cognitive disorders unit 9
TRANSCRIPT
![Page 1: Cognitive disorders unit 9](https://reader035.vdocuments.site/reader035/viewer/2022062319/556383b3d8b42ad2128b473a/html5/thumbnails/1.jpg)
![Page 2: Cognitive disorders unit 9](https://reader035.vdocuments.site/reader035/viewer/2022062319/556383b3d8b42ad2128b473a/html5/thumbnails/2.jpg)
Delirium vs. Dementia
DeliriumRapid onsetPrimary defect in
attentionFluctuates during the
course of a dayVisual hallucinations
commonOften cannot attend to
MMSE or clock draw
DementiaInsidious onsetPrimary defect in short
term memoryAttention often normalDoes not fluctuate
during dayVisual hallucinations
less commonCan attend to MMSE or
clock draw, but cannot perform well
![Page 3: Cognitive disorders unit 9](https://reader035.vdocuments.site/reader035/viewer/2022062319/556383b3d8b42ad2128b473a/html5/thumbnails/3.jpg)
Cognitive DIsorders
Delirium Fluctuating cognitive impairment and
disturbance of consciousness Psychosis and Insomnia
![Page 4: Cognitive disorders unit 9](https://reader035.vdocuments.site/reader035/viewer/2022062319/556383b3d8b42ad2128b473a/html5/thumbnails/4.jpg)
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
![Page 5: Cognitive disorders unit 9](https://reader035.vdocuments.site/reader035/viewer/2022062319/556383b3d8b42ad2128b473a/html5/thumbnails/5.jpg)
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
![Page 6: Cognitive disorders unit 9](https://reader035.vdocuments.site/reader035/viewer/2022062319/556383b3d8b42ad2128b473a/html5/thumbnails/6.jpg)
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.
![Page 7: Cognitive disorders unit 9](https://reader035.vdocuments.site/reader035/viewer/2022062319/556383b3d8b42ad2128b473a/html5/thumbnails/7.jpg)
Treatment
Insomnia Best treated with benzodiazepines with
short or intermediate half-lives Lorazepam 1 to 2 mg at bedtime
![Page 8: Cognitive disorders unit 9](https://reader035.vdocuments.site/reader035/viewer/2022062319/556383b3d8b42ad2128b473a/html5/thumbnails/8.jpg)
Dementia
The treatment for dementia is aimed at : Symptomatic treatment of memory
disturbance Symptomatic treatment of memory
disturbance
![Page 9: Cognitive disorders unit 9](https://reader035.vdocuments.site/reader035/viewer/2022062319/556383b3d8b42ad2128b473a/html5/thumbnails/9.jpg)
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
![Page 10: Cognitive disorders unit 9](https://reader035.vdocuments.site/reader035/viewer/2022062319/556383b3d8b42ad2128b473a/html5/thumbnails/10.jpg)
How is Alzheimer’s disease characterised? Alzheimer’s disease may be characterized by
a diffuse 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
![Page 11: Cognitive disorders unit 9](https://reader035.vdocuments.site/reader035/viewer/2022062319/556383b3d8b42ad2128b473a/html5/thumbnails/11.jpg)
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.
![Page 12: Cognitive disorders unit 9](https://reader035.vdocuments.site/reader035/viewer/2022062319/556383b3d8b42ad2128b473a/html5/thumbnails/12.jpg)
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.
![Page 13: Cognitive disorders unit 9](https://reader035.vdocuments.site/reader035/viewer/2022062319/556383b3d8b42ad2128b473a/html5/thumbnails/13.jpg)
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.
