Pharm - Cognitive Disorders Flashcards
Alzheimer’s Dementia
• May start with mitochondria dysfunction, the change in ATP causes an excessive phosphorylation of the tau protein. Accumulation of Amyloid Beta. The amyloid plaques accumulate and cause an activation of microglia and subsequent release of pro-inflammatory cytokines. The cytokine and inflammatory response causes the death of neuron.
Alzheimer’s Dementia
Agitation / aggression
Atypical anti psychotic drugs (risperidone, lanzepine, quetiapine
Alzheimer’s Dementia
Depression
SSRIs (sertraline, fluoxetine) preferred Tricyclic antidepressants (use with caution)(nortryptyline, tryptyline)
Alzheimer’s Dementia
Psychosis
Hallucinations
Quetiapine, olanzepine, risperidone
Delusions
Atypical anti psychotic drugs
Haloperidol
Haloperidol – a typical antipsychotic, high profile of pyramidal side effects
akinesia
Alzheimer’s Dementia
Sleep disorders
Treated with H1 blockers (promethazine) Sedatives, promethazine etc
Alzheimer’s Dementia
Dimentia
Cholinesterase inhibitors (increase ACh, boosting cholinergic transmission) ONLY MILD TO MODERATE DEMENTIA
Donepezil,(must cross BBB)
Well tolerated
Relatively lower affinity for peripheral cholinesterase
Long plasma T ½ (once a day dosing)
Improves cognition
Cholinergic side effects may appear (diarrhea, nausea and vomiting
Rivastigmine
Effective in patients with mild to moderate AD
Toxicity: Significant nausea vomiting, head aches, anorexia
Must be administered with food
Galatamine Slows the decline in cognition Improves quality of daily activity GI disturbances (anorexia, vomiting nausea diarrhea and weight loss) Effective in mild to moderate AD
Frontotemporal Dementia (FTD)
Focal degeneration of the temporal and frontal lobes
Prevalence: 50 to 60 years,
Abnormalities with 5HT and Dopamine, cholinergic system conserved
Characterize by changes in personality, social behavior or language, progressing to global dementia affecting cognitive domains
Some patients may show extrapyramidal or motor neuron involvement
Abnormal tau or pathologic TDP43 protein aggregation
Frontotemporal Dementia
Treatment
SSRI
sertraline, paroxetine, and fluvoxamine improve anxiety, eating disorders and impulsive repetitive behavior
Anti psychotic agents (only as a last resort)
Atypical anti psychotic agents at low doses
Quetiapine, olanzepine and aripiprazole
Cholinesterase inhibitors (not effective in FTD). Why? The Cholinergic system is spared
Would drugs such as Bapineuzumab (Aβ antibody) be effective in FTD? Why or why not? No because there is no development of amyloid plaque
Lewy Body Dementia
Clinical manifestation
Visual hallucinations
Parkinsonism, Cognitive fluctuations, Dystonia
Sleep disorders, Neuroleptic sensitivity
Lewy Body Dementia
Treatment
Cholinesterase inhibitors
Rivastigmine, donpenzil, galatamine
Atypical anti psychotic drugs
Anti Parkinson’s drugs
Others: REM sleep disorders (Clonzepam, quetiapine)
Vascular Dementia
2nd only to Alzheimer
Characteristics
Large artery infarcts (cortical & sub cortical locations)
Small artery infarctions (exclusively sub cortical esp. to basal ganglia, caudate, thalamus internal capsule)
Chronic ischemia in the periventricular areas
Risk factors: Diabetes, disorders of lipid metabolism
Treatment of dementia
Rivastigmine
Donepezil
Galantamine
Memantine
Treatment of Delirium
Antipsychotics
Benzodiazepines
The most direct cognitive disorders include:
Amnesia
Dementia
Delirium
Attention-deficit/hyperactivity disorder (ADHD)
(Clinical) Manifestations
Inattention, hyperactive, impulsive behavior, seemingly in constant motion
Easily distracted, excessively talkative
Blame it on the mother risk factors:
Risk factors
Maternal drug use during pregnancy (alcohol, smoking)
Premature birth, genetics
Maternal exposure to environmental toxins e.g. poly chlorinated biphenyls (PCPs)
Treatment of ADHD
methylphenidate, dextroamphetamine, lisdexamfetamine
Methylphenidate
Treatment of ADHD
Mechanism of action: acts on the brain stem arousal system, inhibits reuptake of norepinephrine and dopamine
Clinical applications: Effective for management of attention deficit hyperactivity disorder
Adverse effects: May cause weight loss, decrease appetite, insomnia, addiction and
- mania
Treatment of ADHD
Dextroamphetamine and lisdexamfetamine
Mechanism of action: sympathomimetic, increase norepinephrine and dopamine transmission in the brain.
Clinical applications: ADHD and narcolepsy
Adverse effects : may cause myocardial infarct, tachycardia, sudden cardiac arrest, seizures, anaphylaxis etc
Treatment of ADHD
Atomoxetine:
selective norepinephrine (NE) reuptake inhibitor only, may increase transmission at NE synapses in the brain Indicated for management of ADHD May prolong QT interval, seizures, priapism, sudden cardiac death, angioedema etc
Treatment of ADHD
Desipramine
block reuptake of norepinephrine and serotonin in the brain
Used for the management of depression and ADHD in children
May cause fatigue, dizziness, somnolence, cardiac complications (including sudden cardiac arrest, myocardial infarction)
Neuroleptic malignant syndrome has been reported, suicidal thoughts, hepatitis and jaundice
Treatment of ADHD
Clonidine and guanfacine
Clonidine and guanfacine: centrally-acting 2 adrenergic receptor agonist
Clinical applications: used for management of ADHD adjuncted with other treatment options
May cause bradyarrhythmias, peeling of skin (guanfacine), atrioventricular block (clonidine), xerostomia, somnolence (clonidine)
Treatment of ADHD
Bupropion
Bupropion: weakly inhibits neuronal reuptake of norepinephrine and dopamine (but not serotonin reuptake)
Clinical uses: smoking cessation assistance, bipolar disorders, and ADHD
May cause agitation, arthralgia, arrhythmias, xerostomia, suicidal thoughts, mania and Stevens-Johnson syndrome
Delirium
Definition
Acute, transient fluctuating disturbances in attention, and consciousness level
Causes
Drugs (#1 alcohol abuse), anti emetic, anti histamines, anti cholinergic, psychoactive drugs and opioids)
Idiopathic in about 10 to 20% of patient
Encephalitis, meningitis, thiamin or vitamin B12 deficiency
Withdrawal syndromes: alcohol, barbiturates and opioids
Delirium Treatment
Remove aggravating factors (e.g. stopping drug, treating infection)
Maintain a well lit, stable and quiet with visual cues for patient orientation e.g. clocks, calendar family photos etc
Haloperidol to decrease agitation and improve psychotic symptoms
Risperidone , olanzapine (fewer extrapyramidal adverse effect)
Lorazepam may also be used (tranquilizer that brings down aggitation)
