Movement Disorder Drugs

Question 1

Levodopa:
MOA
Therapeutic Use

Answer 1

Metabolized by DOPA-Decarboxylase–> Dopamine in the brain/periphery (crosses BBB)

Treats Parkinsons: Requires Large Dose

• Peripheral decarboxylation
• 40% metabolized in gut
• Rarely given alone

Question 2

Carbadopa:
MOA
Therapeutic Use

Answer 2

Inhibits Peripheral DOPA-Decarboxylase (NO cross BBB)
Inhibits peripheral L-Dopa metabolism
Given with L-Dopa= SINIMET

Question 3

PRAMIPREXOLE:
MOA
Therapeutic Use
* Which patient population is ideal for this drug?

Answer 3

D3 agonist
1) Monotherapy mild Parkinsons
2) Restless Leg
Good for liver disease patients because not metabolized

Question 4

Sinimet

Answer 4

Levodopa + Carbadopa

Question 5

Contraindications to Levodopa Use (3 + caveat)

Answer 5

1) Narrow angle glaucoma
2) MAOis –> HTN crisis
3) Vitamin B6 –> INCREASES L-dopa breakdown in periphery
* Avoid rapid discontinuation

Question 6

Adverse Drug Reactions to Levodopa:

GI, Cardio, Ocular, Psych

Answer 6

1) Nausea, vomiting, anorexia
2) Arrhythmias, hypotension
3) Mydriasis
4) Mood changes, depression, anxiety, psychosis
5) Hallucinations/ Dyskinesia Titrate dose

*Due to dopamine in periphery

Question 7

Dopamine agonists that are ergot derivatives

Answer 7

Bromocriptine

Pergolide

Question 8

Ropinirole:
MOA
Therapeutic Use

Answer 8

D2 agonist

Monotherapy mild Parkinsons or adjunct in severe disease

Question 9

Apomorphine
MOA
Therapeutic Use
ADR*

Answer 9

Dopamine agonist rapidly taken up into brain
Parkinson’s Rescue therapy
Severe nausea, give antiemetic prior to admin.- not DA based

Question 10

Rotigone:
MOA
Therapeutic Use
ADR*

Answer 10

Skin patch delivers continuous Dopamine agonist
Used to treat parkinsons
Discontinued
Crystallization at patch site

Question 11

Antimuscarinic Drugs Used to Treat Parkinson’s

Answer 11

Trihexylphenidyl

Benzotropine

Question 12

Rasageline:
MOA
Therapeutic Use

Answer 12

MAO-B Inhibitor: Stop Dopamine–> DOPAC–> Increase Dopamine, Decrease Oxidative Stress

Parkinson’s:

1) Monotherapy early on/ w sinemet
2) Combo tx. In late disease

• More potent than selegiline

Question 13

Selegiline:
MOA
Therapeutic Use
ADR

Answer 13

MAO-B Inhibitor: Stop Dopamine–> DOPAC–> Increase Dopamine, Decrease Oxidative Stress

Parkinson’s: Prevents On/Off symptoms of L-Dopa tx.

Question 14

Which drugs interact with MAOB’s (3)?

Which foods should these patients avoid (1) ?

Answer 14

• Many drug interactions: SSRis/TCAs, meperidine

- Avoid tyramine (cheese, beer)

Question 15

Etacopone:
MOA
Does it cross BBB?
Therapeutic Use

Answer 15

NO cross BBB (Inhibits peripheral COMT)
Parkinson’s: Prevents 3-OMD formation competitive inhibition w/ L-DOPA for entry @ BBB

Therapeutic Use:
w/ sinemet only for “wearing off”
*alone dopamine formation in periphery

Question 16

Tolcapon:
MOA
Does it Cross BBB?
Therapeutic Use

Answer 16

YES cross BBB (Inhibits peripheral & CNS COMT)
Parkinson’s: Prevents 3-OMD formation competitive inhibition w/ L-DOPA for entry @ BBB

Therapeutic Use:
w/ sinemet only for “wearing off”
*alone dopamine formation in periphery

Question 17

Amantadine

Answer 17

Antiviral used to treat parkinsons; increases dopamine and NE

Question 18

What is the salient side effect associated with Etacapone use?

