Neurodegenerative Disease

Question 1

what is first line treatment for Parkinson’s?

Answer 1

Levodopa wtih carbidopa (AAD inhibitor)

Question 2

What are the actions of levidopa and carbidopa therapy? What are some complications?

Answer 2

• L-dopa is an oral DA analog; carbidopa is an Aromatic amino acid decarboxylase (AAD) inhibitor that prevents peripheral degradation of L-dopa
• effective for 2-5yrs with decreasing effectiveness after (avoid in young pts); use as little as necessary to relieve motor symptoms and delay onset of long-term motor complications

Question 3

What are the possible side effects of levidopa ad carbidopa therapy?

Answer 3

SE’s: Dyskinesias( after 5-8yrs), on-off phenomenon, neuroleptic malignant syndrome (NMS), psychosis possible with chronic use [l-dopa also hallucinations, Nausea/GI distress, hypotension, dizziness; MAO-A inhibitors contraindicated

Question 4

What are the 5 DA receptor agonists? Which one is an ergot derivative?

Answer 4

Bromocryptine (ergot derivative, D1 agonist, D2 antagonist); pramipexole, ropinorole, rotigotine, apomorphine (D2 agonists);

Question 5

What are the side effects of bromocriptine?

Answer 5

Pleural effusions, cough, shortness of breath, pulmonary fibrosis, Peripheral DA-like effects; Must be titrated slowly (wks) due to acute hypotension

Question 6

What are the use and side effects of Apomorphine?

Answer 6

(non-ergot DAR agonist); Rescue therapy for ‘off’ periods (immobility) [injectable SQ, 10 min onset]
SE: severe emesis (anti-emetic given before injection), Peripheral DA SEs (psychosis, drowsiness, hypersexuality), hypotension

Question 7

What class is pramipexole? what are the side effects of this class of drugs?

Answer 7

• non-ergot DAR agonist
• More acute: psychosis, nausea/GI, edema
• pramiprexole- compulsive behavior

Question 8

what are some advantages and disadvantages of ropinitole and pramipexole?

Answer 8

• titrated to therapeutic doses sooner (DAR agonists of choice today)
• more acute side effects and less effective at controlling motor symptoms

Question 9

what are 2 classes of drugs that prevent DA breakdown?

Answer 9

COMT inhibitor (Entacapone, tolcapone); MAO-B inhibitor (selegiline, reasagiline)

Question 10

what is the action and side effects of entacapone and tolcapone?

Answer 10

• Prolong half-life of levodopa, reduce ‘off’ time; primarily works peripherally (short-acting 2hrs)
• Fatal hepatotoxicity (in tolcapone- use only if entacapone fails), increase in dyskinesias, diarrhea (worse than entacapone), urine discoloration

Question 11

what is the action and side effects of Selegiline and Rasagiline?

Answer 11

• Prevents breakdown of DA- treatment of mild (tremors only), early-onset PD as monotherapy; may delay levadopa onset
• Hypotension, GI distress, dyskinesia, psychosis

Question 12

How are anticholinergic drugs used in the treatment of parkinson disease?

Answer 12

rarely used due to side effect but effective in treatment of tremor and drooling

Question 13

what is the action, use and side effects of Amantadine?

Answer 13

• antiviral drug that is dopaminergic, anticholinergic, and anti-NMDA
• used in Mild early Parkinson’s (2nd-line); best as an adjunct to levodopa/carbidopa for long-term treatment; movement disorders in Huntingtons; only adjunct that reduces dyskinesias
• SE: DA side effects, edema, psychosis, NMS upon withdrawal; contraindicated in elderly with dementia

Question 14

what is SINEMET?

Answer 14

carbidopa/levodopa combination in sustained release form; #1 prescribed

Question 15

How does Deep Brain Stimulation work? what is a requirement of patients to receive this treatment?

Answer 15

• stimulation of subthalamic nucleus (STN) with long lasting effects that reduces tremors and dyskinesias
• pts must still be responsive to levodopa/carbidopa therapy

Question 16

What is the only approved therapy for ALS?

Answer 16

RILUTEK