Anti-Parkinson's Drugs

Question 1

What percent of dopamine neurons have been lost before the symptoms of Parkinsons (PD) appear?

Answer 1

70-80%

Question 2

What are the symptoms of Parkinsons Disease (PD)?

Answer 2

Tremor at rest

Bradykinesia (slow movements), difficulty starting movements, rigidity, short fast steps, small handwriting, blank face

Question 3

The subtantia nigra supplies what structures with dopamine?

Answer 3

Straitum (Caudate and putamen)

Question 4

Why is L-Dopa preferred over pure dopamine to give to a pt ?

Answer 4

L-Dopa crosses the BBB much more easily than dopamine

Question 5

What occurs when D1 receptors are activated?

Answer 5

Inc cAMP and stimulates the direct pathway (putaminal/GABA/substance P/dynorphin) that project to medial globus pallidus

Question 6

What occurs when D2 receptors are activated?

Answer 6

Dec cAMP, inhibits the indirect pathway (putaminal GABA/enkephalin) thta projects to lateral globus pallidus

Question 7

Which dopamine neuron plays the major role in PD therapy?

Answer 7

D2

Question 8

What are the characteristics of Levodopa?

Answer 8

Rapid symptomatic benefits, well tolerated, continues to work throughout the disease course, usually combined with carbidopa

Question 9

Why is carbidopa used in conjunction with levodopa?

Answer 9

Allows the largest amount of levodopa to become dopa as possible (keeps the levodopa from entering and be digested by the GI system)

Question 10

What are the side effects of Levodopa?

Answer 10

Not effective for gait imbalance, freezing, or postural instability, N&V, hallucination, illusions, somnolence, edema, compulsions

Question 11

What is the levodopa sparing strategy used in early PD?

Answer 11

The younger the pt, avoid using levodopa so they do not develop complications sooner
Start with a dopamine agonist, amantadine, or anti-cholinergic

Question 12

At what age can you start a person with PD on levodopa?

Answer 12

65 or older

Question 13

What are the positive effects of dopamine agonists?

Answer 13

Effective for tremor, rigidity, and bradykinesia
Action largely via activation of striatal DR receptors
More protective against motor flux and dyskinesias

Question 14

Which treatment has the shortest half life?

Answer 14

L-dopa

Question 15

What are the characteristics of pramipexole?

Answer 15

8-12 hr half life, renal clearance, 1.5-4.5 mg/day

Question 16

What are the characteristics of ropinirole?

Answer 16

4-6 hr half life, hepatic clearance, 3-24 mg/day

Question 17

What are the dopamine agonists?

Answer 17

Bromocriptine (1980), pramipexole, and ropinirole (1997, non-ergots)

Question 18

Where are the dopamine agnoists for bromocroptine?

Answer 18

D2 and partial D1

Question 19

Where are the dopamine agnoists for pramipexole?

Answer 19

Non-ergoline at D3 > D2

Question 20

Where are the dopamine agnoists for ropinirole?

Answer 20

Non-ergoline at D2 > D3

Question 21

Where are the dopamine agnoists for rotigotine?

Answer 21

Mostly D2 (but also 3,4, and 5)

Question 22

What are the benefits to dopamine agonists?

Answer 22

Stimulates dopamine receptors directly, independent of dopamine terminal function, reduces risk for dyskinesia, no effected by diet protein, delays motor complications

Question 23

What are the characteristics of Levodopa?

Answer 23

Rapid symptomatic benefits, well tolerated, continues to work throughout the disease course, usually combined with carbidopa, crosses BBB

Question 24

What are the positive effects of dopamine agonists?

Answer 24

Effective for tremor, rigidity, and bradykinesia, long half life
Action largely via activation of striatal D2 receptors
More protective against motor flux and dyskinesias

Question 25

What are the limitations of dopamine agonists?

Answer 25

Careful titration of doses, N&V, hallucinations, illusions, somnolence, edema, compulsions

Question 26

What is the downside to dopamine agonists?

Answer 26

Less effective than levodopa, ineffective for gait imbalances, freezing, and postural instability More sedating and neurophyschotic

Question 27

What are the side effects of L-dopa?

Answer 27

Development of motor complications within 5 years of disease | Dyskinsia and Dystonia, motor fluctuations

Question 28

How can you extend the benefit of levodopa?

Answer 28

Inc dose per admin | Add dopamine agnoist, monoamine oxidase B inhibitor, catechol-O-methyl transfer inhibitor

Question 29

What are the levodopa and DA metabolism inhibitors for PD treatment?

Answer 29

Levodopa, carbidopa, tolcapone, selegiline

Question 30

Describe parcopa.

Answer 30

Carbidopa/levodopa combo | Dissolves orally w/o water, tastes minty, can be taken as a booster, and should be taken upon waking up

Question 31

What is the monoamineoxidase-B (MAO-B) inhibitor?

Answer 31

Selegiline

Question 32

what is the function of a MAO-B inhibitor?

Answer 32

Inhibits dopamine metabolism, enhances L-dopa transport, produce a small benefits alone, metabolized to amphetamine and methamphetamine, possible neuoprotection

Question 33

What is a side effect of selegiline?

Answer 33

Motor complications

Question 34

What is rasagiline?

Answer 34

An irreversible inhibitor of MAO-B, selectively inhibits enzyme that metabolizes dopamine Enhances L-dopa, possible neuroprotection

Question 35

What does the inhibiton of COMT do in PD?

Answer 35

(Entacapone) | Extends duration of L-dopa (doesn't raise levels), dopaminergic diarrhea, urine discoloration, not so hepatotoxic

Question 36

What is the role of COMT in the body?

Answer 36

Converts L-dopa and dopamine to 3-OMD

Question 37

Describe amantadine.

Answer 37

Enhances synthesis, release or reuptake of dopamine from surviving neurons Reduces dyskinesia

Question 38

What are the three antimuscarinic agents?

Answer 38

Benztropine, trihexyphenidyl, biperiden

Question 39

What are the adverse effects of antimuscarinic agents?

Answer 39

Dry mouth, intraocular pressure, interference with GI peristalsis

Question 40

What was amantadine originally made for?

Answer 40

As an antiviral to protect for influenza type A

Question 41

What are some side effects of amantadine?

Answer 41

Ankle edema, livedo reticularis, and confusion/hallucinations

Question 42

Describe apomorphine.

Answer 42

High affinity for D4 (also 2,3,5 at receptors), very potent, short acting (60 min), needs to be injected

Question 43

What are the side effects to the apomorphine injection?

Answer 43

Dyskinesia, nausea, skin irritation, low blood pressure

Question 44

What is deep brain stimulation?

Answer 44

Surgical treatment for PD, creates a mini lesion using electrical stimuation

Question 45

What are the targets for deep brain stimulation?

Answer 45

Lateral globus pallidus and subthalamic nucleus