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neurodegenerative diseases Flashcards

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1
Q

Pramipexole & ropinirole

mech of action

A

Dopamine Agonists at D2 and D3 receptors

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2
Q

Muscarinic Receptor Antagonists - side effects

A
  • Dry mouth
  • constipation
  • impaired vision
  • urinary retention
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3
Q

MAO - action

A
  • oxidation of monoamines (dopamine, norepi)
  • break down of dopamine and norepi
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4
Q

Anticholinergic Agents - mech of action

A

Prevent cholinergic inhibition of dopamine release

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5
Q

cholinesterase inhibitors - anesthetic consideration

A
  • prolongation of succinylcholine
  • relative resistance to non-depolarizing muscle relaxants
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6
Q

Tau protein - normally found in …

A

in microtubules of neurons to keep organization

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7
Q

Cholinesterase Inhibitors - Mechanism of Action?

A
  • Prevents action of acetylcholinesterase which breaks down Ach
  • Thereby ↑ acetylcholine concentrations in the synapse

used for Alzheimer’s

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8
Q

Dopamine Agonists - mech of action

A

Mimic dopamine in the striatum

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9
Q

ApoE3 gene and AD

A

Normal Risk for AD

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10
Q

mechanism of action for

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

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

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11
Q

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

A

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

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12
Q

Levodopa - Adverse Drug Interaction

A

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

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13
Q

location of cholinergic neuron loss in Alzheimer’s

A
  • hippocampus (memory & learning)
  • frontal cortex (executive function & decision making)
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14
Q

Mementine (Namenda) - mech of action

A

Blocking “leaky” NMDA channels:

  • ↓ Ca2+ induced excitotoxicity
  • reduce background noise, making signals relatively stronger -> allows to perceive the learning signals
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15
Q

Parkinson’s characteristics (presentation)

A
  • Dyskinesias: difficulty of movement
    • Difficulty starting movement & difficulty stopping movement once started
  • Muscle rigidity
  • Tremor at rest
  • Cognitive impairments, depression
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16
Q

anticholinergic drugs - anesthetic consideration

A
  • assess aticholoinergic side effects (especially HR)
  • avoid drugs that impact cholinergic tone (TCAs)
  • avoid drugs that increase side effects (ex: HR)
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17
Q

Levodopa & carbidopa - anesthetic considerations

A
  • 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
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18
Q

Tau hyperphosphorylation effects

A
  • can no longer support microtubules
  • aggregate together -> correlates with neuronal death d/t neuron losing it’s shape
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19
Q

Amyloid Precursor Protein (APP) - Non-Amyloidogenic Pathway

A

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

(makes a protein P3)

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20
Q

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

A

added when effectiveness of Levodopa/Carbidopa wanes

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21
Q

why is Levodopa given with carbidopa

A
  • 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
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22
Q

What are the cholinergic related deficits in Alzheimer’s

A
  • Choline acetyltransferase activity
  • Acetylcholine amount
  • Acetylcholinesterases
  • Choline transport
  • Nicotinic acetylcholine receptor expression
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23
Q

how is the balance between dopamine and cetylcholine affecting movement

Study These Flashcards
A

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

24
Q

Benztropine - class

Study These Flashcards
A

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

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