Neurodegenerative and Movement Disorders Flashcards
what are the 2 main purposes of pharmacotherapy of Parkinsons
increase dopaminergic activity
decrease cholinergic activity
dopamine doesn’t cross the BBB, however its precursor __ does
L-dopa
how is dopamine able to cross the BBB
the prodrug L-dopa crosses the BBB and is converted to dopamine by dopa decarboxylase
what is the effect of dopamine binding to D2 and D3 receptors in the CNS
opens K+channels
most of L-dopa is metabolized in the intestines by MAO and decarboxylation, however some is metabolized in the periphery (blood) by __ and __
COMT
decarboxylation
L-dopa is administered with __ which functions as a __
Carbidopa
peripheral decarboxylase inhibitor
what is the function of Carbidopa
inhibition of peripheral decarboxylase and its metabolism of L-dopa in GIT and blood, therefore increasing CNS bioavailability in the CNS
common side effects of L-dopa include …
nausea/vomiting
orthostatic hypotension
cardiac arrhythmia
what is the main adverse effect of L-dopa
dyskinesias
dyskinesias caused by L-dopa can be decreased by adding what drug
amantadine
wearing off reactions of L-dopa are related to
gradually, the duration of L-dopa effect is decreased
*related to timing
on-off phenomenon with L-dopa
sometimes patients response to L-dopa, sometimes they don’t
*fluctuation in clinical response
what is one of the main drug interactions of L-dopa
vitamin B6
how does vitamin B6 interact with L-dopa
increases dopa decarboxylase
what is the drug of choice for Parkinsons
L-dopa
if L-dopa is ineffective, what drug is used as a backup
dopamine receptor agonist
dopamine receptor agonists are used for ___ and __
response fluctuation
refractory to levodopa
what is the main adverse effect of dopamine receptor agonists
pulmonary and retroperitoneal fibrosis
Cabergoline is a dopamine receptor agonist that leads to what adverse effect
cardiac valvulopathy
Pergolide is a dopamine receptor agonist that lead to what adverse effect
heart valve fibrosis
regurgitation
what type of drug can be given to delay the need for L-dopa
non-ergot derivative dopamine receptor agonist
what is the injectable dopamine agonist Apomorphine used for
advanced Parkinsons with intermittent off episodes
what is given prior to injection of dopamine agonist Apomorphine
anti-emetic (Trimethobenzamide or Domeperidone)
the injectable dopamine agonist Apomorphine is contradicted with use of what drugs
5-HT3 receptor blockers
*can lead to severe hypotension
what is an adverse effect of the MAO-B inhibitor Selegiline
serotonin syndrome
what is the function of Catechol-O-Methyltransferase (COMT)
inhibition of dopa decarboxylase so there will be a decrease in 3-OMD competing for the L-dopa transporter into the CNS
what is the main use of COMT inhibitors
reduce the wearing off/on-off effects of L-dopa
what is an adverse effect of the COMT inhibitor Tolcapone
fatal hepatotoxicity
what type of drug is Tolcapone
COMT inhibitor
what is the function of Amantadine in Parkinsons
enhances release of dopamine
blocks dopamine uptake
what are 3 adverse effects of Amantadine
-livedo reticularis (bluing of skin+ankle edema)
-orthostatic hypotension
-Amantadine keratopathy (corneal edema)
what is the function of central anticholinergics (muscarinic blockers) in Parkinsons
balance dopamine/acetylcholine activity
what is the main use of anticholinergics for Parkinsons
drug induced Parkinsonism (mainly by antipsychotics)
what is the most effective treatment for Parkinsons
L-dopa+Carbidopa
what is the neurological cause of Huntingtons
degeneration of GABAnergic neurons in the neostriatum
what is the mechanism of action of Tetrabenazine, a VMAT inhibitor used for Huntingtons
inhibitor of monoanime uptake and storage
what is the neurological cause of Alzheimers
overstimulation of NMDA receptors
therapy for Alzheimers include __ and __
cholinesterase inhibitors
NMDA antagonists
what is the drug used for management of depression associated with Parkinsons
Rivastigmine
what therapeutic use can be used for Tourette syndrome
Botulinism toxin for tics