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Pharm Block 2 > Cognitive complaints and Impairment > Flashcards

Cognitive complaints and Impairment Flashcards

1
Q

What are the major dopamine tracts?

A
  • Nigostriatal (extra pyramidal motor system)

- Mesolimbic, mesocortical (cognition, emotion, substance abuse, psychosis)

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2
Q

What are the major dopamine targeting pharmacological agents?

A
  • DA-agents (movement disorders, depression)

- DA antagonists (psychosis)

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3
Q

What are the major norepinephrine tracts?

A
  • Synthesized in Locus Ceruleus

- Project to cortex, limbic, Reticular Activating System, spinal cord

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4
Q

What are the major norepinephrine targeting pharmacological agents?

A
  • Adrenergic agents (depression, MAO-Is, tricyclics, venlafaxine)
  • Andrenergic antagonists (tremor, anxiety, beta blockers)
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5
Q

What are the major serotonin tracts?

A
  • Synthesized in raphe nuclei

- Project to cortex, limbic, striatum, cerebellum, blood vessels

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6
Q

What are the major serotonin targeting pharmacological agents?

A

Seretonergic agents (depression, migraine)

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7
Q

What are the major acetylcholine tracts?

A
  • Synthesized in basal forebrain (n. basalis of Meynert)
  • Proj to olfactory bulb, hippocampus, amygdala, cortical association areas
  • NT of NMJ
  • NT of ANS (except post-ganglionic sympa neurons)
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8
Q

What are the major acetylcholine targeting pharmacological agents?

A
  • Anticholinergic agents (movement disorders)

- Cholinesterase inhibitors (MG, AD, organophosphates, nerve gas)

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9
Q

What cofactor is needed for the biosynthesis of GABA?

A

B6

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10
Q

What are the major GABA tracts?

A
  • Widely distributed

- Major inhibitory NT of the CNS (along w/ glycine)

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11
Q

What are the major pharmacologic agents targeting GABA?

A
  • GABA-A (binding sites for benzos, barbiturates)
  • GABA-B (baclofen)
  • GABA-ergic agents (ie AEDs)
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12
Q

What are the major glutamate tracts?

A
  • Widely distributed, major excitatory NT of the brain

- Binds to NMDA-R (ligand, VGCC)

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13
Q

What are the major pharmacologic agents targeting glutamate?

A
  • Glutamate excito-toxicity

- NMDA-R antagonists (memantine for AD)

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14
Q

Attentional disturbances are hallmark features of which disorders?

A
  • Delirium (confusional state)
  • Neglect syndromes
  • ADHD

[ Also common in

  • schizophrenia
  • traumatic brain injury]
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15
Q

What are the alerting attentional networks of the brain?

A

Thalamic

(right) frontal & parietal activation

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16
Q

What are the orienting attentional networks of the brain?

A

-Superior. colliculus, frontal eye fields, temporopariental, parietal activation (spatial)

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17
Q

What are the executive attentional networks of the brain?

A

Anterior cingulate & DLPFC activation

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18
Q

What are examples of executive functions?

A

Mediated by frontal lobes:

  • Volition
  • Planning
  • Purposeful action
  • Performance
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19
Q

What part of the brain is responsible for executive function/working memory?

A

Dorsolateral prefrontal lobe

20
Q

What part of the brain is responsible for “social intelligence”?

A

lateral orbitofrontal lobe

21
Q

What part of the brain is responsible for motivation?

A

Medial ventral frontal lobe

22
Q

What part of the brain is responsible for will and/or movement?

A

Anterior cingulate

23
Q

What are 2 examples of pro-cholinergic agents?

A

Acetylcholinesterase inhibitors
- Donepezil
Acetylcholine precursors
- CDP-Choline

24
Q

To what drug class does donepezil belong?

A

Acetylcholinesterase inhibitor

25
Q

What is the action of donepezil?

A

Inhibition of synaptic acetylcholinesterase

26
Q

Describe the kinetics of donepezil.

