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Dr Kreshnik Hoti BPharm, MPS, AACPA, PhD
Best Practice Pharmacy Dementia care
Curtin University is a trademark of Curtin University of TechnologyCRICOS Provider Code 00301J
2
Learning outcomes
Develop and understanding on medications used in dementia
Identify medications that can worsen cognition
Develop an understanding on medication related monitoring needs and outcomes in patients with dementia
Develop an understanding on pharmacists’ role in Dementia care
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What is dementia?
Latin word ‘demens’
Broad term
Symptoms descriptive of a range of conditions
• Brain function impairment
• Language, memory, perception, personality and cognitive skills
>65 years of age, likelihood doubles in 5 year intervals
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Definition (WHO)
“a syndrome due to disease of the brain, usually of a chronic or progressive nature, in which there is disturbance of multiple higher cortical functions, including memory, thinking, orientation, comprehension, calculation, learning capacity, language, and judgement. Consciousness is not clouded. The impairments of cognitive function are commonly accompanied, and occasionally preceded, by deterioration in emotional control, social behaviour, or motivation. This syndrome occurs in Alzheimer’s disease, in cerebrovascular disease, and in other conditions primarily or secondarily affecting the brain”
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Early signs
Ability to learn and remember new information
Difficulties with tasks which are familiar
Progression
More basic activities affected
Higher mental function impairment progress over months to years
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Cognitive, psychiatric and behavioural symptoms
memory problems
communication difficulties
confusion, wandering, getting lost
personality changes and behaviour changes such as agitation, repetition, following
depression, delusions, apathy and withdrawal
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Dementia – national figures
Source: Alzheimer’s Australia
280.000 Australians
1600 new cases weekly
3rd leading
cause of death
Worldwide cost: US$604 billion in 2010
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Source: Alzheimer’s disease international; World Alzheimer’s report 2010. The global economic impact of dementia
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Dementia major contributor to disability
dem
entia
stro
ke
mus
culos
celet
al
card
iovas
cular
canc
er
0
2
4
6
8
10
12
years lived with disability
Source: World Health Organization. World Health Report 2003—Shaping the future. Geneva: WHO, 2003.
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Dementia predictions
35.6 million worldwide
4.6 million cases every year
People affected double every 20 years
81.1 million people affected by 2040
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Dementia predictions cont’d
Ferri et al. Global prevalence of dementia: a Delphi consensus study. Lancet 2005; 366: 2112–17
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Dementia – causes
62% (Alzheimer’s disease)
17% (vascular dementia)
10% (mixed dementia)
3% (other)
2% (fronto- temporal)
4% (lewy bodies)
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Dementia – causes
• Alzheimer’s disease causes:
• Biological• Genetics• Inflammation
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Risk factors
Modifiable:
• Obesity
• Smoking
• Physical activity and exercise
• Alcohol
• Cognitive reserve
• *head injury
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Risk factors
Treatable medical conditions:
• stroke
• diabetes
• midlife hypertension
• midlife hypercholesterolemia
• hyperhomocysteinaemia
• depression (?)
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Risk factors
Non-Modifiable:
• age
• family history
• small head size
• male gender
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Treatment
Patients and family involvement as soon as diagnosis is made
Support for daily activities
Address co-existing medical conditions
Avoid medications exacerbating cognitive function
Treat Vitamin B12 or folate deficiency if present
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Treatment
No cure
None of the available drugs prevent Alzheimer’s or modifies its pathology
Symptoms such as memory loss and confusion may be reduced (for a limited time)
Acetylcholinesterase inhibitors& memantine
Combination
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Treatment - Acetylcholinesterase inhibitors
• Donepezil
• Galantamine
• Rivastigmine
Decrease the breakdown of acetylcholine and therefore reduce the deficiency of cholinergic neurotransmitter activity
First line agents
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Treatment - Acetylcholinesterase inhibitors
25-50% of patients experience delayed deterioration of cognition by 6 months
12-20% of patients by 1 year
Benefits in cognition, function and global outcomes (MMSE gain 1.5-2 points)
Benefits assessed after 3 months
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Acetylcholinesterase inhibitors-ADVERSE EFFECTS
Incidence related to dose
Use in some patients is limited by adverse effects, especially gastrointestinal
Common: nausea, vomiting, loss of appetite, diarrhoea
Commonly increase bladder and bowel urgency and contribute to incontinence
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Treatment - memantine
AD associated with excess glutamate, therefore memantine reduces glutamate-induced neuronal degradation
Specialist initiated
Moderate to severe AD
Benefits in cognition, function, global outcome
Common adverse effects: Headache, constipation, confusion and dizziness
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Treatment summary
Generic Dosage form Dose Approved for Contraindicated
Donepezil(Aricept)
tablet 5mg up to 10mg evening
All stages GI/ureteric obstruction; Active PU
Galantamine(Reminyl, Galantyl)
CR capsule 8mg daily up to 16mg morning with food
Mild to moderate Severe hepatic impairment; CrCl <10 mL/minute; GI/ureteric obstruction; Active PU
Rivastigmine(Exelon)
Capsule, oral liquid, patch
Oral: 1.5mg BD up to 6mg BD CCPatch: 4.5mg up to 9.5mg daily
Mild to moderate Severe hepatic impairment; GI/ureteric obstruction; Active PU
Memantine(Ebixa)
Tablet 5 mg up to 20mg daily
Moderate to severe
History of seizures
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Pharmaceutical Benefits Scheme implications
Acetylcholinesterase inhibitors and memantine require authority approval
Donepezil example: • INITIAL APPLICATION FOR THE TREATMENT OF MILD TO
MODERATELY SEVERE ALZHEIMER'S DISEASE - Patients with an (S)MMSE of 10 or more
• Confirmation of diagnosis must be made by or in consultation with a specialist/consultant physician (including a psychiatrist).
