Alzheimer's and Parkinson's Medication Flashcards Preview

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Flashcards in Alzheimer's and Parkinson's Medication Deck (65):
1

Pathophysiology of Parkinson's Dz

Progressive depletion of dopaminergic neurons in the substantia nigra of the basal ganglia

Functional increase in ACh occurs (causing the characteristic resting tremor)

Lewy bodies (protein aggregates) found post-portem in remaining DA cells in the SN

2

Percentage of dopamine lost by the time a patient presents w/ symptoms

70-80%

3

4 core clinical features of Parkinson's

1. Bradykinesia
2. Resting Tremor
3. Rigidity
4. Postural Instability

4

What is needed to make the dx of Parkinson's?

Bradykineasia and at least one of the following:
--Resting tremor
--Rigidity
--Postural Instability

Bradykinesia + 1 = possible PK
Bradykinesia + 2= probably PK
Bradykinesia +2/3 +response to meds = PD

5

5 predictors of Parkinson's disease progression (these make a worse prognosis)

1. Older age at onset
2. Rigidity as presenting symptom
3. Male
4. Presence of comorbidities
5. Decreased response to dopamine

6

What are the two MAO-B inhibitors used to treat PD? Which is used 1st line?

Selegiline and Rasagiline

-->Rasagiline is 1st line

7

Is levodopa 1st line in a patient w/ PD?

You can begin levodopa tx 1st line in a PD pt who is older, has cognitive impairment, or has mod-severe functional impairment. Otherwise hold off on using this and use rasagiline 1st line

8

Why is Rasagiline used above Selegiline?

Rasagiline is neuroprotective so it has fewer adverse effects (Selegiline can cause insomnia, jitteriness, dyskinesias, orthostasis, and serotonin syndrome)

9

MOA of Amantadine (Symmetrel)

Unclear - Augmentation of dopamine release from presynaptic terminals and inhibition of dopamine reuptake. Might also inhibit NMDA (glutamate inhibition)

10

Place in therapy for Amantadine

Initiated early stages w/ mild symptoms of PD and it improves bradykinesia, rigidity, and tremors

11

Side effects of Amantadine:

Orthostatic hypotension
confusion
nightmares
hallucinations
nervousness
irritability
livedo reticularis

12

When would you give a Parkinson's pt an anticholinergic agent?

If a patient presents early w/ resting tremor and has minimal bradykinesia or rigidity. Can be monotherapy or adjunct

13

In what types of patient's with PD would you want to avoid anticholinergic agents?

Pt's w/ cognitive deficits
BPH
Urinary issues
Glaucoma

**AKA - the elderly!

14

MOA of dopamine agonists

Direct stimulation of striatal dopamine receptors. Have longer half lives than LD so they produce more constant stimulation of dopamine receptors

15

Dopamine agonsts can delay the need for levodopa by _____ years in ____% of pts

4-5 years in 80% of patients

16

Important note about dosing of dopamine agonists.

START LOW AND GO SLOW
Effects will take 4-8 weeks to take effect

17

A patient who is currently taking LD wants to add a dopamine agonist. What needs to be done to either LD or DA?

LD needs to be decreased by 20-30%

18

Name the 4 dopamine agonists - non-ergot derivatives

1. Pramipexole (Mirapex)
2. Ropinirole (Requip)
3. Rotigotine (Neupro)
4. Apomorphine (Apokyn)

19

What is apomorphine (amokyn) used for?

"Rescue therapy" for "delayed on"/"no on"/ or "freezing episodes"

PRN tx of hypomobility in pts w/ advanced PD

20

If you want to start a pt on apomorphine what must you also do/prescribe?

Start trimethobenzamide 3 days prior to administering apomorphine and then continue trimethobenzamide for the 1st two months of treatment

21

Do not use apomorphine with _______ because the combination could result in severe hypotension

serotonin agonists (ondansetron)

22

What is the formulation of apomorphine?

