acetylcholinesterase ( AchE)
enzyme that causes the inactivation of ACh present on the postsynaptic membrane or immediately outside of the membrane with its active site facing the synaptic cleft hydrolyzes acetylcholine into acetate and choline, which can then reenter the presynaptic axon terminals and be resynthesized into acetylcholine
Alzheimer's disease (AD)
A progressive disease that destroys the brain's neurons, gradually impairing memory, thinking, language, and other cognitive functions, resulting in the complete inability to care for oneself; the most common form of dementia.
A structural change in the cerebral cortex associated with Alzheimer's Disease, in which dense deposits of a deteriorated protein called amyloid develop, surrounded by clumps of dead nerve and glial cells
slowness of voluntary movement and speech
a region in the brain that controls unconscious muscle movement
a slowly progressive decline in mental abilities, including memory, thinking, and judgment, that is often accompanied by personality changes
a complex neural structure (shaped like a sea horse) consisting of gray matter and located on the floor of each lateral ventricle
multiple sclerosis (MS)
disease of the central nervous system characterized by the demyelination (deterioration of the myelin sheath) of nerve fibers, with episodes of neurological dysfunction (exacerbation) followed by recovery (remission)
a dying neuron containing intracellular accumulations of beta-amyloid and twisted protein filaments that formerly served as the cell's internal skeleton
*a degenerative disorder of the central nervous system characterized by tremor and impaired muscular coordination
*Chronic neurological disorder affects extrapyramidal motor tract (controls posture, balance, and locomotion)
*It is known as a Syndrome because it is a combination of symptoms
primary- progressive MS
One of the four recognized forms of Multiple Sclerosis named for gradual advance of the disease from onset and with no superimposed relapses (new or resurfacing symptoms) and remissions (periods of recovery).
progressive- relapsing MS
One of the four recognized forms of Multiple Sclerosis named for gradual advance of the disease; there is significant recovery immediately following a relapse, but there is a gradual worsening of symptoms.
relapse- remitting MS
One of the four recognized forms of Multiple Sclerosis named whenever new symptoms appear or when they resurface or worsen (relapse); the patient then partially or fully recovers from the acquired deficits (remitting).
secondary- progressive MS
One of the four recognized forms of Multiple Sclerosis named for gradual advance of the disease; superimposed relapses (new or resurfacing symptoms) and remissions (periods of recovery) may occur, but they tend to tail off over time.
a layer of deeply pigmented gray matter in the midbrain
Ex. associated with the striate body; is involved in metabolic disturbances associated with Parkinson's disease and with Huntington's disease
Degenerative Diseases of CNS
Common debilitating and progressive conditions:
*Parkinson's disease: muscle tremor, rigidity, movement disorder
*Alzheimer's disease: progressive loss of brain function, mostly older adults
*Multiple Sclerosis: progressive weakness
Characteristics of Neurological Degenerative Diseases
*Etiology typically unknown
*Most progress from very subtle symptoms early in disease to profound neurologic, cognitive, or sensory and/or motor deficits
*Medications cannot stop or reverse the progressive nature of the disease, but may offer some relief from symptoms
Parkinson's Disease Overview
*Cause: death of neurons that produce the neurotransmitter Dopamine (inhibitory)
*Second most common degenerative disease of the nervous system
*Affects more than 1.5 million Americans
*Typically patients are over 50 years old, but can develop in teenagers
*Slightly more men than women
*Progressive, may take years for expression of full symptoms to develop
*Medications reduce some of the symptoms
Parkinson's Disease Major Features
1. Tremors: head and hands develop shaking at rest; pill rolling - rubbing thumb and forefinger together
2. Muscle Rigidity: abnormal increased muscle tone causing rigidity that increases with movement; difficulty bending over or moving limbs progressive over course of disease
3. Bradykinesia: slow movement; difficulty chewing, swallowing or speaking; shuffling walk
4. Postural instability: slightly humped over and easily loose their balance causing frequent falls
5. Affective flattening: masked facial appearance with little facial expression or blinking of the eyelids
Associated Health Problems/Cause of Parkinson Disease
Autonomic Nervous System (Involuntary) Problems
Sexual performance problems
Possible Causes: Possible genetic link
Trauma, infection, CVA
Symptom Development of Parkinson Disease
(do not need to know the details)
Symptoms result from degeneration and destruction of Dopamine producing neurons in the substantia nigra of the brain; neurons in this region supply Dopamine to the corpus striatum in the brain that controls unconscious muscle movement
Balance, posture, muscle tone, and involuntary muscle movement depend on a balance of Dopamine (inhibitory) and Acetylcholine (excitatory) neurotransmitters. When Dopamine is lost balance is lost causing development of Parkinson symptoms.
