Movement Disorders Flashcards
Levodopa
Catecholamine Precursor Anti-Parkinson Drug
Use:
- Patients with severe Parkinson symptoms which interfere with daily living
- Levodopa/Carbidopa combo has highest efficacy of all anti-Parkinson drugs, with fewest adverse side effects in the short-term
Mechanism:
- converted to dopamine by aromatic amino acid decarboxylase in and out of the CNS
- restores normal dopamine levels to synapses of the Basal Ganglia Direct Pathway
Side effects:
- Long-term use associated with efficacy fluctuations and dyskinesias. These dyskinesias are severe and very hard to control, explaining why this treatment is delayed as long as possible
Carbidopa
Aromatic Amino Acid Decarboxylase Inhibitor
Anti-Parkinson Drug
Use:
- Levodopa/Carbidopa combo has highest efficacy of all anti-Parkinson drugs, with fewest adverse side effects in the short-term
Mechanism:
- inhibits action of aromatic amino acid decarboxylase. Because it cannot cross the BBB, only has effect in periphery, decreasing the peripheral metabolism of levodopa
- levodopa can then cross BBB intact, increasing the amount of levodopa available in the CNS
- restores normal dopamine levels to synapses of the Basal Ganglia Direct Pathway
Side effects:
- Long-term use associated with efficacy fluctuations and dyskinesias. These dyskinesias are severe and very hard to control, explaining why this treatment is delayed as long as possible
Entacapone
Tolcapone
Catechol-O Methyl Transferase (COMT) Inhibitor
Anti-Parkinson Drug
Use:
- Parkinson’s, when Levo/Carbi fail by themselves
- Used as adjunct to dopamine-based drugs, not effective alone. Decreases “off” periods
Mechanism:
- converts L-dopa to 3-O-methyldopa, a partial agonist at dopamine receptors which enhances dopamine reuptake
Side effects:
- Tolcapone = hepatic toxicity
- Increase length of dopamine in synapse = increase in peak dose dyskinesia
Selegiline
Rasagiline
Mono-Amine Oxidase-B (MAO-B) Inhibitor
Anti-Parkinson Drug
Use:
- Parkinson’s, when Levo/Carbi fail by themselves
- Used as adjunct to dopamine-based drugs
- not effective on its own
Mechanism:
- selectively blocks MAO-B from metabolizing dopamine in the CNS
- because it selectively inhibits MAO-B, there is no risk of tyramine interactions (See MAO-A antidepressants)
Side effects:
- Dyskinesias
- Psychosis
- Insomnia (dopamine metabolism into amphetamine, selegiline only)
NOTE: MAO-A metabolizes tyramine, serotonin, NE, and dopamine
alpha-synucleiopathies
- Idiopathic Parkinson’s
- Dementia with Lewy Bodies
- Mixed System Atrophy
Lewy body
Neuronal intracytoplasmic inclusion with with clear halo seen in IPD and DLB
Familial PD genes
Leucine-rich repeat kinase 2 (LRRK2) - most common
alpha-synuclein (PARK1) - AD, young onset
Parkin (PARK2) - AR, juvenile onset
Not a comprehensive list
Bromocriptine
Pramipexole
Ropinirole
Dopamine Receptor Agonists
Anti-Parkinson Drug
Use:
- less effective than other anti-Parkinson drugs, but fewer side effects
- Bromocriptine no longer used for PD
Mechanism:
- activate D2 and D3 dopamine receptors
Side effects:
- Dyskinesias
- Psychosis
- Impulse control disorders, hypersexuality
Benztropine
Trihexyphenidyl
Anticholinergics
Anti-Parkinson Drug
Use:
- Parkinsonian patients <60 y.o. (older patients get way more side effects)
- decreases tremors and rigidity, but minimal effect on bradykinesia
Action:
- decreased ACh formation, muscarinic blockers
Side effects:
- constipation
- glaucoma
- urinary retention
- significant cognitive effects in elderly
Amantidine
NMDA glutamate receptor antagonist
Anti-Parkinson Drug
Use:
- Parkinsonian patients >60 y.o.
- used in combination with other dopamine based drugs
- used to either shorten duration of L-dopa use, or after L-dopa associated dyskinesias become too severe
Action:
- glutamate receptor antagonist
- increases dopamine release and blocks uptake (weak effect)
Side effects:
Progressive Supranuclear Palsy (PSP)
Onset? Cause? Symptoms? Treatment?
Onset:7th decade (late onset)
Cause: Tauopathy - Midbrain atrophy (hummingbird sign)
Symptoms:
- Gait and balance w/ frequent falls
- eye movement abnormalities (vertical gaze palsy), square-wave jerks
- involuntary neck hyperextension
- parkinsonism (symmetric, poor response to levodopa)
- NO DYSAUTONOMIA
Tauopathies
- PSP
- CBD
Mixed System Atrophy
Onset? Cause? Symptoms? Treatment?
Onset: 6th decade
Cause: glial cytoplasmic alpha-synuclein. Hot-cross bun sign of pons, T2 hypointense putamen w/ bright rim
Symptoms:
- all have poorly levodopa-responsive parkinsonism
- autonomic dysfunction, severe orthostasis, urinary incontinence, impotence, laryngeal dystonia
- forward neck flexion
- ataxia and frequent falls
MSA - A = Predominantly dysautonomia
MSA - P = predominantly Parkinsonism
MSA - C (sporadic olivopontocerebellar atrophy) = cerebellar dysfunction
Corticobasilar Syndrome
Onset? Cause? Symptoms? Treatment?
Cause: Tauopathy with intranuclear inclusions, deposition in cortex, thalamus, basal ganglia
Symptoms:
- focal limb rigidity/dystonia, alien limb, apraxia
- cortical myoclonus
- cortical sensory loss (i.e. astereognosia, agraphesthesia, loss of 2-point discrimination, w/o sensation loss)
- cognitive dysfyunction
- Parkinsonism
Essential Tremor
Treatment?
Treatment: Propranolol, primidone (barbituate, - rare treatment for essential tremor in conjunction with beta blocker)
