T2 L7: Parkinsons disease and drug therapy of basal ganglia disorders Flashcards
What is Ballsismus?
A high amplitude flailing of the limbs on one side of the body
What is the pathophysiology of Ballismus?
A lesion of the subthalamic nucleus. Most common cause is a stroke
What is coprolalia?
Swearing as a symptom of tic disorders
What are the common co-morbidities of tic disorders?
50% have ADHD
33.5% have OCD
Up to 50% have anxiety
What is Chorea?
Jerky, brief, irregular contractions that appear to flow from one muscle to another. The patient will appear fidgety or restless
What is the pathophysiology of Chorea?
A problem with the striatum nucleus. This can be caused by Huntington’s disease or drugs like Neuroepiletics that antagonise dopamine
What causes Huntington’s disease?
It’s a trinucleotide repeat on chromosome 4 that is autosomal dominant. The longer the repeat sequence, the earlier the disease presents
What are the clinical presentation of Huntington’s disease?
Inability to make decisions or multitask because of slowness of thought
Irritability, depression, apathy, anxiety, delusions
Chorea, motor persistence, dystonia, eye movements
What is astryxis?
(Liver flap) caused by muscular inhibitions
What is Myoclonus?
Brief movements with rapid onset and offset. It’s a symptoms not a disease
What is the pathophysiology of Myoclonus?
Unknown. Believed to be an imbalance between excitatory and inhibitory neurotransmitters since it can be treated with antiepileptic drugs
What causes Myclonus?
Juvenile Myoclonic Epilepsy, Brain hypoxia, Prion disease
What is Dystonia?
An abnormal twisting posture which may be associated with a jerky tremor
What is the pathophysiology of Dystonia?
Not understood. PET scans show problems in motor cortex, supplementary motor areas, cerebellum, and basal ganglia.
What causes Dystonia?
Stroke, brain injury, encephalitis, Parkinson’s disease, Huntington’s disease
What are the 3 types of tremor occurrence?
At rest, postural, and kinetic
Which parts of the body can a tremor affect?
Limbs, head, chin, soft palate
What type of tremor is an essential tremor?
Predominantly postural
What is the postulated theory of a tremor?
That there is increased activity in the cerebellothalamocortical circuit
What are the different types of drugs used to treat hyperkinetic movement disorders like Tics, Chorea, and Ballismus?
Dopamine receptor blocking agents, dopamine depleting agents, and atypical anti-psychotics
Haloperidol, Chlorpromazine, Pimozide, and Risperidone are part of which drug type?
Dopamine receptor blocking agents
Tetrabenazine and Reserpine are part of which drug type?
Dopamine depleting agents
Clozapine, Olanzapine, and Aripiprazole and part of which drug type?
Atypical anti-psychotics
What are the side effects of dopamine blocking agents?
Over days-weeks
Oculogyric crisis, Neuroleptic malignant syndrome
Over weeks-months
Drug induced Parkinsonism
Over months/years
Dyskinesis
What us Oculogyric crisis?
Spasmodic movements of the eyeballs into a fixed position, usually upwards
What is Neuroleptic malignant syndrome?
A rare, but life-threatening condition characterized by fever, muscular rigidity, altered mental status, and autonomic dysfunction
What is Drug induced Parkinsonism?
Symptoms include tremor, rigidity, bradykinesia, and gait disturbance (similar to those of Parkinson’s disease)
What is Dyskinesis?
Involuntary movements like twitches, jerks, twisting or writhing movements. Treated by gradually withdrawing the offending agent
What is Akinetic-Rigid Syndrome?
Another name for Parkinson’s disease
What are the physical symptoms of Parkinson’s disease?
Slowness of movement, stiffness, shaking
What are some physical signs of Parkinson’s disease?
- Slowness and poverty of movement (Bradykinesia) Eg, loss of facial expression and arm swing
- Akinesia
- Rigidity
- Resting tremor
What are some non-physical symptoms of Parkinson’s disease?
Depression and anxiety
Dementia: Slow thoughts, mental inflexibility
Autonomic: Postural hypotension, Hypersalivation
Sleep: Restless legs, REM parasomnia
Reduced sense of smell
What is the pathophysiology of Parkinson’s disease?