A

Well absorbed when taken orally
Highly protein bound, metabolized partially in liver, then excreted in bile.
Elimination half-life 50-70 hrs.

27
Q

What adverse drug reactions are related to donepezil?

A

Nausea, vomiting (10%).
Sinus bradycardia and 1st degree AV block relative contraindications.
Monitor liver function tests.

28
Q

What are the primary interactions with donepezil?

A
  • Agents that inhibit hepatic metabolism via CYP450, 3A4, and 2D6 enzymatic pathways (e.g. ketoconazole and quinidine) may increase blood levels of donepezil.
  • Inducers of hepatic metabolism (phenobarbital, phenytoin, carbamazepine, dexamethasone, rifampin) may decrease therapeutic blood levels.
29
Q

In what other disorders can cholinesterase inhibitors be used?

A
  • Traumatic brain injury
  • Down Syndrome with Dementia
  • Parkinson’s Disease
  • Dementia with Lewy Bodies (DLB)
    • Cholinergic deficits in Lewy Body Disorders greater than in AD => respond better with cholinesterase inhibitors
30
Q

To what class does Methylphenidate (Ritalin) belong?

A

CNS stimulant, structurally related to amphetamine

31
Q

How does methylphenidate act?

A

Blocks re-uptake of norepinephrine and dopamine. May also enhance release of catecholamines.

32
Q

Describe the kinetics of methylphenidate.

A

Rapidly absorbed when taken orally
Peak levels in 1-2 hours
Metabolized in liver, excreted in urine

33
Q

What adverse drug effects are associated with methylphenidate?

A

Nervousness, insomnia.

Potential for dependence and abuse.

34
Q

What interactions are prominent with methylphenidate?

A
  • Do not use with MAOIs.
  • May potentiate the effects of Phenobarbital and phenytoin by delaying absorption
  • Increase the noradrenergic effects of tricyclic antidepressants
  • Increase the dopaminergiceffects of antiparkinsonian agents
  • Potentiate the analgesic properties of meperidine.
35
Q

What is Dextroamphetamine used for?

A
  • ADD
  • Treat attention and memory impairment following TBI
  • Beneficial effects on cognition, depression, anergia, and impaired motivation following TBI
  • Abuse concerns
36
Q

What is atomexetine (straterra) used for?

A
  • Norepinephrine re-uptake inhibitor
  • Used in ADD
  • Some use in TBI-related attentional deficits
37
Q

What is duloxetine (cymbalta) used for?

A
  • Selective norepinephrine re-uptake inhibitor

- Mainly used as an antidepressant but may have attention-enhancing properties

38
Q

To what drug class does atomexetine belong?

A

Selective norepinephrine re-uptake inhibitor

39
Q

What is the action of atomexetine?

A

Inhibition of norepinephrine transporter

40
Q

Describe the kinetics of atomexetine.

A
  • Rapid GI absorption.

- CYP2D6 metabolism.

41
Q

What are adverse drug reactions with atomexetine?

A

Liver toxicity

Suicidal ideation

42
Q

What interactions are prominent with atomexetine?

A

CYP2D6 inhibitors (e.g. quinidine)

43
Q

What are the amantadine and memantine?

A

Moderate-affinity uncompetitive NMDA receptor antagonists

44
Q

What are the actions of dopamine agonists (ropinirole)?

A
  • increase dopamine release
  • decrease presynaptic dopamine reuptake
  • stimulate dopamine receptors
  • enhance post-synaptic dopamine receptor sensitivity
45
Q

What is modafinil used for?

A
  • Approved for the treatment of excessive daytime somnolence in patients with narcolepsy
  • May have a role in treatment of post-TBI fatigue and cognitive impairment
46
Q

What are the mechanisms of actions of modafinil?

A
  • Activation of hypocretin (orexin) neurons in the lateral hypothalamus
  • Indirect dose-dependent reduction of gamma-aminobutyric acid (GABA) release
  • Increases in glutamate release in the ventrolateral and the ventromedial thalamus
  • Increases in dopamine in the nucleus accumbens

Pharm Block 2 (15 decks)

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