Parkinson's Flashcards
4 Aims of drugs
prevent DA breakdown, replace DA, increase DA release, DA receptor agonists.. Also alter Ach activity
Selegiline? (+ Rasagiline)
selective, irreversible MAO B inhibitor, more effective in combo with L-dopa. No cheese reaction with L dopa
Location of MAO b and MAO a?
both enzymes in outer membrane of mitochondria. MAO a- liver, pulmonary vascular endothelium, GIT, metabolises NA, 5HT and DA. MAO b- in brain glial cells and 5HT neurones and blood platelets, mainly metabolises DA.
how do Monoamine oxidases work?
catalyse oxidation of monoamines
COMT stands for?
catechol-o-methyl transferase- degrades A, NA, DA.
COMT I examples and side effects
Entacapone, nitecapone, dyskinesis, GIT issues, abdominal pain, dry mouth
What are the two main issues associated with L-dopa?
Dyskinesis- irregular jerky movements (within two years) particularly face and limb movements. occurs at peak therapeutic effect, L-dopa has a short half life, so more frequent. The on/off effect; due to sustained L-dopa treatment. hypokinesia and rigidity suddenly worsen and then improve
L-Dopa formation?
Tyrosine hydroxylate catalyses tyrosine to L-Dopa formation. Dopa decarboxylase catalyses L-dopa to dopamine.
L-dopa action?
L-dopa crosses BBB and enters neurones via carrier mechanism. broken down to DA. (replace DA) DA cannot cross BBB. increase release of DA from remaining nerve cells.
what is the use of carbidopa?
inhibits dopa decarboxylase but cannot cross the BBB, therefore prevents excessive DA in periphery (avoid side effects) reduces dose of L-dopa needed by 10 fold. higher proportion of L-dopa reaches brain.
what are bromocriptine and pergolide?
D1 and D2 Dopamine receptor agonists
More L-dopa side effects?
hypotension, insomnia, confusion, schizophrenia effects
COMT inhibitor side effects?
nausea, diarrhoea, abdominal pain, dry mouth
