Parkinson's disease drugs Flashcards
Motor symptoms of PD
Pill-rolling RESTING tremor, bradykinesia, rigidity, postural instability
ANS symptoms of PD
olfactory dysfunction, postural hypotension, consitpatioo
Cognitive symptoms of PD
sleep disturbances, dementia, depression, irritability
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
DAergic pathway affected in PD
nigrostriatal. Neurodegeneration of DAergic neurones
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
Drugs used to Induce increased production of DA in existing neurones
LevoDOPA
Carbidopa/benserazide
LevoDOPA MOA
Substrate (literally DOPA)/ precursor for production of DA
Synthesis of DA
tyrosine -> DOPA by tyrosine hydroxylase
DOPA -> DA by DOPA decarboxylase
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
Carbidopa MOA
Peripheral DOPA-decarboxylase inhibitor
AS DO NOT CROSS BBB
Why is LeviDOPA co-administered with Carbidopa?
Prevents peripheral DA synthesis, more specific as only central synthesis
Smaller dose of LevoDOPA needed
Drugs groups used to Increased synaptic DA by inhibition of breakdown
MAO-B inhibitors
COMT inhibitors
Mechanisms of DA breakdown
MAO-B (monoamine oxygenase B) = specific DA breakdown. On mit. membrane, intraneuronal
COMT = bound to post-synaptic membrane, extraneural breakdown
Examples of MAO-B inhibitors
Selegiline/deprenyl
Rasagiline