Answer 18

Delayed Diarrhea 2-12 weeks

Question 19

Why is Tolcapone discontinued after three weeks without symptomatic improvement?

Answer 19

Fulminating Hepatic Necrosis; remove drug from regimen after 3 weeks if no symptomatic improvement

Question 20

Typical Antipsychotics used to treat Huntington’s (2)

Answer 20

CHLORPROMAZINE

HALOPERIDOL

Question 21

Atypical Antipsychotics Used to treat Huntington’s Disease (2)

Answer 21

RISPERIDOME

OLANZAPINE

Question 22

Reserpine:
MOA
Therapeutic Use
ADRs

Answer 22

Inhibits uptake of dopamine into vesicles cytosolic–> Increases metabolism of dopamine
Huntingtons: mild chorea

ADR: MAOI’s; QT prolonging agents (increase efficacy)

Question 23

Absolute contraindications to Reserpine Use

Answer 23

actively suicidal/ depressed patients

Question 24

BACLOFEN:
MOA
Metabolism
Therapeutic Use

Answer 24

Muscle relaxant used to treat spasticity in Huntington’s Disease and MS

*Limited metabolism, low and slow in brain

Question 25

ADRs with Baclofen | Which population of patients is most sensitive to the drug's effects?

Answer 25

Drug Interactions: All depressant drugs (benzos, ETOH, etc.) *Elderly more prone to effects.

Question 26

Riluzole: Metabolism + Contraindications Therapeutic Use

Answer 26

Hepatic Metabolism CYP1A2 Contraindications: hepatic impairment Prolongs time before need for life support in patients with ALS

Question 27

AchE Inhibitors used to treat Alzheimer's Disease

Answer 27

1. Tacarine 2. Donepazil 3. Rivastigmine 4. Galantamine

Question 28

What is a possible side effect to using AchE inhibitor to treat Alzheimer's Disease? How might you combat this problem? What are 2 possible ADRs asstd. with AchE Inhibitors?

Answer 28

Insomnia- Give Dose Early, titrate | Avoid succinylcholine/ NSAIDs

Question 29

How do AchE Inhibitors help treat Alzheimer's disease?

Answer 29

- 40-70% inhibition Early cognitive improvement | - Slow course of disease

Question 30

MEMANTINE: MOA Therapeutic use How is it excreted?

Answer 30

NMDA Antagonist; Bings Mg site to block Ca++ channel Used to treat Alzheimers Excreted in Alkalized urine, so avoid carbonic anhydrase inhibitors or any other drug that might decrease using pH

Question 31

Methylene Blue: MOA Weird side effect

Answer 31

Strong MAOI | Alzheimers patients may get this over the counter and it will turn their urine funny colors

Question 32

IFNS: MOA Therapeutic Use Side effects

Answer 32

Change cytokine profile in brain + Strengthen BBB Treat RRMS Flu symptoms

Question 33

Glatramir: MOA Therapeutic Use Side Effects

Answer 33

``` Angelically similar to myelin basic protein--> Stimulates bystander effects Treats RRMS (w/ IFN) ``` Pain, anxiety, weakness, chest pain

Question 34

Mitoxantrone: MOA Therapeutic use How is it administered?

Answer 34

Antineoplastic agent used to treat aggressive and unresponsive RRMS IV admin every 3 mos

Question 35

Natiluzamab: MOA Therapeutic Use Side Effect*

Answer 35

Monoclonal Ab against alpha 4 integrins on lymphocytes Treats RRMS (second line agent) IV infusion every 4 weeks Reduces size of lesions ADR: PML*

Question 36

Methylprednisone: MOA Therapeutic Use Side Effect*

Answer 36

Decreases Inflammation, suppresses immune system, Tightens BBB Treats Acute Attacks in Progressive MS; reduces relapse ADR: Cushings