11.2 Treating ND Conditions Flashcards
What is Parkinsons Disease?
A slow, progressive neurodegenerative condition of the dopinergic neurones in the substantia nigra, affecting the nigrostriatal pathway
What can cause Parkinsons Disease?
Drug Induced - anti-psycotics
Vascular
Idiopathic
Progressive Supranuclear Palsy
How do you diagnose IPD?
Rule out other causes
Clinical Signs
If responds to treatment it is idiopathic
Can do a functional MRI scan - PET, DAT
What is a DAT scan?
A scan which highlights the presynaptic dopiminergic neurones in the SNi as they synapse on the striatum.
In PD there will be less glowing
What are the symptoms of Parkinsons Disease?
Bradykinesia
Pill-rolling Tremor
Postural Instability
Cog-wheel rigidity, Lead Pipe Rigidity
Pedestal Turning, Slow to Start, Fenestrating Gait
Lack of expression/monotone voice
Other:
Non-motor (mood changes, sleep disturbances and cognitive disturbances)
What is the pathophysiology of Parkinsons Disease?
Damage to SNi D neurones
Accumilations of misfolded alpha-synclein proteins
Form Lewy Bodies
These damage the neurones leading to cell death
What are the PD treatments?
Dopamine Replacement
Dopamine Receptor Agonists
MOAB-inhibitors
COMT Inhibitors
How does Levidopa work?
What does it improve?
It is L-DOPA, a precursor to Dopamine. It can cross the BBB and uses the dopaminergic neurones to change into Dopamine.
Need to use with a decarboxylase inhibitor to prevent breakdown in the periphery
This improves the motor symptoms.
What are the ADRs of Levidopa?
Hallucinations Lack of Sleep Hypotension Can increase the tremor Nausea Tachycardia
Describe the PK of Levidopa?
It is Oral
Has a poor oral bioavailabilty (only 1% goes to brain)
Active transport (vs amino acids) through gut wall
90% broken down in intestinal wall
Short Half Life
Distributed in periphery ( 9% converted into dopamine )
Crosses the BBB
Any DDIs with Levidopa?
Vitamin B6
What are Dopamine Receptor Agonists?
Agonists of the D receptors in the striatum
They are either ergot or non-ergot derived
Examples of Dopamine Receptor Agonists?
Ropinirole
Why use Dopamine Receptor Agonists?
Less dyskinesia
Might be neuroprotective
What are the ADRs of Dopamine Receptor Agonists?
Ergot derived: Fibrosis
Impulse Control Disturbances
Sedation (daytime sleepiness)
Hypotension
How do you take Dopamine Receptor Agonists?
Patch
Subcutaneous
What drugs inhibit the breakdown of Dopamine?
Decarboxylase Inhibitors (in periphery) COMT inhibitors (mostly act on peripheral breakdown) MOA-B inhibitors
Describe the breakdown of Dopamine
Dopamine is broken down either by MOA orCOMT
into two different things (3,4 Dihydrophylacetic Acid, 4-Methoxytyramine)
They then unite at a common point - homovanillic acid
Describe how Dopamine is created
Created from Precursor - L-DOPA
Converted by enzyme - DOPA Decarboxylase
When do you use COMT inhibitors?
Alongside Levidopa
Prolongs motor effects of Levidopa
Why do you use MOA-B inhibitors?
Alongside Levidopa or on its own
May be neuroprotective
Reduces motor effects of IPD
What is Myasthenia Gravis?
Autoimmune
IgG blocks ACh receptor on post-synaptic membrane
Increases ACh breakdown by AChE
What are the symptoms of Myasthenia Gravis?
Fast tiring, fatiguable, weak muscles
No problems with reflexes
Cannot hold upwards gaze too long
How do we treat Myasthenia Gravis?
Corticosteroids or Azathroprine
AChE inhibitors
