parkinsons disease pharmacology

Question 1

what is dopamine

Answer 1

catecholamine neurotransmitter - synthesised from tyrosine and metabolised by MAOB in the synaptic terminal

Question 2

what are the two types of dopamine receptors

Answer 2

D1 like - act via G alpha S - increase cAMP (excitatory)
D2 like - act via G alpha I - decrease cAMP (inhibitory)

Question 3

what are the D1 like receptors

Answer 3

 D1 – most abundant, nigrostriatal, mesolimbic and mesocortical pathways
 D5 – limbic system

Question 4

what are the D2 like receptors

Answer 4

 D2- nigrostriatal, mesolimbic and Tuberhypophyseal pathways and CTZ
 D3
 D4

Question 5

what pathways are dopamine involved in

Answer 5

nigrostriatal - movement
mesolimbic - behavioural reward pathways
mesocortical - cognition and thought
Tuberhypophyseal - control of secretion

Question 6

what is the pathophysiology of PD

Answer 6

loss of dopaminergic containing cells in the nigrostriatal pathway - between the substantia nigra and striatum

Question 7

what are the 2 dopamine pathways in the nigrostriatal pathway

Answer 7

direct pathway - enables movement D1R
indirect pathway - inhibits movement (inhibited by the presence of dopamine) D2R

Question 8

what is the effect of dopamine on ACh

Answer 8

• Dopamine usually inhibits ACh in the striatum – lack of dopamine leaves ACh unopposed – contributes to tremor in PD

Question 9

what are lewy bodies

Answer 9

Intracellular aggregations of alpha-synuclein found in neuronal cells – normally involved in exocytosis of vesicles - associated with early onset

Question 10

what role does mitochondrial damage play in PD

Answer 10

• Parkin/PINK1 mutations lead to PD through mitochondrial turnover
  -Mitochondrial damage leads to cell death of dopaminergic neurons

Question 11

what is levodopa and how does it work

Answer 11

dopamine precursor - crosses BBB
once in CNS, levodopa will be metabolised to dopamine

Question 12

what medications can be co-administered with levodopa to reduce its metabolism

Answer 12

DOPA decarboxylase inhibitor – carbidopa or benderizine - Reduces dopamine in periphery – does not cross BBB- less s/e
Metabolism of dopamine in the CNS can be inhibited by inhibiting MAO-B
o Selegiline and rasagiline

Question 13

what are dopamine agonists and how do they work in the treatment of PD

Answer 13

• Agonises D1/2 receptors in the place of dopamine
• More D2 selective
  o Pramipexole, ropinirole, Rotigotine

Question 14

what is amantadine

Answer 14

NMDAR agonist