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65 Cards in this Set

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  • Back
How many does Parkinson's affect?
1% over 50
Symptoms of Parkinson's
akinesia
tremor
rigidity
alteration of posture, mask-like face, shuffling gait, loss of associative movment, and hypersalivation
Most obvious early sign of Parkinson's?
Tremor- usually pill-rolling
How is the rigidity in PK's characterized?
cogwheel
How long w/o treatment before death?
With?
9 years
20 years
Which tissues in the brain are affected because of PK's?
Striatal tissue (caudate and putamen) show 10% of normal dopamine
What is the offending neurotransmitter in PK's?
Dopamine
Where is dopamine made? What does this area display in PK's?
Pars compacta of the substantia nigra
Degeneration of the dopaminergic neurons
How much degeneration do you need in PK's to show disfunction?
≧70%
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)
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
Can we give exogenous dopamine for treatment of PK's?
No, doesn't cross BBB, give L-dopa which does.
How much L-dopa do we give? Why?
Large doses, more than 95% ingested is decarboxylated in peripheral tissues.
Why give l-dopa gradually? What does L-dopa do?
Reduce side effects and toxicity
Reduces bradykinesia and rigidity, less effective in reducing tremor.
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 receptors

Psychotic-like symptoms- Activate DAr in mesolimbic system.
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
What is the on-off phenomenon?
Partial l-dopa resistance due to pronlonged treatment leads to asymptomatic followed by severe symptom cycles.
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.
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.
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).
When given with carbidopa, how much l-dopa should be give to reach the TE?
75% less than w/o carbidopa
Is the on-off phenomenon avoided by combination with carbidopa?
No, may even be worse.
Sinemet
1 part carbidopa to 10 parts l-dopa, most widely used med for Parkinson's
Selegiline (Deprenyl)
(se le' ji leen)
MAO B inhibitor, predomintates in the brain
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
Bromocriptine, Pergolide
Dopamine agonists
Ropinirol
Pramipexole
Dopamine agonists
Side effects of agonists
Nausea, hypotension, dyskinesia, hallucinations, and delusions
Why combine bromocriptine with l-dopa?
Reduce on-off phenomenon
Why are side effects such as emesis and hypotension a problem w/dopamine agonists?
They activate peripheral dopamine receptors
How can we avoid agonist side effects?
Achieve a higher T.I. by combining with a dopaminergic antagonist
Centrally acting anticholinergics (CAA)
Benztropine
Trihexyphenidyl
Why use CAAs? Side effects?
Reduce tremor
dry mouth, blurred vision, urinary retension
Amantidine
Antiviral drug found to improve Parkinson symptoms.
Releases endogenous DA
COMT inhibitors
Tolcapone* may cause liver damage
Entacapone
Prevent the breakdown of l-dopa
Recommendations for early stage Parkinson's
Dopamine agonists (pramipexole or ropinirole)
Recommendations when DA agonists no longer work
Add l-dopa and carbidopa
Can add COMT inhibitors (entacapone) to reduce wearing off periods
What are the low dose atypical antipsychotics? Why use them?
Risperidone, Olanzapine, Quetiapine
Control hallucinations caused by l-dopa
Why use selegiline in newly diagnosed patient?
May delay the onset of symptoms
Dopamine precursors
Replenishes dompamine in striatum
l-dopa
Side effects of l-dopa
nausea, orthostatic hypotension, arrhythmias, hallucinations, delusions, dyskinesias
peripheral l-aromatic decarboxylase inhibitor (does not enter brain)
Carbidopa
MA of Carbidopa
prevents conversion of l-dopa to dopamine in peripheral tissues
Side effects of Carbidopa
None
MAO B inhibitor
Selegiline
MA of Selegiline, side effects
Prevents oxidation of dopamine in brain
May cause HTN at high dose
Dopamine agonists
Bromocriptine/Pergolide
Effect of DA agonists
Stimulate DP receptors in striatum. Reduce on-off
Side effects of DA agonists
Nausea, Ortho hypotension, hallucinations, delusions, dyskinesias
Somewhat selective D2,D3 DA receptor agonists
Ropinirole/Pramipexole
Muscarinic cholinergic receptor antagonists
Benztropine
Trihexyphenidyl
MA for MS cholinergic receptor antagonists
Block muscarinic receptors in striatum- useful only very early in dz
Side effects of MSCR antagonists
Dry mouth, blurry vision, urinary retention
Indirectly causes the release of endogenous DA
Side effects?
Amantidine
Hallucinations
COMT inhibitors
Tolcapone
Entacopone
MA of COMT inhibitors
prevent breakdown of l-dopa by COMT
Most common form of dementia
Alzheimer's- progressive impairment of memory and cognitive fxn.
Pathology of Alzheimer's
Brain accumulation of plaques and tangles composed of Beta amyloid
Four drugs used to treat Alzheimer's. All are...?
Tacrine
Donepezil
Rivastigimine
Galantamine
All ACEi
Difference between Tacrine and donepezil, rivastigmine, and galantamine?
Tacrine is non-selective, the others are brain-selective
Adverse effects of Alzheimer drugs
Nausea, vomiting, diarrhea, abdominal pain, anorexia
*Tacrine has hepatic toxicity
Memantine
NMDA receptor antagonist may have neuroprotective properties may slow progression of Alzheimer's
Other drugs being considered for Alzheimer's
NSAIDS, estrogen, nicotine, statins
L-dopa, carbidopa, Sinemet, bromocriptine, ropinirole, pramipexole, amantadine, selegiline, propranolol, benztropine, trihexyphenidyl, entacapone
Parkinson's
Tacrine, donepezil, rivastigmine, galantamime, memantine
Alzheimer's