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
Cognitive DIsorders Delirium Fluctuating cognitive impairment and disturbance of consciousness Psychosis and Insomnia
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
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
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.
Treatment Insomnia Best treated with benzodiazepines with short or intermediate half-lives Lorazepam 1 to 2 mg at bedtime
Dementia The treatment for dementia is aimed at : Symptomatic treatment of memory disturbance Symptomatic treatment of memory disturbance
What are the common forms ofdementia? 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
How is Alzheimer’s disease Alzheimer’s disease may be characterized by a diffusecharacterised? 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
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.
Clinical features of vasculardementia 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.
Clinical features of vasculardementia 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.
Clinical features of Dementia withLewy 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)
AcetylcholinesteraseInhibitors Can improve cognitive functions in patients diagnosed with: Alzheimer’s disease Vascular dementia and Diffuse Lewy body disease
AcetylcholinesteraseInhibitors Donezepil Rivastigmine Galantamine Tacrine Used very rarely due to its hepatotoxicity
AcetylcholinesteraseInhibitors 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
AcetylcholinesteraseInhibitors 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
AcetylcholinesteraseInhibitors 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)
AcetylcholinesteraseInhibitors 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
AcetylcholinesteraseInhibitors Rivastigmine Contraindication Hypersensitivity to rivastigmine, other carbamate derivatives, or any component of the formulation
AcetylcholinesteraseInhibitors 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
AcetylcholinesteraseInhibitors 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%
AcetylcholinesteraseInhibitors 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
AcetylcholinesteraseInhibitors Galantamine PHARMACODYNAMICS / KINETICS Bioavailability: 80% to 100% Half-life elimination: 6-8 hours Time to peak: 1 hour Excretion: Urine (25%)
AcetylcholinesteraseInhibitors 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%)
AcetylcholinesteraseInhibitors 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
Symptomatic Treatment of BehavioralDisturbance in Dementia Patients Delusions and hallucinations: rivastigmine, risperidol, quetiapine Depression: citalopram, fluoxetine>> TCA Agression and anxiety: trazodone, carbamazepine, valproate, gabapentin