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pharmacology year 3.1 > movement disorder > Flashcards

movement disorder Flashcards

1
Q

classification of tremor

A
  1. 14-18Hz primary orthostatic tremor
  2. 7-12Hz physiological tremor
  3. 4-12Hz essential tremor, dystonic tremor syndromes
  4. 2-12Hz neuropathic tremor, drug induced tremor, multiple sclerosis
  5. s disease
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2
Q

essential tremor?

A
  • rhythmic
  • symmetrical
  • postural
  • family history
  • alcohol response 50%
  • increase cerebellar outflow
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3
Q

treatment of essential tremor (level A effective)

A
  • propranolol and primidone
  • may combined
  • may used for dystonic tremor
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4
Q

treatment of essential tremor (level B probably effective)

A
  • alprazolam
  • atenolol
  • gabapentin
  • sotalol
  • topiramate
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5
Q

treatment of essential tremor (level C possibly effective)

A
  • nadolol
  • nimodipine
  • clonazepam
  • botulinum toxin A
  • deep brain stimulation
  • thalamotomy
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6
Q

treatment of essential tremor (not effective)

A
  • levetiracetam
  • 3,4- diaminopyridine
  • flunarizine
  • pregabalin
  • zonisamide
  • clozapine
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7
Q

parkinson’s disease diagnostic criteria

A
  • progressive neurodegenerative disease
  • age >60
  • mutations in LRRK, PRKN, PINK1, DJ1, SNCA genes
  • loss of dopaminergic nigrostriate neurones in substantia nigra
  • synucleinopathy (alpha-synuclein aggregates)
  • neurotoxicity/necrosis
  • apoptosis
  • bradykinesia and rigidity/ rest tremor/ postural instability (not cause by proprioception problem)
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8
Q

staging of alpha-synuclein pathology

A

stages 1 & 2: presymptomatic (inclusion bodies medulla and pons, olfactory
stages 3 & 4: classic (SN, midbrain, forebrain)
stages 5 & 6: dementia (neocortex)

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9
Q

types of dopamine pathway

A
  • nigrostriate (origin: SN)
  • mesocortical (origin: ventral tegmental area)
  • mesolimbic (origin: VTA to nucleus accumbens)
  • tuberoinfundibular (origin: hypothalamus)
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10
Q

stimulatory G protein

A

dopamine D1 and D5 receptors

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11
Q

inhibitory G protein

A

dopamine D2, D3, D4 receptors

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12
Q

levodopa?

A
  • precursor dopamine and first line treatment
  • always given with DOPA decarboxylase inhibitor
  • either benserazide or carbidopa
  • start at low dose and increase slowly
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13
Q

levodopa effects

A
  1. benefits:
    - treats Bradykinesia
    - treats Rigidity
    - tremor responds to ANTIMUSCARINIC
  2. disadvantages:
    - short half life (2 hours)
    - dyskinesia
    - fluctuation
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14
Q

levodopa short term problems

A
  1. short half life
    - need to control release
    - need to give as intraduodenal infusion
    - need to watch dietary protein and timing
  2. side effects:
    - nausea, vomiting
    - dizzy
    - flushing, rash
    - sweating
    - hypotension
    - delusions, hallucination
    - arrhythmias
    - liver function
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15
Q

levodopa long term problems

A
  1. levodopa therapy:
    - cumulative dose
    - duration of therapy-3hours
  2. dyskinesia:
    - peak dose dyskinesia
    - diphasic dyskinesia
    - off period dystonia
  3. on-off:
    - wearing off
    - freezing
    - fluctuations ‘on-off’ effect
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16
Q

dopamine agonists drugs

A
  • ropinirole D2
  • pramipexole D3
  • apomorphine
  • rotigotine patch
17
Q

characteristics of dopamine agonists drugs

A
  • non ergot drugs
  • do not need enzymatic conversion
  • no toxic metabolites
  • less dyskinesia
  • help restless legs
  • may be antioxidant
  • can be use monotherapy or adjunctive therapy
  • older drugs (bromocriptine, pergolide) cause cardiac valve fibrosis!
18
Q

side effects of dopamine agonist drugs

A
  • somnolence (sleepiness)
  • impulsive control disorder (ICD)
  • hallucinations (psychiatric effects)
  • D2 side effects
19
Q

apomorphine?