![Page 14: Cognitive disorders unit 9](https://reader035.vdocuments.site/reader035/viewer/2022062319/556383b3d8b42ad2128b473a/html5/thumbnails/14.jpg)
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)
![Page 15: Cognitive disorders unit 9](https://reader035.vdocuments.site/reader035/viewer/2022062319/556383b3d8b42ad2128b473a/html5/thumbnails/15.jpg)
![Page 16: Cognitive disorders unit 9](https://reader035.vdocuments.site/reader035/viewer/2022062319/556383b3d8b42ad2128b473a/html5/thumbnails/16.jpg)
Acetylcholinesterase Inhibitors Can improve cognitive functions in
patients diagnosed with: Alzheimer’s disease Vascular dementia and Diffuse Lewy body disease
![Page 17: Cognitive disorders unit 9](https://reader035.vdocuments.site/reader035/viewer/2022062319/556383b3d8b42ad2128b473a/html5/thumbnails/17.jpg)
Acetylcholinesterase Inhibitors Donezepil Rivastigmine Galantamine Tacrine
Used very rarely due to its hepatotoxicity
![Page 18: Cognitive disorders unit 9](https://reader035.vdocuments.site/reader035/viewer/2022062319/556383b3d8b42ad2128b473a/html5/thumbnails/18.jpg)
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
![Page 19: Cognitive disorders unit 9](https://reader035.vdocuments.site/reader035/viewer/2022062319/556383b3d8b42ad2128b473a/html5/thumbnails/19.jpg)
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
![Page 20: Cognitive disorders unit 9](https://reader035.vdocuments.site/reader035/viewer/2022062319/556383b3d8b42ad2128b473a/html5/thumbnails/20.jpg)
Acetylcholinesterase Inhibitors Donezepil PHARMACODYNAMICS / KINETICS Bioavailability: 100% Half-life elimination: 70 hours; time to
steady-state: 15 days
Time to peak, plasma: 3-4 hours Excretion: Urine (as unchanged drug)
![Page 21: Cognitive disorders unit 9](https://reader035.vdocuments.site/reader035/viewer/2022062319/556383b3d8b42ad2128b473a/html5/thumbnails/21.jpg)
Acetylcholinesterase Inhibitors Donezepil Significant Adverse Effects in
>10% Central nervous system: Headache Gastrointestinal: Nausea, diarrhea
Significant Adverse Effects in <10% Cardiovascular: Syncope, chest pain,
hypertension, atrial fibrillation, hypotension, hot flashes
Central nervous system: Fatigue, insomnia, dizziness, depression, abnormal dreams,
somnolence
![Page 22: Cognitive disorders unit 9](https://reader035.vdocuments.site/reader035/viewer/2022062319/556383b3d8b42ad2128b473a/html5/thumbnails/22.jpg)
Acetylcholinesterase Inhibitors Significant Adverse Reactions in
<10% cont. Dermatologic: Bruising Gastrointestinal: Anorexia, vomiting,
weight loss, fecal incontinence, GI bleeding ,
bloating, epigastric pain Genitourinary: Frequent urination Neuromuscular & skeletal: Muscle cramps
, arthritis, body pain
![Page 23: Cognitive disorders unit 9](https://reader035.vdocuments.site/reader035/viewer/2022062319/556383b3d8b42ad2128b473a/html5/thumbnails/23.jpg)
Acetylcholinesterase Inhibitors Significant Adverse Reactions in <1%
Cholecystitis, CHF, delusions, dysarthria, dysphasia, dyspnea, eosinophilia, hallucin
ations, heart block, hemolytic anemia, hyponatre
mia, intracranial hemorrhage, neuroleptic mali
gnant syndrome, pancreatitis, paresthesia, rash,
seizures, thrombocytopenia
![Page 24: Cognitive disorders unit 9](https://reader035.vdocuments.site/reader035/viewer/2022062319/556383b3d8b42ad2128b473a/html5/thumbnails/24.jpg)
Acetylcholinesterase Inhibitors Contraindication
Hypersensitivity to donepezil, piperidine derivatives, or any component of the formulation
![Page 25: Cognitive disorders unit 9](https://reader035.vdocuments.site/reader035/viewer/2022062319/556383b3d8b42ad2128b473a/html5/thumbnails/25.jpg)
Acetylcholinesterase Inhibitors Rivastigmine
Dose: 1.5mg oral BID with titration every 2 weeks up to 6mg BID
![Page 26: Cognitive disorders unit 9](https://reader035.vdocuments.site/reader035/viewer/2022062319/556383b3d8b42ad2128b473a/html5/thumbnails/26.jpg)
Acetylcholinesterase Inhibitors Rivastigmine PHARMACODYNAMICS /
KINETICS Absorption: Fasting: Rapid and
complete within 1 hour Distribution: Vd: 1.8-2.7 L/kg Protein binding: 40%
![Page 27: Cognitive disorders unit 9](https://reader035.vdocuments.site/reader035/viewer/2022062319/556383b3d8b42ad2128b473a/html5/thumbnails/27.jpg)
Acetylcholinesterase Inhibitors Rivastigmine PHARMACODYNAMICS / KINETICS Metabolism: Extensively via
cholinesterase- mediated hydrolysis in the brain;