SubQ - so pt may require someone else to inject it d/t hypomobility
NO ORAL DOSING!!

23

Why is carbidopa given with levodopa?

Levodopa is metabolized to dopamine by L-amino acid decarboxylase so that it cannot cross the BBB. Levodopa alone also causes significant N/V and the doses we require to get it into the substantia nigra.

Because of this problem, we give carbidopa which is a peripheral decarboxylase inhibitor used to increase LD's bioavailability.

24

____ less LD dose required to achieve same effect when it is dosed with carbidopa.

80% less

25

Immediate release CD/LD should be dosed @ ________.

Extended release CD/LD should be dosed @ ________.

IR: Take 30 min before a meal or 60 min after

CR: Should be taken with food

26

A PD pt comes to you explaining that her symptoms are returning just prior to her next dose of CD/LD. To fix this "wearing off effect" you....

Decrease dosing interval of LD (inc. it's frequency)

Could also add MAO-B inhibitor, COMT inhibitor, or DA

27

How to manage a pt's PD meds when they are experiencing "peak-dose dyskinesia" or excessive movement secondary to excessive striatal dopamine stimulation.

Smaller and more frequent doses of CD/LD

Could add amantadine

28

How do you correct "delayed on" and "no on" problems with a PD pts meds?

Since this may be d/t delayed gastric emptying or decreased absorption in the duodenum...

...Give CD/LD on empty stomach before meals using ODT formulation (avoid controlled release)
...Could add apomorphine

29

What is "freezing" or "start hesitation" in relation to PD?

Sudden, episodic inhibition of lower-extremity motor function. Often exacerbated by anxiety or when perceived obstacles are encountered

30

How can we fix "freezing?"

Inc. CD/LD dose
Add DA or MAO-B inhibitor
Utilize physical therapy and assistive walking devices or sensory cues

31

What is "off period dystonia" and how can we treat this in PD?

Sustained muscle contraction that is common in distal lower extremity. These often occur in early morning hours just prior to the first dose of L-dopa.

To tx:
--Add CR CD/LD
--Add ropinirole CR at bedtime
--Initiate Baclofen
--Initiate Botulinum toxin

32

A pt is experiencing myoclonic jerks during sleep. They are already on CD/LD. What to do?

Decrease nighttime LD dose
Initiate clonazepam

33

MOA of COMT Inhibitors

Prevent peripheral conversion of LD to 3-O-Methyldopa
-->Allows more LD across the BBB

34

Can we use COMT-Inhibitors as monotherapy for Parkinson's?

NO! It only works w/ CD/LD

35

2 COMT Inhibitors we use:

Entacapone (comtan, stalevo)
Tolcapone (Tasmar)

36

Which COMT-Inhibitor should you monitor LFT's in d/t its potential serious liver dysfunction

Tolcapone

37

What two Parkinson drugs need to be tapered when taking a patient off? (give reasons as to why too)

1. Anticholinergics - could cause withdrawl rxns

2. Amantadine - to avoid rebound Parkinsonism

38

Parkinson drugs that needs to be adjusted if a patient has renal dysfunction

Pramipexole (Mirapex)

39

PD drugs that need to have LFTs monitored d/t liver issues

1. Tolcapone
2. Ropinirole

40

Typical progression of Alzheimer symptoms

Cognitive impairment --> Behavioral impairment --> Functional impairment

41

Stages of Alzheimer's and MMSE scores associated

Mild Cognitive Impairment - Memory loss only, no evidence of AD

Mild AD: MMSE 26-18 - forgetful, short-term memory loss, hobbies lost, impaired ADLs

Mod AD: MMSE 17-10 - further progression...transition into care, behavioral/psychological symptoms of dementia start

Severe AD: MMSE 9-0 - agitation, altered sleep patterns, assistance required for everything, dementia, speech involved

42

3 cholinesterase inhibitors used to tx AD

Donepezil
Galantamine
Rivastigmine

43

NMDA antagonist used to tx AD

Memantine (Namenda)

44

What are Cholinesterase inhibitors indicated for?

