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Cognitive Disorders Dementia, Delirium and Psychotic Disorders Dementia Progressive and degenerative CNS disorder Nearly 50% of persons >85 years old have some form of dementia Rates increasing as population ages Several types ◦ Alzheimer’s (most common type, may be a genetic disease ◦ Vascular ◦ General medical condition (e.g. Parkinson’s) ◦ Substances (e.g. alcohol) ◦ HIV/AIDS related ◦ Mixed or Unknown Memory Impairment of Dementia Difficulty learning new information Forgetting learned information Spatial disorientation Poor judgment Disinhibition Poor insight Potential for violence Loss of motor skills Possible mood and sleep disturbances Sometimes psychotic (delusional or hallucinatory) experiences especially paranoia Potentially Reversible Dementias Toxic Causes Alcohol, Polypharmacy, Illicit drugs Electrolyte Disturbances K+ loss, hepatic disease Nutritional Causes Prolonged neglect, B12 deficiency, malabsorption syndrome, starvation Infections Respiratory infections, TB Metabolic Hypothyroidism, Pituitary insufficiency Cerebral Disease Brain tumor, multiple cerebral emboli, hydrocephalus Alzheimer’s Dementia 60%-80% of cases of dementia are Alzheimer’s type dementia (AD) >5.3 million people in the US have AD Characterized by the presence of amyloid plaques on autopsy ◦ Mental deterioration is related to amount of plaque formation Plaques interfere with cell-to-cell communication Plaques cause neurofibrillary tangles that collapse microtubules Result is a reduced availability of the neurotransmitter ACh (acetylcholine) which is associated with memory and learning Amyloid Plaques (in rabbit cells) Neurofibrillary Tangles Lewy Body Dementia Discovered by Frederic Lewy in 1913 Often seen in late Parkinson’s disease Characterized by additional neuronal lesions (colored cells) that are found in the substantia nigra – an area that controls unconscious muscle activity Onset of dementia is early – around age 60 years! 20%-25% of cases have Lewy bodies present on autopsy Lewy Body Cells Vascular Dementia 15-20% of all cases are vascular dementia Formerly called multi-infarct dementia Caused by multiple cerebrovascular accidents (CVAs), or ‘strokes’ Vascular Dementia Frontotemporal Lobar Dementia Formerly called Pick’s Disease 10% of dementia cases are FTLD Affects the frontal and temporal lobes Causes changes in personality, social skills, and emotions, behavior disinhibition, and language abnormalities Frontotemporal Lobe Dementia Prion (Creutzfeldt-Jakob) Disease Rare disorder caused by spongiform encephalopathy as a result of prions Prions are infectious proteins found in the CNS of certain animals (cattle, deer) but also from corneal transplants & human growth hormone Starts with confusion, depression and progresses in weeks or months to dementia, ataxia, palsy (involuntary jerky movements) and sometimes blindness Occurs in 1per 1-million persons Creutzfeldt-Jacob Disease Down’s Syndrome Related Dementia Down’s syndrome is 3 copies of chromosome 21 (trisomy 21) Extensive amyloid lesions found on autopsy Early onset - 50% of persons with Down’s syndrome have dementia symptoms onset around age 40 Dementia is difficult to diagnose if IQ is substantially low to start with AIDS-related Dementia HIV infection causes damage to neurons involved with judgment, language, memory, motor function and socialization Occurs in 40-60% of persons with HIV if no treatment is provided* Minor cognitive motor disorder associated with HIV is more common (15-30%) http://aids.gov/hiv-aids-basics/staying-healthy-with-hivaids/potential-related-health-problems/dementia/ Pharmacology: Drugs for Alzheimer’s Disease Pathophysiology of Alzheimer’s Dementia Disorder Degeneration of the cholinergic neuron Deficiency in ACh (Acetylcholine) Plaque formation outside of neurons and in the cerebral cortex Beta-amyloid protein accumulation Presence of neurofibrillary tangles with twists inside the neurons Some inflammatory (cytokine) response Acetylcholinesterase Inhibitors “esterase” indicates an enzyme reaction that breaks down a molecule Acetylcholine – esterase refers to the breakdown of Ach Inhibitors of ACh-esterase means that the breakdown of ACh is blocked or reduced thus leading to higher ACh levels AChE-inhibitors are the primary drugs to treat Alzheimer’s dementia (not effective in vascular dementia) Primary ACh-E Inhibitors PROTOTYPE: Aricept (donepezil) ◦ Most commonly prescribed drug, once daily Exelon (rivastigmine) ◦ Available in a topical skin patch Glanatamine (Razadyne) ◦ Derived naturally from daffodil bulbs These drugs work by increasing ACh levels in the neuron