Parkinson's disease (PB) Flashcards
steps of conversion of tyrosine to adrenaline
tyrosine L-DOPA dopamine noradrenaline adrenaline
DA receptor families and subtypes
D1 receptor family -> excitatory, inc cAMP and Ca
- D1
- D5
D2 receptor family -> inhibitory, dec cAMP and Ca
- D2
- D3
- D4
What type of disorder is Parkinsons?
degenerative
What causes Parkinsons (basic)?
degeneration of dopamine secreting nerve cells
excess free radicals causes degeneration of neurons
What are Lewy bodies?
cytoplasmic inclusions in surviving neurons
mechanisms that cause neuron cell death
environmental toxins, aging, neuronal metabolism
- > free radical formation, oxidative stress, excitotoxicity, vulnerable neurons
- > DNA damage, lipid peroxidation, protein damage
- > cell death
symptoms of Parkinson’s
motor sympyoms (TRAP)
- tremor
- rigidity
- akinesia
- postural instability
non-motor symptoms
- neuropsychiatric
- sleep disturbances
- autonomic disturbances
- sensory disturbances
risk factors for Parkinson’s
non-smokers, low caffeine drinkers
genetic mutations in gene LRRK-2
mutations in parkin gene
neuroleptic drugs
antiemetics (prochloperazine, metoclopramide)
Where is DA produced?
substantia nigra within the basal ganglia
role of basal ganglia
co-ordinate performance of well-learnt, voluntary, semi-automatic motor skills and movement sequences
roles of DA
cognitive tasks
- maintaining attention
- switching focus of attention
- mood
- problem solving
- decision making
- visual perception
What does progressive denegeration of DA producing neurons lead to formation of?
Lewy bodies
When are clinical signs of disease evident?
when 80% of DA producing neurons are lost
dopamine acetylcholine balance
DA neurons in substantia nigra and corpus striatum
striatum also rich in excitatory ACh neurons that counteract the action of DA
DA ergic system inhibits the ACh system
UK Brain bank disgnostic criteria for PD
step 1: diagnosis
- bradykinesa and one of: rest tremor, rigidity, postural instability
step 2: exclusion criteria
- Hx of repeated strokes, neuroleptic meds, head injury, definite encephalitis
- presence of atypical features: early falls, supranuclear gaze palsy, ataxia and cerebellar features, early autonomic features, early cognitive decline, poor response to L-dopa
step 3: supportive slinical features (at least 3)
- unilateral onset, rest tremor, evidence of progression, persistent asymmetry, response to L-dopa, L-dopa induced dyskinesias, L-dopa response for 5+yrs, clinical course of 10+yrs
diagnosis of PD
based on TRAP (motor symptoms)
can get MRI/CT brain scans
referral time if PD is suspected
not >6 weeks normal cases
not >2 weeks in severe/complex cases
differential diagnosis for tremor disorders
psychological tremor - anxiety, thyrotoxicosis, fine tremor essential tremor dystonic tremor cerebellar disorders vascular parkinsonism drug induced parkinsonism atypical parkinsonism disorders dementia with Lewy bodies functional (non organic) normal pressure hydrocephalus others
2 drug types for PD
- drugs that restore DA levels in nigro striatal DAergic tract
- drugs that restore the DA-ACh balance
DA in nigro striatal tract drugs
levodopa and carbidopa/benserazide DA agonists MAO-B inhibitors COMT inhibitors miscellaenous (amantadine)
drugs for DA/ACh balance
antimuscarinic
2 brand/generics of L-dopa
Madopar - co-beneldopa
Sinemet - co-careldopa
drugs in Madopar (co-beneldopa)
L-dopa + benserazide
drugs in Sinemet (co-careldopa)
L-dopa + carbidopa
formulations of Madopar
capsules
dispersible tabs
CR capsules
What drug has the highest conc in Madopar/Sinemet?
levodopa is the higher strength
eg. Madopar 62.5mg caps = levodopa 50mg and benserazide 12.5mg
What is duodopa?
intestinal gel with 20mg/ml levodopa and 5mg/ml carbidopa
examples of dopamine agonists
bromocriptine carbergoline pergolide pramiprexole ropinrole - Requip rotigotine- Neupro
subcutaneous DA preparation
apomorphine - APO-go
MAO-B inhibitor
selegiline
resagiline
COMT inhibitors
entacapone
tolcapone
L-dopa/carbidopa/entacapone - Stalevo
antimuscarinics
trihexyphenidyl
orphenadrine
procyclodine- Kemadrin
miscellaneous
amantadine
most effective med for Parkinsons
levodopa
standard release preparations of levodopa
levodope/carbidopa - Sinemet
levodopa/benserazide - Madopar
prolonged release preps of levodopa
levodopa/carbidope - Simemet CR
levodopa/benserazide - Madopar CR
How are therapeutic/adverse effects got from levodopa?
from its decarboxylation to DA
What prevents peripheral breakdown of levodopa?
given with peripheral decarboxylase inhibitor to prevent peripheral break down
- carbidopa
- benserazide
smaller dose of levodopa needed to treat symptoms then