18 Drug treatment of movement disorders.

Question 1

Describe the progression of Parksinon’s disease:

Answer 1

Slow.
Occurs over 10-15 years.
Remission at times of high emotion.

Question 2

What are the characteristics of a Parkinsonian tremor?

Answer 2

4-7Hz.
Sometimes unilateral.
‘Pin-rolling’.

Question 3

Describe the symptoms of Parkinson’s disease:

Answer 3

Tremor.
Limb rigidity.
Akinesia: difficulty starting to walk, serpentine stare.
Slurred and monotonic speech.
Postural: stoop, shuffle, little arm swinging.
Telegraph pole falls.

Question 4

Describe the pathology of Parkinson’s disease:

Answer 4

Neuronal death in substantia nigra.
Lewy bodies.
Dopaminergic cells affected.

Question 5

What are the causes of Parkinson’s? (4).

Answer 5

Idiopathic.
Drug induced.
MPTP induced.
Post-encephalitic.

Question 6

How is dopamine synthesised?

Answer 6

Tyrosine -> tyrosine hyroxylase -> L-DOPA -> DOPA decarboxylase -> Dopamine

Question 7

How does L-DOPA work?

Answer 7

Increases dopamine release from remaining neurones.

Question 8

What is the main problem with L-DOPA delivery and how is this overcome?

Answer 8

99% is metabolised before reaching the brain.

Carbidopa. Inhibits DOPA decarboxylase, but can’t cross BBB.

Question 9

What are the side effects of L-DOPA? (7).

Answer 9

On-off effect.
D + V.
Dyskinesias.
Tachycardia + extrasystoles.
Hypotension.
Insomnia + schizophrenia.
Effect wears off over time.

Question 10

Which drugs are given to minimise the side effects of L-DOPA? (2).

Answer 10

Domperidone to stop tachycardia + extrasystoles.

Clozapine for insomnia and schizophrenia.

Question 11

How is dopamine broken down?

Answer 11

Via COMT to 3-MT then MAO to homovanillinic acid.
OR
MAO to DOPAC then COMT to homovanillinic acid.

Question 12

How do MAO inhibitors work?

Name one:

Answer 12

Inhibit the breakdown of dopamine.

Selegiline. (MAOB selective).

Question 13

How is selegiline used in Parkinson’s? (2).

Answer 13

Effective alone in early stages.

Used to prolong L-DOPA effect in later stages.

Question 14

Pro’s and con’s of selegiline use in Parkinson’s?

Answer 14

Few side effects of it’s own. Possibly neuroprotective.

Potentiates central side effects of L-DOPA.

Question 15

How does COMT act? (2).

Answer 15

Breaks down dopamine to homovanillinic acid.

Breaks down L-DOPA to 3-O-methyl DOPA.

Question 16

Name a COMT inhibitor:

Answer 16

Entacapone.

Question 17

What are the adverse effects of entacapone? (4).

Answer 17

Aggravates L-DOPA dyskinesias.
N + V.
Dry mouth.
Abdominal pain.

Question 18

Name two dopamine agonists:

State their specificity:

Answer 18

Bromocriptine (D1+2)

Pergolide (D2).

Question 19

What are the side effects of dopamine agonists?

Answer 19

Similar to L-DOPA.

Plus hallucinations.

Question 20

Name two antimuscarinics used in Parkinson’s:

Who are they used in?

Answer 20

Benzhexol, orphenadrine.

Only in young with severe tremor.

Question 21

What are the adverse effects of antimuscarinics in Parkinson’s? (4).

Answer 21

Peripheral side effects rare.

Confusion, delusions, hallucinations, mood changes.

Question 22

Which types of surgery are used in Parkinsons? (4)

Answer 22

Thalamotomy (motor thalamus).
Pallidotomy (globus pallidus).
Subthalamotomy (sub thalamus).
Implantable stimulators.

Question 23

Describe the clinical features of Huntington’s (2):

Prognosis:

Answer 23

Chorea and dementia.

Starts at 30/50. Death in 10-20 years.

Question 24

What does a CT/MRI show in Huntington’s?

Answer 24

Cerebellar atrophy.

Question 25

Where does cell loss occur in Huntington's?

Answer 25

Selective cell loss in corpus striatum and cerebral cortex.

Question 26

Which cells are affected in Huntington's?

Answer 26

Medium sized spiny neurones containing GABA and encephalin.

Question 27

How are neurotransmitter levels affected in Huntington's? (5).

Answer 27

GABA ↓, GAD ↓ | ACh ↓, choline acetyltransferase ↓ DA ↔ or ↑

Question 28

What is the genetic basis of Huntington's disease? | Position. Change. Inheritance.

Answer 28

4p16.3. Polyglutamine (CAG repeat). Autosomal dominant.

Question 29

What is the treatment for Huntington's? (2,2)

Answer 29

D2 antagonists: haloperidol, chlorprozamine. | DA depletion: reserpine, tetrabenzine.

Question 30

What are the adverse effects of D2 antagonists? (2). | Used in Huntington's.

Answer 30

Parkinsonism. | Restlessness.

Question 31

What are the adverse effects of DA depletion? (4). | Used in Huntington's.

Answer 31

Hypotenison. Depression. Sedation. GI disturbances.

Question 32

Which drugs are used to treat dystopias? (5)

Answer 32

``` DOPA replacement. Anticholinergics. Benzodiazepines. Baclofen. Botulinum toxin. ```