receptors. They are most effective in mild to moderate Alzheimer’s as they slow cognitive deterioration. They do not stop the disease. Side & Advers Effects of ACh-E Inhibitors Side effects: GI - Nausea and diarrhea occur in approximately 10% of clients Administer with or without food. Adverse effects: Bradycardia • Teach the family to monitor pulse rate for the client who lives at home. The client should be screened for underlying heart disease. Contraindications/precautions Should be used with caution in clients with preexisting asthma or other obstructive pulmonary disorders as bronchoconstriction may be caused by an increase of acetylcholine. NMDA Receptor Antagonist (Glutamate receptor blockade) Glutamate is an excitatory neurotransmitter. Excessive glutamate is toxic to the brain and causes cell death. One drug, memantine (Namenda) blocks excess glutamate by blocking the entry of calcium into nerve cells, thus slowing down brain-cell death. Namenda is approved in moderate to severe Alzheimer’s disease and can (perhaps should) be taken along with ACh-E inhibitors. Side Effects of memantine (Namenda) Dizziness Headache Confusion Excitability/emotional lability Constipation Contraindications/precautions Memantine (Namenda) should not be used in patients with renal disease Alternative or Complementary Treatments Gingko biloba is a plant that is thought to improve memory. ◦ Gingko biloba may increase risk for bleeding and have an additive effect with anticoagulants, and it may increase the risk for seizures in susceptible patients. Antioxidants may be helpful due to their anti-inflammatory effects (e.g. Omega 3 fatty acids “fish oil”). Delirium Acute state of confusion and memory loss Develops rapidly Fluctuating course Occurs in 10%-30% of hospitalized persons Reversible Causes ◦ Medical condition (e.g. infection, head injury) ◦ Substance (e.g. opioids, other Rx meds, illicit drugs) ◦ Unknown Risk factors: age, visual/hearing deficits, illness Example: Delirium tremens in alcohol withdrawal Delirium Delirium may or may not have memory loss The individually is often agitated and frightened Disorientation to place, time, even self May have hallucinations and delusions Delirium constitutes a major safety risk for hospitalized patients Depending on the underlying cause, delirium may be life-threatening Schizophrenia & Other Psychotic Disorders History & Etiology of Schizophrenia 1800’s – described as dementia praecox Bleuler coined the term schizophrenia, meaning “to split”, and “the mind” Not to be confused with multiple personality disorder (now called dissociative identity disorder) Occurs in 1% (1:100) of the population <age 12 is rare (1:40,000) Onset generally in late adolescence/early adulthood Accounts for up to 50% of mental health care costs Chronic disabling condition Phases of Schizophrenia Acute Phase During this time, symptoms are prominent and disabling and hospitalization may be required Recovery & Maintenance Phase Symptoms may be present but are less intense and clients may live independently Stable (Residual) Phase Symptoms are in remission or are mild & chronic 1-2 years may elapse from the onset of symptoms to first medical treatment Other Psychotic Disorders Schizoaffective disorder - a chronic condition where a thinking disorder exists alongside a mood disorder such as bipolar or major depression. Each must be treated individually. Substance-induced psychotic disorder - psychosis clearly related to a substance, drug or medication. Cannot diagnose schizophrenia until substance use is ruled out. Psychotic disorder due to a medical condition – psychosis from Pick’s disease, renal failure, dementia, fever, hypoxia, hypothyroidism, etc. (any medical cause). Schizophrenia cannot be diagnosed until all medical causes are ruled out. Classification of Symptoms Positive Also called psychotic, or florid, symptoms False perceptions (hallucinations) False beliefs (delusions) Bizarre (odd or eccentric) behavior Agitation Confused or obsessive thoughts Disorganized thoughts Positive symptoms tend to respond to dopamine blocking medications called antipsychotics Classification of Symptoms Negative Apathy or indifference to others Avolition – lack of motivation Blunted or flat emotional affect Loss of warmth or vibrancy in life Poverty of thoughts – reduced thought variety Alogia – poverty of speech Anhedonia – loss of pleasure in things Anergia – lack of energy Negative symptoms are hard to treat but may respond some to serotonin based medications. These symptoms cause most of the disability of the disease. Schizophrenia Simulator Anderson Cooper experiences simulated auditory hallucinations: