pharm movement disorders

Question 1

Describe the two components of Sinemet and their functions.

Answer 1

Sinemet = L-dopa and carbidopa
Carbidopa inhibits dopa decarboxylase, which converts L-dopa to NE
L-dopa can cross the blood-brain barrier and then be converted to dopamine

Question 2

Give one reason daily doses of L-dopa are decreased over time.

Answer 2

Cells become sensitized to L-dopa over time. also to avoid side effects.

Question 3

Explain the “on-off phenomenon” and give one treatment for it.

Answer 3

“off” periods marked by akinesia which alternate with “on” periods of improved mobility but marked dyskinesia
Off periods can be treated with SubQ apomorphine

Question 4

Give two reasons COMT inhibitors entacapone and tolcapone improve responsiveness to L-dopa.

Answer 4

Decreases metabolism of L-dopa in the periphery and decreases competitive 3-O-methyldopa making L-dopa more effective

Question 5

Give the 3 components of Stalevo

Answer 5

Stalevo = L-dopa, carbidopa, and entacapone

Question 6

Give two advantages of DA agonists over L-dopa.

Answer 6

Do not require enzymatic conversion
Have no toxic metabolites
Do not compete with other substances to actively cross into blood and the BBB
Have fewer AE
Lower incidence of response fluctuations and/or dyskinesias

Question 7

Give two indications for pramipexole.

Answer 7

Can be used effectively as monotherapy
Mild PD
As adjunctive therapy
Advanced PD to lower L-dopa dose/smooth out fluctuations

Question 8

Give the specific indication for apomorphine.

Answer 8

Temporary relief of off-periods of akinesia in patients on dopamine therapy

Question 9

Give the symptoms of PD that improve with treatment with Ach blockers.

Answer 9

Improve the tremor and rigidity
Little effect on bradykinesia

Question 10

Give the class of drugs given for postural tremor and one in this class not to give.

Answer 10

Can be alleviated with propranolol (blocks β1 and β2 receptor)
But not metoprolol (β1 receptor blocker)
Tremor mediated through activation of β2 receptor

Question 11

Give four drugs to be given for essential tremor.

Answer 11

Propranolol, primodone, topiramate, alprazolam

Question 12

Give three drugs used to treat Huntington’s disease.

Answer 12

Dopamine receptor antagonists (Perphenazine, haloperidol), Reserpine, tetrabenazine

Question 13

Give the MOA of tetrabenazine and an advantage it has over reserpine.

Answer 13

Inhibits vesicular monoamine transporter 2
Depletes central monoamines
Fewer AE compared to reserpine

Question 14

Give one drug approved for ALS.

Answer 14

Riluzole

Question 15

Explain the inherent difficulty in treating tardive dyskinesia.

Answer 15

Offending drug should be tapered off, if clinically possible
Switch to Atypical antipsychotic (2nd generation)
Reducing the dopamine receptor blocker often worsens the dyskinesia
Treat with drugs that interfere with dopamine signaling

Question 16

Give one drug used to treat restless leg syndrome.

Answer 16

Dopamine agonists (ropinirole)

Question 17

Describe the dosing regimen for Sinemet.

Answer 17

Doses start small x 3/day (Sinemet is carbidopa 25 mg/ L-dopa 100 mg)
Dose can be increased but can enhance side effects
Keep low and add additional drug therapies
EX: dopamine agonist/additional enzyme inhibitors

Question 18

Give a class of drugs contraindicated with L-dopa and what the combination can cause.

Answer 18

Psychotic patients – exacerbates mental disturbances (remember typical anti-psychotics mostly block DA2 receptors)
Angle-closure glaucoma (increased IOP)
History of melanoma/undiagnosed skin lesions
L-dopa precursor to skin melanin  malignant melanoma

Question 19

Give the indication for selegiline.

Answer 19

Prolongs antiparkinsonism effect of L-dopa (allowing for lower doses)
May reduce mild on-off or wearing-off phenomena
Adjunctive therapy
May potentiate the AE of L-dopa

Question 20

Give the specific indication for apomorphine.

Answer 20

Temporary relief of off-periods of akinesia in patients on dopamine therapy