Week 11 - Drugs for Parkinson's Disease Flashcards
What dopamine pathway is important in Parkinson’s Diseases (PD)?
Nigrostriatal system (Striatum and Substantia nigra)
What is Nigrostriatal system responsible for?
Fine motor control
Prepares motor system for next movement in a sequence of movements
What are pathological changes that occur in PD
loss of dopamine in striatum and of neurons in substantia nigra
What is the pathway of making dopamine?
Tyrosine –> Dopa –> Dopamine
Enzymes = Tyrosine hydroxylase, Dopa decarboxylase
What is Levadopa?
A dopamine pre-cursor -> helps increase dopamine pathway -> more dopamine
What must Levadopa be combined with to preserve its levels in the body?
Must be combined with peripheral DDC inhibitors that do not cross the blood-brain barrier -> More Levadopa to CNS
Eg. DDC inhibitors -> Carbidopa, Benserazide
What are AEs of Levadopa?
Dyskinesias
Nausea
Hallucinations
How are drugs that directly activate the dopamine receptor advantageous to dopamine pre-cursors?
- bypass enzymatic conversion to dopamine
- less dyskinesiaas than levadopa
- longer half life than levadopa
What are drugs that directly activate the dopamine receptors? and what are AEs?
Pramipexole
Rotigotine
AEs:
- nausea
- hallucinations
- impulse control disorders
How can Dopamine be metabolised?
Can undergo reuptake into pre-synaptic neuron -> then metabolised by monoamine oxidase (MAO)
If MAO can be inhibited -> more dopamine bc less is broken down
What are MAO inhibitors and examples?
inhibit MAO enzyme
eg - Selegiline
What are Catechol-O-methyl-transferase (COMT) inhibitors? Eg?
COMT inhibitors preserve levodopa and dopamine levels
Eg - Entacapone, Tolcapone
What are key cortical regions for speech and language?
Broca’s Area
Wernicke’s Area
Arcuate Fasciculus
What are Broca’s and Wernicke’s areas functions?
Broca’s:
- Speech prod
- Receives input from Wernicke’s area
- Near motor cortex
Wernicke’s:
- Speech understanding
- Near auditory cortex
What are the 7 components of the Wernicke-Geschwind Model
- Primary Motor Cortex
- Broca’s Area
- Primary Auditory Cortex
- Wernicke’s Area
- Angular Gyrus
- Primary Visual Cortex
- Arcuate Fasciculus
What does Angular gyrus do?
Converts info from prim. visual cortex into an auditory type signal that can be processed by Wernicke’s
For looking at written word
What is Aphasia?
= partial or complete loss of language abilities following brain damage
What is Dysarthria?
= group of motor speech disorders -> slow/poor coordination of speech muscles
What is Apraxia?
= Motor speech disorder
What categories can you split Aphasia into?
Nonfluent & Fluent
Nonfluent:
- Struggle to produce speech but can relay meaning/theme still
Fluent:
- Can speak properly but speech lacks meaning
What is Broca’s Aphasia? What is the cause? What does it affect?
= Motor/expressive Aphasia
- Caused by lesions of left frontal lobe -> associated w damage to prim motor cortex and post frontal lobe
- Affects ability to prod language efficiently but language comprehension is fine
What is Broca’s Aphasia? What is the cause? What does it affect?
= Sensory/Receptive Aphasia
- Caused by damage to left temporal lobe over Wernicke’s area
- Can speak in long sentences but has no meaning
What is Conduction Aphasia?
- Lesion located at arcuate fasciculus
- difficulty or unable to repeat what is spoken
- Could say ‘hosical’ or ‘hotel’ instead of ‘hospital’
Summary of all types of Aphasia
