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Neurology 2 > Drugs for Movement Disorders - Kruse > Flashcards

Drugs for Movement Disorders - Kruse Flashcards

1
Q

Dopamine vs. ACh in the basal ganglia

A

Dopamine - inhibit GABA output from striatum

ACh - excite GABA output from striatum

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2
Q

How does loss of dopaminergic neurons lead to difficult movements?

A

Less inhibition of the inhibitor (striatum), thus leading to decreased movements

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3
Q

So, how would you treat Parkinson’s?

A

Increase Dopamine activity onto the GABAergic striatum neurons via Dopamine agonists or metabolism antagonists

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4
Q

Why treat with L-dopa, not dopamine?

A

L-dopa can cross BBB, but dopamine cannot

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5
Q

What is L-dopa?

A

Immediate metabolic precursor to dopamine

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6
Q

Levodopa action

Downside to levodopa alone

A

Dopamine receptor agonist

97-99% is metabolically altered before reaching the brain, via decarboxylation into dopamine

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7
Q

How to increase the effects of levodopa?

A

Give w/ a DOPA decarboxylase inhibitor
= CARBIDOPA
Causes reduced peripheral metabolism, so more enters the brain unaltered

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8
Q

A patient is taking Levodopa therapy for a long time. Eventually, each dose ends and rapidly leads to a return of symptoms. This is an example of?

Can you just give more levodopa?

A

Wearing-off phenomenon

Eventually you impair voluntary movements (dyskinesia)

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9
Q

A patient is on levodopa (with or without carbidopa). What symptoms are she most likely to exhibit? (4)

A

Anorexia, nausea, vomiting, choreoathetosis

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10
Q

Does carbidopa help with the side effects of levodopa?

A

Yes, but only in 20% of patients

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11
Q

A patient is on levodopa but has trouble with vomiting. What causes the vomiting?

A

Activation of chemoreceptor trigger zone within the brainstem (outside the BBB)

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12
Q

What is the choreoathetosis side effect of levodopa?

A

Intermediate-speed movements of the face and distal extremities

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13
Q

A patient is taking Levodopa therapy for a long time. Eventually, the patient starts having occasional episodes of inability to move at all. This is an example of?

How is this problem fixed?

A

On-off phenomenon

Apomorphine - DOPAMINE agonist that can provide temporary relief

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14
Q

A patient is taking Levodopa, but needs another drug to supplement. Which drug type should NOT be taken with Levodopa?

Why?

A

Non-selective MAO or selective MAO-A inhibitors

Lack of MAO-A leads to build-up of norepinephrine, which can cause a HYPERTENSIVE CRISIS in the patient

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15
Q

Contraindications for Levodopa therapy

A

Psychosis, closed-angle glaucoma, melanoma, active peptic ulcer

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16
Q

Why would a patient take a dopamine receptor agonist rather than Levodopa?

A

Less response fluctuation phenomena and dyskinesias

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17
Q

Can dopamine receptor agonists be given WITH Levodopa?

What about for wearing-off or on-off phenomena?

A

YES

YES (Apomorphine is a dopamine receptor agonist)

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18
Q

Bromocriptine

A

D2 agonist, ergot alkaloid

Extensive first pass metabolism (3A4)

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19
Q

Pramipexole

A

D3 agonist

Treats RLS also

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20
Q

A patient is taking Pramipexole and develops renal insufficiency. What might the doctor have to do?

A

Change the dose of Pramipexole, sine 90% is excreted renally

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21
Q

Ropinirole

A

D2 agonist
Treats RLS also
Metabolized by 1A2

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22
Q

Issue with Bromocriptine?

A

Causes digital vasospasm with long-term use

Should be discontinued if patient has peripheral edema, peripheral vascular disease, or cardiac arrhythmias

23
Q

Issue with Pramipexole or Ropinirole?

A

May feel uncontrollable tendency to fall asleep at random times

24
Q

Psychosis is a contraindication for Levodopa treatment. What about dopamine receptor agonists?

A

DO NOT USE - causes more severe mental disturbances than Levodopa

25
Q

MAO-A vs. MAO-B

A 
A = metabolism of NE and serotonin
B = metabolism of phenylethylamine and benzylamine
26
Q

Dopamine is metabolized by which MAO?

