Movement Disorder Drugs

Question 1

2 components of Sinemet and their fuctions.

Answer 1

L-dopa – precursor to Dopamine. Carbidopa – prevents breakdown of L-dopa to Dopamine in the periphery.

Question 2

Reasons that daily doses of L-dopa are decreased over time.

Answer 2

to avoid effects that are not initially present. Patients become less responsive.

Question 3

What is the On-Off phenomenon?

Answer 3

Off periods of akinesia alternating with On periods of improved mobility but marked dyskinesia.

Question 4

Tx for On-Off phenomenon.

Answer 4

Off periods treated with sub-Q Apomorphine. Entacapone can extend On time.

Question 5

2 reasons that COMT inhibitors improve responsiveness to L-Dopa.

Answer 5

catecholomethyltransferase metabolizes L-dopa in the periphery and the brain. More active when dopa decarboxylase is inhibited. COMT metabolism of L-dopa produces 3Omethyldopa which is associated with a poor response to L-dopa. They also compete for the same active transport across the BBB and the intestinal mucosa.

Question 6

COMT inhibitors

Answer 6

entacapone and tolcapone

Question 7

3 components of Stalevo

Answer 7

L-dopa, Carbidopa, Entacapone

Question 8

2 advantages to using Dopamine Agonists over L-Dopa.

Answer 8

Do not require enzymatic conversion. No toxic metabolites. No competition to cross into blood and BBB. Fewer AEs.

Question 9

2 indications for Pramipexole.

Answer 9

Solely for mild PD. Adjunct to lowered L-dopa in advanced PD.

Question 10

Indication for Apomorphine

Answer 10

potent dopamine agonist. Relief of Off period akinesia. Temporary.

Question 11

Symptoms of PD that improve with Tx of Ach blockers.

Answer 11

Improve tremor and rigidity. Little effect on bradykinesia.

Question 12

Class of drugs for postural tremor. Except one.

Answer 12

Beta Blockers (B2, propranolol). Except Metoprolol (B1)

Question 13

Four drugs for essential tremor.

Answer 13

Propranolol (B-blocker), Primidone or Topiramate (antiepileptics), Alprazolam (BZ), thalamic stimulation – advanced non-responsive cases.

Question 14

Three drugs given for Huntington’s Disease.

Answer 14

Phenothiazines (Perphenazine), Butyrophenones (Haloperidol), Reserpine, Tetrabenazine

Question 15

MOA of Tetrabenazine

Answer 15

Inhibits vesicular monoamine transporter 2 – depleting central monoamines. Unknown antichorea mechanism.

Question 16

Advantage of Tetrabenazine to Reserpine.

Answer 16

fewer adverse effects – except suicide and depression.

Question 17

Drug approved for ALS.

Answer 17

Riluzole

Question 18

Inherent difficulty in treating Tardive Dyskinesia

Answer 18

Reducing affecting drug often worsens effects.

Question 19

Drug for Restless Leg Syndrome.

Answer 19

Ropinerole (Dopamine agonist)

Question 20

Dosing regimen of Sinemet.

Answer 20

start small 3x/day, can increase dose (AE risk). Doses can be increased, but should be kept low with adjunct therapies as needed (DA agonists, enzyme inhibitors).

Question 21

Parcopa

Answer 21

Sinemet that can be dissolved orally.

Question 22

Class of drugs contraindicated with L-dopa and what the potential effects are.

Answer 22

MonoAmineOxidase A. When given with in 2 weeks of eachother may cause a hypertensive crisis.

Question 23

Population that should be careful with L-dopa and describe why.

Answer 23

Psychotic patients – exacerbates mental disturbances. Angle closure glaucoma – increases IOP. Hx of Melanoma/ undiagnosed skin lesions – L-dopa precursor to skin melanin (malignant melanoma).

Question 24

Indication for Selegiline.

Answer 24

Selective irreversible MAO-B inhibitor. Adjunct to L-dopa that lengthens effect allowing for lower doses. May reduce mild ON-OFF or wearing off phenomena. Can potentiate AE of L-dopa as well.

Question 25

Amantadine

Answer 25

antiviral with antiparkinsonian properties. Less potent. Short-lived benefits.