Parkinson's Flashcards
What can cause Parkinsonism?
Idiopathic - Parkinson's disease Vascular disease Drugs Viral infections Trauma Multiple system atrophy Progressive supranuclear palsy
What is multiple system atrophy?
Degeneration if nerve cells in specific areas of the brain
Causes problems with movement, balance and other autonomic functions of the body eg bladder control and blood pressure
What is Wilson’s disease?
Accumulation of copper in tissues, resulting in neurological and hepatic disease
Copper-dopamine complexes form, producing Parkinsonism symptoms
What is corticobasal degeneration and what is it characterised by?
A progressive, neuro degenerative disease involving the cerebral cortex and basal ganglia
Disorders in movement and cognitive function
What is the pathology behind Parkinson’s disease?
Selective and progressive destruction of the pigmented neurones in the substantia nigra, accompanied by deposition of granules of neuro-melanin pigment
Residual pigmented neurones contain Lewy bodies
What is the normal function of the pigmented neurones of the substantia nigra?
Release dopamine and project to the corpus striatum
What does loss of dopaminergic neurones in the substantia nigra result in?
Reduced inhibition of the neostriatum allowing less inhibition of the globus pallidus, increasing the inhibition on the thalamus, leading to less movement
Symptoms and signs of Parkinson’s?
Resting tremor (pill-rolling) Bradykinesia Rigidity Postural instability Mood changes eg depression Pain Cognitive changes Urinary symptoms Sleep disorders Somnolence
Pathway of dopamine synthesis?
L-tyrosine -> L-DOPA -> Dopamine (-> NA -> adrenaline)
What enzymes degrade dopamine?
Monoamine oxide (MAO)
Catechol-O-methyl transferase (COMT)
How can drugs help to diagnose Parkinson’s?
If patients respond well, confirms the diagnosis
What drugs can be given for Parkinson’s?
L-DOPA Dopamine receptor agonists Monoamine oxidase B inhibitors COMT inhibitors Anticholinergics
Why give L-DOPA over dopamine?
Can cross the blood brain barrier and then converted to dopamine
What is L-DOPA commonly administered with and why?
A peripheral DOPA decarboxylase inhibitor to prevent conversion of L-DOPA to dopamine in peripheral tissues
Therefore more L-DOPA will cross the BBB and not act peripherally
What are the names of combined L-DOPA and DOPA decarboxylase inhibitor drugs?
Co-carepolda
Co-beneldopa
What is the administration and absorption of L-DOPA?
Orally
Poorly absorbed as 90% is inactivates in the intestinal wall
Half-life of L-DOPA?
2 hours
Get fluctuations in blood levels leading to fluctuations in symptoms
Benefits of L-DOPA?
Highly efficacious and minimal side effects
ADRs of L-DOPA?
Nausea and vomiting
Hypotension
Psychosis
Tachycardia
What can happen with long-term use of L-DOPA?
Loss of efficacy due to loss of dopaminergic neurones
Involuntary movements
Motor complications such as
- on/off wearing off
- dyskinesia
- dystonia
- freezing
Mechanism of action of dopamine receptor agonists?
Bind directly to dopamine receptors
Advantages of dopamine receptor angonists in Parkinson’s?
Direct acting
Less motor complications
Possible neuro-protective role
Disadvantages of dopamine receptor agonists?
Less efficacy than L-DOPA
Tendency to produce impulse control disorders
Expensive
Psychiatric side effects
ADRs of dopamine receptor agonists?
Sedation Hallucination Confusion Nausea Vomiting
Mechanism of action of monoamine oxidase B inhibitors?
Stop MAO from breaking down dopamine, enhancing dopamine levels
Can be used alongside L-DOPA
Mechanism of action of COMT inhibitors?
Reduce peripheral breakdown of L-DOPA but no therapeutic effect alone
Can be used to produce an L-DOPA sparing effect and prolong the response to L-DOPA
Mechanism of action anticholinergics?
Acetylcholine is thought to have an antagonistic effect to dopamine
Effects of anticholinergics with symptoms in Parkinson’s?
Good for the tremor
No effect on bradykinesia
ADRs of anticholinergics for Parkinson’s?
Confusion
Drowsiness
Anti-cholinergic side effects eg dry mouth, urinary retention
What is the triad of symptoms seen in Parkinson’s?
Resting tremor
Rigidity
Bradykinesia