Parkinson's Disease & Movement Disorders Flashcards
End Test 4
What is a tremor?
Slow repetitive/rhythmic movement that a person doesn’t know they’re doing
What is a hallmark symptom of Parkinsons?
Tremor AT REST
What is likely the reason for a tremor with movement?
Brain lesion
Alcohol/drug toxicity
What is chorea?
Quick muscle jerks that can cause impaired movement/coordination
What is ballismus?
Wild, violent, abnormal movement
What is ballismus associated with?
This wild, violent, abnormal movement is associated with huntington’s disease
What is athetosis?
Slow, rotational/twisting movements (writhing)
What is Dystonia?
Abnormal posture
What is Tic?
Single repetitive movements, esp. in the face
What are tics normally associated with?
Antipsychotic drugs
What is Choreathetosis?
Combo of Chorea, Athetosis, Dystonia
What causes Choreathetosis?
Trauma
Chorea Gravidarum
Turmors
Cerebral Palsy
Huntingtons
Ataxia Telangectasia
Kernicterus
What are most movement issues associated with?
Problems with Basal Ganglia cells
Where are Basal Ganglia cells located? What do these areas do? What is the most important area when it comes to movement disorders?
Striatum
Substantia nigra
Globus pallidus
Subthalamic nucleus
Regulate motor activity
Substantia nigra
Why is the Substantia nigra the most important area of the Basal Ganglia?
it can inhibit the indirect pathway & stimulate the direct pathway.
Both pathways are important in fine muscle tuning & fine control in the thalamus
Movement disorders are related to dysfunction in the _______
Basal ganglia
What does the Basal ganglia cells in the substantial nigra secrete? To where?
Dopamine
To the striatum
What causes Parkinsons? What predisposes you to this? What decreases/increases symptoms?
Genetics: SNCA gene produces Alpha-synuclein
————————-
Environmental: Increases: cigarette smoke, coffee, antiinflammatories, uric acid
Decreases: lead, manganese, Vitamin D
What are symptoms of Parkinsons?
Idiopathic, progressive
Cognitive decline
TRAP:
Tremor
Rigidity
Akinesia (impairment in voluntary movement)
Posture
Describe Alpha-Synuclein’s role in movement disorders
Protein produced by the gene SNCA
Primary gene associated with parkinsons
Found in CNS neurons specifically in the substantia nigra in areas that can glomerate into Lewy Bodies
What are Lewy bodies?
Areas that show up as small white spots in the brain
small areas the brain that are concentrated with protein. Usualy seen in substantia nigra from alpha-synuclein
T/F: Alpha Synuclein should be diffused through the cell
T
What is Prion disease?
Mad cow disease
another cause of dementia
What neurodegeneration disorders are associated with proteins?
Parkinsons: Alpha-synuclein
Alzheimer’s: APP (Amyloid Precursor Protein)
MSA (Multiple system atrophy): Amyloid proteins
Patient’s with parkinson’s will have ______ upon an autopsy
Lewy bodies
What is the only way to confirm parkinsons?
autopsy
What is Dementia without parkinson’s symptoms, but with Lewy bodies upon autopsy?
Lewy Body disease
What are Parkinson’s risk factors?
- > 60 y/o
- hereditary
-Men:women 2:1
-Occupation: teaching, healthcare, farming
-toxin exposure
What drugs do you want to avoid in parkinsons?
Dopamine-R antagonist (antipsychotics)
Street drugs
What do you want to do to improve QOL with Parkinsons?
Exercise/PT
Increase/restore dopamine levels
CNS antimuscarinics
Drugs: Levodopa/Carbidopa
1 Treatment for Parkinson
MOA: Levodopa: Prodrug crosses BBB –> Converts to dopamine
-L-isomer of dopamine
Carbipoa MOA: COMT inhibitor
Carbidopa prevents the breakdown of L-dopa by increasing reliance in COMT when combined with Levodopa
Racemic mixture
Decreased effectiveness with time
AE: Hallucinations, Delusions
-this is increased with carbidopa!!!
-Give Pimavanserin to combact this
-Dyskinesias- choreathethosis (mild)
Drug interactions: MAOIs, Vitamin B6
Contraindications: Psychosis, Glaucoma, Melanoma
-increase in dopamine
-dopanergic pathway produces melanin & produces needed for the eye
What is the active form of Levodopa? Inactive?
Active: L-dopa
Inactive: D-dopa
Drug: Pimavanserin
Class: Antipsychotic
MOA: 5-HT(2A) Inverse agonist
-visual cortex at thalamus substantia nigra
uses: assist with psychotic SE of Levodopa/Carbidopa
What is the On-Off Phenomen?
