Study your flashcards anywhere!

Download the official Cram app for free >

  • Shuffle
    Toggle On
    Toggle Off
  • Alphabetize
    Toggle On
    Toggle Off
  • Front First
    Toggle On
    Toggle Off
  • Both Sides
    Toggle On
    Toggle Off
  • Read
    Toggle On
    Toggle Off
Reading...
Front

How to study your flashcards.

Right/Left arrow keys: Navigate between flashcards.right arrow keyleft arrow key

Up/Down arrow keys: Flip the card between the front and back.down keyup key

H key: Show hint (3rd side).h key

A key: Read text to speech.a key

image

Play button

image

Play button

image

Progress

1/27

Click to flip

27 Cards in this Set

  • Front
  • Back
What causes Parkisons? Heriditory or Environmental?
Environmental
Sx of Parkinson's?
akinesia, tremor, rigidity (cogwheel), mask-like face, shuffling gait, hypersalivation. The tremor is a 'pill-rolling' tremor
What happens to an untreated PD's pt?
death occurs in about 9 years. Treatment can take that and make it 20 years from time of dx. Currently NO CURE.
What's the pathological basis for PD?
lack dopaminergic neurons (degenerated) in pars compacta of substantia nigra.
Basis of DA action in Caudate Nuc.?
DA neurons from substantia nigra come into caudate nucleus, and secrete DA there on to D2 receptors.
What are the two actions of DA on D2-R?
1. inhibits cholinergic neurons > decreased cholinergic > decrease ACh > no positive action on GABA neuron (GABA inhibition) so EXCITATION. //

In other words, DA inhibits ACh from activating GABA neurons via muscarinic receptors.//

2. DA also DIRECTLY inhibits GABA neuron via D2-R. //
So what happens in PD then?
Well, no Dopamine, means ACh activating GABA neurons (disinhibition) AND lack on direct DA inhibition on GABA neurons all resulting in increased GABA neuron firing.//
Tx of PD?
strategy is to replenish DA in the brain
L-dopa
L-dopa, unlike DA which doesn't cross brain barrier, is a precursor of DA. Enters brain by using aa transporter.

Converted to DA by L-amino acid decarboxylase.//

95% ends up in peripheral tissues, so large doses are needed.//

effective in reducing bradykinesia and rigidity but not tremor.//
Early Side effects of L-dopa
nausea (area postrema), orthostatic hypotension (b/c D2 inhibitory to NE release), cardiac arrhythmias (beta-R stimulation of heart), psychotic-like syndrome (activation of DA-R in mesolimbic systme; antipsychotic drugs are DA-R blocking drugs).//
Late term side effects of L-dopa
dyskinesia: abnormal involuntary movement (faciolingual tics, boobing and rocking movements)

On-Off phenomenon: l-dopa effectiveness becomes variable... sxs come and go, very variable.//
What to do for cardiac arrhythmias?
use beta blocker, propranolol//

These pts should only receive it only when necessesary.
Why not to take l-dopa with MAOIs?
result in massive buildup of sympathomimetic amines with possibility of hypertensive crisis.
Why not to take l-dopa with antipsychotic drugs such as phenothiazines, or butyrophenoms?
Because they are DA-R blockers and will antagonize the therapeutic efficacy of l-dopa.//
How to tackle the issue of peripheral enzymes converting l-dopa to DA and causing it to not be able to enter CNS, requiring huge doses?
Use the l-aromatic amino acid decarboxylase INHIBITOR 'carbidopa', allowing you to use 75% less l-dopa for same efficacy. This is because you are blocking the periphery enzyme from converting l-dopa and you have more l-dopa to enter the brain.//

Also reduces side effects due to DA in the periphery (hypotension, arrhythmias etc) however Late-appearing side effects still remain.//
Why combine L-dopa with selective MAO B inhibitor?
MAO B (in the brain) is inhibited by SELEGILINE, causing decrease breakdown of DA in the brain, yet not causing catecholamine buildup in the periphery, since you have MAO A at work there and not effected by MAO B inhibitor. Anotherone is RASAGILINE.
How about COMT inhibitors and l-dopa
Tolcapone and entacapone, are COMT inhibitors, mainly work in the periphery to prevent l-dopa breakdown, therefore less l-dopa needs to be administered, and less 'off time". Tolcapone may cause liver damamge though.//
Dopamine Agonists
Bromocriptine**, pergolide, ropinirole, pramipexole.//

no effect on beta-R in heart, so no arrhythmias; decrease on-off phenomenon when combined with l-dopa. However, have peripheral action too and side effects a problem.
How would you control the side effects of peripheral DA-R activation?
use DA-R antagonist that wouldn't cross blood-brain barrier, which is Domperidone.//
How about controlling the indirect GABA activation via muscarinic-R through Ach?
use anticholinergic drugs i.e. Benztropine, trihyphenidyl. Side effects, dry mouth, blurred vision, urinary retension.//
How about another 'unexpected' drug that might help in PD?
Amantadine, an antiviral drug, act as a DA releasing agent by displacing DA from nerve terminals. Not as effective as l-dopa. Sometimes used in initial treatmetn of PD.
So, with all these drugs for PD, what's the recommendation?
Early stages: use agonists such as ropinirole or pramipexole.

Then: add l-dopa and carbidopa.

Then COMT-i such as entacapone to prolong l-dopa effects.

You may add atypical antipsychotics to reduce hallucinatins.//
see page 6, Lec 34 for the table of all these drugs
block II, Pharm
Alzheimer's Disease
most common form of dimentia, plaques and tangles of beta amyloid accumulations. Marked decreased in cholinergic neuron activity, changes in brain glutamate, DA, NE, 5-HT, somatostatin.
So what meds for AD?
AChE-I: donepezil, rivastigmine, galantamine

adverse effects: nausea, vomiting, diarrhea.

NOT A LOT of IMPROVEMENT, transient stabilization and little improvement in cognition only. NO TREATMENT FOR AD.
Memantine and NMDA-R antagonist and their role in Tx of AD?
may have neuroprotective properties and slow the progression of the disease.
Some other things that affect occurence of AD?
NSAIDs, statins, red wine (resveratol), low cholesterol.//