Drugs for Parkinson's and Movement Disorders

Question 1

What drug is a dopamine precursor, given orally, and absorbed in the small intestine?

Answer 1

Levodopa

Question 2

Levodopa is used in combination with what other drug as a first-line treatment for Parkinson’s?

Answer 2

Carbidopa

Question 3

When would you NOT want to use levodopa as a first line treatment for Parkinson’s?

Answer 3

When the patient is young

Question 4

What enzyme and reaction does carbidopa affect, and where does it act?

Answer 4

AAD (aromatic amino acid decarboxylase) inhibitor, which prevents conversion of L-dopa to dopamine; acts in the periphery (does not cross BBB)

Question 5

What class of drugs are contraindicated in a Parkinson’s patient who is taking levodopa and carbidopa?

Answer 5

MAO-A inhibitors are contraindicated

Question 6

What Parkinson’s treatment is associated with on-off phenomenon, NMS (neuroleptic malignant syndrome), and possibly accelerating PD progression?

Answer 6

Levodopa+carbidopa

Question 7

Which 2 Parkinson’s drugs are ergot derivatives? Which one is no longer used and why?

Answer 7

Bromocriptine and pergolide; pergolide is no longer used because it can cause cardiac valve regurgitation

Question 8

What are 3 therapeutic uses for bromocriptine, what receptor does it affect to do its job, and is it an agonist or antagonist?

Answer 8

Treat mild Parkinson’s, NMS, and hyperprolactinemia; D2 receptor agonist

Question 9

In what organ does bromocriptine (and pergolide) cause the most side effects? Give some specific examples

Answer 9

In the lung; ex. pulmonary effusions, cough, shortness of breath, and pulmonary fibrosis

Question 10

What effects does the Parkinson’s drug bromocriptine have on dopamine receptors?

Answer 10

D2 receptor agonist and D1 receptor antagonist

Question 11

What receptor is targeted by the Parkinson’s drugs pramipexol, ropinerole, and rotigotine? Which one is given using a transdermal patch?

Answer 11

D2 receptor (agonists); rotigotine

Question 12

Of the 3 D2-selective non-ergot agonists, which ones are used together as first-line therapy for mild Parkinson’s? Which ones can also be used to treat restless leg syndrome?

Answer 12

Pramipexole and ropinerole are used together; Ropinerole and rotigotine are used for restless legs syndrome

Question 13

Which non-ergot DA agonist can cause compulsive behavior as a side effect? What receptor in which area of the brain mediates this effect?

Answer 13

Pramipexol; D3 receptors in the nucleus accumbens

Question 14

How effective are the non-ergots compared to the ergot derivative bromocriptine in treating Parkinson’s? How do their side effects compare?

Answer 14

Non-ergots are less effective at treating PD motor symptoms; they also have more acute side effects (psychosis, nausea/GI problems, edema) but less long-term side effects

Question 15

Which non-ergot DA agonist can cause daytime sleep attacks as a side effect?

Answer 15

Ropinerole

Question 16

What is apomorphine used for, and how is it administered?

Answer 16

Rescue from Parkinson’s “off” periods; given by injection only

Question 17

What kind of drugs are contraindicated for a patient on apomorphine? Why?

Answer 17

Serotonin receptor antagonists, because they will cause hypotension

Question 18

What two classes of drugs inhibit DA breakdown? Give the 2 drugs from each of these classes.

Answer 18

COMT inhibitors: entacapone and tolcapone

MAO-B inhibitors: selegiline and rasagiline

Question 19

Do entacapone and tolcapone mostly act centrally or peripherally, and what Parkinson’s drug do they augment? Is their half-life long or short?

Answer 19

Peripherally (tolcapone has some central effects) to extend the half-life of levodopa; short (2 hours)

Question 20

Why is tolcapone only to be used if entacapone fails?

Answer 20

Tolcapone can cause fatal hepatotoxicity

Question 21

What receptors are targeted by benztropine, procyclidine, and ethopropazine? Are they agonists or antagonists?

Answer 21

Muscarinic cholinergic antagonists

Question 22

What receptors are targeted by biperiden and trihexyphenidyl? Are they agonists or antagonists?

Answer 22

Muscarinic cholinergic antagonists

Question 23

What is the primary theraputic use for anticholinergic drugs in Parkinson’s patients? What kind of patients should not be given these drugs?

Answer 23

To treat excessive drooling; contraindicated in demented Parkinson’s patients because the anticholinergics can cause mental problems like confusion, impaired memory and hallucinations

Question 24

What kind of drug is amantidine? What 3 receptors does it affect and how?

Answer 24

Anti-viral (and anti-Parkinson’s); dopamine receptor agonist, ACh receptor antagonist, NMDA receptor antagonist

Question 25

Name the only adjunct to levodopa+carbidopa that reduces dyskinesias in Parkinson's. For what other disease is this adjunct used?

Answer 25

Amantidine; also used for Huntington's

Question 26

What part of the brain is targeted by deep brain stimulation, and what 3 therapeutic effects can this produce?

Answer 26

The subthalamic nucleus; treats dyskinesia refractory to other medications, reduces 'off' time, and may reduce levodopa dosage

Question 27

What are 2 potential side effects of deep brain stimulation?

Answer 27

Intracerebral hemorrhage and cognitive impairment

Question 28

What two drugs are used to treat spasticity in ALS?

Answer 28

Baclofen and tizanidine

Question 29

What receptors are targeted by baclofen and tizanidine, and are they agonists or antagonists?

Answer 29

Baclofen: GABA-B agonist Tizanidine: alpha2 agonist

Question 30

What is the only drug used to treat ALS progression? What receptors does it affect and how?

Answer 30

Riluzole; kainate and NMDA (both glutamate receptors) antagonist

Question 31

What is the most important possible side effect of riluzole? What drug can be used to reverse some of riluzole's clinical actions?

Answer 31

Can cause hepatotoxicity; pertussis toxin

Question 32

What drug is used to treat tardive dyskinesia in Huntington's? How does it work?

Answer 32

Tetrabenazine; inhibits VMAT2 which decreases dopamine in the brain

Question 33

What kind of drug is dantrolene, and what condition is it used to treat?

Answer 33

Muscle relaxant; treats malignant hyperthermia (associated with NMS)

Question 34

Levodopa/carbidopa, amantadine, and tetrabenazine are all associated with what side effect, also seen with anti-psychotic drugs?

Answer 34

NMS

Question 35

Which Parkinson's drug is associated with side effects of psychosis, drowsiness, hypersexuality (increase in erections), and emesis? Pre-administration of trimethobenzamide or domiperidone can help alleviate these symptoms.

Answer 35

Apomorphine

Question 36

Which 2 Parkinson's drugs are associated with the side effect of urine discoloration, as well as the usual GI and DA overload problems?

Answer 36

Tolcapone and entacapone (the COMT inhibitors)