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NMSP > Drugs for Movement Disorders (Wolff) > Flashcards

Drugs for Movement Disorders (Wolff) Flashcards

1
Q

What are the 2 drugs used for Wilson’s Disease?

A

Basically low copper diets and agents that reduce serum copper levels

  1. Penicillamine: Copper chelating agent
  2. Potassium disulfide: Reduces intestinal absorption of copper
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2
Q

What is the Levodopa combination?

A

Levodopa + carbidopa
OR
Levodopa + carbidopa + entacapone

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3
Q

Tx for Essential Tremor Algorithm

A
  • Mild tremor, no disability –> No rx therapy
  • Intermittent disability –> First line agent: Propranolol (unknown MOA, blockade of beta receptors in muscle spindles) –> second line agent: Benzodiazepine
  • Persistent disability due to tremor –> First line agents: Propranolol, Primidone (a barbiturate anticonvulsant), or both –> poor response –> second line agents: Gabapentin –> poor response plus predominant limb tremor or head or voice tremor: Botulinum toxin injections (binds to high affinity presynaptic recognition sites on cholinergic nerve terminals –> decreases ACh release, causing a neuromuscular blocking effect)
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4
Q

Tx of Restless Leg Syndrome Algorithm

A
  1. Check iron stores, if serum ferritin < 75 ng/mL –>
  2. Replete iron –>
  3. Moderate to severe symptoms 2 or more days per week?
    - -> No, then intermittent therapy of Carbidopa-levodopa PRN
  4. –> Yes: Daily rx recommended –> Comorbidities (obesity, depression, gait, respiratory failure, substance abuse)?
    - -> yes, then give Dopamine agonist (ex. prampipexole, ropinirole, or rotigotine)
    - -> no, then give Alpha 2 delta calcium channel ligand (ex. gabapentin, enacarbil, pregabalin, or gabapentin)
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5
Q

What are the treatments for Restless Leg Syndrome?

A
  1. Correct iron deficiency anemia
  2. Non-ergot dopamine agonist (e.g. ropinirole) if comorbid depression, obesity/metabolic syndrome
  3. Alpha-2-delta calcium channel ligand (e.g. gabapentin) - no co-morbidities. Hx of impulsive control DO
  4. For intermittent but disabling sx, use DA agonist or carbidopa-levodopa, benxodiazepines or opioids

if pregnant - nonpharmacologic strategies, iron supplement, clonazepam or carbidopa-levodopa

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6
Q

What are the treatments for Huntington Disease?

A

No current therapy slows dz progression.

Treat non-motor symptoms
- fluoxetine for depression and irritability
– carbamazepine for depression
– avoid agents with substantial anticholinergic effects since can exacerbate chorea

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7
Q

Where are the Dopaminergic neurons in the brain?

A

Substantia nigra

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8
Q

Where are the Dopaminergic neurons in the brain?

A

Substantia nigra

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9
Q

What is the main function of Dopamine in normal movement?

A

movement happens when the “brake” is released

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10
Q

What is the function of Ach in normal movement?

A

It stimulates the release of GABA which slows movement

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11
Q

Name of drug with “unknown” exact MOA

A

amantadine

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12
Q

Name of drug that is a weak, noncompetitive NMDA receptor antagonist

A

amantadine

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13
Q

What is the main effect of amantadine?

A

reduces Parkinson disease symptoms

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14
Q

What drug is used for Amyotrophic Lateral Sclerosis (ALS)?

A

Riluzole

- prolongs survival by a few months

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15
Q

Tx for Essential Tremor Algorithm

A
  • Mild tremor, no disability –> No rx therapy
  • Intermittent disability –> First line agent: Propranolol (unknown MOA, blockade of beta receptors in muscle spindles) –> second line agent: Benzodiazepine
  • Persistent disability due to tremor –> First line agents: Propranolol, Primidone (a barbiturate anticonvulsant), or both –> poor response –> second line agents: Gabapentin –> poor response plus predominant limb tremor or head or voice tremor: Botulinum toxin injections (binds to high affinity presynaptic recognition sites on cholinergic nerve terminals –> decreases ACh release, causing a neuromuscular blocking effect)
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16
Q

What are the 3 clinical applications of amantadine?

