Lecture 37: Drugs of Movement Disorders Flashcards Preview

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Flashcards in Lecture 37: Drugs of Movement Disorders Deck (34):
1

You disrupt balance of which two NTs in indirect pathway in PD?

ACh and DA

2

Broadly, DA activity is ___-movement. What is ACh?

Pro; anti-movement

3

Broadly, PD drugs do one of which two things?

Enhance DA function or inhibit ACh function

4

At first, PD disease treatment is generally what kind of therapy? Which drugs?

Monotherapy w/ L-DOPA, DA agonist OR MAO-B inhibitor

5

Overtime, what monotherapy becomes most popular? What happens (treatment-wise) next?

L-DOPA; L-DOPA requires supplemental therapy

6

L-DOPA is a ___-drug. Enzyme?

Pro-drug; DOPA decarboxylase

7

Three reasons to not just give DOPA

Low oral bioavailability, significant peripheral effects, poor access to brain

8

What drug is L-DOPA always administered with and why

Carbidopa; peripheral inhibitor of DOPA decarboxylase (fewere systemic effects [hypotension, arrhythmias], more L-DOPA to brain)

9

What is the effect of L-DOPA on the brain?

Increases DA stored in remaining nigrostriatal terminals

10

What symptoms of PD are relieved by L-DOPA

Cardinal motor symptoms (bradykinesia, resting tremor, muscular rigidity, gait/postural impairments)

11

Name the two stages of loss of efficacy of L-DOPA. Which responds to dosing regimen changes?

1. "Wearing-off"; 2. "On-Off" effect; the first

12

Three main CNS SEs of L-DOPA

Dyskinesias (choreoathetoid), psychiatric changes (anxiety, hallucinations, insomnia), N/V

13

Recent study demonstrated what about L-DOPA?

Initial treatment with L-DOPA was superior to L-DOPA sparing

14

When do clinicians use direct DA agonists? (2)

Monotherapy early in disease and as adjunct to L-DOPA + carbidopa

15

Why do direct DA agonists work as adjuct therapy to L-DOPA?

Decrease dose, smooth out loss of efficacy fluctuations

16

Two key DA agonists and their mechanism

Pramipexole and Ropinirole; selective D2 receptor agonist (D2 >>> D1)

17

How do the SEs compare between direct DA agonists and L-DOPA?

Greater central effects (like impulse control disorder), similar peripheral effects

18

Use of Apomorphine

Used as rescue drug to terminate off periods during L-DOPA therapy

19

Mechanism of Apomorphine; what is a serious SE?

Non-selective agonist at most DA receptors; emetic (causes vomiting)

20

Mechanism of MAO-B inhibitors

Reduce degradation of DA by MAO-B (specific to DA), irreversible inhibitor

21

What is a serious concern about MAO inhibitors?

Interact with drugs and foods --> tyramine, resulting in hypertensive crisis (due to cross MAO-A inhibition) and can cause serotonin syndrome if given with other drugs (meperidine or SSRIs)

22

Two MAO-B inhibitors

Selegiline and Rasagiline

23

What's important to remember about selegiline?

Metabolits = meth/amphetamine so it can cause anxiety and insomnia

24

What are the benefits of rasagline? (3)

1. More selective for MAO-B; 2. Effective as a monotheraphy early on; 3. No amphetamine metabolites

25

What is the mechanism of Entacapone? What is side effect?

Doubles t1/2 of L-DOPA in plasma via COMT inhibition; diarrhea

26

Amantadine is what kind of drug normally? Describe PD treatment. SEs are mainly...

Anti-viral; controls mild symptoms and motor SEs of L-DOPA; psychiatric

27

What role does ACh play in the striatum?

Provides excitatory tone to MSNs in indirect pathway via muscarinic receptors --> reduced thalamic drive to cortex (opposite of DA effect on D2 receptors)

28

Name an anticholinergic used for PDs and describe its beneficial mechanism

Trihexyphenidyl; high ratio of central to peripheral antimuscarinic activity

29

Trihexyphenidyl is best for treating what PD symptom? What SEs are significant?

Tremor; CNS SEs = confusion, sedation...

30

How does Tetrabenazine work?

Catecholamine depleter --> reduces DA activity in straiatum to reduce excitatory thalamcortical drive

31

What does Tetrabenazine do? SEs?

Improves HD motor symptoms; SEs = depression, suicidal ideation, hypotension

32

What is the goal of treatment for anti-spasticity drugs?

Reduce excitatory output from spinal MNS

33

Four drugs that treat spasticity and their mechanisms

1. Botulinum toxin (most effective, interferes w/ ACh release); 2. Dantrolene (interferes w/ Ca2+ release from SR, also for malignant hypothermia); 3. Baclofen (GABA-B agonist, dampens CST input to motor neurons via direct inhibition); 4. Tizanidine (alpha-2 agonist, inhibits MNs through inhibition of corticospinal inputs)

34

Which two spasticity drugs act on the CNS? How about peripherally?

Baclofen and Tizanidine; Botulinum toxin and Dantrolene

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