Module 13 - Parkinsons + MS Flashcards
Pathophys of PD*
- Neurodegenerative disorder of the extrapyramidal system associated with the disruption of neurotransmission in the striatum
- characterized by dyskinesia’s and akinesia
- proper function of the striatum requires a balance between the neurotransmitters dopamine and acetylcholine
- imbalance between dopamine and ACh results from the degeneration of neurons that supply dopamine to the striatum
- Without adequate dopamine, ACh causes excessive stimulation of neurons that release gamma-aminobutyric acid
- Overactivity of GAA neurons contributes to the motor symptoms of PD
Symptoms *
Diagnostic: bradykineseia with either tremor or rigidity
Slowed movements (bradykinesia)
+/- Resting tremor
+/- Muscle rigidity
( reduce arm swing and impaired gait )
- Loss of balance (postural instability) - usually later though
Diagnostics Tests*
- None needed
- Dopaminergic agent trial 1st test (improvement in symptoms confirms diagnosis)
- MRI or CT will most likely only rule out other causes
== most idiopathic PD will show no abnormal imaging - Functional neuroimaging (dopamine transport imaging such as FP-CIT or Beta CIT SPECT, or fluorodopa PET) will show decreased basal ganglia presynaptic dopamine reuptake
When to start treatment for PD *
treatment starts when symptoms become bothersome
Initial Treatment *
Mild Symptoms: MAO-B Inhibitor
- selegiline or rasagiline
More Severe Symptoms: Levodopa carbidopa as dopamine replacement or dopamine agonist
*If improving motor function: levodopa is preferred
* if improving dyskinesias: dopamine agonist is preferred
- levodopa is more effective than dopamine agonist, but long-term use carriers a higher risk for disabling dyskinesias
Management of Motor Fluctuations:
- Drug induced dyskinesias
- OFF times can be reduced with dopamine agonist (COMT inhibitors and MAO-B Inhibitors)
== On-Off: Freezing
== Wearing off
Levodopa *
- only given in combo with carbidopa or carbidopa/entacapone
- Diagnosis of PD questioned if levodopa fails
- Several months of treatment needed for full therapeutic response
- Highly effective, but benefits diminish over time
( symptoms well-controlled for first 2 years)
( Return to pretreatment state at the end of 5 years) - As the dx advances: other meds will be added
- Orally administered; rapidly absorbed from small intestine
( food delays absorption )
( high protein foods reduce therapeutic effects )
( levodopa, which as no direct effects of its own, is converted to dopamine, its active form )
Levodopa Wearing Off *
- Gradual Loss (wearing off): develops near the end of dosing interval and indicates that drug levels have declined to a subtherapeutic value
- Wearing off can be minimized in three ways
1. shortening dosing interval
2. giving a drug that prolong levodopa plasma half-life (entacapone)
3. give a direct-acting dopamine agonist
Adverse Effects of Levodopa *
Dyskinesias
- what are dyskinesias in PD
- develop just before or soon after optimal levodopa dosages have been achieved
- !!!!! Can be managed in 3 ways
1. reduce dosage of levodopa
2. amantadine or dopamine agonist
3. surgery or electrical stimulation
Other A/E:
- Darkens sweat and urine
- Activates malignant melanoma: important to perform a careful skin assessment of patients who are prescribed levodopa
Nonergot Dopamine Agonists
Pramipexole *
Pramipexole
- used alone in early PD and with levodopa in advancing PD
—- can be use first line in younger pts (<50)
—- can be added to levodopa to reduce off time, improve symptoms, or manage dyskinesias due to levodopa
- if given for dyskinesias then levodopa must be reduced
- max benefits take several weeks to develop
- not as effective as levodopa-carbidopa
Pramipexole AE *
- Monotherapy: nausea, dizziness, daytime somnolence, insomnia, constipation, weakness, hallucinations
- Combined: orthostatic hypotension, dyskinesias, increase in hallucinations
- Rarely sleep attacks occur
- Rare instances of gambling or other OCD rewarding behaviors
Nonergot Dopamine Agonists
Ropinirole *
- share same indication as pramipexole
( PD and RLS) - can be used as monotherapy for early PD as well as adjunct to levodopa in advanced PD
- SE: nausea, dizziness, somnolence, hallucinations
- Rarely sleep attacks occur
- Combined (levodopa): dyskinesias, hallucinations, postural hypotension
- Compulsive gambling, shopping, eating, hypersexuality
Selegiline and Rasagiline *
MAO-B inhibitors
- Monotherapy or with levodopa
- Modest improvement in motor function
- Cause selective and irreversible MAO-B
- Can supress the destruction of dopamine derived from levodopa and prolong effects of levodopa
- Benefits decline dramatically within 12-24 months
- Use as a first line therapy for a pt with PD who has mild impairment and bradykinesia as the main symptoms
Amantadine *
- developed as antiviral agent
- later found effective for PD
- effects much less profound than with levodopa or dopamine agonist
- responses may begin to diminish within 3-6mo
- not considered first line agent
- may be helpful for dyskinesias caused by levodopa
- AE: livedo reticularis: condition characterized by mottled discoloration of the skin
Benztropine (Cogentin) *
Centrally Acting Anticholinergic
- Reduces tremors and possibly rigidity
- Most appropriate for yonger patients with mild symptoms
- Less effective than levodopa or dopamine agonist but better tolerated
- Avoided in the elderly, who are intolerant of CNS side effects (sedation, confusion, delusions, hallucinations)
- Also has anticholinergic effects of dry mouth, urinary retention, constipation
Bob begins having drooling? What medication would be best for him now?
BENZTROPINE
MS
pathophys
inflammation and demyelination of CNS
MS
s/s
Types of MS
Relapsing MS (most common)
Relapsing-Remitting MS
Active Secondary Progressive MS.
MS
Classes of treament
especially DMD/IMDs
MS
treatment intitation
MS
goals of treatment