A
  1. treatment of drug-induced extra-pyramidal symptoms
  2. adjunctive therapy for dyskinesias in patients receiving Levodopa
  3. used as monotherapy for pts with mild motor symptoms
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17
Q

What drug has the following toxicities:

  1. CNS depression
  2. impulse control disorders
  3. psychosis
  4. suicidal ideation/depression
  5. causes livedo reticularis (purple discoloration of legs)
A

amantadine

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18
Q

Tx of Restless Leg Syndrome Algorithm

A
  1. Check iron stores, if serum ferritin < 75 ng/mL –>
  2. Replete iron –>
  3. Moderate to severe symptoms 2 or more days per week?
    - -> No, then intermittent therapy of Carbidopa-levodopa PRN
  4. –> Yes: Daily rx recommended –> Comorbidities (obesity, depression, gait, respiratory failure, substance abuse)?
    - -> yes, then give Dopamine agonist (ex. prampipexole, ropinirole, or rotigotine)
    - -> no, then give Alpha 2 delta calcium channel ligand (ex. gabapentin, enacarbil, pregabalin, or gabapentin)
19
Q

What are the treatments for Restless Leg Syndrome?

A
  1. Correct iron deficiency anemia
  2. Non-ergot dopamine agonist (e.g. ropinirole) if comorbid depression, obesity/metabolic syndrome
  3. Alpha-2-delta calcium channel ligand (e.g. gabapentin) - no co-morbidities. Hx of impulsive control DO
  4. For intermittent but disabling sx, use DA agonist or carbidopa-levodopa, benxodiazepines or opioids

if pregnant - nonpharmacologic strategies, iron supplement, clonazepam or carbidopa-levodopa

20
Q

What drug has the following toxicity [black box]:

antidepressants increased risk of suicidal thoughts and behaviors in pediatric and young adult patients in short-term studies

A

selegiline

21
Q

What are the 2 main clinical applications of selegiline?

A
  1. adjunct in the management of PD when levodopa/carbidopa use during the on-off phenomenon
  2. early PD
22
Q

What drug has the following toxicity [black box]:

antidepressants increased risk of suicidal thoughts and behaviors in pediatric and young adult patients in short-term studies

A

selegiline

23
Q

What are the treatments for Huntington Disease?

A

No current therapy slows dz progression.

Treat non-motor symptoms
- fluoxetine for depression and irritability
– carbamazepine for depression
– avoid agents with substantial anticholinergic effects since can exacerbate chorea

24
Q

Name of drug that is another MAO-B selective irreversible inhibitor, has greater potency, and has similar efficacy and adverse effects to the OG drug

A

rasagiline

25
Q

Name of drug that is another MAO-B selective REVERSIBLE inhibitor

A

safinamide

26
Q

What is the main MOA of ropinirole

A

increases DA-mediated effects in the CNS by binding to D2 and D3 DA receptors

27
Q

What is the 2 main clinical application of ropinirole?

A
  1. treatment of Parkinson disease

2. can be administered in addition to levodopa/carbidopa

28
Q

What drug has the following toxicities:

  1. dyskinesias
  2. impulse control disorders/compulsive behaviors
  3. inc. risk for melanoma
  4. orthostatic hypotension
  5. psychotic effects
  6. somnolence
  7. N/V, constipation
  8. headaches
A

ropinirole

29
Q

Which drug is a D2 agonist, has low risk for hypotension and somnolence but has an inc. risk for hallucinations when compared to ropinirole

A

pramipexole

30
Q

Which drug is a D2 agonist and is supplied as a 24 hr transdermal patch

A

rotigotine

31
Q

Which drug is a DA agonist and is given sublingual or subQ injection; it’s used to quickly treat “off” episodes

