Drugs for Movement Disorders - Kruse

Question 1

Dopamine vs. ACh in the basal ganglia

Answer 1

Dopamine - inhibit GABA output from striatum

ACh - excite GABA output from striatum

Question 2

How does loss of dopaminergic neurons lead to difficult movements?

Answer 2

Less inhibition of the inhibitor (striatum), thus leading to decreased movements

Question 3

So, how would you treat Parkinson’s?

Answer 3

Increase Dopamine activity onto the GABAergic striatum neurons via Dopamine agonists or metabolism antagonists

Question 4

Why treat with L-dopa, not dopamine?

Answer 4

L-dopa can cross BBB, but dopamine cannot

Question 5

What is L-dopa?

Answer 5

Immediate metabolic precursor to dopamine

Question 6

Levodopa action

Downside to levodopa alone

Answer 6

Dopamine receptor agonist

97-99% is metabolically altered before reaching the brain, via decarboxylation into dopamine

Question 7

How to increase the effects of levodopa?

Answer 7

Give w/ a DOPA decarboxylase inhibitor
= CARBIDOPA
Causes reduced peripheral metabolism, so more enters the brain unaltered

Question 8

A patient is taking Levodopa therapy for a long time. Eventually, each dose ends and rapidly leads to a return of symptoms. This is an example of?

Can you just give more levodopa?

Answer 8

Wearing-off phenomenon

Eventually you impair voluntary movements (dyskinesia)

Question 9

A patient is on levodopa (with or without carbidopa). What symptoms are she most likely to exhibit? (4)

Answer 9

Anorexia, nausea, vomiting, choreoathetosis

Question 10

Does carbidopa help with the side effects of levodopa?

Answer 10

Yes, but only in 20% of patients

Question 11

A patient is on levodopa but has trouble with vomiting. What causes the vomiting?

Answer 11

Activation of chemoreceptor trigger zone within the brainstem (outside the BBB)

Question 12

What is the choreoathetosis side effect of levodopa?

Answer 12

Intermediate-speed movements of the face and distal extremities

Question 13

A patient is taking Levodopa therapy for a long time. Eventually, the patient starts having occasional episodes of inability to move at all. This is an example of?

How is this problem fixed?

Answer 13

On-off phenomenon

Apomorphine - DOPAMINE agonist that can provide temporary relief

Question 14

A patient is taking Levodopa, but needs another drug to supplement. Which drug type should NOT be taken with Levodopa?

Why?

Answer 14

Non-selective MAO or selective MAO-A inhibitors

Lack of MAO-A leads to build-up of norepinephrine, which can cause a HYPERTENSIVE CRISIS in the patient

Question 15

Contraindications for Levodopa therapy

Answer 15

Psychosis, closed-angle glaucoma, melanoma, active peptic ulcer

Question 16

Why would a patient take a dopamine receptor agonist rather than Levodopa?

Answer 16

Less response fluctuation phenomena and dyskinesias

Question 17

Can dopamine receptor agonists be given WITH Levodopa?

What about for wearing-off or on-off phenomena?

Answer 17

YES

YES (Apomorphine is a dopamine receptor agonist)

Question 18

Bromocriptine

Answer 18

D2 agonist, ergot alkaloid

Extensive first pass metabolism (3A4)

Question 19

Pramipexole

Answer 19

D3 agonist

Treats RLS also

Question 20

A patient is taking Pramipexole and develops renal insufficiency. What might the doctor have to do?

Answer 20

Change the dose of Pramipexole, sine 90% is excreted renally

Question 21

Ropinirole

Answer 21

D2 agonist
Treats RLS also
Metabolized by 1A2

Question 22

Issue with Bromocriptine?

Answer 22

Causes digital vasospasm with long-term use

Should be discontinued if patient has peripheral edema, peripheral vascular disease, or cardiac arrhythmias

Question 23

Issue with Pramipexole or Ropinirole?

Answer 23

May feel uncontrollable tendency to fall asleep at random times

Question 24

Psychosis is a contraindication for Levodopa treatment. What about dopamine receptor agonists?