metabolite undergoes N-demethylation and/or
sulfate conjugation hepatically
![Page 28: Cognitive disorders unit 9](https://reader035.vdocuments.site/reader035/viewer/2022062319/556383b3d8b42ad2128b473a/html5/thumbnails/28.jpg)
Acetylcholinesterase Inhibitors Rivastigmine PHARMACODYNAMICS / KINETICS Bioavailability: 40% Half-life elimination: 1.5 hours Time to peak: 1 hour Excretion: Urine (97% as
metabolites); feces (0.4%)
![Page 29: Cognitive disorders unit 9](https://reader035.vdocuments.site/reader035/viewer/2022062319/556383b3d8b42ad2128b473a/html5/thumbnails/29.jpg)
Acetylcholinesterase Inhibitors Rivastigmine
Significant Adverse Reactions in >10% 21Central nervous system: Dizziness ( %) (17%) vvv vvvvv : ( 4 7 %), (31%), 19 17diarrhea ( %), anorexia ( %) (13%)
![Page 30: Cognitive disorders unit 9](https://reader035.vdocuments.site/reader035/viewer/2022062319/556383b3d8b42ad2128b473a/html5/thumbnails/30.jpg)
Acetylcholinesterase Inhibitors Rivastigmine
Significant Adverse Reactions in 2-10% 9Central nervous system: Fatigue ( %), 9 8insomnia ( %), confusion ( %), depression (
6%), ( 5 %), ( 5 %), ( 5
%), (4%), (3%) 3Cardiovascular: Syncope ( %), hypertension (3%) : ( 9 %), 5 4constipation ( %), flatulence ( %), weight loss
(3%)
![Page 31: Cognitive disorders unit 9](https://reader035.vdocuments.site/reader035/viewer/2022062319/556383b3d8b42ad2128b473a/html5/thumbnails/31.jpg)
Acetylcholinesterase Inhibitors Rivastigmine Significant Adverse Reactions in 2-
10% cont. 7Genitourinary: Urinary tract infection ( %) & : ( 6 %), (4%)tremor : ( 4 %) : ( 4 %), - (3%)flu like syndrome
![Page 32: Cognitive disorders unit 9](https://reader035.vdocuments.site/reader035/viewer/2022062319/556383b3d8b42ad2128b473a/html5/thumbnails/32.jpg)
Acetylcholinesterase Inhibitors Rivastigmine
Contraindication vv vvvvvvvvvvvvv vvvvv vvvvvvvvv, vv vvv vvv vvvvvv vv vvv vvvv v,
vvvvvv
![Page 33: Cognitive disorders unit 9](https://reader035.vdocuments.site/reader035/viewer/2022062319/556383b3d8b42ad2128b473a/html5/thumbnails/33.jpg)
Acetylcholinesterase Inhibitors Galantamine Newer agent Galantamine has shown modest benefit
in patients with a clinical diagnosis of eithervascular dementia or combination of AD and CVA
Dose: 4 4Initial: mg twice a day for weeks 8If mg per day tolerated vv v vv vvvvv , 8
vv v v vvvvv >=4 16If mg per day tolerated 12, increase to mg
vvvvvv vvvvv; : - 1624 2mg/day in dividev vvvvv
![Page 34: Cognitive disorders unit 9](https://reader035.vdocuments.site/reader035/viewer/2022062319/556383b3d8b42ad2128b473a/html5/thumbnails/34.jpg)
Acetylcholinesterase Inhibitors Galantamine PHARMACODYNAMICS /
KINETICS Absorption: Rapid and complete Distribution: 1.8-2.6 L/kg; levels in
the brain are 2-3 times higher than in plasma Protein binding: 18%
![Page 35: Cognitive disorders unit 9](https://reader035.vdocuments.site/reader035/viewer/2022062319/556383b3d8b42ad2128b473a/html5/thumbnails/35.jpg)
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
![Page 36: Cognitive disorders unit 9](https://reader035.vdocuments.site/reader035/viewer/2022062319/556383b3d8b42ad2128b473a/html5/thumbnails/36.jpg)
Acetylcholinesterase Inhibitors Galantamine PHARMACODYNAMICS /
KINETICS Bioavailability: 80% to 100% Half-life elimination: 6-8 hours Time to peak: 1 hour Excretion: Urine (25%)
![Page 37: Cognitive disorders unit 9](https://reader035.vdocuments.site/reader035/viewer/2022062319/556383b3d8b42ad2128b473a/html5/thumbnails/37.jpg)
Acetylcholinesterase Inhibitors Galantamine Significant Adverse Reactions in>10%
6 24Gastrointestinal: Nausea ( % to %) (4% 13%), (6% 12%)
Significant Adverse reactions in 1-10% Cardiovascular: Bradycardia (2 % to 3 %),
- syncope (0 .4 % to 2 .2 %: dose related), chest p ai n
(>or=1%) Central nervous system: Dizziness (9 %),
headache (8%), depression (7%), fatigue (5%), insomnia (5 %), somnolence (4 %), tremor (3 %)
![Page 38: Cognitive disorders unit 9](https://reader035.vdocuments.site/reader035/viewer/2022062319/556383b3d8b42ad2128b473a/html5/thumbnails/38.jpg)
Acetylcholinesterase Inhibitors Galantamine ADVERSE REACTIONS SIGNIFICANT <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
![Page 39: Cognitive disorders unit 9](https://reader035.vdocuments.site/reader035/viewer/2022062319/556383b3d8b42ad2128b473a/html5/thumbnails/39.jpg)
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