A

apomorphine

32
Q

Which drug is an early DA agonist and alkaloid derivative

A

bromocriptine

33
Q

Treatments for non motor features of Parkinson Disease

  1. Sialorrhea?
  2. Orthostatic hypotension?
  3. REM sleep behavior disorder?
  4. Depression?
  5. Psychosis?
  6. Dementia?
A
  1. Sialorrhea? Botulinum toxin A injections
  2. Orthostatic hypotension? Alpha- adrenergic agonist midodrine, peripheral D2 antagonist domperidone, and mineralocorticoid fludrocortisone
  3. REM sleep behavior disorder? Melatonin or Clonazepam
  4. Depression - general depression tx
  5. Psychosis? atypical antipsychotics quetiapine and clozapine are standard treatment; recently joined by pimavanserin, a selective serotonin 5- hydroxytryptamine 2A (5-HT2a) inverse agonist
  6. Dementia? cholinesterase inhibitors such as rivastigmine or donepezil and/or NMDA-antagonist memantine
34
Q

Treating Parkinson Disease tx rationale

  1. Mild signs/symptoms?
  2. Modest antiparkinson effects?
  3. Most potent antiparkinson therapy?
  4. Mild symptoms/little interference with daily function?
  5. Diminished daily function and quality of life?
A
  1. Mild signs/symptoms? No therapy needed.
  2. Modest antiparkinson effects? amantadine and MAO-B inhibitors
  3. Most potent antiparkinson therapy? levodopa
  4. Mild symptoms/little interference with daily function? prefer MAO-B inhibitor… modest effects, but generally well tolerated and are given once daily
    – amantadine… alternative, modest effects, useful if predominant tremor
  5. Diminished daily function and quality of life? If under 65 y/o use either DA agonist (1x day dose) or levodopa. If over 65 y/o, use immediate-release levodopa and switch to controlled release tablets for fewer daytime doses
35
Q

What are the clinical applications for benztropine (anticholinergic drug for parkinsonism)?

A
  • predominantly for tremor and dystonia in younger people

* can also be helpful in reducing the amount of saliva to treat excessive drooling

36
Q

When should benztropine be avoided?

A
  • should be avoided in elderly

* should be avoided in those with cognitive impairment

37
Q

What is the other anticholinergic drug besides benzotropine?

A

Trihexyphenidyl

38
Q

Which drug is causes this [black box] toxicity:

risk of potentially fatal acute fulminant liver failure, only use in Parkinson dz patients on L-dopa/carbidopa who are experiencing symptom fluctuations and are not responding satisfactorily to other agents

A

tolcapone

39
Q

what is the drug that is a selective and reversible inhibitor of COMT

A

tolcapone

40
Q

What is the main effect of tolcapone

A

COMT inhibition–> more sustained plasma levels of levodopa and enhanced central DA activity

41
Q

What is the main clinical application of tolcapone

A

adjunct to levodopa and carbidopa for tx of signs and symptoms of idiopathic Parkinson dz

42
Q

What are the toxicities associated with carbidopa (decarboxylase inhibitor) + levodopa?

A

• gastrointestinal effects… levodopa w/o carbidopa –> anorexia, nausea, and vomiting in ~ 80% of patients (activates chemoreceptor trigger in brainstem outside of BBB); ↓ to ~20% by addition of carbidopa
• postural hypotension, often diminishes with continuing treatment
• hypertension and/or cardiac arrhythmias if large doses or used with nonselective monoamine oxidase inhibitors or sympathomimetics
• dyskinesias… occur in ~80% of patients
• typically choreoathetosis (movement of
intermediate speed of the face and distal extremities); dose-related, but individual variation in the dose required
• behavioral effects including depression, anxiety, agitation, insomnia, somnolence, confusion, delusions, hallucinations, nightmares, euphoria, other changes in mood or personality
• can be treated with atypical antipsychotic agents (clozapine, olanzapine, quetiapine, risperidone)
• wearing-off and on-off phenomena

43
Q

What drug can also be given with carbidopa + levodopa?

A

Entacapone (a COMT inhibitor that does not cross BBB)

44
Q

What is another COMT inhibitor that cannot cross the BBB, acts in periphery to block levodopa degradation, less toxic for the liver… used to treat “off” symptoms

A

entacapone

NMSP (3 decks)

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