Cognitivedisorders unit 9 2
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Cognitivedisorders unit 9 2






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Cognitivedisorders unit 9 2 Cognitivedisorders unit 9 2 Presentation Transcript

  • 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
  • Delirium vs. Dementia Delirium  4 causal subcategories  General medical condition  Substance induced  Cocaine, opioids, PCP  Multiple causes  Trauma, Kidney disease  Other  Lack of sleep
  • 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 (Ativan) 1 to 2 mg at bedtime
  • Dementia Progressive impairment of cognitive function in clear consciousness (in the absence of delirium)
  • 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 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
  • AcetylcholinesteraseInhibitors 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
  • AcetylcholinesteraseInhibitors Contraindication Hypersensitivity to donepezil, piperidine derivatives, or any component of the formulation
  • AcetylcholinesteraseInhibitors Rivastigmine  Dose: 1.5mg oral BID with titration every  2 weeks up to 6mg BID
  • AcetylcholinesteraseInhibitors Rivastigmine PHARMACODYNAMICS / KINETICS Absorption: Fasting: Rapid and complete within 1 hour Distribution: Vd: 1.8-2.7 L/kg Protein binding: 40%
  • AcetylcholinesteraseInhibitors Rivastigmine PHARMACODYNAMICS / KINETICS Metabolism: Extensively via cholinesterase- mediated hydrolysis in the brain; metabolite undergoes N-demethylation and/or sulfate conjugation hepatically
  • AcetylcholinesteraseInhibitors Rivastigmine PHARMACODYNAMICS / KINETICS Bioavailability: 40% Half-life elimination: 1.5 hours Time to peak: 1 hour Excretion: Urine (97% as metabolites); feces (0.4%)
  • AcetylcholinesteraseInhibitors 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%)
  • AcetylcholinesteraseInhibitors 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%)
  • AcetylcholinesteraseInhibitors 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%)
  • 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