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
