Pharmacology of Movement Flashcards
What are the 3 characteristics of neurodegnerative disorders?
- Loss of neurones
- progressive
- irreversible
What is an alternative name for Parkinson’s disease
What type of syndrome / disorder is it?
“Shaking palsy”
it is common worldwide and incidence increases over 70
it is an akinetic-rigid syndrome involving loss of movement and increased muscle tone
it is an extrapyramidal disorder
What is the progression of Parkinson’s disease like?
- It is slow and progressive
- causes mild inconvenience at first but becomes intrusive
- remission is rare
- it usually lasts 10-15 years, but can last decades
- death is usually from bronchopneumonia
What are the characteristics of tremor, rigidity and speech in Parkinson’s disease?
Tremor:
- 4 - 7 Hz
- “pill rolling”
- sometimes unilateral
Rigidity:
- limb stiffness - “lead piping”
speech:
- slurred and monotone
- dribbles
- dysphagia occurs later
What is akinesia and postural changes in Parkinson’s disease?
Akinesia:
- difficulty in initiating movement
- facial immobility
- blinking reduced - “serpentine stare”
Postural changes:
- stoop
- shuffling
- poor arm swinging
- balance impaired
- “telegraph pole” falls
What is the pathology involved in Parkinson’s disease?
- Loss of neurones in substantia nigra
- Lewy bodies - spherical, eosinophilic, contain cellular proteins
- DA-ergic neurones affected
- loss of nigro-striatal inhibitory / excitatory pathway
- midbrain nuclei
What are the causes of Parkinson’s disease?
- Unknown - idiopathic
- Associated disorders
- drug-induced (iatrogenic)
- MPTP-induced
- post-encephalic
What are the components involved in the Parkinson’s disease pathway?
How much of the pathway involved in Parkinson’s needs to disappear for there to be loss of symptoms?
50% loss for symptoms
80%+ loss at autopsy
What are the 2 general approaches to Parkinson’s disease treatment?
Increase DA activity
Decrease ACh activity
How can DA activity be increased?
Which drugs are used?
- Replace DA - L-DOPA
- reduced DA breakdown - MAO inhibitors, COMT inhibitors
- increase DA release - amantidine
- DA agonists - bromocriptine, pergolide
What type of drugs are used to decrease ACh activity?
Antimuscarinics - benzhexol, orphenadrine
How does L-DOPA work?
It replaces DA to increase DA activity
L-DOPA is converted to dopamine by DOPA decarboxylase
Increase in brain dopamine concentrations improves nerve conduction and assists in movement disorders
What is MOA?
How does it work and interact with neurones?
It is a dopamine precursor
it crosses the blood-brain barrier and enters neurones via carrier mechanism
it is converted to DA in neurones and glia
it is retained mainly by neurones and leads to increased DA release from remaining neurones
What are the problems associated with L-DOPA?
- Metabolism in the periphery
- 90% metabolism in the intestinal wall by DOPA decarboxylase / MAO
- 9% metabolism in other peripheral sites
- 1% reaches the brain
What is L-DOPA usually given alongside and why?
It is usually given with carbidopa which doesn’t pass the blood-brain barrier
carbidopa inhibits DOPA decarboxylase
What is selegiline?
How does it work and when is it given?
It is a MAOB selective inhibitor
it is effective alone in early stages
it is ineffective alone in later stages and is usually given to prolong L-DOPA action
What is the main COMT inhibitor?
How does it work?
Entacapone is an adjunct to L-DOPA / carbidopa combinations
it is used for patients with “on-off” problems
it is a drug which inhibits catechol-O-methyltransferase - an enzyme which methylates catecholamines such as dopamine
what is the pathology involved in Huntingdon’s disease?
Selective cell loss in the corpus striatum of the cerebral cortex
first affected are the medium-sized spiny neurones containing GABA and enkephalin
