Anti parkinsonian drugs Flashcards
what is dopmamine
monoamine neurotransmitter,
describe dopamine metabolism
Tyrosine - L-DOPA - Dopamine
what enzymes are involved in dopamine metabolism
Tyrosine Hydroxylase (TH)
DOPA Decarboxylase (DD)
what trnasporters transport dopamine from the synapse and into
cells
Dopamine Transporter (DAT)
Noradrenaline/Norepinephrine Transporter (NET)
where are these transporters found
dopaminergic neurones and glial cells
what metabolises monamines
Monoamine Oxidases:
A - all monamines
B - specific for dopamine
Catechol-0-Methyltransferase
- catecholamines
what are the dopaminergic pathways of the brain
Mesolimbic pathway
Mesocortical pathway
Nigrostriatal pathway
Tuberoinfundibular pathway
describe the mesolimbic pathway
starts in VTA to NAcc - Euphoria
In which conditions is the mesolimbic pathway disrupted in
addiction and schizophrenia
describe the mesocortical pathway
starts in VTA - cerebral cortex (frontal lobe)
controls executive and behavioural functions
problem in schizoids
describe the nigrostriatal pathway
starts in Substansia nigra pc - striatum
coordinates motor movement
what part of the striatum is the NAcc in
ventral striatum
describe the tuberoinfundibulnar pathway
from Arcuate nucleus - median eminence
(connects hypothalamus to pituitary
what are some affects that having too much prolactin would cause
Galactorrhoea, Ammenorhoea, loss of libido
describe the epidemiology of Parkinson’s
1-2% of individuals over 60
5% of cases are due to what mutation in….
certain genes SNCA, LRRK2, Parkin
categorise the symptomology of Parkinson’s
Motor
Autonomic
Neuropsychiatric
what are the motor symptoms of Parkinson’s
Lead pipe rigidity Bradykinesia Resting tremor postural instability parkinsonian gait
describe the parkinsonian gait
loss of arm swing, shuffling steps
what are the autonomic symptoms of Parkinson’s
anosmia
postural hypotension
constipation
neuropsychiatric symptoms of Parkinson’s
sleep disorders
Depression
Irritability
describe the pathology of Parkinson’s
loss of dopaminergic neurones in substantia nigra pc
what % loss of neurones do u need before motor symptoms appear
80%
what do you see on the post mortem of a Parkinson’s patient
Lewy bodies (protein aggregates in cell bodies)
Lewy neurites (protein aggregates in cell axons)
what are these protein aggregates made off
alpha-synuclein and ubiquitin
categorise the treatment for Parkinson’s
replace the dopamine - L-DOPA or agonist)
reduce the breakdown on dopamine (MAO inhibitor)
what is L-DOPA also known as
Levodopa
why is L-DOPA the preferred choice of dopamine replacement
TH is rate limiting enzyme
Rapidly converted to DA by DOPA-D
can cross BBB
what does peripheral breakdown of L-DOPA cause
Nausea and vomiting
long term side effects of Levodopa
dyskinesias & ‘on-off’ effects. NOT disease-modifying
what adjuncts are often given with levodopa therapy
DOPA decarboxylase inhibitors: Carbidopa & Benserazide
COMT inhibitors: Entacapone & Tolcapone
how do the DOPA-D inhibitors work
Do not cross BBB - prevent peripheral breakdown of levodopa
Reduce required levodopa dosage
how do the COMT inhibitors work
increase amount of levodopa in the brain
which receptors does dopamine act on
D1,5(Gs linked) or
D2-4 (Gi-linked) receptors
what are the dopamine agonists divided into
(potent D2 rc agonists):
Ergot derivatives:
Non-ergot derivatives:
what problems are ergot derivatives associated with
Associated with cardiac fibrosis
give examples of ergot derivative’s
Bromocriptine, Carbergoline and Pergolide.
give examples of non ergot derivative’s
Ropinirole and Rotigatine
Side-effects of Dopamine Agonists
Nausea
Vomiting
Hallucinations
Impulse Control Disorders (e.g. pathological gambling)
Psychosis
Raynaud’s Phenomenon
L-DOPA vs Dopamine Agonists which is better
L-DOPA = more effective, gold standard + less side effect
how do MonoAmine Oxidase B Inhibitors help
Not as effective as L-DOPA
useful in combination with L-DOPA to reduce doses
used to delay the time which a patient starts
L-DOPA
give an example of MAO-B inhibitor
Selegiline
give an example of Catechol-O-MethylTransferase Inhibitors
are these a good treatment
Entacapone , Tolcapone
NOT liscenced as monotherapy
categorise Schizophrenia Symptomology
Positive symptoms:
↑ Mesolimbic dopaminergic activity
Negative symptoms:
↓ Mesocortical dopaminergic activity
+ve symptoms in schizophrenia
Hallucinations: Auditory & visual
Delusions: Paranoia
Thought disorder: Denial about oneself
-ve symptoms in schizophrenia
Affective flattening: lack of emotion
Alogia: lack of speech
Avolition/ apathy: loss of motivation
Schizophrenia – Who Gets It?
1% of population & has genetic influences
Onset : 15-35 years (YOUNG)
Higher incidence in ethnic minorities (eg Afro-Caribbean
immigrants)
- Second Generation Specifically
what is the basis of schizophrenia pharmacology
The Anti-Psychotics are antagonists
