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Phar 507 > Parkinson's Disease Pharmacotherapy > Flashcards

Parkinson's Disease Pharmacotherapy Flashcards

1
Q

T/F: Treatments for Parkinson’s only manange the disease but do not delay or stop the disease

A

True

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2
Q

What are the six types of medications used to treat Parkinson’s Disease

A

1) Levodopa
2) Dopamine agonists
3) Monoamine oxidase (MAO) B inhibitors
4) Catechol-O-Methyl-Transferase (COMT) inhibitors
5) Amantadine
6) Anticholinergic agents

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3
Q

T/F: In Parkinson’s the Substantia Nigra is being destroyed leading to less Dopamine release causing the symptoms of the disease

A

True

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4
Q

How is Dopamine created and released at Nigrostriatal neurons

A

1) Tyrosine is converted to L-DOPA by tyrosine hydroxylase
2) L-DOPA is converted to dopamine by DOPA Decarboxylase (DDC)
3) Dopamine is stored in vesicles ready for release due to an action potential
4) Dopamine that is left over is brought back into the cell by the dopamine transporters

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5
Q

What is the enzyme that converts L-DOPA into an inert compound, converts Dopamine into an inert compound

A

COMT converts L-DOPA in 3-OMD, MAO-B and COMT convert dopamine into an inert compound

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6
Q

What drug is used to increase dopamine levels by being converted to dopamine

A

Levodopa

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7
Q

What are the dopamine agonists

A

Ropinirole, pramipexole, rotigotine, apomorphine

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8
Q

What are the MAO-B inhibitors

A

Selegiline, Rasagiline, Safinamide

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9
Q

What are the COMT inhibitors

A

Entacapone and Tolcapone

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10
Q

What drug has an unknown MOA but is theorized to cause exocytosis, agonist of dopamine and inhibit dopamine uptake

A

Amantadine

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11
Q

What is the benefit of using anticholinergics

A

Reduce how bad tremors are

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12
Q

Why cant just dopamine be given

A

It does cross the BBB

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13
Q

What is the biggest side effect of levodopa, why

A

Causes nausea and vomitting, when L-Dopa is converted to Dopamine in the periphery it binds to the chemoreceptor trigger zone (CTZ) outside the BBB thus causing nausea

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14
Q

T/F: Levodopa is given by itself so some patients can handle the nausea while others cannot

A

False: Carbidopa is given with Levodopa to cause less side effects

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15
Q

How does carbidopa aid in the efficacy of Levodopa

A

Carbidopa competitively inhibits Dopa Decarboxylase from converting Levodopa in the periphery allowing for less side effects and more Levodopa to enter the brain

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16
Q

What should be counseled about Carbi/Levo when given with food

A

Do not eat with a high protein meal because the bioavailability is reduced

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17
Q

What are the two most notable side effects of Carbi/Levo, others

A

Nausea and orthostatic hypotension/ confusion, delusions, agitation, psychosis, motor fluctuations, parkinsonism hyperpyrexia syndrome

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18
Q

What is a tip to not have nausea with Carbi/Levo

A

Slower transiotion with food, supplemental doses of carbidopa 30 minutes before, ondansetrons, certain anticholinergics

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19
Q

What should NOT be given with Carbi/Levo

A

Dopamine antagonist (Metoclopramide, Prochlorperazine, Promethazine)

20
Q

What happens with longer Carbi/Levo use with regards to motor fluctuations

A

In the beginning the drug works quickly, however with disease progression and tolerance the drug wears off quicker and it takes higher concentrations to achieve an effect, there is also dyskinesia due to the drug as the disease progress ALL DUE TO INCREASED DEPENDENCE

21
Q

T/F: Due to the wearing off effect of Carbi/Levo there is clenching of feet upon waking in the morning but this can be mittigated through wooden shoes and long acting Carbi/Levo

A

True

22
Q

How is the off period managed

A

Take Carbi/Levo more frequently OR adding COMT inhibitors OR MAO-B inhibitor OR Dopamine Agonist

