Parkinson pathophysiology and pharmacology Flashcards
what age group does Parkinson’s disease generally occur more commonly in?
60yrs and over
what is young onset Parkinson’s disease?
when people younger than 40years old experience Parkinson’s disease
what is the average life expectancy of those with parkinsons?
7-14years post diagnosis
what is the most well-known symptom of Parkinson’s disease (PD)?
tremor
when is the tremor maximal?
when the patient is at rest - reduces when patient is moving or sleeping
-can be experienced in the later stages of the disease
what is bradykinaesia?
slowness of movement - so the patient experiences difficulty planning, initiating and executing movement.
-experienced in the early stages of the disease
what is rigidity?
stiffness and resistance to limb movement caused by increased muscle tone
two types of rigidity?
- uniform
2. cogwheel/ratchet
where does rigidity affect in early stages of the disease?
-the neck and shoulder muscles
what is the pathology of PD?
- Degeneration of DAergic neurones of the nigrostriatal pathway
- this causes a loss of dopamine transmission in the striatum
what is Parkinsonism?
Any condition with loss of striatal Dopamine transmission e.g.
pharmacological blockade, brain lesion etc
what are the four dopamine pathways in the brain?
- nigrostriatal
- mesolimbic
- mesocortical
- tuberoinfundibular
how is dopamine synthesised?
Tyrosine enters the neurone and tyrosine hydroxyls turns it to DOPA. Then DOPA becomes dopamine via DOPA decarboxylase.
why can’t we give dopamine itself as a drug?
- coz it is polar so doesn’t cross membranes
- it is metabolised by MAO in the gut
what do we give to treat Parkinson’s?
L-DOPA which is a precursor to dopamine
what is the problem with giving L-DOPA?
it would get metabolised in periphery by amino acid decarboxylase present there so need to give high dose
how do we overcome the L-DOPA metabolism?
give L-DOPA with a peripheral acting decarboxylase inhibitor e.g. carbidopa
which monoamine oxidase metabolises dopamine?
type b (MAOb)
give an example of a MAOB inhibitor?
Selegiline
what effect does D2 receptor have on adenylate cyclase?
inhibits it
what effect does D1 receptor have on adenylate cyclase?
stimulates it
give examples of D2 receptor agonists and what do they do?
- bromocriptine
- apomorphine
- lisuride
- they inhibit the striatal output neurone directly (so they mimic dopamine as dopamine has an inhibitory effect)
anticholinergic drugs can also be given for PD, give examples?
- benztropine
- benzhexol
side effects of anticholinergic drugs are?
- confusion
2. anticholinergic effects
what enzyme breaks down L-DOPA?
COMT - catecholamine-o-methyl transferase
-so inhibiting this enzyme helps to increase L-DOPA concentration. But can’t give this inhibitor alone, have to give with L-DPOA.
what is iatrogenic Parkinsonism?
- when the drugs given to block D2 receptors/lower dopamine concentration and transmission, cause deficiency in dopamine and its action resulting in too low dopamine levels.
- e.g. in schizophrenia we give D2 receptor agonists causing Parkinsonism.