Decreased dopamine release from the substantia nigra causing reduced activation of the direct pathway and reduced inhibition of the indirect pathway
What is Parkinson’s disease defined as?
A neurodegenerative condition, primarily affecting dopaminergic cells of the substantia nigra
What is the Histopathological hallmark of Parkinson’s disease?
Lewy bodies
What are some Neurodegenerative causes of Parkinsonism?
Idiopathic Parkinson’s disease (80%), Diffuse Lewy Body disease, Atypical Parkinsonism caused by Multiple system atrophy, Progressive supranuclear Palsy, and Corticobasal degeneration
What are some secondary causes of Parkinsonism?
Drugs, cerebrovascular disease, Hydrocephalus, Toxicity/metal deposition disorders
What are some genetic causes of Parkinsonism?
Metabolic issues caused by Wilson’s disease (Copper deposition) or some rare familial causes
What is Dopamine broken down into?
Homovanillic acid
What are 3 early drug therapies for Parkinson’s disease?
- Amantadine (A Glutamate agonist)
- Anti-Cholinergics like Procyclidine and Benzhexol to help with tremor but they are limited by side-effects like confusion urinary retentions, and dry mouth
- Mono-amine oxidase inhibitors
What are the 4 types of Monoamine oxidase inhibitors and what is each used for?
MAO-type A: Serotonin, Adrenaline, Noredrenaline, and Dopamine
MAO-type B: Dopamine
Non-selective MOA-I: for depression but rarely used because it causes problems with metabolising dietry amines
More selective MAO-IB: for Parkinsons disease (Eg. Selegiline, Rasagiline)
What is L-dopa usually combined with and why?
Combined with Dopa decarboxylase inhibitor to prevent peripheral conversion of dopamine
What are the 2 commercial preparations of L-dopa and how do they differ?
Madopar which is immediate release and Sinemet which is controlled release. First is used during the day and the other during the night
What happens to the therapeutic window of L-dopa as Parkinson’s disease develops?
The therapeutic window gets smaller so dosage is harder to control. Too much causes Dyskinesis
What are the drugs Entacapone and Tolcapone used for?
They reduce peripheral metabolism of L-dopa which increases the duration of action of L-dopa, efficacy of L-dopa
What are some side effects of using Entacapone?
Makes Dyskinesia worse and causes diarrhoea
What are some side effects of using Tolcapone?
Makes Dyskinesia worse, causes diarrhoea, and causes liver disease
When is duodenal L-dopa infusion used?
With advanced Parkinson’s disease when the therapeutic window is advanced. It’s expensive and doesn’t affect disease progression
Why are Ergot dopamine agonists no longer used?
Because they caused cardiac and pulmonary fibrosis
What are the following drugs used for: Pergolide (Ergot), Cabergoline (Ergot), Pramipexole (Non-Ergot), Ropinirole (Non-Ergot), Rotigotine (Patch), Apomorphine (Subcutaneous infusion)?
They are dopamine agonists that reduce the frequency of motor complications with Parkinson’s disease but they can cause dopamine dysregulation syndrome
What is Dopamine dysregulation syndrome?
A dysfunction of the reward system observed in some individuals taking dopaminergic medications for an extended length of time
What is Apomorphine, how is it administered and what are the pros and cons of using it?
It’s a Dopamine agonist given as a subcutaneous infusion.
Pros: Instant effect. It reduces dyskinesia by allowing continuous dopaminergic stimulation. The pulsatile dopaminergic stimulation is though to prime the basal ganglia for motor complication
Cons: Can only be used to specific patients. Causes skin nodules
How is deep brain stimulation used to treat Parkinson’s disease?
It’s a non-drug way of disrupting abnormally synchronous basal ganglia rhythms. The subthalamic nucleus us targeted in Parkinson’s disease
Disease will still progress
What is Apraxia?
A neurological disorder characterized by loss of the ability to execute or carry out skilled movements and gestures, despite having the desire and the physical ability to perform them
