Parkinson's Flashcards

1
Q

What are the approaches to treating Parkinson’s

A
  • Increase endogenous dopamine
  • Decrease cholinergic activity
  • Activate dopamine receptors with synthetic dopamine agonists
  • Block adenosine A2A receptor activity
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2
Q

How do you increase endogenous dopamine?

A
  • Use of L-dopa
  • Inhibit metabolism of dopa decarboxylase
  • Inhibit metabolism by COMT
  • Inhibit central/peripheral metabolism by MAO-B
  • Increase dopamine release and inhibits reuptake
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3
Q

Drugs that inhbit COMT

A
  • Entacapone
  • Tolcapone
  • Opicapone
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4
Q

Drugs that inhbit MAOB

A
  • Rasagiline
  • Selegiline
  • Safinamide
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5
Q

What PK drugs that induce endogenous dopamine can also be used as monotherapy?

A

MAOB inhibitors

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6
Q

Which PK drug can produce methamphetamines if a toxicology report is done?

A

Selegiline

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7
Q

What PK drug increases dopamine release and inhibits it reuptake?

A

Amantadine

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8
Q

Dosing for Rasagiline as adjunctive and as monotherapy

A

Adjunctive: 0.5 mg
Monotherapy: 1 mg

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9
Q

What should you be cautious with in Safanimide therapy?

A

Hepatic impairment (Child Pugh Class C)
Abrupt discontinuation - withdrawal emergent NMS-like syndrome

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10
Q

What is the effect of Amantadine?

A

It reduces rigidity, tremor, bradykinesia and L-Dopa induced dyskinesia

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11
Q

What should you monitor with Amantadine dosing?

A

Renal elimination; adjust dose with renal impairment

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12
Q

What’s a transient adverse effect of Amantadine

A

Livedo reticularis; mottling of the skin

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13
Q

What is a side effect of selegiline?

A

It can cause insomnia and jitteriness

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14
Q

What PK drug is potentially disease modifying?

A

Rasagiline

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15
Q

What is the PKPD and dosing strategy surrounding Opicapone?

A

With a mod fat/calorie meal, its Cmax, AUC and Tmax decrease
It is also to be dosed at bedtime at least 1 hour before and 1 hour after eating

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16
Q

What PK drug is available in combo with Carbidopa/Levodopa?

A

Entacapone (200 mg)
STALEVO

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17
Q

True or False. Carbidopa can be used a monotherapy to help treat Parkinson’s

A

False. Never you give it alone

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18
Q

True or False. COMT inhibitors can be used as monotherapy to help treat Parkinson”s

A

False. No effect in absence of L-Dopa

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19
Q

True or false. MAOB inhibitors can be used as monotherapy to help treat Parkinson’s.

A

True

20
Q

How can you activate dopamine receptors?

A

With the use of synthetic dopamine agonists

21
Q

True or False. Dopamine agonists can be used a monotherapy to help treat Parkinson’s

A

True. Only in young healthy patients

22
Q

What are your synthetic dopamine agonsits?

A
  • Pramipexole
  • Ropinirole
  • Rotigotine
  • Apomorphine
23
Q

What is the benefit of using a synthetic dopamine agonist over L-Dopa

A

It has a reduced risk of developing motor complications when used as monotherapy

24
Q

What are the side effects of dopamine agonists?

A

Impulsive behaviors, psychosis
n/v, vivid dreams, daytime sedation, orthostatic hypotension

25
Q

What formulation is Rotigotine and what is a side effect?

A

Patch
Application site reaction

26
Q

When is Apomorphine used?

A

In advanced Parkinson’s as needed for “off” episodes

27
Q

How should you initiate Apormorphine therapy?

A

A test dose of 2mg SC done under medical supervision
Be sure to pre-treat with an antiemetic that is is not a 5HT3 antagonist or an antidopamingeric

28
Q

What is the PK profile of Apormorphine?

A

It has a short half life of 40 mins that is why it is used for refractory, acute off episodes.

29
Q

What is a serious DDI with Apomorphine pre-treatment?

A

It is contraindicated with 5HT3 antagonits and antidopaminergics due to hypotensive effects

30
Q

Why might we need to block adenosine A2A receptor activity?

A

Its appears as so that inhibition of motor function occurs when there is overactivation of adenosine A2A receptor pathway

31
Q

What drug can you use to block adenosine A2A receptor activity?

A

Istradefylline (A2A receptor antagonist)

32
Q

How is Istradefylline used?

A

It’s used in combo with levodopa/carbidopa in patients experiencing off episodes

33
Q

When might you need to dose adjust Istradefylline?

A

In concomitant tobacco smoking by increasing the dose

34
Q

What are your non-pharm options for treatment of Parkinson’s

A
  • Surgery: Deep Brain Stimulation
  • Physical therapy/Exercise
  • Nutrition (Fluids, Fiber, Omega 3)
  • Occupational Therapy
35
Q

What are L-Dopa related long term complications?

A

There are fluctuations in motor performance with wearing off and response deterioration as well as peak effect dyskinesia phenomenon
There is also dyskinesias/abnormal involuntary movement

36
Q

What should you do if there is a wearing off or an “on-off” response?

A

Increase the frequency or switch to Sinemet CR or use an adjunctive dopa agonist/COMTi/MAOBi

*The med isn’t working long enough

37
Q

What should you do if there is an “off, no on” response?

A

Increase the dose, the frequency or drink more water with med OR use an ODT. If it’s advanced Parkinson’s use Apomorphine.

*The med isn’t working well enough

38
Q

What should you do if there is a delayed onset of the medication?

A

Take on an empty stomach, drink a lot of water and avoid protein. You can also switch to Sinemet CR or add IR to CR

*The med isn’t working fast enough

39
Q

What should you do if you have peak-effect dyskinesia?

A

Decrease the dose, increase the frequency, add amantadine, use Sinemet CR, dopa agonist

40
Q

What should you do if you experience dystonia?

A

Take in early morning, take Sinemet CR at bedtime, a dopa agonist, baclofen or botox

41
Q

What should you do if you experience freezing?

A

Increase dose, dopa agonist, gait modification, physical therapy***

42
Q

What can you give a Parkisnson’s patient with depression?

A

Pramipexole or Venlafaxine

43
Q

How can you manage dementia and cognitive impairment in Parkinson’s patients?

A

Anticholinesterase inhibitors

44
Q

How should you deal with Psychosis in Parkinson’s

A
  • Evaluate hypoxia, infection or Elyte imbalance
  • Simply regime; d/c anticholi’s, taper, selegiline
  • Consider atypicals like quietapine and clozapine (and nuplazid)
45
Q

What new drug is indicated for hallucinations and delusions in Parkinson’s?

A

Nuplazid

46
Q

How does Nuplazid work?

A

inverse agonist at the 5HT2A/2C receptor