Medications: focus is restoring Dopamine and blocking Acetylcholine
Extrapyramidal Side Effects (EPS)
*Parkinson's-like symptoms d/t typical anti-psychotics
*Develop for the same neurochemical reasons as Parkinson's disease.
*Antipsychotic medications act by blocking dopamine receptors that results in a loss of the balance between Dopamine and Acetylcholine resulting in the symptoms
*May develop suddenly and can be a medical emergency - muscle spasms or muscles "locking up" causing it to become fatal, but typically the
*Goal: restore balance of Dopamine and Acetylcholine in specific regions of the brain
Dopaminergic medications - increase Dopamine levels
Anticholinergic medications (Cholinergic blockers) - cholinergic medications act like Acetylcholine so blocking has opposite
Dopaminergic medications -
*increase Dopamine levels
*Treatment goal: increase patient's ability to perform their ADLs and improve quality of life
*Dopaminergic medications increase Dopamine levels in the corpus striatum
*Levodopa (Larodopa): medication of choice; it is a precursor of Dopamine synthesis
*Effectiveness is boosted by combining it Levodopa with medications like Carbidopa giving the medication - Sinemet
Anticholinergic medications (Cholinergic blockers) -
cholinergic medications act like Acetylcholine so blocking has opposite
Other Medications to Enhance Dopamine
(both names will be given on the test)
*Inhibit enzymes that destroy Levodopa and Dopamine: Tolcapone (Tasmar), Entacapone (Comtan), and Selegiline (Carbex, Eldepryl)
*Direct activation of Dopamine receptor (Dopamine agonist): Apomorphine (Apokyn), Bromocriptine (Parlodel), Pramipexole (Mirapex), and Ropinirole (Requip)
*Stimulate release of Dopamine from nerve terminals: Amantadine (Symmetrel)
*These medications are all adjuncts to therapy because they are not as effective as Levodopa
Medications for Parkinson's Disease
treat parkinsonism, relief of extrapyramidal, block the action of acetylcholine in the CNS to help normalize the acetylcholine-dopamine imbalance -(excreted by cellular pathways)
*class of drugs that increases level of dopamine in substantia nigra, stimulate dopamine receptors in area, restore balance between inhibitory and stimulating neurons
*inhibits the enzyme dopa decarboxylase allowing levodopa to reach the brain
Stimulates dopamine receptoors and increases the effect of levodopa (for Parkinson's)
Inhibits breakdown of dopamine (MAO-B)
Does not inhibit MAO-A (metabolizes NE and serotonin)
Improves motor function in Parkinson's disease. Very limited use.
Reduce destruction of dopamine in the peripheral tissues, allowing more dopamine to reach the brain, Ex: entacapone which has no affect when used alone, must be taken with levadopa, blocks the action of an enzyme (catechol-O-methyltransferase, COMT) that breaks down levodopa
*Action: inhibit action of Acetylcholine (Excitatory); used early in the course of disease; blocking Acetylcholine inhibits over activity
*Centrally acting Anticholinergics not as effective as levodopa but result in fewer side effects
*Side Effects: Anticholinergic - dry mouth, blurred vision, tachycardia, urine retention, hypotension, and constipation
*Use: early in the disease when symptoms are less severe, in patients who cannot take Levodopa, or in combination with other anti- Parkinson medications
**Patient is having side effects of anticholinergic medications, what are they? What is the nurse looking for in symptoms?
