Complete List of Terms and Definitions for Block 2: Neurodegenerative Disorders

Terms Definitions
Memantine NMDA receptor antagonist may have neuroprotective properties may slow progression of Alzheimer's
Why combine L-dopa with Selegiline? This is a MAO B inhibitor. It decreases dopamine breakdown in the brain, but does not cause catecolamine build-up in the peripheral tissues (no HTN crisis).
Why give l-dopa gradually? What does L-dopa do? Reduce side effects and toxicityReduces bradykinesia and rigidity, less effective in reducing tremor.
Which tissues in the brain are affected because of PK's? Striatal tissue (caudate and putamen) show 10% of normal dopamine
What are the low dose atypical antipsychotics? Why use them? Risperidone, Olanzapine, QuetiapineControl hallucinations caused by l-dopa
Most obvious early sign of Parkinson's? Tremor- usually pill-rolling
Long term complications of L-dopa abnormal involuntary movements, faciolingual tics, bobbing,and rocking movements. *decreased affectiveness of l-dopa leading to on-off phenomenon
COMT inhibitors TolcaponeEntacopone
Somewhat selective D2,D3 DA receptor agonists Ropinirole/Pramipexole
L-dopa, carbidopa, Sinemet, bromocriptine, ropinirole, pramipexole, amantadine, selegiline, propranolol, benztropine, trihexyphenidyl, entacapone Parkinson's
Dopamine agonists Bromocriptine/Pergolide
Where is dopamine made? What does this area display in PK's? Pars compacta of the substantia nigraDegeneration of the dopaminergic neurons
Recommendations for early stage Parkinson's Dopamine agonists (pramipexole or ropinirole)
What is the on-off phenomenon? Partial l-dopa resistance due to pronlonged treatment leads to asymptomatic followed by severe symptom cycles.
Why do you combine Carbidopa with L-dopa? Carbidopa is a peripheral L-aromatic Decarboxylase inhibitor. Coadministration allows lower doses of L-dopa to be given and still get to the brain.
What is the normal pathway of dopamine? Pars Compacta of Substantia Nigra -- release of DA -- D2 (inhibits cholinergic release Ach)and D2 (inhibits muscarinic release GABA to Globus Pallidus)
Dopamine precursorsReplenishes dompamine in striatum l-dopa
What is the offending neurotransmitter in PK's? Dopamine
Why combine bromocriptine with l-dopa? Reduce on-off phenomenon
What's the affect of decreased dopamine on the pathway? How should we treat the defect? Decreased D2 inhibition, increased release of Ach. Replace dopamine and block Ach
Contraindication of L-dopa Never with MAOI- would result in massive increase of sympathomimetic amines leading to hypertensive crisis. Antipsychotic drugs (pnenothiazine or butyrophenone) antagonize l-dopa.
Selegiline (Deprenyl)(se le' ji leen) MAO B inhibitor, predomintates in the brain
Pathology of Alzheimer's Brain accumulation of plaques and tangles composed of Beta amyloid
MA of Selegiline, side effects Prevents oxidation of dopamine in brainMay cause HTN at high dose
Can we give exogenous dopamine for treatment of PK's? No, doesn't cross BBB, give L-dopa which does.
Other drugs being considered for Alzheimer's NSAIDS, estrogen, nicotine, statins
RopinirolPramipexole Dopamine agonists
Side effects of l-dopa nausea, orthostatic hypotension, arrhythmias, hallucinations, delusions, dyskinesias
Muscarinic cholinergic receptor antagonists BenztropineTrihexyphenidyl
Why are side effects such as emesis and hypotension a problem w/dopamine agonists? They activate peripheral dopamine receptors
Effect of DA agonists Stimulate DP receptors in striatum. Reduce on-off
Why use CAAs? Side effects? Reduce tremordry mouth, blurred vision, urinary retension
Indirectly causes the release of endogenous DASide effects? AmantidineHallucinations
Amantidine Antiviral drug found to improve Parkinson symptoms. Releases endogenous DA
peripheral l-aromatic decarboxylase inhibitor (does not enter brain) Carbidopa
How many does Parkinson's affect? 1% over 50
Side effects of Carbidopa
How much degeneration do you need in PK's to show disfunction? ≧70%
Bromocriptine, Pergolide Dopamine agonists
Why use selegiline in newly diagnosed patient? May delay the onset of symptoms
How can we avoid agonist side effects? Achieve a higher T.I. by combining with a dopaminergic antagonist
Most common form of dementia Alzheimer's- progressive impairment of memory and cognitive fxn.
MAO B inhibitor Selegiline
How long w/o treatment before death? With? 9 years20 years
MA for MS cholinergic receptor antagonists Block muscarinic receptors in striatum- useful only very early in dz
Recommendations when DA agonists no longer work Add l-dopa and carbidopaCan add COMT inhibitors (entacapone) to reduce wearing off periods
Tacrine, donepezil, rivastigmine, galantamime, memantine Alzheimer's
What are the side effects of L-dopa? Nausea- stimulation of DA receptors in area postrema of medulla. Orthostatic hypotension- presynaptic DAr inhibit NE release that would normally constrict vessels.Cardiac arrhythmias- DA stim of Beta receptorsPsychotic-like symptoms- Activate DAr in mesolimbic system.
Symptoms of Parkinson's akinesiatremorrigidityalteration of posture, mask-like face, shuffling gait, loss of associative movment, and hypersalivation
Side effects of MSCR antagonists Dry mouth, blurry vision, urinary retention
Is the on-off phenomenon avoided by combination with carbidopa? No, may even be worse.
Difference between Tacrine and donepezil, rivastigmine, and galantamine? Tacrine is non-selective, the others are brain-selective
MA of Carbidopa prevents conversion of l-dopa to dopamine in peripheral tissues
How much L-dopa do we give? Why? Large doses, more than 95% ingested is decarboxylated in peripheral tissues.
Side effects of agonists Nausea, hypotension, dyskinesia, hallucinations, and delusions
MA of COMT inhibitors prevent breakdown of l-dopa by COMT
Four drugs used to treat Alzheimer's. All are...? TacrineDonepezilRivastigimineGalantamineAll ACEi
When given with carbidopa, how much l-dopa should be give to reach the TE? 75% less than w/o carbidopa
Centrally acting anticholinergics (CAA) BenztropineTrihexyphenidyl
Side effects of DA agonists Nausea, Ortho hypotension, hallucinations, delusions, dyskinesias
How is the rigidity in PK's characterized? cogwheel
What does selegiline do? What are it's advantages? decrease breakdown of dopamine in brain, but don't cause catecholamine build up in peripheral tissues, therefore no HTN crisis
Sinemet 1 part carbidopa to 10 parts l-dopa, most widely used med for Parkinson's
Adverse effects of Alzheimer drugs Nausea, vomiting, diarrhea, abdominal pain, anorexia*Tacrine has hepatic toxicity