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Flashcards in Drugs for Parkinson's Deck (14)
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1
Q

Three cardinal features of Parkinson’s

A

tremor
rigidity
akinesia (bradykinesia)

2
Q

Increased risk of Park

A
  • age (1% of ppl over 60)
  • genetic (esp for younger): alpha synuclein aa mutation–>AD form
  • drink well water, work with pesticides or metals like iron and copper have higher risk
  • lower risk if drink coffee and tea
  • lower risk for smokers
3
Q

Final common pathology of Park

A

destruction of DA cells in pars compacta of Substantia Nigra

and loss of NT DA in caudate and putamen

4
Q

Metabolism of DA

A

synth: tyrosine –(TH)–>L-DOPA–(DDC)–>Dopamine

Breakdown:
DA–(MAO)–>DOPAC–(COMT)–>HVA

5
Q

Most important drug for treating Park

A

L-DOPA (500-1500 mg): crosses BBB and converted to DA by aromatic L-amino acid decarboxylase in surviving DA nerve terminals.
(combine with peripheral decarboxylase inhibitor carbidopa (250mg, doesn’t cross BBB) to reduce dosage of L-DOPA)
Ex of combo: Sinemet

SE: GI; dyskinesia @ peak blood levels (long term); psychosis, nausea, hypotension, depression

6
Q

Dopamine receptor agonists

A
  • direct stim of caudate and putamen DA recep
  • most are D2 dopamine receptor agonists
  • developed for longer half lives to blunt on/off L-DOPA response
  • often started at diagnosis to delay need for L-DOPA

a. Bromocriptine (Parlodel), dose 2-60 mg/day
b. Pergolide (Permax), dose 0.25 to 3 mg/day–>OFF MARKET (heart valve defects)
c. Pramipexole (Mirapex), D2 + D3 agonist, dose 1-5 mg/day
d. Ropinirole (Requip), D2 agonist, dose 0.5-10 mg/day
e. Cabergoline (Dostinex), D2 agonist, very long half-life, approximately 65 hours.
Dose 0.5-2mg/week.

7
Q

Dopamine Receptor Agonist Toxicity

A

nausea, hallucinations, sudden onset of sleep,

*eventually nearly all need L-DOPA

8
Q

Drugs that extend L-DOPA

A

Carbidopa (blocks DOPA decarboxylase in int, liver, others, delivers 90% to brain; 10-25 mg w/ each 100mg L-DOPA

MAO inhibitor–blocks breakdown of DA : Selegiline (eldepryl) 10mg/d
SE: worse postural hypotension
(Rasagiline)

COMT inhibitors: blocks metabolism of L-DOPA and DA

9
Q

COMT inhibitors

A

blocks metabolism of L-DOPA and DA:

Tolcapone(300-600 mg/d)
–>hepatotox in some

Entacapone (Comtan) 200mg w/ each dose of L-DOPA/Carbidopa

10
Q

MAOIs

A

Selegiline

Rasagiline

11
Q

Anticholinergics

A

less effective than L-DOPA
-sometimes initial therapy for tremor.
(dopamine is inhibitory to cholinergic interneurons onto medium spiny neurons that project to GP)
-these block muscarinic receptors
-SE: dry mouth, constip, urinary retention

a. Trihexyphenidyl (Artane) Dose 2-8 mg/day
b. Benztropine (Cogentin) Dose 1-2 mg/day
c. Diphenhydramine (Benadryl) Dose 75-200 mg/day

12
Q

Amantadine

A
  • beneficial effects discovered when Park pts took it for flu sx
  • uncertain mech
  • facilitate release of endogenous DA
  • Glutamate antagonist
13
Q

Surgical therapy for Park

A

Thalamotomy: relieves tremor
Pallidotomy: relieves drug-induced dyskinesias
DBS-reversible thalamotomy or pallidotomy (thal, internal pallidum, STN)
Fetal DA cell transplantation

?stem cells.

14
Q

Pathway pic

A

(phone)