Check pulse at baseline, monthly during titration, and every six months thereafter. A pulse of <50bpm or 50-60bpm with syncope indicates the need for withdrawal.
Explain how GI disturbances should be managed in a patient taking Donepezil.
GI disturbances are a common side effect of Donepezil and can be dose-limiting.
Consider switching to an alternative anticholinesterase inhibitor if intolerable.
Explain how nausea and/or vivid dreams and nightmares can be managed in a patient taking Donepezil.
Donepezil is typically initiated on doses taken before bedtime to avoid daytime nausea. However, patients experiencing vivid dreams and nightmares can be switched to morning dosing.
Explain the role in therapy of NMDA Receptor Antagonists
NMDA Receptor Antagonists, such as Memantine HCl, are used in moderate to severe Alzheimer’s disease when cholinesterase inhibitors are contraindicated or intolerable, or as combination therapy for modest symptomatic benefit on cognition and behaviour.
State the side effects of Memantine HCl
Dizziness, constipation, hypertension, dyspnoea, headache , drowsiness, hypersensitivity.
Explain the ‘strong’ risk factors of dementia
Advanced age
Family History
Genetics
Down’s Syndrome
Cerebrovascular disease
Medications
Less than secondary school education
Briefly summarise the mini-ACE screening tool.
A cognitive screening tool for mild cognitive impairment and dementia. Higher scores indicated better cognitive ability.
Normal cognitive function (26-30)
Mild cognitive impairment (22-25)
Dementia (<21)
The tool considers attention, memory, verbal fluency, visuospatial abilities and memory recall.
State the treatment goals of Alzheimer’s Disease management.
1.) Slow symptoms of disease progression by preserving memory and functional abilities.
2.) Reduce behavioural disturbance.
3.) Delay entry into institutional care settings.
State the treatment goals of Alzheimer’s Disease management.
1.) Slow symptoms of disease progression by preserving memory and functional abilities.
2.) Reduce behavioural disturbance.
3.) Delay entry into institutional care settings.
Discuss the formulation considerations for anticholinesterase inhibitors.
Both Donepezil and Galantamine are reversible anticholinesterase inhibitors metabolised by CYP2D6 and CYP3A4. Rivastigmine is pseudo-irreversible and metabolised by AChe and BuChe.
Rivastigmine is available as a patch that is only subsidised if the GI disturbances of Donepezil are intolerable. Given that the half-life of Rivastigmine is much shorter (2 hours compared to 50-90 hours in Donepezil), capsules are dosed TWICE daily.
Explain the role in therapy of non-pharmacological treatment for BPSD.
Non-pharmacological treatment is the preferred approach to BPSD and should be trialled for 1-4 weeks before initiating pharmacological management.
Provide non-pharmacological treatment options to manage BPSD.
- Identify treatable causes such as pain, loud noise or change in routine.
- Seek information from patients and carers regarding about the patient’s routine, preferences and things important to them
- Introduce sleep hygiene (e.g. reducing caffeine intake after a certain time, reducing daytime naps, keeping the bedroom dark and quiet)
- Engage patients in meaningful or creative activities.
- Physical exercise
Explain the treatment approach for depression in dementia patients.
Antidepressants should be initiated in patients with dementia only when diagnosed with depression. SSRIs, particularly Citalopram, are preferred due to their favourable side-effect profile.
TCAs should be avoided due to their association with worsening cognitive function.
Benzodiazepines can be considered for acute anxiety but should be used at low doses and limited to short periods.
Explain the treatment approach for aggression, delusion and hallucinations in dementia patients.
The efficacy of antipsychotics in managing aggression, delusion and hallucinations in dementia patients is limited. Additionally, antipsychotics have been associated with an increased risk of cerebrovascular events/deaths.
Atypical antipsychotics (e.g. risperidone) are perceived to have fewer ADRs at lower doses and effectively reduce agitation and aggression in BPSD.
Risperidone 2mg/day can be prescribed with a review period and an aim to stop the medication. Monitor one week after initiation.
Compare and contrast dementia and delirium. (Hint: TOAST)
Dementia is a slow, progressive disease that occurs over months to years, whereas delirium has a rapid onset over hours to days.
Attention and concentration are mildly affected in dementia and severely affected in delirium.
Sleep is only mildly disturbed in dementia. In delirium, patients experience day/night reversals.
Speech is normal in dementia but incoherent and muddled in delirium.
Orientation is usually impaired in dementia.
Dementia patients experience scarcity of thought, with words hard to find. In delirium, thoughts are disorganised and incoherent.
Briefly define dementia and state the associated symptoms.
An umbrella term for symptoms relating to a decline in cognitive functioning involving memory, reasoning or other thinking skills.
Symptoms involve memory decline, changes in thinking skills, poor judgement/reasoning, decreased focus and attention, and changes in language and behaviour.
Explain the hypothesised pathophysiology of Alzheimer’s Disease
AD is characterised by the accumulation of two abnormal protein aggregates in the brain: amyloid-beta plaques and tau protein tangles. These proteins disrupt normal cellular functions and contribute to the death of neurons in the brain, which leads to Alzheimer’s disease symptoms.
- Aβ is produced when amyloid precursor protein (APP) is broken into smaller fragments. In healthy brains, Aβ is cleared away by microglia and astrocytes, but in AD, this clearance mechanism is impaired, accumulating Aβ plaques. These plaques disrupt communication between neurons and cause inflammation in the brain.
- Tau is a protein that helps stabilise the structure of neurons. In AD, tau becomes abnormally phosphorylated and forms tangles, which disrupts the normal functioning of neurons and contributed to their death.
Overall, the accumulation of beta-amyloid plaques and tau tangles in the brain can impair the functioning of cholinergic neurons and lead to decreased levels of ACh, which is thought to contribute to the cognitive deficits observed in Alzheimer’s disease.
What is the mechanism of NMDA receptor antagonists?
Memantine HCl blocks NMDA receptors, preventing calcium influx into neurons and reducing the release of glutamate, an excitotoxic neurotransmitter. Inhibition of NMDA receptors also disinhibits acetylcholine release. Therefore, balancing the neurotransmitters glutamate and acetylcholine reduces neuronal damage, enhances cholinergic neurotransmission, and improves cognitive function.
What is the difference between typical and atypical antipsychotics?
Typical antipsychotics primarily block D2 receptors in the brain, which can reduce psychosis. They also have varying affinities for other receptors, which can lead to side effects such as sedation, weight gain and movement disorders.
Atypical antipsychotics block dopamine D2 receptors and serotonin 5-HT2A receptors. This dual mechanism provides greater efficacy against psychosis.
Atypical antipsychotics are preferred, particularly in older adults, as they are less likely to cause movement disorders such as extrapyramidal symptoms and tardive dyskinesia.
