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Cognitive disorders unit 9
1.
2. Delirium vs. Dementia
Delirium Dementia
Rapid onset Insidious onset
Primary defect in attention Primary defect in short term
Fluctuates during the course memory
of a day Attention often normal
Visual hallucinations Does not fluctuate during
common day
Often cannot attend to Visual hallucinations less
MMSE or clock draw common
Can attend to MMSE or clock
draw, but cannot perform
well
3. Cognitive DIsorders
Delirium
Fluctuating cognitive impairment and disturbance
of consciousness
Psychosis and Insomnia
4. Treating Delirium
Primary goal treat underlying cause
Cause: Anticholinergic toxicity
Physiostigmine salicylate 1 to 2 mg IV or IM with
repeated doses in 15 to 30 minutes may be indicated
5. Treatment
Psychosis
Haloperidol
2 to 6 mg IM, repeated in an hour if necessary
Depending on patient’s age, weight and physical
condition.
Once patient is calm begin oral medication
Liquid concentrate or tablet
2 daily oral doses, 2/3 of the dose at bedtime
Effective daily dose of Haloperidol 5 to 40 mg for most
patients
6. Treatment
Atypical antipsychotics
Risperidone: for those with side effects from
haloperidol or contraindications
Starting dose: .5mg HS or BID
Olanzapine: agent of choice for patients with PD
with hallucinations/delirium
Starting dose 2.5mg PO HS or BID
Clozapine, quetiapine, aripiprazole may also be
considered although clinical trial experience is
limited.
7. Treatment
Insomnia
Best treated with benzodiazepines with short or
intermediate half-lives
Lorazepam 1 to 2 mg at bedtime
8. Dementia
The treatment for dementia is aimed at :
Symptomatic treatment of memory disturbance
Symptomatic treatment of memory disturbance
9. What are the common forms of
dementia?
There are four main types of dementia:
Alzheimer’s disease (60%; of cases)
Vascular dementia (30–40%; including about
20% where dual pathology exists)
Dementia with Lewy bodies (15% of cases)
Fronto-temporal dementia (5%)
Percentages total more than 100 because of
variability in studies
10. How is Alzheimer’s disease
Alzheimer’s disease may be characterized by a diffuse
characterised?
pattern of cortical deficits including: Aphasia – loss or
impairment of language caused by brain dysfunction
Apraxia – inability to execute learned movements on
command
Agnosia – inability to recognize or associate meaning to
a sensory perception
Acalculia – inability to perform arithmetical calculations
Agraphia – inability to write
Alexia – inability to read
11. Vascular dementia
Vascular dementia is the second most common
cause of dementia. It results from vascular or
circulatory lesions or from diseases of the
cerebral vasculature leading to ischaemia or
infarction.
12. Clinical features of vascular
dementia
problems concentrating and communicating
depression accompanying the dementia
symptoms of stroke, such as physical weakness or
paralysis
memory problems (although this may not be the
first symptom)
a 'stepped' progression, with symptoms remaining
at a constant level and then suddenly deteriorating
epileptic seizures
periods of acute confusion.
13. Clinical features of vascular
dementia
Other symptoms may include:
hallucinations (seeing things that do not exist)
delusions (believing things that are not true)
walking about and getting lost
physical or verbal aggression
restlessness
incontinence.
14. Clinical features of Dementia with
Lewy Bodies
Dementia of six months’ duration with: Periods of
confusion
Fluctuations in cognition (especially attention and
alertness)
Visual hallucinations
Spontaneous extrapyramidal signs such as rigidity or
slowing (mild parkinsonism)
Bradykinesia (paucity of movement)
18. Acetylcholinesterase
Inhibitors
Donezepil
Adminestered once daily
Generally well tolerated
Dose: 5mg oral/ day for 4 weeks then
increase dose to 10mg/day
Effective in Parkinsonian cognitive impairment
19. Acetylcholinesterase
Inhibitors
Donezepil
PHARMACODYNAMICS / KINETICS
Absorption: Well absorbed
Protein binding: 96%, primarily to albumin (75%)
&
alpha1-acid glycoprotein (21%)
Metabolism: Extensively to four major
metabolites
(two are active) via CYP2D6 and 3A4; undergoes
glucuronidation
33. Acetylcholinesterase
Inhibitors
Galantamine
Newer agent
Galantamine has shown modest benefit
in patients with a clinical diagnosis of either
vascular dementia or combination of AD and CVA
Dose: Initial: 4 mg twice a day for 4 weeks
I f 8 mg per day tolerated, increase to 8 mg twice
daily for > or =4 weeks
I f 16 mg per day tolerated, increase to 12 mg
twice daily; range: 16-24 mg/day in 2 divided
doses
35. Acetylcholinesterase
Inhibitors
Galantamine
PHARMACODYNAMICS / KINETICS
Metabolism: Hepatic; linear, CYP2D6 and
3A4;
metabolized to epigalanthaminone and
galanthaminone both of which have
acetylcholinesterase inhibitory activity 130
times less than galantamine
36. Acetylcholinesterase
Inhibitors
Galantamine
PHARMACODYNAMICS / KINETICS
Bioavailability: 80% to 100%
Half-life elimination: 6-8 hours
Time to peak: 1 hour
Excretion: Urine (25%)
37. Acetylcholinesterase
Inhibitors
Galantamine
Significant Adverse Reactions in>10%
Gastrointestinal: Nausea (6% to 24%)
vomiting (4% to 13%), diarrhea (6% to 12%)
Significant Adverse reactions in 1-10%
Cardiovascular: Bradycardia (2% to 3%),
syncope (0.4% to 2.2%: dose-related), chest pain
(> or =1%)
Central nervous system: Dizziness (9%),
headache (8%), depression (7%), fatigue (5%),
insomnia (5%), somnolence (4%), tremor (3%)
38. Acetylcholinesterase
Inhibitors
Galantamine
A D V E R S E R E A C T IO N S S IG N IF IC A N T
<1%
Aggression, alkaline phosphatase increased,
aphasia, apraxia, ataxia, atrial fibrillation, AV block,
bundle branch block, convulsions, dehydration,
delirium, diverticulitis, dysphagia, epistaxis,
esophageal perforation, gastrointestinal bleeding,
heart failure, hypokalemia, hypokinesia, hypotension,
melena, palpitations, paranoid reaction, paresthesia,
vertigo
39. Symptomatic Treatment of Behavioral
Disturbance in Dementia Patients
Delusions and hallucinations:
rivastigmine, risperidol, quetiapine
Depression: citalopram, fluoxetine>> TCA
Agression and anxiety: trazodone,
carbamazepine, valproate, gabapentin