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Io Pharm > neurodegenerative diseases > Flashcards

neurodegenerative diseases Flashcards

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

A

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

24
Q

Benztropine - class

A

Muscarinic Receptor Antagonists

25
Q

Selegiline - mech of action

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

MAO-B is not involved in NE metabolism

26
Q

nonselevtive MAO inhibitors action

A

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

27
Q

Mementine (Namenda) - side effects

A
  • Dizziness,
  • Headache,
  • Fatigue,
  • Sedation,
  • Hypertension,
  • Rash,
  • Diarrhea,
  • Weight Gain,
  • Urinary Frequency,
  • Anemia
28
Q

Basal Ganglia - Function

A
  • starts purposeful movement
  • suppresses unwanted movement
29
Q

Memantine (Namenda) - class of drug

A

NMDA Receptor Antagonist - examples

30
Q

Dopaminergic Agents - mechanism of action

A

↑ amounts of dopamine in striatum

by

↑ delivery or ↓ degradation

31
Q

Synthetic dopamine agonist - anesthetic considerations

A

assess for side effects :

  • CV
  • hypotension
  • pleuropulmonary fibrosis
32
Q
  • Nausea
  • diarrhea
  • dizziness
  • headache
  • bronchoconstriction
A

Cholinesterase Inhibitors - side effects

33
Q

ApoE4: gene and AD

  • one copy
  • two copies
A

↑ Risk for AD

  • One copy: 3 fold ↑ risk
  • Two copies: 12-15 fold ↑ risk
34
Q

Blocking “leaky” NMDA channels:

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

used for Alzheimer’s

A

NMDA Receptor Antagonist - mechanism of action

35
Q

Parkinson’s pharmacotherapy strategies

A

Dopaminergic Agents

&

Anticholinergic Agents

36
Q

Levodopa - side effects

A
  • Involuntary movements (dyskinesias)
  • ‘On-off’ effect: fluctuations between hypokinesia & improvements
37
Q

Levodopa - acute/transient side effects

A
  • Nausea
  • Anorexia
  • Hypotension
  • Psychosis: schizophrenia like symptoms with excess dopamine
38
Q

ApoE gene - action

A

encodes for a protein that facilitates the clearance of Aβ

39
Q

Parts of basal ganglia involved in Parkinson’s

A
  • Striatum,
  • Globus Pallidus,
  • Subthalamic nuclei,
  • Substantia nigra
40
Q

Selergine - anesthetic considerations

A
  • avoid ephedrine, meperidine
  • use extreme caution with vasoactive medications
  • pronounced effect with neuromuscular blockers, sedative agents, diuretics - titrate very carefully
41
Q
  • Donepezil (Aricept)
  • Rivastigmine (Exelon)
  • Galantamine (Razadyne)
A

Cholinesterase Inhibitors - Examples

42
Q

mechanism of action for galantamine (Razadyne)

A

blocks cholinesterase activity => prevents breakdown of Ach

43
Q

ApoE2 gene and AD

A

Lower risk for AD

44
Q

who degrades levodopa

A
  • dopamine decarboxylases (DDC)
  • catecholamine O-methyltransferase (COMT)
45
Q

Amyloid Precursor Protein (APP) -Amyloidogenic Pathway

A
  • APP gets cleaved by β-secretase followed by γ-secretase
  • makes Aβ 40/42
  • Aβ 40/42 aggregates forms plaques in the brain
46
Q

what is Levodopa

A

Precursor to Dopamine

47
Q

what are the protein aggregates in Alzheimer’s?

A
  • Amyloid plaques (amyloid β or Aβ)
  • Neurofibrillary tangles (hyperphosphorylated tau)
48
Q

Pramipexole & ropinirole - side effects

A
  • fewer than old dopamine agonists
  • hallucinations
  • compulsive behaviors (eating, gambling, etc)
49
Q

ApoE genotype - action

A

perevents the clearance of Aβ

50
Q

Muscarinic Receptor Antagonists - mech of action

A
  • 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
Q

Amantandine - mech of action

A
  • Dopamine usually sits in presynaptic vesicles & amantadine helps dopamine release into synapse
  • Enhances dopamine release into synapse
52
Q

Memantine (Namenda) anesthetic consideration

A

clearance is reduced with higher pH (careful with bicarbonate)

53
Q

amantadine - anesthetic consideration

A
  • evaluate for anti-cholinergic like side effects
  • rule out CHF side effect
54
Q

carbidopa - class

A
  • peripheral dopamine decarboxylase inhibitor
  • prevents levodopa from being converted to dopamone in the periphery
55
Q

entacapone - class

A
  • COMT (catecholamine O-methyltransferase) inhibitor
  • prevents levodopa from being converted to dopamone in the periphery
56
Q

mechanism of action for Rivastigmine (Exelon)

A

blocks cholinesterase activity => prevents breakdown of Ach

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