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Flashcards in Rapid - Dementia Deck (51):
1

Levodopa

  • Increases DA in brain
    • Crosses BBB
    • Dopa Decarboxylase (aka Aromatic L-amino acid decarboxylase) converts to DA in CNS
  • Use: Parkinson's
    • Given w/Carbidopa
  • S/E:
    • Arrhythmias (from peripheral catecholamine formation)
    • Anxiety + agitation
    • Progressive nigrostriatal degeneration → dec therapeutic window → dyskinesia following administration + akinesia btwn doses (“on-off” phenomenon)
  • Vit B6 reduces effectiveness → increases peripheral metabolism

2

Carbidopa

  • Peripheral Dopa Decarboxylase (Aromatic L-amino acid decarboxylase) inhibitor
  • Use: Given w/Levodopa to increase bioavailability & decrease peripheral S/E for Parkinson's

3

Selegiline

  • Selectively inhibits MAO-B
    • Decreases DA metabolism
  • Use:
    • Adjunctive agent to L-dopa for Parkinson's
    • MPTP-induced Parkinson's
  • S/E: May enhance L-dopa adverse effects

4

Rasagiline

  • Selectively inhibits MAO-B
    • Decreases DA metabolism
  • Use:
    • Adjunctive agent to L-dopa for Parkinson's
    • MPTP-induced Parkinson's
  • S/E: May enhance L-dopa adverse effects

5

Memantine

  • NMDA receptor antagonist
    • helps prevent Ca2+-mediated excitotoxicity
  • Use: Alzheimer's
  • S/E:
    • Dizziness
    • Confusion
    • Hallucinations

6

Donepezil

  • Noncompetitive AchE Inhibitor
    • Increases Ach availability
  • Use: Alzheimer's
  • S/E:
    • Nausea
    • dizziness
    • insomnia

7

Galantamine

  • Competitive AchE Inhibitor
    • Increases Ach availability
  • Use: Alzheimer's
  • S/E:
    • Nausea
    • dizziness
    • insomnia 

8

Rivastigmine

  • Noncompetitive AchE + BuChE Inhibitor
    • Increases Ach availability
  • Use: Alzheimer's
  • S/E:
    • Nausea
    • dizziness
    • insomnia
  • Metabolized by esterases → no drug interaxns

9

Tacrine

  • Noncompetitive AchE + BuChE Inhibitor
    • Increases Ach availability
  • Use: Alzheimer's
  • S/E:
    • Nausea
    • dizziness
    • insomnia

10

Tetrabenazine

  • Inhibits vesicular monoamine transporter (VMAT2)
    • Dec DA vesicle packaging and release
  • Use: Huntington's, esp large-amplitude chorea
  • S/E:
    • HypOtension
    • Suicidal ideation

11

Reserpine

  • Inhibits vesicular monoamine transporter (VMAT)
    • Decreases DA vesicle packaging and release
  • Use: Huntington's

12

Riluzole

  • Decreases glutamate release/excitotoxicity via unclear mechanism
  • Use: ALS (prolongs survival a few months)
  • S/E: Hepatotoxicity

13

Tolcapone

  • COMT inhibitor
    • Enhances levodopa uptake
    • Central + peripheral
    • Normally, COMT metabolizes L-dopa → 3-O-methyldopa
  • Use: Parkinson's
  • S/E: Hepatotoxicity

14

Entacapone

  • Peripheral COMT inhibitor
    • Does not cross BBB
  • Use: Parkinson's
  • S/E: less/no hepatotoxicity

15

Bromocriptine

  • Ergot alkaloid
    • D2 agonist (Gi) + alpha agonist
  • Use:
    • Parkinson's
    • HypERprolactinemia
    • Acromegaly
  • S/E: (alpha effects)
    • HTN
    • Gangrene

16

Pergolide

  • Ergot alkaloid
    • D2 agonist (Gi) + alpha agonist
  • Use:
    • Parkinson's
    • HypERprolactinemia
    • Acromegaly
  • S/E: (alpha effects)
    • HTN
    • Gangrene

17

Pramipexole

Direct D2 agonist (Gi) with NO alpha activity (non-ergot)

18

Ropinirole

Direct D2 agonist (Gi) with NO alpha activity (non-ergot)

19

Amantidine

  • Inc DA release + Dec DA reuptake
    • Also M2 protein inhibitor → prevents viral uncoating
  • Use:
    • Parkinson's
    • Influenza A
  • S/E:
    • Livedo reticularis (capillary occlusion → lace-like pattern on skin on limbs)
    • Ataxia

20

Benztropine

  • Muscarininc blocker
    • Decreases Ach activity
  • Use:
    • Parkinson's → Decrease tremor/rigidity
      • Little effect on bradykinesia
    • Drug-induced Parkinson’s
  • S/E: Anti-muscarinic effects

21

Trihexyphenidyl

  • Muscarininc blocker
    • Decreases Ach activity
  • Use:
    • Parkinson's → Decrease tremor/rigidity
      • Little effect on bradykinesia
    • Drug-induced Parkinson’s
  • S/E: Anti-muscarinic effects

