Flashcards in Pharm: movement disorders Deck (20):
What are the two components of Sinemet and their functions?
L-dopa and Carbidopa = sinemet
L-dopa is meatabolized to dopamine and carbidopa prevents peripheral dopa decarboxylase from converting L-dopa to dopamine (which cannot cross the BBB) before it crosses the BBB.
Why is L-dopa dosage progressively decreased over time as a patient progresses thru Parkinson Disease?
As patients progress thru PD they lose DA producing cells in the Substantia Nigra which are required for L-dopa to be effective. As they lose cells, the amount of L-dopa can become toxic if the dose is not decreased as the number of cells decreases.
What is the "on-off" phenomenon and give one treatment for it.
Off periods are marked by akinesia (rigid joints) and on periods are marked by dyskinesia (dance-like chorea or ballismus).
These periods will alternate.
Off periods can be treated with SubQ apomorphine.
Give two reasons why entacapone and tolcapone improve responsiveness to L-dopa.
The are COMT inhibitors
1. COMT metabolism of L-dopa increase levels of 3-O-methyldopa (3OMD) which competes with L-dopa for the same active transporter across the intestinal and BBB epithelia.
2. COMT also degrades L-dopa in the periphery, so COMT-Is will allow L-dopa to get into the CNS.
Name the 3 components of Stalevo.
What are two advantages of DA agonists over L-dopa?
1. Do not require enzymatic conversion
2. No toxic metabolites
3. Do not have to compete to cross the BBB
4. Fewer adverse effects
What are 2 indications for pramipexole?
D3 receptor agonist.
1. Mild Parkinson Disease (by itself or monotherapy)
2. Advanced PD to smooth out L-dopa fluctuations
What is the specific indication for apomorphine?
SubQ injection for relief of akinesia (Off phase) in patients on DA therapy.
Which symptoms of PD improve with ACh blockers?
Improve the tremor and rigidity.
Little effect on bradykinesia.
What is the drug class given for the postural tremor? Name the drug class NOT to give for this.
1. Non-selective beta blockers (propranolol)
2. Do not give selective Beta 1 blockers because the tremor is mediated thru Beta 2 receptors.
What 4 drugs can be given for essential tremors?
1. Propranolol (beta blocker)
2. Primidone (antiepileptic)
3. Topiramate (antiepileptic)
4. Alprazolam (antiepileptic)
Name 3 drugs used to treat Huntington Disease.
Perphenazine or Haloperidol (DA antagonists)
Reserpine (prevents intraneuronal storage of DA)
Tetrabenazine (inhibits VMAT2)
What advantage does tetrabenazine have over reserpine?
Fewer adverse effects like low BP, depression, sedation, diarrhea, and nasal congestion.
Name 1 drug approved for ALS.
Riluzole (inhibits glutamate signaling)
Name 1 drug used to treat Restless leg syndrome.
Ropinirole (DA agonist)
What is the dosing regimen for Sinemet?
1. Small Dose starting 3x/day
2. Dose can be increased but it will increase side effects.
(sinemet = Carbidopa 25mg/L-dopa 100mg)
What drug class is contraindicated with L-dopa and what is the problem when this class is combined with L-dopa?
Anti-psychotics: they block the DA2 receptor
Which population should be careful with L-dopa treatment and why?
Patients with a history of melanoma need to be careful b/c L-dopa can increase risk to develop a malignant melanoma.
What is the indication for selegiline?
Selective irreversible inhibitor of Monoamine Oxidase B and is used to prolong the antiparkinsonism effect of L-dopa.