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Flashcards in neurodegenerative diseases Deck (56):
1

Pramipexole & ropinirole

mech of action 

Dopamine Agonists at D2 and D3 receptors

2

Muscarinic Receptor Antagonists - side effects

  • Dry mouth
  • constipation
  • impaired vision
  • urinary retention

3

MAO - action

  • oxidation of monoamines (dopamine, norepi)
  • break down of dopamine and norepi

4

Anticholinergic Agents - mech of action

Prevent cholinergic inhibition of dopamine release

5

cholinesterase inhibitors - anesthetic consideration

  • prolongation of succinylcholine
  • relative resistance to non-depolarizing muscle relaxants

6

Tau protein - normally found in ...

in microtubules of neurons to keep organization

7

Cholinesterase Inhibitors - Mechanism of Action?

  • Prevents action of acetylcholinesterase which breaks down Ach

  • Thereby ↑ acetylcholine concentrations in the synapse 

used for Alzheimer's 

8

Dopamine Agonists - mech of action 

Mimic dopamine in the striatum

9

ApoE3 gene and AD

Normal Risk for AD

10

mechanism of action for 

  • Donepezil (Aricept) 
  • Rivastigmine (Exelon)
  • Galantamine (Razadyne)

Prevents action of acetylcholinesterase (which breaks down Ach -> increased Ach)

11

How does Parkinson's affect the balance between dopamine and cetylcholine affecting movement

↓ dopamine in the striatum (basal ganglia) creats an imbalance between DA & ACh -> moevemnt disorder

12

Levodopa - Adverse Drug Interaction

non-selective MAO Inhibitors & levodopa -> an overload of dopamine & norepinephrine -> may cause peripheral side effects

13

location of cholinergic neuron loss in Alzheimer's

  • hippocampus (memory & learning)
  • frontal cortex (executive function & decision making)

14

Mementine (Namenda) - mech of action

Blocking “leaky” NMDA channels:

  • ↓ Ca2+ induced excitotoxicity
  • reduce background noise, making signals relatively stronger -> allows to perceive the learning signals

15

Parkinson's characteristics (presentation)

  • Dyskinesias: difficulty of movement
    • Difficulty starting movement & difficulty stopping movement once started
  • Muscle rigidity
  • Tremor at rest
  • Cognitive impairments, depression

16

anticholinergic drugs - anesthetic consideration

  • assess aticholoinergic side effects (especially HR)
  • avoid drugs that impact cholinergic tone (TCAs)
  • avoid drugs that increase side effects (ex: HR)

17

Levodopa & carbidopa - anesthetic considerations

  • must be give Q 6-12 hrs
  • administer 20 min preop and interop per NG tube to avoid sudden loss of effect (to avoid neuromuscular/respiratory failure)
  • assess side effects: cardiac dysrhythmia, adrenergic stimulation, orthostatic hypertension, GI 

18

Tau hyperphosphorylation effects

  • can no longer support microtubules
  • aggregate together -> correlates with neuronal death d/t neuron losing it’s shape

19

Amyloid Precursor Protein (APP) - Non-Amyloidogenic Pathway

APP protein gets cleaved by α-secretase followed by γ-secretase

(makes a protein P3)

20

why is entacapone added to the parkinson's pharm regimen?

added when effectiveness of Levodopa/Carbidopa wanes

21

why is Levodopa given with carbidopa 

  • Despite large doses of Levodopa, when given alone only a small amount of will reach the brain 
  • large amounts of dopamine cause problems in the periphery -> levodopa needs carbidopa ->

  •  to cross the the blood brain barrier → then metabolized to dopamine
  • same amount of Levodopa can reach the brain with a smaller dose 

22

What are the cholinergic related deficits in Alzheimer's 

  • Choline acetyltransferase activity
  • Acetylcholine amount
  • Acetylcholinesterases
  • Choline transport
  • Nicotinic acetylcholine receptor expression

23

how is the balance between dopamine and cetylcholine affecting movement

when Dopamine (DA) & Acetylcholine (ACh) are balanced -> results in controlled movement

24

Benztropine - class

Muscarinic Receptor Antagonists

25

Selegiline - mech of action 

  • MAO-B inhibitor -> ↓ dopamine degradation
  • increases DA in the synapse

 

MAO-B is not involved in NE metabolism

26

nonselevtive MAO inhibitors action

will block the natural pathway for MAO’s in converting dopamine & NE to other substances thus → ↑ dopamine & NE