22

Diphenhydramine

  • Muscarininc blocker
    • Decreases Ach activity
  • Use:
    • Parkinson's → Decrease tremor/rigidity
      • Little effect on bradykinesia
    • Drug-induced Parkinson’s
  • S/E: Anti-muscarinic effects

23

Rx Huntington's rigidity

  • Clozapine
  • quetiapine
  • carbamazepine  

24

Rx Huntington's depression/irritability

Fluoxetine

25

Rx Huntington's seizures

  • Clonazepam
  • valproate

26

Rx Huntington's psychosis

Haloperidol (D2 blocker)

27

Rx clasped-knife spasticity

  • Baclofen
  • tizanidine
  • clonazepam

28

NT Changes in Alzheimer's

  • DEcreased Ach
  • INcreased Glutamate

29

NT Changes in Huntington's

  • INcreased DA
  • DEcreased GABA, Ach

CAG repeat → Caudate loses ACh and GABA

30

NT Changes in Parkinson's

  • DEcreased DA
  • INcreased Ach

31

Huntington's Genetics

  • Chrom 4
  • CAG repeat
  • Demonstrates anticipation

32

Huntington's Findings

  • Depression
  • Progressive dementia
  • Choreiform movements
  • Athetosis
  • Atrophy of caudate and putamen
  • Hydrocephalus ex vacuo
  • Basal ganglia affected
  • Neuronal death via NMDA-R binding and glutamate excitotoxicity

33

NT synthesis locations & disease associations

A image thumb
34

Parkinson's Findings

  • Tremor (pill-rolling tremor at rest)
  • Rigidity (cogwheel)
  • Akinesia (or bradykinesia)
  • Postural instability
  • Shuffling gait
  • α-synuclein Lewy bodies
  • Basal ganglia affected
    • Depigmentation of substantia nigra pars compacta
  • Sometimes assoc w/defects in ubiquitin-proteasome system
  • PD-like symptoms can be drug-induced (DA blockers)

35

Mesocortical Pathway

  • Dopaminergic
  • Dec activity → “negative” symptoms (flat affect, limited speech)

36

Mesolimbic Pathway

  • Dopaminergic
  • Inc activity → “positive” symptoms (delusions, hallucinations)
  • Primary therapeutic target of antipsychotic drugs that dec pos symp

37

Nigrostriatal Pathway

  • Major Dopaminergic pathway in brain
  • Dec activity → extrapyramidal symptoms (dystonia, akathisia, parkinsonism, tardive dyskinesia)
  • Significantly affected by movement disorders and antipsychotic drugs

38

Tuberoinfundibular Pathway

  • Dopaminergic
  • Dec activity → Inc prolactin → Dec libido, sexual dysfunction, galactorrhea, gynecomastia (in men)

39

Athetosis

  • Slow, writhing, snake-like movements, esp in fingers
  • Basal ganglia lesion

40

Chorea

  • Sudden, jerky, purposeless movements
  • Basal ganglia lesion

41

Dystonia

  • Sustained, involuntary muscle contractions
  • Ex:
    • Writer’s cramp
    • Blepharospasm (sustained eyelid twitch)

42

Essential tremor

  • High-frequency tremor with sustained posture (eg, outstretched arms)
  • Worsened w/movement or when anxious
  • Often familial (AD)
  • Pts often self-medicate with alcohol, which decreases tremor amplitude
  • Rx:
    • Nonselective β-blockers (propranolol)
    • Primidone

43

Hemiballismus

  • Sudden, wild flailing of 1 arm +/− ipsilateral leg (half of body ballistic)
  • Contralateral subthalamic nucleus lesion (eg, lacunar stroke

44

Intention tremor

  • Slow, zigzag motion when pointing/extending toward a target
  • Cerebellar dysfunction

45

Myoclonus

  • Sudden, brief, uncontrolled muscle contraction
  • Ex:
    • Jerks
    • hiccups
  • Common in metabolic abnormalities such as renal and liver failure

46

Resting tremor

  • Uncontrolled movement of distal appendages (most noticeable in hands) at rest
  • Alleviated by intentional movement
  • Seen in Parkinson's ("pill-rolling")

47

Alzheimer's Findings

  • Progressive memory loss
  • Widespread cortical atrophy w/narrowing of gyri and widening of sulci
  • Assoc w/:
    • ApoE4 → Inc risk
    • ApoE2 → Dec risk
    • presenilin-1, presenilin-2
    • APP → Aβ-amyloid deposition
    • Early onset in Down Synd
  • Senile plaques in gray matter
  • Neurofibrillary tangles (hypERphosphorylated tau protein)

48

Best Rx for Drug-Induced Parkinson's

Antimuscarinics

  • Benztropine
  • Trihexiphenidyl
  • DIphenhydramine

49

Vitamin E / a-tocopherol

Neuroprotective antioxidant that may slow functional losses in Alzheimer's

50

Baclofen

  • GABAB agonist
  • Use: Spasticity caused by brain or spinal cord disease (incl MS)

51

Tizanidine

  • Centrally-acting a2 agonist
  • Use: Spasticity caused by brain or spinal cord disease (incl MS)
  • S/E: Hepatotoxicity