18 Drug treatment of movement disorders. Flashcards
Describe the progression of Parksinon’s disease:
Slow.
Occurs over 10-15 years.
Remission at times of high emotion.
What are the characteristics of a Parkinsonian tremor?
4-7Hz.
Sometimes unilateral.
‘Pin-rolling’.
Describe the symptoms of Parkinson’s disease:
Tremor.
Limb rigidity.
Akinesia: difficulty starting to walk, serpentine stare.
Slurred and monotonic speech.
Postural: stoop, shuffle, little arm swinging.
Telegraph pole falls.
Describe the pathology of Parkinson’s disease:
Neuronal death in substantia nigra.
Lewy bodies.
Dopaminergic cells affected.
What are the causes of Parkinson’s? (4).
Idiopathic.
Drug induced.
MPTP induced.
Post-encephalitic.
How is dopamine synthesised?
Tyrosine -> tyrosine hyroxylase -> L-DOPA -> DOPA decarboxylase -> Dopamine
How does L-DOPA work?
Increases dopamine release from remaining neurones.
What is the main problem with L-DOPA delivery and how is this overcome?
99% is metabolised before reaching the brain.
Carbidopa. Inhibits DOPA decarboxylase, but can’t cross BBB.
What are the side effects of L-DOPA? (7).
On-off effect. D + V. Dyskinesias. Tachycardia + extrasystoles. Hypotension. Insomnia + schizophrenia. Effect wears off over time.
Which drugs are given to minimise the side effects of L-DOPA? (2).
Domperidone to stop tachycardia + extrasystoles.
Clozapine for insomnia and schizophrenia.
How is dopamine broken down?
Via COMT to 3-MT then MAO to homovanillinic acid.
OR
MAO to DOPAC then COMT to homovanillinic acid.
How do MAO inhibitors work?
Name one:
Inhibit the breakdown of dopamine.
Selegiline. (MAOB selective).
How is selegiline used in Parkinson’s? (2).
Effective alone in early stages.
Used to prolong L-DOPA effect in later stages.
Pro’s and con’s of selegiline use in Parkinson’s?
Few side effects of it’s own. Possibly neuroprotective.
Potentiates central side effects of L-DOPA.
How does COMT act? (2).
Breaks down dopamine to homovanillinic acid.
Breaks down L-DOPA to 3-O-methyl DOPA.
Name a COMT inhibitor:
Entacapone.
What are the adverse effects of entacapone? (4).
Aggravates L-DOPA dyskinesias.
N + V.
Dry mouth.
Abdominal pain.
Name two dopamine agonists:
State their specificity:
Bromocriptine (D1+2)
Pergolide (D2).
What are the side effects of dopamine agonists?
Similar to L-DOPA.
Plus hallucinations.
Name two antimuscarinics used in Parkinson’s:
Who are they used in?
Benzhexol, orphenadrine.
Only in young with severe tremor.
What are the adverse effects of antimuscarinics in Parkinson’s? (4).
Peripheral side effects rare.
Confusion, delusions, hallucinations, mood changes.
Which types of surgery are used in Parkinsons? (4)
Thalamotomy (motor thalamus).
Pallidotomy (globus pallidus).
Subthalamotomy (sub thalamus).
Implantable stimulators.
Describe the clinical features of Huntington’s (2):
Prognosis:
Chorea and dementia.
Starts at 30/50. Death in 10-20 years.
What does a CT/MRI show in Huntington’s?
Cerebellar atrophy.
Where does cell loss occur in Huntington’s?
Selective cell loss in corpus striatum and cerebral cortex.
Which cells are affected in Huntington’s?
Medium sized spiny neurones containing GABA and encephalin.
How are neurotransmitter levels affected in Huntington’s? (5).
GABA ↓, GAD ↓
ACh ↓, choline acetyltransferase ↓ DA ↔ or ↑
What is the genetic basis of Huntington’s disease?
Position. Change. Inheritance.
4p16.3.
Polyglutamine (CAG repeat).
Autosomal dominant.
What is the treatment for Huntington’s? (2,2)
D2 antagonists: haloperidol, chlorprozamine.
DA depletion: reserpine, tetrabenzine.
What are the adverse effects of D2 antagonists? (2).
Used in Huntington’s.
Parkinsonism.
Restlessness.
What are the adverse effects of DA depletion? (4).
Used in Huntington’s.
Hypotenison.
Depression.
Sedation.
GI disturbances.
Which drugs are used to treat dystopias? (5)
DOPA replacement. Anticholinergics. Benzodiazepines. Baclofen. Botulinum toxin.
