Lecture 37: Drugs of Movement Disorders Flashcards Preview

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

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

ACh and DA


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

Pro; anti-movement


Broadly, PD drugs do one of which two things?

Enhance DA function or inhibit ACh function


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

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


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

L-DOPA; L-DOPA requires supplemental therapy


L-DOPA is a ___-drug. Enzyme?

Pro-drug; DOPA decarboxylase


Three reasons to not just give DOPA

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


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)


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

Increases DA stored in remaining nigrostriatal terminals


What symptoms of PD are relieved by L-DOPA

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


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


Three main CNS SEs of L-DOPA

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


Recent study demonstrated what about L-DOPA?

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


When do clinicians use direct DA agonists? (2)

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


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

Decrease dose, smooth out loss of efficacy fluctuations


Two key DA agonists and their mechanism

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


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

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


Use of Apomorphine

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


Mechanism of Apomorphine; what is a serious SE?

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


Mechanism of MAO-B inhibitors

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


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)


Two MAO-B inhibitors

Selegiline and Rasagiline


What's important to remember about selegiline?

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


What are the benefits of rasagline? (3)

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


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

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


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


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)


Name an anticholinergic used for PDs and describe its beneficial mechanism

Trihexyphenidyl; high ratio of central to peripheral antimuscarinic activity


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

Tremor; CNS SEs = confusion, sedation...


How does Tetrabenazine work?

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


What does Tetrabenazine do? SEs?

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


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

Reduce excitatory output from spinal MNS


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)


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

Baclofen and Tizanidine; Botulinum toxin and Dantrolene

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