T1L9 parkinsons and drug therapy of the basal ganglia Flashcards
(21 cards)
disorders of movement terminology
hyperkinesis
hypokinesis
ataxia
apraxia
hyperkinetic- jerky movements eg tics
non jerky movements eg tremor, dystonia
hypokinetic movements- eg hypokinesis
disturbance of coordination - ataxia
disturbance of planning - apraxia
ballismus
- a high amplitude flailing of the limbs unilaterally
- stroke is most common cause
tic disorders
- brief repetitive stereotypes movements with a preliminary urge
simple: eg blinking, coughing
complex: jumping or twirling
corprolalia: swearing - reduced concentration
- made worse by fatigue
- tourettes is a more severe tic disorder
cormorbidity:
- 50% also have adhd
- 33% have ocd
- 50% have anxiety
complex genetic inheritance/ post infection
basal ganglia involvement
cognitive loop: forward planning of complex motor intentions
when this becomes automatic, the motor loop takes over
chorea
brief irregular jerky contractions that are not repetitive but flow from one muscle to the next- patient fidgety, restless
as indirect pathway cannot be used
causes:
- huntingtons
- drugs (neuroleptics)
huntingtons clinical presentation
cognitive:
- bad decision making
- bad multitasking
- slowness of thought
behavioural:
- irritability
- depression
- apathy
- anxiety
- delusions
physical:
- chorea, dystonia, eye movements
myoclonus
- brief movement
- rapid onset and offset
- positive (muscular contractions) and negative (muscular inhibitions)
upset balance between excitatory and inhibitory neurotransmitters (so treatable with antiepileptics)
causes:
- brain hypoxia
- prion disease
- juvenile myoclonic epilepsy
dystonia
abnormal twisting posture- may be associated with jerky tremor
not fully understood
- abnormal dopaminergic activity in basal ganglia
causes:
- stroke
- brain injury
- encephalitis
- parkinsons
- huntingtons
tremor
involuntary, rhythmic sinusoidal alternating movements of part of the body
different parts of body:
- limbs, head, chin, soft palate
drug treatment of hyperkinetic movement disorders
- dopamine D2 receptor blockers eg chlorpromazine
- lots of side effects both short term and long term - dopamine depleting agents eg tetrabenazine
- atypical antipsychotics eg clozapine
oculogyric crisis
- fixed stare, upwards elevation of eyes
- neck extension
- trunk extension
acute dystonic reaction
neuroleptic malignant syndrome NMS
acute medical emergency developing over hours/days in response to D2 blocking drugs
- rigidity/muscle breakdown
- fever
- autonomic instability
- confusion
tardive dyskinesia
choreic oral facial movements, dystonic trunk posturing
dopamine supersensitivity of basal ganglia
treatment- gradual withdrawl of offending agent , substituting with a traditional antipshycotic
hypokinetic movement disorders - parkinsonism
parkinsonism = akinetic rigid syndrome
symptoms:
- slowness of movement and thought
- stiffness
- shaking
physical signs: - bradykinesia - loss of facial expression - rest tremor rigidity
non motor symptons:
- depression and anxiety
- dementia (slowed thought, autonomic flexibility)
- autonomic involvement (hypotension, hypersalivation)
- sleep disturbance
- loss of sense of smell
parkinsons
a neurodegenerative conditions, primarily affecting dopaminergic cells of substantia nigra
causes:
neurodegenerative:
- idiopathic parkinsons disease
- diffuse lewy body disease
- atypical parkinsonism
secondary:
- drugs eg MPTP
- cerebrovascular disease
- hydrocephalus
- toxicity disorders
genetic:
- metabolic (wilsons disease)
- rare familial causes
parkinsons early drug therapy
amantadine - glutamate agonist
anticholinergic (eg procyclidine) - may help with tremor. side effects
monoamine oxidase inhibitors
acetylcholine/dopamine balance in basal ganglia
- striatum is rich in acetylcholine as well as dopamine
- reduction of dopamine within basal ganglia in parkinsons disease leads to functional excess of acetylcholine
- this is balanced out using anti-muscarinic agents
monoamine oxidase inhibitors
- prevents breakdown of monoamine chemical neurotransmitters:
MAO a - serotonin, adrenaline, noradrenaline, dopamine
MAO b - dopamine
nonselective for depression. b selective for parkinsons
L-dopa
old and good.
entacapone - reduces metabolism of L-dopa so the duration of the effect is longer. makes side effects worse
dopamine agonists
- directly activate dopamine receptor
- no need for enzymatic conversion
- more stable and long acting
eg apomorphine
non drug therapies
deep brain stimulation in Parkinsons
- subthalamic nucleus
- high frequency stimulations
disease will still progress, as this has no effect on non motor aspects of disease