blood pressure drop
*Medications: Trihexyphenidyl (Artane), benztropine (Cogentin), Biperiden (Akineton), Procyclidine (Kemadrin), Ethopropazine (Parsidol), and Orphenadrine (Norflex)
*Action: parasympatholytic (anticholinergic) and inhibit release of acetylcholine
*Use: Parkinsonism and drug induced parkinsonism
*SE/AR: dry mouth, blurred vision, drowsiness, muscle weakness, constipation, confusion
Contraindications: glaucoma, GI obstruction, severe ulcerative colitis, BPH, myasthenia gravis
*Avoid: alcohol and CNS depressants
HINT= lyse or litic = stop
*Devastating, progressive, degenerative disease generally begins after age 60 while by age 85 approximately 50% of the population may be affected
*Cause is unknown, familial disease is associated with gene defects of Chromosomes 1, 14, or 21
*Medication has limited success improving cognitive function of Alzheimer's patients
*Responsible for 70% of all dementia - degenerative disorder characterized by progressive memory loss, confusion, and inability to think or communicate effectively
*Known causes of dementia: multiple cerebral infarcts, severe infections, and toxins, but the cause of most cases are unknown
Structural Damage in Brain in Alzheimer's Disease
*Amyloid plaques (protein fragments in the brain accumulate to form hard, insoluble plaques)
*Neurofibrillary tangles (insoluble twisted protein fibers found inside the brain's cells)
Found in brains of almost all Alzheimer's patients; possibly as result of chronic inflammatory or oxidative cellular damage to surrounding neurons resulting in loss of function in number and function of neurons
Loose ability to perform tasks requiring
Symptoms of Alzheimer's Disease
*Impaired memory and judgment
Including forgetting to eat and take meds
*Confusion or disorientation
*Inability to recognize family or friends
*Psychoses including paranoia and delusions
Medications for Alzheimer's Disease
*Goal: slow memory loss and other progressive symptoms of dementia
*Some medications are given to treat associated symptoms i.e. depression, anxiety, or psychoses
*Acetylcholinesterase (enzyme that breaks down Acetylcholine) inhibitors; most widely used class
*Action: intensifying effect of Acetylcholine at the cholinergic receptor
(do not need the technical (action) will not go into that much depth)
*Parasympathomimetic: stimulate Parasympathetic Nervous System - rest and digest system
*Action: Acetylcholine naturally degraded by AChE (enzyme acetylcholinesterase); blocking AChE allows Acetylcholine levels to increase resulting in a strong effect on the receptor
*Goal: improve function in ADLs, behavior, and cognition; it slows the progression of the disease
Use: given early in the disease and ineffective later in the disease
*Side Effects: nausea, vomiting, and diarrhea; Tacrine -hepatotoxicity, Rivastigmine - weight loss
(do not need the drug class for this test)
Classification: N-methyl-D-aspartate (NMDA) receptor antagonist.
Action: reduces abnormally high levels of glutamate (may be responsible for brain cell death) by binding to the receptors
Use: moderate to severe Alzheimer's Disease
Side Effects: headache, dizziness, GI upset, constipation, hypertension, pain, somnolence, hallucination, dyspnea
Combination medication: Memantine and Acetylcholinesterase Inhibitor - Aricept
*Use: treatment of moderate to severe Alzheimer's Disease by enhancing effects of acetylcholine in neurons in cerebral cortex that have not been damaged
*Action: AchE inhibitor
*Dosage: Given once daily due to long half life; may take 6 months for maximum effect to be evaluated
*Side effects: vomiting, diarrhea, dark urine, insomnia, syncope, depression, headache, irritability, muscle cramps, arthritis, bone fractures, and blurred vision
*Contraindications: GI bleeding and jaundice
*Drug Interactions: several
*Start low and slowly increase dosage
*has a long half life
*takes 6 mos. to begin to work
*may cause insomnia due to forcing the brain to work harder/more...
