Parkinson's Disease Flashcards
Pathophys. of PD
Cell death in the substantia nigra
Loss of dopaminergic innervation in the basal ganglia
Reduction of direct and increase in indirect
This leads to decreased thalamic activity, causing motor symptoms
Some important PD risk factors
Pesticide exposure, DA toxic
Familial (Prkin, LRRK2, synuclein)
Why are the effects of DA replacement therapy limited?
They rely on remaining, liva DA neurons to produce the dopamine. As the DA neurons die, the approach becomes less effective.
How can DA D2 and D3 agonists improve PD symptoms?
Name some
Mimic the activity of DA in the indirect pathway
Pramipexole, Ropinirole
Formerly, pergolide, but discontinued from cardiac valvulopathy
L-Dopa problems
Large first pass effect
Small amount makes it to CNS
Short half-life
What is carbidopa?
An inhibitor of peripheral L-dopa metabolism, helps get more of it to the CNS
This lets you have lower doses, decreasing dyskinesias, GI problems
Name for the levodopa+carbidopa combo
Sinemet
Why don’t you give L-dopa as soons as a patient is diagnosed?
Motor dyskinesias (chorea, dystonia, athetosis)
First approach that should be taken to PD
Non-ergoline monotherapy
Why add MAO-B and COMT to a PD regimen?
MAO-B Inhibt – Stop DA breakdown
COMT inhib – prevent methylation in liver or l-dopa
Huntington’s Disease Pathophysiology
Selective destruction of the medium spiny neurons of the neostriatum (esp. those projecting to the GPe
inhibition of GPi, STN –> Disinhibited Thalamus/Cortex
Common components of a Huntington Disease patient pharmacotherapy
Carbemazepine for depression
Tetrabenazine to elevate monamines (DA)
Benos if severely agitated, anxious, or stressed
Important details on Tizanidine
Alpha 2 agonist that acts presynaptically to reduce motor neuron activity
Used usually after stroke, MS, ALS to reduce spasticity
Important details on Baclofen
GABA-B agonist that can act directly on the motor neron an presynaptically on the excitatory corticospinal glutamate fiber
used with ALS
Important detailso n Dantrolene
Interferes with excitation contraction coupling in muscle by blocking SR calcium release
