Parkinson's Disease Flashcards
(45 cards)
What is Parkinson’s disease?
A degenerative condition caused by the loss of dopamine-secreting neurons in the midbrain area of the substantia nigra causing tremor and impairment.
It is progressive due to death of dopaminergic neurones as well as presence of Lewy Bodies
What are the main functions of DA?
Memory
Movement
Motivation
Mood
Learning
Sleep
Attention
Good behaviour
Thinking
What is the purpose of Lewy Bodies?
Disruption of neurotransmitter balance and loss of connection between nerves and ultimately destruction of dopamine.
If something attacks substantia nigra what are the symptoms?
Tremors and moto impairment
Where is DA released/contained from?
Substantia nigra
DA released from nucleus accumbens and hippocampus normally functions with?
Pleasure
DA released from substantia nigra normally functions as?
Motor function & memory
What are the three areas that DA can be released from?
Substantia nigra, nucleus accumbens & hippocampus
If DA drops then ACh what?
Increase vice versa
3 Functions of DA?
Voluntary movement
Produces Neurotransmitter DA
Regulates mood
What are motor and non-motor symptoms of parkinsons?
Motor - Bradykinesia - slow movement
Hypokinesia - delayed action
Stiffness & rigidity
Rest tremor due to increase of ACh
Non-motor - Depression - DA = pleasure - decrease will decrease happiness
Also due to reduced movement which is depressing
Reduced cognitive impairment
Diagnose parkinsons?
Take a med history and physical examination
Within examination monitor motor function and also if there was a positive response to Levodopa
CT & PET - not useful
Biomarkers in urine, blood and CSF - not useful
Is PD linked to aging?
No
What is the ideal of clinical management for PD?
To restore DA & ACh levels
No cure so aim to slow deterioration
What are 4 drug functions used to manage PD?
Replace DA
Inhibit ACh
Mimic role of DA
Prevent destruction of DA/ Allow reuptake of DA
What are the three main treatments of early stages of PD? & THEIR DRUG TYPE
Levodopa - precursor of dopamine
Oral/transdermal NON ERGOT dopamine agonists - stimulate release of DA from substantia nigra
Monoamine-oxidase-B inhibitors - ACh inhibitor
What is the cheese interaction?
Patient on MAOI means increased levels of tyramine which is vasoconstrictive. Cheese contains tyramine resulting in hypertensive crisis
Why don’t you start pt on Levodopa?
Can develop resistance so preserve this as another stage of treatment (most effective treatment)
Start with DA Agonist
Why can Levodopa cross BBB?
Lipophilic & small
Why is levodopa given as a combo rather than on its own?
Levodopa can cross BBB. It is a prodrug meaning it needs activation - we require these to be in the brain not the periphery.
These enzymes are - Dopa decarboxylase - breakdown levodopa to da in the peripheral system meaning they can’t cross BBB and work in CNS.
Combination of levodopa and enzyme inhibitors to inhibit peripheral metabolism of levodopa to dopamine & allow levodopa to cross BBB and be converted to DA in central. It also means you are giving pt lowest dose - reduces adverse effects & increase therapeutic effect
What are the three LD enzymes that breakdown L-dopa to DA?
COMT -p&c
DD - DOPA DECARBOXYLASE - p&c
MAO- c only
What does carbidopa do?
Protective enzyme which acts on DD and allows DA to cross BBB
What are the two main examples of peripheral dopa-decarboxylase inhibitors? When are these given?
Carbidopa & Benserazide
Later stage treatments
Why is a lower dose of Levodopa administered when in conjunction with carbidopa or benserazide?
These inhibit peripheral conversion of Levodopa to DA - therefore more can cross BBB