Answer 24

DO NOT USE - causes more severe mental disturbances than Levodopa

Question 25

MAO-A vs. MAO-B

Answer 25

``` A = metabolism of NE and serotonin B = metabolism of phenylethylamine and benzylamine ```

Question 26

Dopamine is metabolized by which MAO?

Answer 26

Both equally

Question 27

A patient is taking Levodopa but needs something to help relieve the on-off and wearing-off phenomena. What can be taken along with it?

Answer 27

Selegiline (MAO-B inhibitor)

Question 28

Selegiline

Answer 28

Irreversible MAO-B inhibitor | Prolongs the effects of Levodopa

Question 29

Rasagiline

Answer 29

Irreversible MAO-B inhibitor | More potent form of Selegiline

Question 30

COMT role in dopamine stuff

Answer 30

Breaks Levodopa into a competitor for transport across the BBB, thus making Levodopa less effective

Question 31

Tolcapone

Answer 31

COMT inhibitor Prolongs activity of levodopa by preventing its peripheral metabolism, thus decreasing clearance CENTRAL and PERIPHERAL effects

Question 32

Entacapone

Answer 32

``` Like Tolcapone (COMT inhibitor) But only PERIPHERAL effects ```

Question 33

A patient is on Levodopa and Tolcapone. What is a potential side effect of the Tolcapone?

Answer 33

Hepatic toxicity (increased liver enzymes)

Question 34

Benefit of Apomorphine vs. other dopamine agonists for relief of Levodopa phenomena

Answer 34

SubQ INJECTION = quick, temporary relief

Question 35

A patient is taking Levodopa therapy for a long time. Eventually, the patient starts having occasional episodes of inability to move at all. How is this problem fixed? What is the potential side effect of this fix? How is this side effect fixed?

Answer 35

Apomorphine Nausea, vomiting Pre-treat w/ TRIMETHOBENZAMIDE (anti-emetic)

Question 36

Trimethobenzamide

Answer 36

Anti-emetic, used in the relief of nausea and vomiting due to anti-parkinson drugs

Question 37

A patient is on Levodopa therapy for PD that is supplemented with another drug. However, over time, the patient developed purple discoloration of the LE skin including very apparent superficial vasculature. What drug is he on? What is this condition called?

Answer 37

Amantadine Livedo reticularis (side effect of the drug)

Question 38

Amantadine

Answer 38

Anti-viral agent that somehow helps with parkinsonism

Question 39

Anticholinergic drugs used in the treatment of Parkinsonian symptoms What are they?

Answer 39

Benztropine, biperiden, orphenadrine, procyclidine, trihexyphenidyl Centrally-acting anti-muscarinic

Question 40

Purpose of anticholinergic drugs here?

Answer 40

Improve tremor and rigidity by balancing the low dopamine level in the basal ganglia with an equally low acetylcholine level

Question 41

Adverse effects of anticholinergic drugs here?

Answer 41

Sedation, confusion, constipation, urinary retention, blurred vision (typical CNS sympathetic symptoms)

Question 42

Propranolol, Metoprolol

Answer 42

Beta-1 antagonists used to stop tremor

Question 43

Primidone

Answer 43

Anti-epileptic drug used to stop tremor (smaller doses)

Question 44

Topirimate

Answer 44

Serotonin receptor agonist used to stop tremor

Question 45

BOTOX

Answer 45

IM injection used to help tremor

Question 46

Reserpine

Answer 46

IRREVERSIBLE dopamine reuptake (MAT) agonist | Used for treatment of Huntington

Question 47

Tetrabenazine

Answer 47

REVERSIBLE dopamine re-uptake (MAT) agonist | Used for treatment of Huntington

Question 48

Patients with Huntington often need treatment for psychiatric symptoms (depressed, irritable). What are treatment options? (2)

Answer 48

Fluoxetine - depression and irritability | Carbamazepine - depression

Question 49

Pimozide, haloperidol

Answer 49

Neuroleptic antipsychotics used for TICS

Question 50

A patient needs meds for a TIC but doesn't want the side effects of Pimozide. What are other options? (3)

Answer 50

Clonidine, Guanfacine (alpha agonists) | Botulinum toxin A

Question 51

Treatment for restless leg syndrome

Answer 51

``` Dopamine agonists (non-ergot) - Pramipexole, Ropinirole ```

Question 52

Riluzole

Answer 52

ALS

Question 53

Penicillamine

Answer 53

Wilson's disease (chelating agent)

Question 54

Other drugs for Wilson's disease besides Penicillamine? (3)

Answer 54

Trientine, Zinc acetate, Zinc sulfate