Alzheimer's Disease

Question 1

Explain the place in therapy of Cholinesterase Inhibitors in Alzheimer’s Disease.

Answer 1

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.

Question 2

State the dose of Donepezil for Alzheimer’s Disease.

Answer 2

Initially, 5mg ONCE daily at bedtime. Increase if necessary after at least one month to a maximum of 10mg daily.

Question 3

Explain the mechanism of Donepezil.

Answer 3

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.

Question 4

Explain the mechanism of Rivastigmine.

Answer 4

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.

Question 5

Explain the mechanism of Galantamine.

Answer 5

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.

Question 6

Explain how anticholinesterase inhibitors may cause heart block and bradycardia, which medicines to caution and how patients initiated on Donepezil need to be monitored.

Answer 6

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.

Question 7

Explain how GI disturbances should be managed in a patient taking Donepezil.

Answer 7

GI disturbances are a common side effect of Donepezil and can be dose-limiting.

Consider switching to an alternative anticholinesterase inhibitor if intolerable.

Question 8

Explain how nausea and/or vivid dreams and nightmares can be managed in a patient taking Donepezil.

Answer 8

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.

Question 9

Explain the role in therapy of NMDA Receptor Antagonists

Answer 9

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.

Question 10

State the side effects of Memantine HCl

Answer 10

Dizziness, constipation, hypertension, dyspnoea, headache , drowsiness, hypersensitivity.

Question 11

Explain the ‘strong’ risk factors of dementia

Answer 11

Advanced age
Family History
Genetics
Down’s Syndrome
Cerebrovascular disease
Medications
Less than secondary school education

Question 12

Briefly summarise the mini-ACE screening tool.

Answer 12

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.

Question 13

State the treatment goals of Alzheimer’s Disease management.

Answer 13

1.) Slow symptoms of disease progression by preserving memory and functional abilities.
2.) Reduce behavioural disturbance.
3.) Delay entry into institutional care settings.

Question 14

State the treatment goals of Alzheimer’s Disease management.

Answer 14

1.) Slow symptoms of disease progression by preserving memory and functional abilities.
2.) Reduce behavioural disturbance.
3.) Delay entry into institutional care settings.

Question 15

Discuss the formulation considerations for anticholinesterase inhibitors.

Answer 15

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.

Question 16

Explain the role in therapy of non-pharmacological treatment for BPSD.

Answer 16

Non-pharmacological treatment is the preferred approach to BPSD and should be trialled for 1-4 weeks before initiating pharmacological management.

Question 17

Provide non-pharmacological treatment options to manage BPSD.

Answer 17

• 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

Question 18

Explain the treatment approach for depression in dementia patients.

Answer 18

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.

Question 19

Explain the treatment approach for aggression, delusion and hallucinations in dementia patients.

Answer 19

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.

Question 20

Compare and contrast dementia and delirium. (Hint: TOAST)

Answer 20

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.

Question 21

Briefly define dementia and state the associated symptoms.

Answer 21

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.

Question 22

Explain the hypothesised pathophysiology of Alzheimer’s Disease

Answer 22

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.

Question 23

What is the mechanism of NMDA receptor antagonists?

Answer 23

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.

Question 24

What is the difference between typical and atypical antipsychotics?

Answer 24

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.

Question 25

What is the mechanism of Citalopram?

Answer 25

Citalopram is a selective serotonin reuptake inhibitor (SSRI) that blocks the reuptake of serotonin into the nerve endings, increasing the amount of serotonin available in the brain and alleviating symptoms of depression and anxiety.

Question 26

What are the side effects of Risperidone?

Answer 26

Sedation, dizziness, headache, nausea and vomiting, constipation, dry mouth

Question 27

What is the mechanism of Risperidone?

Answer 27

Risperidone is a serotonin-dopamine antagonist that selectively blocks the activity of dopamine D2 receptors and serotonin 5-HT2A receptors in the brain, reducing activating of dopaminergic neurons, which are involved in hallucinations and delusions.

Question 28

Identify and provide a management option for the risk factors of vascular dementia

Answer 28

Age (>60)

Obesity – improve diet and include exercise into the daily routine

Hypertension – consider antihypertensive

Dyslipidaemia – consider statin and lifestyle changes

Smoking and alcohol – consider cessation.

Cognitive difficulties – engage in mentally stimulating activities.

Question 29

State the methods by which a pharmacist can help manage vascular dementia in the community

Answer 29

Offer delivery, blister pack, sachets?

Enrol in LTC, free delivery

Raise the profile of clients in the database who may be selective in taking reg meds.

Raise concern to GP/practise nurse if compliance declines and confusion increases.

Employ good communication skills (e.g. talking slowly, speaking to patients as adults, looking for understanding, and using visual aids)

Question 30

Conisder post-stroke complications and how to treat them

Answer 30

Spasticity: involves involuntary muscle activity and limb positioning – give baclofen

Pain: neuropathic and musculoskeletal – non-pharmacological or NSAIDs, and TCA’S or gabapentin

Depression & Anxiety: due to reduced QoL due to limited independence or due to damage to the brain – SSRIs, TCAs

Seizures: common post-stroke – can consider AED

Dysphagia: impaired swallowing – consider speech and language therapist, constituting food to be easy to swallow

Question 31

State risk factors for vascular dementia

Answer 31

Age (>60)

Obesity – improve diet and include exercise into daily routine

Hypertension – consider antihypertensive

Dyslipidaemia – consider statin and lifestyle changes

Smoking and alcohol – consider cessation

Cognitive difficulties – engage in mentally stimulating activities

Question 32

State secondary complications of stroke

Answer 32

Spasticity: involves involuntary muscle activity and limb positioning – give baclofen

Pain: neuropathic and musculoskeletal – non-pharmacological or NSAIDs, and TCA’S or gabapentin

Depression & Anxiety: due to reduced QoL due to limited independence or due to damage to the brain – SSRIs, TCAs

Seizures: common post-stroke – can consider AED

Dysphagia: impaired swallowing – consider speech and language therapist, constituting food to be easy to swallow

Question 33

Briefly describe the acute management of stroke

Answer 33

Fibrinolysis
* Mechanism: activates plasminogen to form plasmin, which degrades fibrin which causes thrombolysis
* Tenecteplase: used in larger clots, more fibrin specific, longer duration of action, higher efficacy and lower haematological complications

Alternatively – PCI, or clot retrieval

Question 34

Explain how blood pressure should be managed in a patient with an ischaemic stoke

Answer 34

All stroke patients with BP >140/90 mmHg should receive BP therapy. Target <130/80mmHg - depending on comorbidity and patient factors.

However, early BP reduction is associated with worsening symptoms - do not start until >48 hours post ischaemic stroke.

Unless thrombolysis requires BP <180/105 mmHg for 24 hours post-stroke.