• To continue treatment: patient demonstrated improvement in cognitive function
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Vitamins and supplements
Do they help?
B vitamins
Omega 3
Mediterranean diet
Vitamin E
Ginkgo Biloba
Aspirin
Brahmi
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Other agents
Statins
Testosterone
Oestrogen
Anti-inflammatory agents
Selegiline
Future therapies
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Medications negatively affecting dementia
Drugs with anticholinergic effects (Australian Medicines Handbook 2012)
amantadine, amitriptyline, atropine
belladonna alkaloids, benzhexol, benztropine, biperiden, brompheniramine
chlorpheniramine, chlorpromazine, clomipramine, clozapine, cyclizine, cyclopentolate, cyproheptadine
darifenacin, dexchlorpheniramine, dimenhydrinate, diphenhydramine, disopyramide, dothiepin, doxepin
glycopyrrolate
homatropine, hyoscine (butylbromide or hydrobromide)
imipramine, ipratropium (nebulised)
mianserin
nortriptyline
olanzapine, orphenadrine, oxybutynin
pericyazine, pheniramine, pizotifen, prochlorperazine, promethazine, propantheline
solifenacin
tiotropium, tolterodine, trimeprazine, trimipramine, triprolidine, tropicamide
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Medications negatively affecting dementia
Anticholinergic Cognitive Burden (ACB)• Score 1-3
• Definite anticholinergics score 2&3
• Every definite anticholinergic increases the risk of cognitive impairment by 46% over 6 years
• 1 point increase in ACB score = 0.33 decline in MMSE over 2 yrs
Antipsychotics
Sedatives
Tricyclic antidepressants
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Behavioural and psychological symptoms in dementia (BPSD)
Challenging & distressing
Causes: • Brain cells progressively deteriorate
• Environmental
• Medications
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BPSD
Early stages:irritability
anxiety
depression
Later stages:aggression
agitation
emotional distress
hallucinations
outbursts
delusion
sleep disturbances
restlessness
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BPSD
Review/Treat potential underlying causes:
Possible physical causes of distress or delirium• Pain, dehydration, LUTS, infection…
Medications which impair cognition
Environmental factors
Depression
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BPSD treatment
Non-drug options – first line
Antipsychotics (hallucinations, delusions or seriously disturbed behaviour)
Mood stabilizers such as carbamazepine or valproate
Antidepressants
Acetylcholinesterase inhibitors or memantine
Anxiety and agitation (oxazepam for no longer than 2 weeks)
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Antipsychotics – considerations:
Risperidone approved for BPSD
Recommended for use when symptoms cause severe distress or immediate risk of harm
Monitor if behaviour improved and adverse effects tolerated
Therapy reviewed every three months
Many troublesome symptoms do not respond
BPSD often resolves spontaneously within 12 weeks
Antipsychotics increase the risk of death in BPSD patients
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Pharmacists’ role
Refer patients with suspected cognitive impairment
Early diagnosis
Patient & family counselling and education
Promotion of risk reduction strategies
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Pharmacists’ role
Source of information• Patient,
• Family,
• Health professionals
Monitoring drug interactions
Monitoring drug contraindications
Monitor medication compliance
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Pharmacists’ role
Dose administration aids
Medication reviews• Medication usage reviews
• Home medication reviews
Identifying medications contributing/exacerbating cognitive decline
Quality use of medicines
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References Australian Medicines Handbook 2012
eTherapeutic Guidelines, Neurology
Alzheimer’s Australia; http://www.fightdementia.org.au
Alzheimer’s Association; www.alz.org
Ballard et al. Alzheimer’s disease. Lancet 2011; 377: 1019–31
Ferri et al. Global prevalence of dementia: a Delphi consensus study. Lancet 2005; 366: 2112–17
Alzheimer’s disease international; World Alzheimer’s report 2010. The global economic impact of dementia
World Health Organization. World Health Report 2003—Shaping the future. Geneva: WHO, 2003.
McCullagh CD et al. Risk factors for dementia. Advances in Psychiatric Treatment 2001; 7:24–31
Australian Institute of Health and Welfare 2007. Dementia in Australia. National data analysis and development
Archer et al. The effects of commonly prescribed drugs in patients with Alzheimer’s disease on the rate of deterioration. J Neurol Neurosurg Psychiatry 2007;78:233–239.
The Aging Brain Program at the IU Center for Aging Research. Anticholinergic Cognitive Burden List (ACB). 4/4/12
Campbell N, Boustani M, Limbil T, Ott C, et al. The cognitive impact of anticholinergics: a clinical review. Clinical Interventions in Aging. 2009;4(1):225-33