Other possible treatments for Alzheimer Disease
Antioxidants (Vitamin E) investigated for use in oxidative cellular damage
Anti-inflammatory agents (COX-2) inhibitors
Additional treatments for Alzheimer Disease
(helps with other symptoms)
*Atypical antipsychotic medications: Risperidone and Olanzapine for treatment of agitation, delusions, paranoia, hallucinations, or other psychotic symptoms
*Conventional antipsychotics: Haloperidol for symptoms as above, but patient at risk for EPS side effects
*Antianxiolytics: Buspirone or some benzodiazepines for apprehension
*Mood Stabilizers: Sertraline, Citalopram, or Fluoxetine for major depression
(do not need to know definition)
*Chronic inflammatory, autoimmune disorder (prevalent in young adults) with antibodies slowly targeting and destroying the myelin sheath in CNS, and axonal membranes of nerve fibers in the brain and spinal cord causing progressive sensory and motor deficits.
*As axons are destroyed nerves cannot conduct electrical impulses resulting in inflammation and formation of multiple filamentous plaques called scleroses
*As disease progresses antibodies continue to attach with worsening of damage leading to eventual neuronal death
Etiology of MS
Possible theoretical causes
Genetic or microbial factors
Climate - more common in colder climates
Microscopic pathogens - viruses, but there is no strong evidence to support this theory
Signs and Symptoms of MS
*Associated with axonal injury, Slow onset with periods of remissions and exacerbations resulting from neuronal damage, course unpredictable, variety of symptoms depending on extent and localization of demyelination
*Neuropathic pain; spasticity
*Impaired cognitive ability
*Disruption of balance and coordination
*Visual disturbances; slurred speech
*Bowel and bladder symptoms
Medications for MS
*Medications do not cure the patient but provide relief for patients with recurring symptoms: relapse-remitting MS and secondary-progressive MS
*Medications slow progress and modify associated symptoms
*Immunomodulators - main medication, work by reducing severity and frequency of symptoms
For Relapse-remitting MS and Secondary-Progressive MS
1. Interferon beta (Avonex, Rebif, Bataseron) Injection
Reduce severity of symptoms and number of lesions
Side effects: flu like symptoms, anxiety, discomfort at injection site, and liver toxicity
2. Glatiramer acetate (Copaxone) Injection
Synthetic protein stimulates myelin basic protein that resembles myelin so it reduces body's attack on the myelin and decreases new brain lesions
Side effects: pain, redness, swelling, itching or lump at injection site, flushing, chest pain, weakness, infection,
*For Progressive-relapsing MS
*Mitoxantrone (Novantrone) Injection: FDA approved for patients who have not responded to interferon or glatiramer acetate
*Chemotherapeutic agent, more toxic
*Side Effects: reversible hair loss, GI discomfort, allergic symptoms, blue-green tint to urine
*Toxicity is concern - irreversible cardiac injury and potential harm to fetus
Treatment of MS- Phase Acute Attack
Characteristics: Fatigue, motor weakness, optic neuritis
Treatment Strategies: Tapering course of glucocorticoids (Predisone)
ACTH stimulates the adrenal cortex to secrete cortisol
6-alpha methylprednisonone sodium succinate (MP)
GOAL: to decrease inflammatory process
Treatment of MS-Phase Remission-Exacerbation
Characteristics: Recurrence of clinical MS symptoms, spasticity
Treatment Strategies: Biological (immune) response modifiers such as interferon-β, Glatiramer acetate
Goal is to reduce spasticity and improve muscle movement
Immunosuppressant drug therapy (Imuran)
Goal is to reduce exacerbations
Treatment of MS - Phase Chronic Progressive
Characteristics: Progressive MS symptoms (pt usually wheelchair bound)
Treatment Strategies: Immunosuppressant cyclophosphamide (Cytoxan), Mitoxantrone
Tapering doses of ACTH
Goal is to try to prevent further progression
Degenerative diseases of nervous system cause
progress loss of neuron function
Parkinson's disease symptoms -
tremors, muscle rigidity, and postural instability with ambulation difficulty caused by destruction of Dopamine producing neurons in the corpus striatum due to lack of Dopamine and over activity of Acetylcholine
Levodopa, drug of choice for
Parkinson's disease attempts to restore Dopamine levels in the corpus striatum
Centrally acting Anticholinergic medications occasionally used for
Parkinson's disease, but less effective
Alzheimer's disease -
progressive degenerative disease of older adults with symptoms of disorientation, confusion, and memory loss; 70% of dementia cases
Acetylcholinesterase inhibitors used to slow progression of but not cure
MS characterized by
progression of neurological dysfunction
Disease modifying medications slow progression of MS but
do not cure it
Degenerative diseases of the nervous system such as Parkinson's disease and Alzheimer's disease cause a progressive loss of
Parkinson's disease is characterized by symptoms of
tremors, muscle rigidity, and postural instability and ambulation caused by the destruction of dopamine- producing neurons found within the corpus striatum. The underlying biochemical problem is lack of dopamine activity and a related overactivity of acetylcholine.
