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PH3501- Neuropharmacology > Lec 13-Dementia I > Flashcards

Lec 13-Dementia I Flashcards

1
Q

What is dementia

A
  • Chronic or persistent disorder behaviour and higher intellectual function due to organic brain disease
  • Memory disorders, changes personality, deterioration in personal care, impaired reasoning ability and disorientation
  • Lose cognition
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2
Q

Demographics

A
  • Dementia primarily disease of old age
  • Avoid stereotypes
    • Most older people live independently
    • Look after themselves
    • Contribute to society rather the burden
    • All need similar service
  • Average life expectancy- Female (77.7); Male (71.9)
  • Projected population- 1995-2025
    • 80+= increase by half
    • 90+ likely to double
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3
Q

Prevalence dementia US/Europe

A
  • USA today about 4 million with Alzheimers disease
  • USA 2050: greater than 14 million AD
  • US primary care review 66% cases dementia undetected
  • UK today: 0.75 million dementia
  • UK 2050: greater 1.5 million dementia
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4
Q

The financial cost

A
  • USA= £100 billion annually
  • UK= £10 billion annually
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5
Q

Baby Boomers

A
  • Next stage global epidemic dementia “baby boomers” reach old age
    • Post war 1945-64
    • Bill clinto, G Bush, Tony Blair
  • US new schools were built
  • 60s generation discovered sex also generation discover dementia
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6
Q

Symptoms- general

A
  • Memory loss
    • General forgetfulness- diagnosis difficult
    • Forget recent events
    • Forget people, personal care
  • Difficulties learning and retaining new information
    • Misplace objects (e.g. car keys or spectacles)
  • Difficulty complex tasks- cooking, driving financial matters
  • Reduced ability reason and problem solving
  • Impairment of spatial and visuospatial awareness
    • Bumping into objects, getting lost in a familiar place
    • Maintain same environment- avoid hospital admission
  • Language problems- inability find words, follow the conversation
  • Behavioural changes- irritability suspiciousness, withdraw, delusions and hallucinations
  • Apart from early stages- patients lack insight
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7
Q

Assessment of symptoms

A
  • Various rating scales- NPI; ADAS-cog, ADL scale
  • Mini mental state examinations (MMSE) measure cognition
  • Total score = 30
  • Mild= 21-26
  • Moderate= 10-20
  • Severe= <10
  • Cognition assessed in 5 domains- Orientation; registration; attention; recall; language
  • Patients and carers practical thrings more important- e.g. ability to dress, feed or undertake activities
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8
Q

Symptoms and illness phase

A
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9
Q

Dementia types and symptoms

A
  • Over-classification- diagnosis only confirmed PM
  • Alzheimer’s disease- classic form 70% of cases
  • Vascular dementia- vascular component
    • Symptoms- insight and personality retained longer
    • Control risk factors e.g. hypertension, diabetes, smoking
  • PD dementia- associated PD
  • Dementia with Lewy bodies (DLB)- Psychotic symptoms, extrapyramidal symptoms; rigidity; bradykinesia; tremor
  • DLB/PDD- consider effect treatments on movement- PDD and DLB may be related
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10
Q

Pathology AD

A
  • Brain atrophy- Wasting away normally developed organ or tissue due to degeneration of cells
  • Amyloid plaques- pathological hallmarks of AD- Neurofibrillary tangles and amyloid plaques occur more frequently in with dementia
  • Neurofibrillary tangles
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11
Q

Medication and treatment

A
  • 1st review for medication worsen cognition
  • Cognitive enhancers
    • Cholinesterase inhibitor
    • Memantine
    • NICE guidelines
  • Treatment for behavioural symptoms
    • Non-medication
    • Medication
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12
Q

Review medication impair cognition

A
  • Sedative compounds- BZs; H2 antagonist; Anti-psychotics
  • Medication anti-cholinergic activity
    • Anti-psychotics, Anti-depressants
    • Anti-cholinergics e.g. procyclidine, benztropine
    • H2 antagonists e.g. ranitidine, cimetidine
      • Odds ratio- cognitive impairment
  • Physical drugs e.g. furosemide, digoxin, warfarin, prednisolone
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13
Q

Acetylcholinesterase inhibitors

A
  • ACh inhibitors licensed symptomatic treatment mild- moderate AD
    • Tacrine never licensed- hepatic toxicity
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14
Q

Major cholinergic changes AD

A
  • Significant Ach deficit- 40-90% depletion acetyl choline moderative/severe disease
  • Decrease Ach correlates decline memory and cognitive
  • Ach metabolized acetylcholinesterase (AchE)
  • Meds such donepezil inhibits enzyme AchE
    • Slow down metabolism and increase Ach
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15
Q

