Pharmacotherapy of movement disorders

Question 1

4 Cardinal symptoms of Parkinson’s Disease

Answer 1

1) Bradykinesia- slow movements
2) Rigidity- inc muscle tone and resistance
3) Resting tremor that goes away with voluntary movement
4) Postural instability

Question 2

Hallmark feature of Parkinsons pathophysiology

Answer 2

Loss of dopaminergic neurons in the substantia nigra pars compacta

Question 3

When Basal Ganglia decides we need to move, how does it react?

Answer 3

Shuts down the indirect pathway and cranks up the direct.

Question 4

Why do D2 blockers have the potential to cause parkinsonism?

Answer 4

Because they prevent dopamine from binding the D2 receptors inhibiting the indirect pathway. Indirect pathway is always on.

Question 5

4 methods of parkinson dz treatment?

Answer 5

1) Replacement of Dopamine
2) Stmulate D2 receptor
3) Increase Dopamine release
4) Inhibit dopamine metabolism

Question 6

Can dopamine cross the BBB

Answer 6

no

Question 7

What do you give instead of just giving dopamine?

Answer 7

L- DOPA

Question 8

L-Dopa tx is inhibited by?

Answer 8

Food

Question 9

99% of L-Dopa is converted in the periphery to DA. This is problematic because as we just discussed, Dopamine cannot cross the BBB. How do you get around this?

Answer 9

Give L-DOPA with Carbidopa….Blocks peripheral L-AAD so that more of the L-DOPA enters the CNS before it is converted to Dopamine.

Question 10

Adverse effects of L-DOPA

Answer 10

GI, CV (arrhythmias and orthostatic htn)

Question 11

LDOPA + Carbidopa AE

Answer 11

Behavioral change and Dyskinesia

Question 12

Treatment with L-DOPA usually quits working after how long

Answer 12

3-5 years

Question 13

See Contraindications for L-DOPA

Answer 13

psychotics, CV dz, PUD, Melanoma

Question 14

What is the preferred initial course of therapy for parkinsons

Answer 14

Stimulate the D2 receptor with a D2 receptor agonist

Question 15

Amorphine

Answer 15

Non-specific dopamine receptor agonist

Question 16

Bromocriptine

Answer 16

D2 and D1

Question 17

Pramiprexole

Answer 17

D2 specific, free radical scavengar

Question 18

Ropinirole

Answer 18

D2 specific. CYP 1A2

Question 19

Amantadine

Answer 19

Antiviral that increases dopamine release

Question 20

Adverese effects of Amantadine therapy

Answer 20

Psychosis with overdose

Question 21

Dopamine is metabolized into what by what?

Answer 21

DOPAC by Monoamine oxidase- B

Then DOPAC is converted in HVA by COMT

Question 22

Monoamine oxidase B inhibitors

Answer 22

Selegilline and Rasagilline

Question 23

Depression in Huntington’s disease is treated with

Answer 23

Fluoxetine (SSRI) and Carbamezapine (voltage gated Na blocker)

Question 24

Reserpine in HD?

Answer 24

Reserpine depletes DA

Question 25

Tetrabenzine in HD

Answer 25

Tetrabenzine depletes DA

Question 26

Chlorpromazine

Answer 26

D2 Antagonist in parkinsons

Question 27

Haloperidol in HD

Answer 27

D2 antagonists

Question 28

D2 antagonists do what?

Answer 28

cause parkinsons