The most commonly used medications for parkinsonism attempt to restore levels of
dopamine in the corpus striatum of the brain. Levodopa ( Larodopa) is the drug of choice for Parkinson's disease.
Centrally acting anticholinergic drugs are sometimes used to relieve symptoms of
parkinsonism, although they are less effective than levodopa ( Larodopa).
Alzheimer's disease is a progressive, degenerative disease of older adults. Primary symptoms include
disorientation, confusion, and memory loss.
Acetylcholinesterase inhibitors are used to slow the progression of
Alzheimer's disease symptoms. These agents have minimal efficacy, and do not cure the dementia.
MS patients often have recurrent episodes of neurologic dysfunction, which progress at a fairly rapid rate. Symptoms depend on
the extent and location of central demyelination.
Disease-modifying drugs slow the progression of MS and
modify associated symptoms. There is no cure for MS.
The family member caring for a patient with Parkinson's disease at home notifies the nurse that the patient is demonstrating a dramatic increase in extrapyramidal symptoms. The nurse should instruct the caregiver to:
1. give diphenhydramine ( Benadryl) 25 mg PO.
2. transport the patient to the emergency department.
3. increase the dosage of antiparkinsonism drugs.
4. make an appointment with the health care provider for evaluation.
Rationale: Extrapyramidal symptoms may be life threatening without intervention. The patient should be immediately transported to the emergency department. Diphenhydramine must be given parenterally for effective treatment. The drug dosage should not be increased, because symptoms may be-come worse. Cognitive Level: Analysis. Nursing Process: Im-plementation. Patient Need: Physiological Integrity.
The patient asks what can be expected from drug therapy for treatment of parkinsonism. What is the best response by the nurse?
1. A cure can be expected within 6 months. 2. Symptoms can be reduced and the ability to perform ADLs can be improved.
3. Disease progression will be stopped.
4. EPS will be prevented.
Rationale: Pharmacotherapy does not cure or stop the dis-ease process but does improve the patient's ability to per-form normal activities such as eating, bathing, and walking. Depending on the drug therapy, EPS may be an adverse ef-fect. Cognitive Level: Analysis. Nursing Process: Implemen-tation. Patient Need: Physiological Integrity.
Levodopa ( Larodopa) is prescribed for a patient with Parkinson's disease. At discharge, which of the following teaching points should the nurse implement?
1. Monitor blood pressure every 2 hours for the first 2 weeks.
2. Expect the urine color to be orange.
3. Report the development of diarrhea.
4. Keep scheduled lab appointments for liver and renal function tests.
Rationale: A decrease in kidney and liver function may slow the metabolism and excretion of the drug, leading to over-dose and toxicity. Levodopa does not cause the urine to turn orange. It is not reasonable for a patient to monitor his or her blood pressure every 2 hours during the first 2 weeks of therapy. Cognitive Level: Analysis. Nursing Process: Imple-mentation. Patient Need: Physiological Integrity.