23
Q

What are ways to manage dyskinesia due to Carbi/Levo use

A

Use lowest effective dose, addition of amantadine, change to or add MAO-B inhibitor, addition of COMT inhibitor, change to or add Dopamine agonist

24
Q

What is Parkinsonism Hyperpyrexia Syndrome, symptoms

A

Patients are on Carbi/Levo for long periods of time and it is suddenly stopped/ mental status changes, rigidity, fever (possibly fatal)

25
Q

T/F: Dopamine agonist work as adjuncts or monotherapy but are generally less effective

A

True

26
Q

What are side effects of Dopamine agonists that occur more often than Carbi/Levo, what is the one benefit

A

Somnolence, constipation, dizziness, hallucinations, nausea, freezing of gait

27
Q

What benefit does dopamine agonists have, what is the caveat

A

Less incidence of dyskinesia BUT the incidence of dyskenesia and Carbi/Levo converge over time

28
Q

What are UNIQUE side effects of dopamine agonists

A

Peripheral edema, drowsiness and narcholepsy, Impulse control dissorders (gambling, sex, winning), Dopaminergic Dysregulation syndrome (addiction), Dopamine agonist withdrawl syndrome (night sweats, anxiety, depression, sweating, drug craving)

29
Q

What are benefits of using MAO-B inhibitors with Carbi/Levo, problem

A

Improve off symptoms, provide extra hour of duration to Carbi/Levo (incosistent), worsens dyskinesia with Carbi/Levo

30
Q

Which MAO-B inhibitors has multiple dosage forms

A

Selegiline

31
Q

What are side effects of MAO-B inhibitors

A

Nausea/vomitting, headaches, confusion in ederly and hallucinations

32
Q

What is something to be cautious about when it comes to selegiline more than rasagiline, how can this be avoided

A

Selegiline has two metabolites, L-amphetamine and L-methamphetamine, that cause insomnia/ should be taken twice a day with breakfast and lunch

33
Q

What are the drugs that Contraindicated with MAO-B inhbitors,

A

Tramadol, St. John’s Wort, MAO inhibitors, Dextromethorphan, Methadone
Serotonin Syndrome

34
Q

T/F: High blood pressure is associated with eating MAO-B inhibitors when eaten with protein

A

False: Foods that have tyramine, cheese wines cured meats and chocolates, cause the release of norepinephrine from vesicles of neurons increasing BP

35
Q

T/F: COMT inhibitors are only used as adjuncts on Carbi/Levo while also increasing the half life

A

True

36
Q

Which COMT inhbitor is no longer used

A

Tolacapone

37
Q

What are the odd side effects of COMT inhibitors

A

Delyaed onset diarrhea and dark colored urine

38
Q

When is amantadine usually used

A

Weakly effective but generally very well tolerated

39
Q

What are the two anticholinergics, what are they used for

A

Benztropine and Trihexyphenidyl, first line for Parkinson’s tremor

40
Q

What are the drug choices for dealing with mild tremor

A

Anticholinergic, Beta blocker, MAO-B inhibitor, Carbi/LEvo, Dopamine agonist

41
Q

What is a drug added for severe tremor resistant to other therapies

A

Clozapine

42
Q

What drugs are used for moderate postural instability and Gait Difficulty (PGID), severe

A

MAO-B inhibitor, Carbi/Levo, Dopamine agonist/ Carbi/Levo

43
Q

What is used to treat Depression in Parkinson’s, Dementia

A

TCAs (exacerbating dementia and narrow angle glaucoma), Nortriptyline or Desipramine/ Reduce anticholinergics

44
Q

What is used to treat Psychosis/Hallucinations in Parkinson’s, what must be monitored

A

Clozapine, WBC and ANC due to risk of agranulocytosis

45
Q

What are way to improve orthostatic hypotension due to drugs or Parkinson’s

A

Increase salt and fluid consumption, elevate head of bed, Midodrine, fludrocortisone

Phar 507 (33 decks)

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