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Flashcards in Parkinson's disease drugs Deck (20)
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1

Motor symptoms of PD

Pill-rolling RESTING tremor, bradykinesia, rigidity, postural instability

2

ANS symptoms of PD

olfactory dysfunction, postural hypotension, consitpatioo

3

Cognitive symptoms of PD

sleep disturbances, dementia, depression, irritability

4

main Dopaminergic pathways in the brain and origin and projection

Nigrostriatal. Substantia nigra pars compacta -> striatum (putamen)
mesolimbic. VTA -> NAcc
Mesocortical. VTA -> cerebral cortices
Tuburoinfundibular. arcuate nucleus of hypothalamus -> pituitary gland

5

DAergic pathway affected in PD

nigrostriatal. Neurodegeneration of DAergic neurones

6

Principles of PD drug therapy

Induce increased production of DA in existing neurones
Increased synaptic DA by inhibition of breakdown
Direct stimulation of dopamine receptors

7

Drugs used to Induce increased production of DA in existing neurones

LevoDOPA
Carbidopa/benserazide

8

LevoDOPA MOA

Substrate (literally DOPA)/ precursor for production of DA

9

Synthesis of DA

tyrosine -> DOPA by tyrosine hydroxylase
DOPA -> DA by DOPA decarboxylase

10

Why isn't tyrosine given to sythesise DA

Tyrosine = amino acid, not specific enough + TH is rate-limiting step in DA synthesis
LevoDOPA omits this

11

Carbidopa MOA

Peripheral DOPA-decarboxylase inhibitor
AS DO NOT CROSS BBB

12

Why is LeviDOPA co-administered with Carbidopa?

Prevents peripheral DA synthesis, more specific as only central synthesis
Smaller dose of LevoDOPA needed

13

Drugs groups used to Increased synaptic DA by inhibition of breakdown

MAO-B inhibitors
COMT inhibitors

14

Mechanisms of DA breakdown

MAO-B (monoamine oxygenase B) = specific DA breakdown. On mit. membrane, intraneuronal
COMT = bound to post-synaptic membrane, extraneural breakdown

15

Examples of MAO-B inhibitors

Selegiline/deprenyl
Rasagiline

16

Examples of COMT inhibitors

Entacapone
Tolocapone

17

Use of MAO-B inhibitors in PD

Used as an adjunct with LevoDOPA and CarbiDOPA to further increase synaptic [DA]

18

Examples of DA D2R agonsits

Ergot derivatives (longer t1/2):
Bromocriptine
Pergolide

Non-ergot derivatives (less SE):
Ropinerol

19

Acute and Long term side effects of LevoDOPA

Acute = N+V due to peripheral DA decerased

Longterm =
On-off symptoms
Dyskinesias

20

Why is there no regression of PD with current treatments?

They treat the lack of DA in nigrostriatal pathway and don't prevent the neurodegeneration, which will innevitably worsen symptoms