Drugs for Movement Disorders Flashcards
MOA: “-dopa”
Levodopa and combinations
Levodopa
Carbidopa
What are the DA receptor agonists? (4)
Apomorphine
Bromocriptine
Pramipexole
Ropinirole
What are the MAO inhibitors used for Parkinson’s? (3)
Rasagiline
Selegiline
Safinamide
What are the catechol-O-methyltransferase inhibitors? (2)
Entacapone
Tolcapone
What are the anticholinergic drugs used in Parkinson’s? (5)
Benztropine Biperidin Orphenadrine Procyclidine Trihexyphenidyl
What is the use of Carbidopa when used with Levodopa?
It is a DOPA decarboxylase inhibitor, thus it ensures that a greater amount of Levodopa crosses the BBB unscathed.
-reduces daily Levodopa needs by 75%
When is Carbidopa most effective?
The first few years of treatment.
What “phenomenon” can ensue after use of Levodopa?
How many people respond to the drug?
“Wearing-off” phenomenon: each dose of Levo effectively improves mobility for a period of time (12 hrs.), but rigidity and akinesia returns rapidly at the end of the dosing interval.
1/3 respond well, 1/3 respond less well, 1/3 are unable to take the medicine or don’t respond at all
What is a significant side-effect of Levodopa if not taken with Carbidopa?
GI-related: anorexia, nausea, vomiting (+ of chemoreceptor trigger zone) in 80% of patients.
If taken w/ Carbidopa, there is less risk for Gi-related problems.
What side-effects (aside from GI-related) are associated with Levodopa? (4 + GI)
CV effects - postural hypotension (often diminishes w/ repeated treatment). HTN may occur if taken in large doses or in combo w/ nonselective MAOIs/sympatheticomimetcs.
Dyskinesias - occurs in 80% of patients. Choreoathetosis of the face and distal extremities.
Behavioral effects - depression, anxiety, agitation, insomnia, etc. Atypical antipsychotics can help counteract behavioral problems.
Fluctuations in response and the “off and on” response.
What can help patients experiencing the “off and on” phenomenon?
Apomorphine
What are the contraindications of Levodopa use? (5)
Patients taking MAOIs (or within 2 wks. of discontinuation) may cause a HTN crisis.
Psychotic patients
Patients w/ closed-angle glaucoma
Patients with a history of melanoma/skin lesions
Use w/ caution in patients with active PUD
What is the indication for use of DA receptor agonists in patients taking Levodopa/Carbidopa?
End-of-dose akinesia or on-off phenomenon
What is the benefit of DA receptor agonists?
Less incidence of fluctuations and dyskinesias with long-term Levo therapy
What is the MOA of Bromocriptine?
What is it indicated for in addition to PD?
What is the unique problem with it?
Ergot alkaloid derivative that is a D2 agonist.
Endocrine disorders.
Extensive first-pass metabolism (28% bioavailability).
What is the MOA of Pramipaxole?
What is it indicated before in addition to PD?
In which patients must dosage be adjusted?
Affinity for D3 receptors.
Moderate to severe RLS.
Patients w/ renal insufficiency.
What is the MOA of Ropinirole?
What is it indicated for in addition to PD?
Affinity for D2 receptors.
RLS.
What are the adverse-effects of DA receptor agonists? (4)
GI-related (reduced if taken after meals).
CV effects
Dyskinesias - similar to Levo.
Mental disturbances - confusion, hallucinations, delusioms.
What are the contraindications for DA receptor agonists? (4)
Psychotic illness
Recent MI
Active PUD
Peripheral vascular disease - vasoconstricting effects
What does MAO-A and MAO-B preferentially metabolize?
MAO-A: NE and serotonin
MAO-B: phenylethylamine and benzylamine
DA and tryptamine are metabolized equally by the two.
What is the MOA of Selegiline, Rasagiline and Safinamide?
What is the problem with it in terms of PKs?
In which patients should it be cautioned to take these drugs?
MAO-B inhibitor (will inhibit MAO-A at high doses); slows breakdpwn of DA and prolongs the antiparkinsonian effects of Levo.
10% bioavailability with peak plasma concentraion within an hour.
Patients taking Meperidine
Patients taking TCAs
Patients taking SSRIs (risk of serotonin syndrome)
What can cause a HTN crisis in a patient taking Levo?
If coadministered with a non-selective (A + B) MAO inhibitor.
What is the effect of inhibiting COMT?
How does it improve Parkinsonian symproms?
COMT metabolizes Levo to 3-O-methyldopa, which competes with Levo for transport in the intestines and across the BBB.
It inhibits peripheral metabolism, which decreases clearance and increases bioavailability.
Which COMT inhibitor is central and peripheral acting?
Which is only peripheral acting?
Tolcapone
Entacapone
What are the side-effects of COMT inhibitors? (4)
*Levodopa-like side-effects
Orange urine
Diarrhea/abdominal pain
Sleep disturbances
What is the MOA of Apomorphine?
What is it best used for?
What are its adverse-effects?
DA agonist at D2 receptors.
SubQ injections for quick and temporary relief of akinesia in patients on DA therapy.
Nausea, dyskinesias, drowsiness, sweating, hypotension and injection-site bruising.
What is Trimethobenzamine used for?
Pretreatment antiemetic for patients who need Apomorpine
What is Amantadine?
What are the side-effects?
An antiviral agent whose MOA in parkinsonism is unknown.
Livedo reticularis in legs (purplish skin)
Mood changes
HA, HF and postural hypotension
What do mAChR antagonists treat primarily in PD?
Tremor and rigidity, but little effect on bradykinesia.
Anticholinergic-like: sedation, confusion, constipation, urinary retention, blurred vision, etc.
Which 2 drugs treat HD?
Reserpine and Tetrabenazine
What is the only drug known to impact survival in ALS?
What is the MOA?
What are major side-effects?
Riluzole
Inhibition of glutamate release and blockage of NMDA and kainite glutamate receptors and VG Na+ channels.
Nausea and weakness.
