Flashcards in 11.2 Treating ND Conditions Deck (37):
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
Progressive Supranuclear Palsy
How do you diagnose IPD?
Rule out other causes
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?
Cog-wheel rigidity, Lead Pipe Rigidity
Pedestal Turning, Slow to Start, Fenestrating Gait
Lack of expression/monotone voice
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 Receptor Agonists
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?
Lack of Sleep
Can increase the tremor
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?
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?
Why use Dopamine Receptor Agonists?
Might be neuroprotective
What are the ADRs of Dopamine Receptor Agonists?
Ergot derived: Fibrosis
Impulse Control Disturbances
Sedation (daytime sleepiness)
How do you take Dopamine Receptor Agonists?
What drugs inhibit the breakdown of Dopamine?
Decarboxylase Inhibitors (in periphery)
COMT inhibitors (mostly act on peripheral breakdown)
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?
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?
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
What drugs can worsen Myasthenia Gravis?
What is a Myasthenia Crisis?
A flare up of MG (acute exaccerbation)
Can weaken respiratory muscles and require ventilation
What is a Cholinergic Crisis?
When you overtreat a patient with MG with AChE-i
How do AChE inhibitors work?
Block the enzyme which breaks down ACh
ACh stays in the cleft longer
Increases its action
Why is timing of AChE-i crucial?
Lasts for 3-6 hours
Time it well to meals as it can affect whether someone can swallow or not
What are the ADRs of AChE-i?
Cholinergic Side Effects
How do you take AChE-i?
What surgery can you do for PD?
DBS on STN
Lesion in the thalamus (reduce tremor)
Lesion in the GPi (lessen dyskinesia)
How could Anticholinergic drugs help PD?
Believed ACh antagonises dopamine
Could treat the tremor but has no effect on bradykinesia
How could you use Amantidine?
May enhance dopamine release and inhibit ACh
Poor but few side effects
What does COMT do?
Inhibits breakdown to 3-MO
So dopamine is around longer
3-MO normally inhibits the transport into the CNS as well
Why use MOAB-i not just a MOA-i?
As B are normally found in dopamine regions of the brain
Don't have a risk of hypertensive crisis unlike non selective ones