Movement Disorder Drugs Flashcards
2 components of Sinemet and their fuctions.
L-dopa – precursor to Dopamine. Carbidopa – prevents breakdown of L-dopa to Dopamine in the periphery.
Reasons that daily doses of L-dopa are decreased over time.
to avoid effects that are not initially present. Patients become less responsive.
What is the On-Off phenomenon?
Off periods of akinesia alternating with On periods of improved mobility but marked dyskinesia.
Tx for On-Off phenomenon.
Off periods treated with sub-Q Apomorphine. Entacapone can extend On time.
2 reasons that COMT inhibitors improve responsiveness to L-Dopa.
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.
COMT inhibitors
entacapone and tolcapone
3 components of Stalevo
L-dopa, Carbidopa, Entacapone
2 advantages to using Dopamine Agonists over L-Dopa.
Do not require enzymatic conversion. No toxic metabolites. No competition to cross into blood and BBB. Fewer AEs.
2 indications for Pramipexole.
Solely for mild PD. Adjunct to lowered L-dopa in advanced PD.
Indication for Apomorphine
potent dopamine agonist. Relief of Off period akinesia. Temporary.
Symptoms of PD that improve with Tx of Ach blockers.
Improve tremor and rigidity. Little effect on bradykinesia.
Class of drugs for postural tremor. Except one.
Beta Blockers (B2, propranolol). Except Metoprolol (B1)
Four drugs for essential tremor.
Propranolol (B-blocker), Primidone or Topiramate (antiepileptics), Alprazolam (BZ), thalamic stimulation – advanced non-responsive cases.
Three drugs given for Huntington’s Disease.
Phenothiazines (Perphenazine), Butyrophenones (Haloperidol), Reserpine, Tetrabenazine
MOA of Tetrabenazine
Inhibits vesicular monoamine transporter 2 – depleting central monoamines. Unknown antichorea mechanism.
Advantage of Tetrabenazine to Reserpine.
fewer adverse effects – except suicide and depression.
Drug approved for ALS.
Riluzole
Inherent difficulty in treating Tardive Dyskinesia
Reducing affecting drug often worsens effects.
Drug for Restless Leg Syndrome.
Ropinerole (Dopamine agonist)
Dosing regimen of Sinemet.
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).
Parcopa
Sinemet that can be dissolved orally.
Class of drugs contraindicated with L-dopa and what the potential effects are.
MonoAmineOxidase A. When given with in 2 weeks of eachother may cause a hypertensive crisis.
Population that should be careful with L-dopa and describe why.
Psychotic patients – exacerbates mental disturbances. Angle closure glaucoma – increases IOP. Hx of Melanoma/ undiagnosed skin lesions – L-dopa precursor to skin melanin (malignant melanoma).
Indication for Selegiline.
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.
Amantadine
antiviral with antiparkinsonian properties. Less potent. Short-lived benefits.
