Movement Disorders Flashcards
What are the 4 dopamine pathways in the brain?
Mesolimbic
Mesocortical
Nigrostriatal
Tubero-hypophyseal
What are the 4 cardinal symptoms of PD?
Resting tremor
Rigidity (cogwheel/lead pipe)
Akinesia (hypokinesia, bradykinesia)
Postural instability
What are additional features of PD?
Micrographia
Aprosodia
Mask-like face
Sleep disturbances
What are some non-pharmacological approaches to treating PD?
Physiotherapy
Speech
Occupational therapy
Dietary consultations
What’s the principles of pharmacological treatment of PD?
Need to increase DA levels
Not treated until symptoms are severe
Dose titrated gradually against symptoms
What’s the precursor of DA that does cross the BBB?
L-Dopa -> Dopamine by dopa-decarboxylase
What’s the problem with using L-Dopa?
Becomes ineffective after the maximal dose is reached and it’s metabolised quickly
What can you do to prevent breakdown of L-Dopa?
Dopa-decarboxylase inhibitors: Carbidopa to slow down metabolism
Inhibit COMT (Entacapone) and MAOI-B (Selegiline) to prevent breakdown in CNS
How is dopamine broken down?
By two routes:
By catechol-o-methyltransferase or by monoamine oxidase B
What are synthetic DA agonists?
Replace lost DA acting on D2 receptors
Useful in initial treatment and younger patients
Pramiprexole
Rotigotine
Ropinirole
What are some side effects of DA based treatments?
Sudden onset sleep Nausea and vomitting Anorexia Drowsiness Psychosis Hypotension Tachycardia Arrhythmias
What are on-off effects?
Major side effect of long term DA treatment (>2 years)
Duodopa (implanted gel of L-dopa and Carbidopa) useful for treating
Domperidone + Apomorphine can be used to ‘fill in the gaps’
How can anticholinergics be used in PD?
Decrease in DA leads to increase in ACh
Anticholinergics good for iatrogenic (drug induced) PD
Eg Orphenadrine
How does Amantadine work and what can it be good for?
In Parkinsonism treatment of tremor, rigidity and bradykinesia
It’s an NMDA antagonist and weak DA agonist (may reduce dyskinesias)
What are the 3 main groups of PD?
Pure Parkinsonism - idiopathic, iatrogenic, post encephalitic
Parkinsonism with extras - multiple systems atrophy, progressive supranucelar palsy
Pseudoparkinsonism - benign essential tremor, Wilson’s disease, trauma and vascular-related
What’s Wilson’s disease?
Hepatolenticular degeneration caused by copper accumulation
Treatment = reduce copper levels by using copper chelators or zinc
3 forms: dystonic, pseudoparkinsonism, cerebellar
What’s essential tremor and its treatments? How is it different to the tremor seen in pure PD?
Familial progressive tremor characterised by intention tremor - PD has resting tremor whereas intention tremor isn’t present at rest
Tremor first appears in arms then spreads to other areas
Propranolol Primidone (AED)
Which neurones and where degenerate in HD?
GABAergic cells in the Striatum (particularly caudate nucleus)
And Cholinergic dysfunction
What type of disorder in HD?
Autosomal dominant
What are the treatments for HD?
Symptomatic:
DA depleting drugs: Tetrabenazine to reduce involuntary movement
Antipsychotics: Risperidone, Haloperidol to reduce chorea, tics, hallucinations
Benzodiazepines: Diazepam to aid relaxation
Antidepressants
How does Tetrabenazine work?
DA depleting drug VMAT2 blocker (vesicular monoamine transporter) = prevents DA transport into vesicles therefore less is released in the cleft
But it affects all monoamines not just DA
What are tics?
Small involuntary movement - treated with antipsychotics
What’s dystonia and its treatments?
Lasting muscle spasms causing repeated twisting movements or altered posture
Baclofen (GABA agonist)
Diazpeam (BDZ, GABA-A co-agonist)
What’s chorea and its treatments?
Involuntary irregular random dance-like movements from one part of the body to another
2nd generation antipsychotics (DA antagonists)
DA depleting drugs: Tetrabenazine
GABAergic drugs (AEDs Gabapentin and BDZs)
What’s athetosis?
Slow irregular writhing movements of the fingers
What’s choreoathetosis?
When chorea and athetosis occur together
What’s Ballismus? Which nuclei are affected?
Large violent flinging movement of the limbs (hemiballismus is unilateral)
Neurodegeneration of sub thalamic nuclei in basal ganglia
Treated same as chorea: sometimes IV Diazepam and oral Haloperidol
Which classes of drug can be used to treat hypokinetic and hyperkinetic disorders?
Hypokinetic: Dopamine agonists and Anticholinergics
Hyperkinetic: Dopamine antagonists, Antipsychotics and DA-depleting drugs
