11.2 Treating ND Conditions

Question 1

What is Parkinsons Disease?

Answer 1

A slow, progressive neurodegenerative condition of the dopinergic neurones in the substantia nigra, affecting the nigrostriatal pathway

Question 2

What can cause Parkinsons Disease?

Answer 2

Drug Induced - anti-psycotics
Vascular
Idiopathic
Progressive Supranuclear Palsy

Question 3

How do you diagnose IPD?

Answer 3

Rule out other causes
Clinical Signs
If responds to treatment it is idiopathic
Can do a functional MRI scan - PET, DAT

Question 4

What is a DAT scan?

Answer 4

A scan which highlights the presynaptic dopiminergic neurones in the SNi as they synapse on the striatum.
In PD there will be less glowing

Question 5

What are the symptoms of Parkinsons Disease?

Answer 5

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)

Question 6

What is the pathophysiology of Parkinsons Disease?

Answer 6

Damage to SNi D neurones
Accumilations of misfolded alpha-synclein proteins
Form Lewy Bodies
These damage the neurones leading to cell death

Question 7

What are the PD treatments?

Answer 7

Dopamine Replacement
Dopamine Receptor Agonists
MOAB-inhibitors
COMT Inhibitors

Question 8

How does Levidopa work?

What does it improve?

Answer 8

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.

Question 9

What are the ADRs of Levidopa?

Answer 9

Hallucinations
Lack of Sleep
Hypotension
Can increase the tremor
Nausea
Tachycardia

Question 10

Describe the PK of Levidopa?

Answer 10

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

Question 11

Any DDIs with Levidopa?

Answer 11

Vitamin B6

Question 12

What are Dopamine Receptor Agonists?

Answer 12

Agonists of the D receptors in the striatum

They are either ergot or non-ergot derived

Question 13

Examples of Dopamine Receptor Agonists?

Answer 13

Ropinirole

Question 14

Why use Dopamine Receptor Agonists?

Answer 14

Less dyskinesia

Might be neuroprotective

Question 15

What are the ADRs of Dopamine Receptor Agonists?

Answer 15

Ergot derived: Fibrosis
Impulse Control Disturbances
Sedation (daytime sleepiness)
Hypotension

Question 16

How do you take Dopamine Receptor Agonists?

Answer 16

Patch

Subcutaneous

Question 17

What drugs inhibit the breakdown of Dopamine?

Answer 17

Decarboxylase Inhibitors (in periphery)
COMT inhibitors (mostly act on peripheral breakdown)
MOA-B inhibitors

Question 18

Describe the breakdown of Dopamine

Answer 18

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

Question 19

Describe how Dopamine is created

Answer 19

Created from Precursor - L-DOPA

Converted by enzyme - DOPA Decarboxylase

Question 20

When do you use COMT inhibitors?

Answer 20

Alongside Levidopa

Prolongs motor effects of Levidopa

Question 21

Why do you use MOA-B inhibitors?

Answer 21

Alongside Levidopa or on its own
May be neuroprotective
Reduces motor effects of IPD

Question 22

What is Myasthenia Gravis?

Answer 22

Autoimmune
IgG blocks ACh receptor on post-synaptic membrane
Increases ACh breakdown by AChE

Question 23

What are the symptoms of Myasthenia Gravis?

Answer 23

Fast tiring, fatiguable, weak muscles
No problems with reflexes
Cannot hold upwards gaze too long

Question 24

How do we treat Myasthenia Gravis?

Answer 24

Corticosteroids or Azathroprine

AChE inhibitors

Question 25

What drugs can worsen Myasthenia Gravis?

Answer 25

``` Aminoglycosides Beta Blockers Chloraquins ACE Inhibitors Succinylcholine Magnesium ```

Question 26

What is a Myasthenia Crisis?

Answer 26

A flare up of MG (acute exaccerbation) | Can weaken respiratory muscles and require ventilation

Question 27

What is a Cholinergic Crisis?

Answer 27

``` When you overtreat a patient with MG with AChE-i You get: Salivation Sweating Lacrimation Urinary Incontinence Diarrhoea GI disturbances Emesis ```

Question 28

How do AChE inhibitors work?

Answer 28

Block the enzyme which breaks down ACh ACh stays in the cleft longer Increases its action

Question 29

Why is timing of AChE-i crucial?

Answer 29

Lasts for 3-6 hours | Time it well to meals as it can affect whether someone can swallow or not

Question 30

What are the ADRs of AChE-i?

Answer 30

Cholinergic Side Effects | SSLUDGE

Question 31

How do you take AChE-i?

Answer 31

Oral IV Pyridostigmine

Question 32

What surgery can you do for PD?

Answer 32

DBS on STN Lesion in the thalamus (reduce tremor) Lesion in the GPi (lessen dyskinesia)

Question 33

How could Anticholinergic drugs help PD?

Answer 33

Believed ACh antagonises dopamine | Could treat the tremor but has no effect on bradykinesia

Question 34

How could you use Amantidine?

Answer 34

Weak Evidence May enhance dopamine release and inhibit ACh Poor but few side effects

Question 35

What does COMT do?

Answer 35

Inhibits breakdown to 3-MO So dopamine is around longer 3-MO normally inhibits the transport into the CNS as well

Question 36

Why use MOAB-i not just a MOA-i?

Answer 36

As B are normally found in dopamine regions of the brain | Don't have a risk of hypertensive crisis unlike non selective ones

Question 37

Examples of MOA-B Inhibitors

Answer 37

Rasagaline | Selegiline