A
  • dopamine agonist
  • subcutaneous (penject)
  • continuous infusion
  • very emetogenic
  • pretreat with domperidone
  • 3 doses/day
20
Q

rotigotine patch?

A
  • dopamine agonist
  • non ergoline agonist
  • 24 hour duration
  • ensures compliance
21
Q

selegiline (MAO B inhibitor)?

A
  • orally
  • irreversible inhibitor
  • AMPHETAMINE byproducts of catabolism
  • protect dopamine from degradation
  • delay need for levodopa
  • reduce daily dose levodopa
    1. side effects:
  • nausea, weight loss
  • headache
  • agitation (disturbance)
  • interactions
22
Q

rasagilinie (MAO B inhibitor)?

A
  • irreversible inhibitor
  • NO AMPHETAMINE as byproducts
  • available as a patch
23
Q

COMT inhibitors characteristic and drugs

A
  • prolong duration of action of levodopa
  • increase bioavailability
  • no intrinsic benefit alone
  • efficacy high
  • increase dopaminergic adverse events
  • ENTACAPONE- vascular risk
  • TOLCAPONE- affects brain COMT and liver failure. cause orange discolouration of urine
24
Q

amantadine- releasing dopamine

A
  1. avoid in heart failure and ulcer disease
  2. action:
    - anticholinergic
    - NMDA
    - moderately effective
    - may be helpful in dyskinesia
  3. side effects:
    - tolerance
    - hallucinations, confusion
    - dry mouth
    - livedo
    - oedema
    - hypotension
    - leukopenia
    - GI upset
25
Q

antimuscarinic?

A
  • for tremor
  • for drug induced parkinsonism
  • for acute dystonic reactions
  • exacerbate dementia
  • poorly tolerate in olderly
  • ORPHINADRINE, PROCYCLIDINE, TRIHEXYPHENIDYL
    1. side effects:
  • blurred vision
  • constipation
  • retention
  • mentation
26
Q

non-motor findings

A
  1. level A: modafinil for excessive daytime sleepiness
  2. level B: levodopa/ carbidopa for periodic limb movement disorder (PLMS)
  3. level C:
    - sildenafil for erectile dysfunction
    - polyethylene glycol for constipation
    - methylphenidate for fatigue
27
Q

parkinsonism?

A
  • parkinson plus DO NOT respond to levodopa
  • parkinsonism DO NOT respond to levodopa
  • drug induced parkinsonism (DIP) may RESPOND to antimuscarinic
28
Q

what are the clues for DIP?

A
  • subacute bilateral onset
  • early presence of postural tremor
  • concurrent oral dyskinesia
29
Q

risk factors for DIP

A
  • high dose, high potency
  • elderly
  • female
  • hereditary parkinson disease
  • AIDS
30
Q

causes of chorea (st. vitus’s dance)

A
  • sydenhams
  • vascular
  • increase RBC (poplycythemia)
  • toxins: CO, Mg, Hg
  • uremia
  • SLE
  • senile chorea
  • drugs - AED
  • APLA syndromes
  • neurodegenerative
  • conception: preggy, OCP
  • endocrine: hyperthyroidism, hypo/hyperglycemia
31
Q

treatment of chorea

A
  • tetrabenazine (most important)
  • amantadine
  • riluzole
32
Q

actions of botulinum toxin

A
  • inhibits release of ACh into junction
  • causes focal chemodenervation and transient weakness
  • last about 3 months
  • dose depends on site and severity
33
Q

side effects of botulinum toxin

A
  • soreness at site
  • dysphagia
  • dry mouth

pharmacology year 3.1 (8 decks)

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