Drug treatment of movement disorders

Question 1

What are the features of neurodegenerative disorders?

Answer 1

loss of neurons
progressive
irreversible - few areas may be able to regenerate

Question 2

What makes Parkinson’s disease a ‘akinetic-rigid syndrome’?

Answer 2

Loss of movement

Increased muscle tone

Question 3

What does the extra pyramidal system control?

Answer 3

involuntary movements

Question 4

How does Parkinson’s disease start and then progress?

Answer 4

Starts slow i.e. shaking digit is usually first feature
Becomes worse over time, lasts about 10-15 years
Remission is rare - can happen during times of heightened emotion
Death normally from bronchopneumonia/sepsis - immobility of respiratory muscles = unable to clear infections

Question 5

What are the symptoms of Parkinson’s disease?

Answer 5

Tremour - ‘pill rolling’
Rigidity/limb stiffness - due to increase muscle tone
Speech - slurred, monotone, dribbling, dysphagia
Akinesia - difficult to initiate movements and blink → uses a que to start movements
Postural changes - stoop shuffling, poor arm swing, impaired balance
→ telegraph pole fall (falling flat as cannot catch their fall quick enough)

Question 6

How does Parkinsons disease occur pathologically?

Answer 6

Loss of dopamine neurons in SUBSTANTIA NIGRA - controls movement
Lewy bodies present inside neurons
Loss of inhibitory/excitatory pathway

Question 7

What are the 4 causes of parkinsons disease?

Answer 7

Idiopathic
Drug induced e.g. dopamine antagonists
MPTP - opiate analogue used in studies to induce parkinsons
Post encephalitis

Question 8

Explain the direct pathway for involuntary movement?

Answer 8

Neurons of substania nigra project to striatum
Striatum releases dopamine
Dopamine acts on D1 receptors
Goes on to the Globus pallidus
Then projects to the thalamus

Question 9

Explain the indirect pathway for involuntary movement?

Answer 9

Neurons of substania nigra project to striatum
Striatum releases dopamine
Dopamine acts on D2 receptors
Goes on to the Globus pallidus and subthalamic nucleus
Then projects to the thalamus

Question 10

What happens to D1 and D2 pathways in Parkinsons disease?

Answer 10

They are lost

Question 11

How does L-DOPA work as a treatment for Parkison’s disease?

Answer 11

Replaces the lost dopamine

Question 12

What are the advantages of using L-DOPA?

Answer 12

Crosses the BBB
Absorbed and retained by neurons
Increases dopamine release from remaining neurons

Question 13

What are the problems with using L-DOPA orally?

Answer 13

Most of L-DOPA is metabolised before it reaches the bloodstream, let alone the brain

Question 14

How is the problem of L-DOPA’s poor absorption overcome?

Answer 14

Given with carbidopa = DOPA decarboxylase inhibitor

Question 15

What are the side effects of L-DOPA? (11)

Answer 15

'On-off effect' - After time, motor symptoms worsen as dopamine levels drop
Nausea
Vomiting
Anorexia
Dyskinesias = overdose leads to excessive movements
Tachycardia, extrasystoles 
Hypertension
Insominia
Confusuion/schizophrenic effect

Question 16

How do MAO inhibitors work?

Answer 16

STOPS breakdown of dopamine

Selegiline inhibits MAO which is produced in the breakdown of dopamine

Question 17

What are the advantages of MAO inhibitors?

Answer 17

neuroprotective effects?
Few side effects
Eliminates side effects of L-DOPA
Effective alone in early stages

Question 18

How do COMT inhibitors work?

Answer 18

STOPS breakdown of dopamine

Entacapone inhibits COMT which is a product of L-DOPA and dopamine breakdown

Question 19

What are the advantages of COMT inhibitors?

Answer 19

Can be used alongside L-DOPA/carbidopa combinations

Used for patients with ‘on-off’ problems

Question 20

What are the side effects of COMT inhibitors?

Answer 20

Can make L-DOPA dyskinesias more likely/worse
Nausea
Diarrhoea
Abdo pain
Dry mouth

Question 21

What drugs can be used for Huntington’s Disease?

Answer 21

D2 antagonist

DA depletion