The nurse discussed the disease process of multiple scle-rosis with the patient and caregiver. What does the nurse explain is the cause of AD?
1. The cause is unknown. Amyloid plaques and neurofibrillary tangles have been found in the brain at autopsy.
2. The cause is unknown. Many scars located throughout the brain have been found on MRI scans.
3. Loss of circulation to the brain has been found on MRI scans.
4. Loss of dopamine receptors is thought to occur as a part of the aging process.
Rationale: The cause is unknown; however, structural dam-age consisting of amyloid plaques and neurofibrillary tangles has been found within the brain at autopsy. Alzheimer's disease has not been associated with intracranial bleeding, loss of circulation to the brain, or loss of dopamine recep-tors. Cognitive Level: Application. Nursing Process: Imple-mentation. Patient Need: Physiological Integrity.
An overdose of drugs to treat AD may occur if they are taken improperly or if decreased liver or renal function occurs. The nurse assesses the patient for signs of over-dose, which include: ( Select all that apply.)
1. bradycardia and muscle weakness.
2. tachycardia and hypertension.
3. nausea and vomiting.
4. emotional withdrawal and tachypnea.
5. hypotension and increased muscle strength.
Answers: 1, 3
Rationale: Symptoms of overdose include severe nausea and vomiting, sweating, salivation, hypotension, bradycardia, convulsions, and increased muscle weakness, including respiratory muscles. Tachycardia, hypertension, emotional withdrawal, tachypnea, and increased muscle strength are not associated with overdose of these drugs. Cognitive Level: Analysis. Nursing Process: Assessment. Patient Need: Physiological Integrity.
An early sign( s) of levodopa toxicity is (are) which of the following?
1. Orthostatic hypotension
3. Spasmodic eye winking and muscle twitching
4. Nausea, vomiting, and diarrhea
Rationale: Blepharospam ( spasmodic eye winking) and muscle twitching are early signs of potential overdose or toxicity. Orthostatic hypotension, drooling, nausea, vomiting, and di-arrhea are potential adverse effects unrelated to toxicity or overdosage. Cognitive Level: Analysis. Nursing Process: Im-plementation. Patient Need: Physiological Integrity.
A 58- year- old Parkinson's patient is placed on levodopa ( Larodopa). In obtaining her health history, the nurse notes that the patient takes Mylanta on a regular basis for mild indigestion, and also takes multivitamins daily ( vitamins A, B6, D, and E). She also has a history of diabetes mellitus type 2. What should the nurse include in teaching for this patient?
The patient should reassess with a health care provider the need for regular Mylanta. This drug contains magnesium, which may cause increased absorption and toxicity. The patient needs teaching on decreasing foods that contain vitamin B6 ( for example, bananas, wheat germ, and green vegetables) because vitamin B6 may also cause an increase in the absorption of the medication. Teaching should include information about a potential loss of glycemic control ( because this patient is diabetic) and safety issues related to postural hypotension.
A patient is on levodopa and benztropine (Cogentin). During a regular office follow- up, the patient tells the nurse that she is going to Arizona in July to visit her grand-children. What teaching is important for this patient?
A patient on benztropin ( Cogentin) has a decreased ability to tolerate heat. Arizona in July is hot, so the patient should be taught to avoid hot climates, if at all possible, or to increase rest periods, avoid exertion, and observe for signs of heat intolerance. When symptoms occur, the patient must immediately get out of the heat and rest.
A 67- year- old Alzheimer's patient is on donepezil ( Aricept) and has a history of congestive heart failure, diabetes mellitus type 2, and hypertension. The patient's wife asks the nurse if this new medicine is appropriate for her husband to take. How should the nurse respond? What teaching should be done?
The nurse should refer the patient and his wife to a health care provider regarding the appropriateness of this medication (this is not a nursing function). The couple should be educated regarding safety issues such as postural hypotension and bradycardia that may occur with this medication. Anorexia is also a potential problem; this patient has diabetes and thus may have glycemic issues.