Efficacy

A
  • Not cure, but relieve symptoms
  • Arrest decline cognition over 24 weeks
  • No evidence agents slow down underlying disease process or prolong life
  • 25% patients definite response & 40-50% some benefit over clinical prevalence
  • Patients fail to respond to one agent, no evidence second agent effective
  • Help some people, some of the time- overall limited efficacy
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16
Q

Adverse events

A
  • Dose related cholinergic adverse events- start low and go slow- improve tolerability
  • GI adverse events e.g. nausea, vomittin, diarrhoea, ab pain
    • May dissapea, but some cases need discontinued
  • Other adverse events: muscle cramps, fatigue, insomnia, dizziness, falls syncope
  • Serious events include convulsion, bradycardia
    • Caution sick sinus syndrome & supraventricular cardiac conduction disorders
17
Q

Drug interaction

A
  • Donepezil & Galantamine
    • Metabolised by CYP3A4 & CYP2D6
    • Inhibitors (e.g. erythromycin) increase levels- breakthrough cholinergic adverse events
    • Inducers (e.g. phenytoin) decrease levels- reduce the efficacy
    • Dosage adjustments considered
  • Rivastigmine- renally excreted- drug interactions unlikely
18
Q

Memantine

A
  • NMDA (N-methyl-D-aspartate) receptor antagonist
  • Licensed moderatley severe to severe AD
    • Memantine binds NMDA receptors block glutamate-controlled receptor channels
    • Efficacy
    • Adverse events
19
Q

Efficacy and adverse events

A
  • Licensed severe to moderately severe AD
  • Possible agitation associated dementia
  • No evidence
    • Combination memantine and cholinesterase inhibitor
    • Use in the early stages of dementia
  • Side effects- hallucinations (5% v 2.1% placebo); confusion (1.3% v 0.3%); dizziness (5% v 2.8%); headache (5% v 3.1%)
20
Q

Treatment behavioural problems

A
  • Occur in 90% patient dementia
  • Symptoms include aggression, hyperactivity, agitation
  • Strong predictor for caregiver burden & stress, placement institutional setting
  • Anti-psychotics used but associated 1,800 excess deaths due use
21
Q

Treatment BPSD

A
  • Assessment and diagnosis
  • Patient-centred care
    • Identify causality
    • Optimise and individualise clinical care
  • Treatments
    • Complementary & alternative treatments
    • Pharmacological interventions
22
Q

Diagnosis and assessment

A
  • First step accurate diagnosis & assessment extent of problem
  • Identify underlying possible treatable causes- clinical & non-clinical
  • Direct observation, interviewing family, caregivers, patient
  • Assessment past episode BPSD, warning signs, background information including cultural issues
  • Full documentation including severity grading
23
Q

Clinical causes

A
  • Medical conditions e.g. arthritis, diabetes, de-hydration, untreated pain, depression
  • Common caus- delirium or acute confusional state
  • Medication cuase delirium and BPSD
    • Sedatives => confusion
    • Sympathomimetics, anti-psychotics, anti-depressants ==> anxiety/ Akathisia
    • Anti-cholinergics impair cognition => delirium/ confusion
24
Q

Non-clincal issues

A
  • Changes environment => distress lose familiar items
    • Assess environmental factors causing BPSD
  • Non-clinical factors
    • Environment- room temp, noise, TV programmes
    • Thirst, food
    • Issues with care- lack exercise, communication difficulties, boredom, cared by a member of opposite sex
25
Q

Individualise care

A
  • Calm & consistent care environment
    • specific procedures & treatment agreed- all team members & visitors act consistently
  • Constant re-assurance
  • Communication- eye contact and touch
  • Support for carers
    • Charitable sector, religious organisations
  • Reduce boredom
  • Exercise for Wanderers
26
Q

Treatments

A
  • Non-medication interventions
    • Psychoeducational- training care staff
    • Sensory enhancement- music or light therapy
    • Complementary and alternative therapies- lavander etc
  • Only treat danger patient or others
    • Flexible approach harmless behaviour e.g. occasional shouting
  • Pharmacological intervention- anti-psychotics
27
Q

General guidance anti-psychotics

A
  • Only severe distress: immediate risk harm patient or others
    • Best interests patients
  • Other measures tried
  • Start low dose: titrate response and regularly review
  • Dose minimum and attempt withdraw ASAP
  • Use licensed product- risperidone
  • Avoid substituting BZs
28
Q

Summary

A

PH3501- Neuropharmacology (28 decks)

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