A

Both equally

27
Q

A patient is taking Levodopa but needs something to help relieve the on-off and wearing-off phenomena. What can be taken along with it?

A

Selegiline (MAO-B inhibitor)

28
Q

Selegiline

A

Irreversible MAO-B inhibitor

Prolongs the effects of Levodopa

29
Q

Rasagiline

A

Irreversible MAO-B inhibitor

More potent form of Selegiline

30
Q

COMT role in dopamine stuff

A

Breaks Levodopa into a competitor for transport across the BBB, thus making Levodopa less effective

31
Q

Tolcapone

A

COMT inhibitor
Prolongs activity of levodopa by preventing its peripheral metabolism, thus decreasing clearance
CENTRAL and PERIPHERAL effects

32
Q

Entacapone

A 
Like Tolcapone (COMT inhibitor)
But only PERIPHERAL effects
33
Q

A patient is on Levodopa and Tolcapone. What is a potential side effect of the Tolcapone?

A

Hepatic toxicity (increased liver enzymes)

34
Q

Benefit of Apomorphine vs. other dopamine agonists for relief of Levodopa phenomena

A

SubQ INJECTION = quick, temporary relief

35
Q

A patient is taking Levodopa therapy for a long time. Eventually, the patient starts having occasional episodes of inability to move at all. How is this problem fixed?

What is the potential side effect of this fix?

How is this side effect fixed?

A

Apomorphine

Nausea, vomiting

Pre-treat w/ TRIMETHOBENZAMIDE (anti-emetic)

36
Q

Trimethobenzamide

A

Anti-emetic, used in the relief of nausea and vomiting due to anti-parkinson drugs

37
Q

A patient is on Levodopa therapy for PD that is supplemented with another drug. However, over time, the patient developed purple discoloration of the LE skin including very apparent superficial vasculature. What drug is he on?

What is this condition called?

A

Amantadine

Livedo reticularis (side effect of the drug)

38
Q

Amantadine

A

Anti-viral agent that somehow helps with parkinsonism

39
Q

Anticholinergic drugs used in the treatment of Parkinsonian symptoms

What are they?

A

Benztropine, biperiden, orphenadrine, procyclidine, trihexyphenidyl

Centrally-acting anti-muscarinic

40
Q

Purpose of anticholinergic drugs here?

A

Improve tremor and rigidity by balancing the low dopamine level in the basal ganglia with an equally low acetylcholine level

41
Q

Adverse effects of anticholinergic drugs here?

A

Sedation, confusion, constipation, urinary retention, blurred vision (typical CNS sympathetic symptoms)

42
Q

Propranolol, Metoprolol

A

Beta-1 antagonists used to stop tremor

43
Q

Primidone

A

Anti-epileptic drug used to stop tremor (smaller doses)

44
Q

Topirimate

A

Serotonin receptor agonist used to stop tremor

45
Q

BOTOX

A

IM injection used to help tremor

46
Q

Reserpine

A

IRREVERSIBLE dopamine reuptake (MAT) agonist

Used for treatment of Huntington

47
Q

Tetrabenazine

A

REVERSIBLE dopamine re-uptake (MAT) agonist

Used for treatment of Huntington

48
Q

Patients with Huntington often need treatment for psychiatric symptoms (depressed, irritable). What are treatment options? (2)

A

Fluoxetine - depression and irritability

Carbamazepine - depression

49
Q

Pimozide, haloperidol

A

Neuroleptic antipsychotics used for TICS

50
Q

A patient needs meds for a TIC but doesn’t want the side effects of Pimozide. What are other options? (3)

A

Clonidine, Guanfacine (alpha agonists)

Botulinum toxin A

51
Q

Treatment for restless leg syndrome

A 
Dopamine agonists (non-ergot) 
    - Pramipexole, Ropinirole
52
Q

Riluzole

53
Q

Penicillamine

A

Wilson’s disease (chelating agent)

54
Q

Other drugs for Wilson’s disease besides Penicillamine? (3)

A

Trientine, Zinc acetate, Zinc sulfate

Neurology 2 (22 decks)

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