P19: Treatment of Parkinsonism Flashcards
What are the 3 main brain areas that co-ordinate motor function?
- Motor cortex
- Basal ganglia
- Cerebellum
What does the cerebellum regulate?
Posture and movement and speech
What does the cerebellum influence?
Muscle tone and eye movements
Which part of the brain is responsible for motor learning? (riding bike)
Cerebellum
What is the basal ganglia?
A group ofnucleiof varied origin in thebrainsof vertebrates that act as a cohesive functional unit
What is the function of the basal ganglia
- Integrate desire and fine movement (i.e. initiate and stop movement)
- Smooth fine motor behaviour
- Suppress unwanted movements
What are the 3 interacting pathways that regulate cortical activity through the thalamus?
- Direct pathway
- Indirect pathway
- Hyperdirect pathway
What is the direct basal ganglia pathway?
Relieves the inhibitory drive of the internal globus pallidus upon thalamocortical pathways
Permits amplification of cortical signals, eventually leading to motor activation
What is the indirect basal ganglia pathway?
- Inhibits thalamocortical pathways that target areas that would interfere with desired motor behaviour
- Restricts movement to wanted muscles only
What is the hyperdirect basal ganglia pathway?
Rapid stimulation of the subthalamic nucleus by the motor cortex; proposed to prevent premature movements
How does dopamine regulate the basal ganglia?
Via the nigrostriatal dopaminergic pathway, dopamine is released which prevents motor activity
Stimulates direct pathway
Inhibits indirect pathway
What is Chorea?
- Hyperkinetic disorder
- Involuntary, sudden, frequent and purposeless jerks of the extremities, head, & trunk, with facial grimaces (Huntington’s)
What is Athetosis?
Athetosissssssssssss
- Hyperkinetic disorder
- Slow, writhing, continuous, worm-like motions of distal extremities
What is Ballism?
Bald ultras are what?
- Hyperkinetic disorder
- Violent, flinging, continuous movements of the limbs
What is Dystonia?
Dyst rhymes with a word beginning with T
- Hyperkinetic disorder
- Involuntary twisting, slow, contorting movement
What is Akinesia?
- Hypokinetic disorder
- Impairment in motor initiation, rigidity
What is Bradykinesia?
Tom Brady throws a football at maximum….?
- Hypokinetic disorder
- Reduction in the amplitude and velocity of movement
What are symptoms of Parkinson’s disease?
- Resting tremor
- Bradykinesia
- Rigidity
- Postural instability
- Problems with speech & swallowing
- Micrographia
- Dementia in later stages
How is Parkinson’s disease caused?
Caused by degeneration of nigrostriatal dopamine neurones and consequent
dysregulation of the basal ganglia
What is the general method of action for most Parkinson drugs?
- Replace the lost dopamine
- Principal targets are dopamine synthetic pathways, dopamine catabolism and dopamine receptors
What is Levodopa?
- Drug to improve bradykinesia and rigidity in Parkinsons
- Immediate precursor of dopamine, converted into dopamine by endogenous L-DOPA decarboxylase in remaining cells (Boost Dopamine)
How effective is Levodopa (L-DOPA) ?
Therapeutic effect wanes with time (8-10 years of clinical usefulness)
No effect on neurodegeneration, eventually nerve terminals become too sparse for effectiveness
What are some of the unwanted effects of Levodopa?
- Dyskinesia
- On-off effects
- Nausea + vomiting (carbidopa given to treat)
- Hypotension
- Clouds thought
- Schizophrenic-like syndrome
Name some MAO-B inhibitors
selegiline
rasagiline
How do MAO-B inhibitors work?
Stop dopamine from being broken down
How do Anticholinergic Drugs help treat Parkinson’s?
Indirectly stops GABA release so dopamine isn’t broken down
What is Amantadine?
Is a weak antagonist at glutamate NMDA receptors, increases dopamine release, blocks dopamine reuptake and has anti-muscarinic actions
What are the different structures found in the basal ganglia
- Striatum - Caudate, putamen nuclei
- Globus pallidus (interior and exterior)
- Subthalamic nucleus
- Substantia nigra - pars reticulata, pars compacta
What is a hyperkinetic disorder
Excessive involuntary movements
Whats the most common basal ganglia disorder
Parkinson’s
What is given alongside Levodopa and why
Peripheral DOPA decarboxylase inhibitors to prevent nausea e.g. carbidopa or benserazide
What effect do MAO-B inhibitors have on PD and how are they superior to MAO-A inhibitors
Improves motor function in early and advanced PD
Lacks the peripheral cheese reaction of MAO-A inhibitors
How does amantadine interact with L-DOPA
improves the on-off effects of L-DOPA and limits L-DOPA induced dyskinesias
What +ve and -ve effects does amantadine have
- Weak therapy for PD that improves tremor and rigidity
- May act to protect dopamine neurones from degeneration
- sudden withdrawal causes dramatic worsening of PD