Mild to moderate AD

45

What are NMDA antagonists indicated for?

Moderate to severe AD

46

MMSE and ADAS improvements w/ cholinesterase inhibitors

MMSE: 1-1.5 improvement

AGAS: 2.8-4 improvement

47

Average MMSE and ADAS decline in a patient w/ AD on NO MEDICATIONS.

MMSE: 2-4 points/year
ADAS: 7 points/year

48

MOA of Donepezil (Aricept)

Reversible CI that has specificity for acetylcholinesterase and NOT butyrylchoinesterase

49

MOA of Galantamine (Razadyne)

1. Inhibits acetylcholinesterase
2. Modulates nicotinic receptors... inc. release and enhancement of cholinergic function

50

MOA of Rivastigmine (Exelon)

Reversible CI but has a very slow dissociation w/ ACHe
Substantially inhibits butyrylcholinesterase

51

Dosing for Donepezil

5mg, 10mg, 23mg. Start @ 5mg and titrate up to 10mg in 4-6 weeks
-->If pt has mod-severe AD can wait 3 months and again titrate up to 23mg daily.

Package insert recommends dosing at bedtime but most people favor administration w/ lunch to reduce nightmares/vivid dreams

52

Drug interactions of donepezil

Anticholinergics
NSAIDs
CYP2D6 or 3A4 inhibitors

53

Which cholinesterase inhibitor has the worst adverse rxn's? Which has the best?

Worst -- Rivastigmine
Best -- Donepezil

54

Dosing of galantamine:

Comes in IR, ER, and oral solutions
Titrate every 4 weeks..start dose @ 8mg/day

55

Renal dose adjustments of galantamine:

If CrCl < 70 do not exceed 16mgs daily

If CrCl < 9 DO NOT GIVE GALANTAMINE

56

Dosing of Rivastigmine

Comes in capsules, oral solution, transdermal patch

Start dose (capsule) @ 1.5mg BID and titrate up q4weeks to a max dose of 12mg

Take w/ food

57

MOA of Memantine

interfers/slows glutamatergic excitotoxic neurotoxicity. It is specific and noncompetitive antagonist (no interactions w/ other enzymes, receptors, transporters

Rapid association/dissociation w/ the receptor

58

Dosing/titration schedule of Memantine

Titrated weekly:
5mg daily
5mg BID
5mg morning, 10mg afternoon
10mg BID

*Also comes in XR formulation that is titrated similiar:
7mg daily
14mg daily
21mg daily
28mg daily

59

Dose reduction of Memantine if renally impaired

If CrCl < 30 then Max of 10mg/day

60

Is vitamin E indicated for either Parkinson's or Alzheimers?

NO!

61

Besides the pharmacotherapies discussed in the AD lecture (CI and NMDA antagonists) what other therapies can we add to a patient with AD?

Aspirin
Vitamin B (6,9,12)
Ginkgo Biloba

62

A pt diagnosed w/ AD presents with hallucinations and delusions. What is an additional therapy that can be added to address these new symptoms?

Antipsychotic drugs
--> Haloperidol
--> Atypicals

63

A pt diagnosed w/ AD presents with poor appetite, suicidal thoughts, and depression. What is an additional therapy that can be added to address these new symptoms?`

Antidepressants
-->SSRI's are tx of choice (Citalopram, escitalopram, sertraline)

64

A pt diagnosed w/ AD presents with restlessness, anxiety, and insomnia. What can we add to this pts existing meds to address these new presenting symptoms?

Benzodiazepines
-->Lorazepam

65

A pt diagnosed w/ AD presents with agitation and aggression. What can we give to this pt to address these new presenting symptoms

Anticonvulsants
-->Carbamazepine
-->Valproic Acid