27

Mementine (Namenda) - side effects

  • Dizziness,

  • Headache,

  • Fatigue,

  • Sedation,

  • Hypertension,

  • Rash,

  • Diarrhea,

  • Weight Gain,

  • Urinary Frequency,

  • Anemia

28

Basal Ganglia - Function

  • starts purposeful movement
  • suppresses unwanted movement

29

Memantine (Namenda) - class of drug

NMDA Receptor Antagonist - examples

30

Dopaminergic Agents - mechanism of action 

↑ amounts of dopamine in striatum

by

↑ delivery or ↓ degradation

31

Synthetic dopamine agonist - anesthetic considerations

assess for side effects :

  • CV 
  • hypotension
  • pleuropulmonary fibrosis 

32

  • Nausea

  • diarrhea

  • dizziness

  • headache

  • bronchoconstriction

Cholinesterase Inhibitors - side effects

33

ApoE4: gene and AD

  • one copy
  • two copies 

↑ Risk for AD

  • One copy: 3 fold ↑ risk
  • Two copies: 12-15 fold ↑ risk

34

Blocking “leaky” NMDA channels:

  • ↓ Ca2+ induced excitotoxicity
  • reduce background noise, making signals relatively stronger -> allows to perceive the learning signals

used for Alzheimer's 

NMDA Receptor Antagonist - mechanism of action

35

Parkinson's pharmacotherapy strategies

Dopaminergic Agents

&

Anticholinergic Agents

36

Levodopa - side effects

  • Involuntary movements (dyskinesias)
  • ‘On-off’ effect: fluctuations between hypokinesia & improvements

37

Levodopa - acute/transient side effects

  • Nausea
  • Anorexia
  • Hypotension
  • Psychosis: schizophrenia like symptoms with excess dopamine

38

ApoE gene - action 

encodes for a protein that facilitates the clearance of Aβ

39

Parts of basal ganglia involved in Parkinson's

  • Striatum,
  • Globus Pallidus,
  • Subthalamic nuclei,
  • Substantia nigra

40

Selergine - anesthetic considerations 

  • avoid ephedrine, meperidine
  • use extreme caution with vasoactive medications
  • pronounced effect with neuromuscular blockers, sedative agents, diuretics - titrate very carefully

41

  • Donepezil (Aricept) 

  • Rivastigmine (Exelon)

  • Galantamine (Razadyne)

     

Cholinesterase Inhibitors - Examples

42

mechanism of action for galantamine (Razadyne)

 

blocks cholinesterase activity => prevents breakdown of Ach

43

ApoE2 gene and AD

Lower risk for AD

44

who degrades levodopa

  • dopamine decarboxylases (DDC)
  • catecholamine O-methyltransferase (COMT)

45

Amyloid Precursor Protein (APP) -Amyloidogenic Pathway

  • APP gets cleaved by β-secretase followed by γ-secretase
  • makes Aβ 40/42
  • Aβ 40/42 aggregates forms plaques in the brain

46

what is Levodopa

Precursor to Dopamine

47

what are the protein aggregates in Alzheimer's?

  • Amyloid plaques (amyloid β or Aβ)

  • Neurofibrillary tangles (hyperphosphorylated tau)

48

Pramipexole & ropinirole - side effects

  • fewer than old dopamine agonists 
  • hallucinations
  • compulsive behaviors (eating, gambling, etc)

49

ApoE genotype - action 

perevents the clearance of Aβ

50

Muscarinic Receptor Antagonists - mech of action

  • muscarinic receptors (presynaptic) are present in striatum where they inhibit dopamine release from dopamine neurons
  • Blockade of muscarinic receptors relieves the inhibition of dopaminergic neurons -> more dopamine release

51

Amantandine - mech of action

  • Dopamine usually sits in presynaptic vesicles & amantadine helps dopamine release into synapse
  • Enhances dopamine release into synapse

52

Memantine (Namenda) anesthetic consideration

clearance is reduced with higher pH (careful with bicarbonate)

53

amantadine - anesthetic consideration

  • evaluate for anti-cholinergic like side effects
  • rule out CHF side effect

54

carbidopa - class

  • peripheral dopamine decarboxylase inhibitor
  • prevents levodopa from being converted to dopamone in the periphery

55

entacapone - class 

  • COMT  (catecholamine O-methyltransferase) inhibitor
  • prevents levodopa from being converted to dopamone in the periphery

56

mechanism of action for Rivastigmine (Exelon)

 

blocks cholinesterase activity => prevents breakdown of Ach