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. Delirium vs. Dementia
 Delirium
 4 causal subcategories
 General medical condition
 Substance induced
 Cocaine, opioids, PCP
 Multiple causes
 Trauma, Kidney disease
 Other
 Lack of sleep

4. Cognitive DIsorders
 Delirium
 Fluctuating cognitive impairment and disturbance
of consciousness
 Psychosis and Insomnia

5. 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

6. 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

7. 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.

8. Treatment
 Insomnia
 Best treated with benzodiazepines with short or
intermediate half-lives
 Lorazepam (Ativan) 1 to 2 mg at bedtime

9. Dementia
 Progressive impairment of cognitive function
in clear consciousness (in the absence of
delirium)

10. Dementia
 The treatment for dementia is aimed at :
 Symptomatic treatment of memory disturbance
 Symptomatic treatment of memory disturbance

11. 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

12. 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

13. 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.

14. 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.

15. 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.

16. 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
 Can improve cognitive functions in patients
diagnosed with:
 Alzheimer’s disease
 Vascular dementia and
 Diffuse Lewy body disease

19. Acetylcholinesterase
Inhibitors
 Donezepil
 Rivastigmine
 Galantamine
 Tacrine
 Used very rarely due to its hepatotoxicity

20. 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

21. 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

22. 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)

23. 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

24. 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

25. Acetylcholinesterase
Inhibitors
 Significant Adverse Reactions in <1%
 Cholecystitis, CHF, delusions,
dysarthria,
 dysphasia, dyspnea, eosinophilia,
hallucinations,
 heart block, hemolytic anemia,
hyponatremia,
 intracranial hemorrhage, neuroleptic
malignant
 syndrome, pancreatitis, paresthesia, rash,
seizures,
 thrombocytopenia

26. Acetylcholinesterase
Inhibitors
 Contraindication
Hypersensitivity to donepezil, piperidine
derivatives, or any component of the
formulation

27. Acetylcholinesterase
Inhibitors
 Rivastigmine
 Dose: 1.5mg oral BID with titration every
 2 weeks up to 6mg BID

28. Acetylcholinesterase
Inhibitors
 Rivastigmine
 PHARMACODYNAMICS / KINETICS
 Absorption: Fasting: Rapid and complete
within
 1 hour
 Distribution: Vd: 1.8-2.7 L/kg
 Protein binding: 40%

29. Acetylcholinesterase
Inhibitors
 Rivastigmine
 PHARMACODYNAMICS / KINETICS
 Metabolism: Extensively via
cholinesterase-
 mediated hydrolysis in the brain;
metabolite
 undergoes N-demethylation and/or sulfate
 conjugation hepatically

30. 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%)

31. Acetylcholinesterase
Inhibitors
 Rivastigmine
 Significant Adverse Reactions in >10%
 Central nervous system: Dizziness (21%)
 headache (17%)
 Gastrointestinal: Nausea (47%), vomiting
 (31%), diarrhea (19%), anorexia (17%)
 abdominal pain (13%)

32. Acetylcholinesterase
Inhibitors
 Rivastigmine
 Significant Adverse Reactions in 2-10%
 Central nervous system: Fatigue (9%),
 insomnia (9%), confusion (8%), depression (6%),
 anxiety (5%), malaise (5%), somnolence (5%),
 hallucinations (4%), aggressiveness (3%)
 Cardiovascular: Syncope (3%), hypertension
 (3%)
 Gastrointestinal: Dyspepsia (9%),
 constipation (5%), flatulence (4%), weight loss
(3%)

33. Acetylcholinesterase
Inhibitors
 Rivastigmine
 Significant Adverse Reactions in 2-10%
cont.
 Genitourinary: Urinary tract infection (7%)
 Neuromuscular & skeletal: Weakness (6%),
 tremor (4%)
 Respiratory: Rhinitis (4%)
 Miscellaneous: Increased diaphoresis (4%),
 flu-like syndrome (3%)

34. Acetylcholinesterase
Inhibitors
 Rivastigmine
 Contraindication
 Hypersensitivity to rivastigmine, other carbamate
 derivatives, or any component of the formulation

35. 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

36. 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%

37. 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

38. Acetylcholinesterase
Inhibitors
 Galantamine
 PHARMACODYNAMICS / KINETICS
 Bioavailability: 80% to 100%
 Half-life elimination: 6-8 hours
 Time to peak: 1 hour
 Excretion: Urine (25%)

39. 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%)

40. 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

41. 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