Parkinson's Disease Flashcards
Why can’t DA be given peripherally/administered directly to patients?
Why can’t L-DOPA be given alone?
is hydrophilic and polar therefore can’t cross the blood brain barrier
- leads to side effects
= must be given as L-DOPA
L-DOPA would be converted in the periphery to DA by DOPA decarboxylase
- must be given with a peripheral DOPA decarboxylase inhibitor
What are the different methods to increase DA?
give L-DOPA (precursor to DA)
- always with a peripheral DOPA decarboxylase inhibitor
inhibit MAOb
block DA transporter (DAT)
give a DA agonist (D1/D2)
block COMT
What are the side effects of L-DOPA?
- short term and long term
short term - diminish when tolerance kicks in
- nausea and vomiting = GI
- loss of appetite = GI
- postural hypotension = CV
- insomnia = sleep
- confusion = psychiatric
- visual hallucinations = psychiatric
long term
- involuntary movements = peak dose dyskinesia, diphasic dyskinesia, dystonia
- response fluctuations = wearing off
- delusions, illusions
What causes the short term effects L-DOPA?
hyperactivity in mesolimbic dopaminergic pathway
- DAergic neurones project from VTA to the amygdala & hippocampus (where dopamine is released)
hyperactivity in mesolimbic DAergic pathway
- DAergic neurones project from VTA to the nucleus accumbens (where dopamine is released)
associated with schizophrenia, addiction, emesis
How does L-DOPA and D2 agonist cause addiction? What are risk factors?
activation of DAergic neurones in the mesolimbic pathway
- amygdala = reward and pleasure
risk factors
- earlier onset
- personal or family history of substance abuse
How does L-DOPA cause impulse control disorder?
activation of DAergic neurones in the mesolimbic pathway
- amygdala = reward and pleasure
activation of DAergic neurones in the mesocorticol pathway
- frontal cortex = impaired decision making/cognition
What is evidence for the DA hypothesis?
DA release when taking amphetamine
- produces behavioural syndrome that resembles schizophrenia
resperine depletes DA and controls positive symptoms
D2 agonist produce stereotyped behaviour
How is PD linked to emesis?
chemoreceptor trigger zone (CTZ) is a vomiting centre found outside the brain
- is packed with D2 receptors
= increasing dopamine after PD causes activation of CTZ and emesis
What is the first line treatment for PD?
L-DOPA with a peripheral DOPA decarboxylase inhibitor
What are D2 agonist? What are their side effects?
new vs old
old
- Bromocriptine, Ropinirole, Pramipexole
= usually used ad hoc to L-Dopa further into PD progression
- nausea, vomiting, Psychiatric Symptoms
new
Ropinirole, Pramipexole
longer duration of action – lower tendency for dyskinesia
side effects: confusion, delusions, sleep disturbances, predispose to compulsive behaviours (excessive gambling, over eating, sexual excess/reward)
pramipexole – antioxidant effects & protective effect on mitochondria
What are MAOb inhibitors?
Selegiline – selective MAOb inhibitor
protect against MPTP toxicity – no evidence of neuroprotective role in patients
low risk of hallucinations, less adverse effects
What are COMT inhibitors?
Entacapone
- slows elimination of levodopa
- more adverse effects
- low risk of hallucinations
What are antimuscarinics?
Benzatropine, Procyclidine
not used a lot, useful in early stages in young people to tremor, rigidity
not to be used on old people memory problems, confusion
associated with troublesome side effects (dry mouth, impaired vision, urinary retention)