https://www.youtube.com/watch?v=yL9UJ VtgPZY Pharmacology: Antipsychotic Medications Antipsychotic Medications are Dopamine Antagonists Block the activity of dopamine. Dopamine has 5 subtypes (D1-D5) D2 blockade results in motor (muscle) impairment in the extra-pyramidal (motor) part of the brain. This results in a side effect called extra-pyramidal syndrome (EPS), or pseudo-Parkinsonism. Newer antipsychotics are weaker at D2 and stronger at D4, and they also enhance serotonin (5HT) levels similarly to an antidepressant. These reduces side effects and improves negative symptoms of schizophrenia. Conventional Antipsychotics Conventional antipsychotics are used to treat mainly positive psychotic symptoms. They are potent D2 blocking agents and thus are high in neuromuscular side effects. Chlorpromazine(Thorazine) – 1st one ever developed PROTOTYE: Haloperidol (Haldol) New-Generation (Atypical) Antipsychotics Atypical antipsychotics are current preferred medications for psychotic disorders. They generally treat both positive and negative symptoms. Clozapine (Clozaril) 1st one on the market Olanzapine (Zyprexa) Quetiapine (Seroquel) Asenapine (Saphris) Risperidone (Risperdal) Ziprasidone (Geodon) Lurasidone (Latuda) Iloperidone (Fanapt) Paliperidone (Invega) • Aripiprazole (Abilify) Side effects of all Antipsychotics Dopaminergic Histaminergic Muscarinic (Cholinergic) • Extra-pyramidal syndrome (EPS) ~ 11% • Acute skeletal muscle dystonia • Tardive dyskinesia • Akathisia • Neuroleptic Malignant Syndrome (rare but life threatening) • Hyperprolactinemia • Hyperlipidemia • Dry mouth • Sedation • Constipation • Weight gain that • Urinary may be hesitancy associated with the onset of Type II Diabetes Alpha-adrenergic • Orthostatic hypotension The most common side effects for all antipsychotics are dry mouth, constipation, increased appetite, sedation and tremors. Dopaminergic Adverse Events EPS – tremors and sxs similar to Parkinson’s disease. Easily treated with medications. • Acute Dystonia – involuntary contractions of muscles. Treated with PRN medications including injections. • Tardive Dyskinesia – slow, sometimes writhing movements of the muscles. Often around the face, head, neck or trunk. Often irreversible and not responsive to medication treatment. • Akathisia – persistent need to get up and move, stretch, walk around, rock. Difficult to treat and associated with higher suicide completion rates. • Neuroleptic Malignant Syndrome (rare but lifethreatening) – severe hyperthermia, decreased level of consciousness, and hypertension associated with skeletal muscle breakdown. • Drug-Induced Movement Disorders Clinical Example of Tardive Dyskinesia caused by an antipsychotic: https://www.youtube.com/watch?v=BJjXqKa4 cbE Treatment of Dopaminergic Effects EPS and Acute Dystonias respond very well to the use of anticholinergic medications: Benztropine (Cogentin) – PO or IM Trihexyphenidyl (Artane) – PO Amantadine (Symmetrel) - PO Diphenhydramine (Benadryl) – PO, IM or IV • Some studies on the use of mega-doses of Vitamin E for reducing or preventing tardive dyskinesia (800-1600 IU daily) • Akathisia is treated by reducing or changing the antipsychotic or using: -Propanolol (Inderal) -Any of the Benzodiazepines for palliative relief • Hyperprolactinemia • • Dopamine blockage can affect prolactin levels excreted by the pituitary gland resulting in a drug-induced hyperprolactinemia Signs of hyperprolactinemia: • Breast enlargement • Galactorrhea (breast milk production and secretion) • Decreased menstruation • • Patients who present with these symptoms and are not pregnant, should have a prolactin level drawn. Some clinicians will also do an MRI to rule-out pituitary gland tumor (either cancerous or benign). Histaminergic Side Effects Of increasing concern are Medication side effects related to histamine effects: • Increased appetite • Weight gain Metabolic • Hyperlipidemia Syndrome • Sedation, or tiredness These side effects predispose the patient to obesity, Type II DM, hypertension and heart disease. Patients with chronic mental illnesses die an average of 25-years earlier than the general population. Other Antipsychotic Side Effects • All antipsychotics can lower seizure threshold and increase risk for seizure activity. • Clozapine (Clozaril) is associated with significant drops in Absolute Neutrophil Counts (a WBC) allowing opportunistic infections that may be lethal. WBC/ANC monitoring is required with this drug: • Weekly for 6 month; then, • Biweekly for 6 months; then, • Monthly for life COURSE EVALUATIONS Please take the next 20-30 minutes to complete your evaluations of all of your 4th semester of nursing courses.