Associated with long term use of levodopa
Periods of increased mobility followed by marked akinesia
because of this, people woild do drug holidays and stop taking medication for a period of time to prevent this (Prevent the medication from having decreased effects)
Drugs: Pramipexole
Class: Dopamine Receptor Agonist
Less effective than levadopa but good for early treatment
uses: parkinsons (early)
Less SE than levadopa
Drugs: Selegeline
Class: MAOIs
MOA: MAO-B selective: specifically inhibits the dopamine transporter from reuptake
-slower breakdown of substantia nigra
-increase dopamine
ALL OF THESE FOOD, DRUG, HERB INTERACTIONS & SE!!!!!!!
NE, Epi, and Dopamine are all _____
Catecholeamines
F/T: You can take PO catecholamines. Why?
F
They are inactivated by COMT
Drugs: Tolcapone
Class: COMT inhibitor
MOA: inhibits the enzyme that breakdown Dopamine
-increasing dopamine circulation
What is COMT?
Enzyme that inactivates catecholamines….
Dopamine is a catecholamine
Drugs: Apomorphine
Class: Dopamine agonist
uses: parkinsons during “drug vacation” or off period
-relief of akinesia
What are Sx treatments for Parkinsons?
Lesion ablation
Deep brain stimulation of the basal ganglia
Implantation of fetal substantia nigra
Describe Essential tremor
Causes: B1 receptor dysfunction
Tx: beta blockers that cross the BBB
Describe Benign Hereditary Chorea
Jerky movments
Autosomal dominant-50% chance child will have it
-Chorea in childhood
-No progress, no dementia
Tx: Tetrabenazine
Drugs: Tetrabenazine
Class: Dopamine Receptor blocker
Uses: Benign Hereditary Chorea
Drugs: Baclofen
Muscle relaxant
Uses: Cerebral Palsy
Describe Tardive Dyskinesia
Repetitive, involuntary movements in the face caused by antipsychotic drugs
What are other drugs used to treat movement disorders?
Levodopa
Phenytoin
Seizures meds
What is Muscular Dystrophy?
Genetic disorder
Progressive degenerstion of muscle fibers
Characterized by progressive muscle weakness/wasting
Describe Duchenne’s MD
X-linked recessive: more common in males
-Results from gene that encodes Dystrophin
-Dystrophin absent in children with Duchenne
Muscle wasting (late: decrease muscle in diaphragm -> assisted ventilation)
Early onset in childhood
Usually do not survive beyond 20s
Tx: Improve QOL
Corticosteroids
Beta-2 agonist: increases blood flow to increase muscle strength
Children with Duchenne’s _______ have Dystrophin
Dont
What is a marked sign of muscle weakness in children?
Gowers Sign
When you ask them to stand up, they put their hands on their knees to assist them instead of standinf straight up
Describe Cerebral Palsy
Non-progressive motor disorder of the CNS
-alterations in movement & posture
Caused by some something that happened at birth
SE: hyper/hypotonia or reflexes, scissoring of legs, failure to meet milestones seizures
Tx: No cure
Intrathecal pump -> botox or baclofen
Describe Huntington
MOA: GABA reduced in basal ganglia
Includes Ballismus which is wild, violent, abnormal movement
Tx: Tetrabenazine, Haloperidol
Genetic counseling, ST/PT/OT
Drugs: Tetrabenazine, Haloperidol
Class: Haloperidol: Dopamine Receptor Blocker/antagonist
-Tetrabenazine: Depletes dopamine
Uses: Huntington’s diseases
-decrease dopamine levels
Describe Amyotropic Lateral Sclerosis (ALS)
“Lou Gehrig’s disease”
Loss of motor neurons
Death 2-6 years after diagnosis
More common in men than women
Tx: Extend QOL
Riluzole, Edaravone
Drugs: Riluzole
Class: Na+ channel blocker
Uses: “Lou Gehrig’s disease”
Describe Alzheimer’s
Has no definitive cause: hereditary or nonhereditary but more likely to develop if family history
Causes: Neurofibrillary tangles d/t hyperphosphorylation of tile-proteins within the cells
-Senile plaques caused by A-Beta 42 accumulation around protein
S/S: Forgetfulness, emotional, lack of concentration
Dx made by ruling out other causes of dementia
Death in 4-12 years
Prevention: CVS health, NSAIDs, diet/exercise
Tx: Palliative
-Tacrine, Rivastigmine, Memantine
What is the #1 cause of dementia?
Alzheimer disease
T/F: You get get Alzheimer’s at 30
T
Drugs: Tacrine, Memantine
Class: CNS Ach esterase inhibitors
MOA: Prevents the breakdown of Ach which increase Ach circulation
Describe Restless leg syndrom
Discomfort in legs causing an urge to move
Makes it hard to sleep
Increased risk of developing in pregnancy
Tx: dopamine, agonist, gabapentin, benzodiazepines, opiates (clonazepam)
