Anti-Parkinson's Drugs

Question 1

The Direct Pathway of normal movement control causes:

Answer 1

D1 stimulation (excitatory) enables movement

Question 2

The Indirect Pathway of normal movement control causes:

Answer 2

D2 stimulation (inhibitory) inhibits movement

Question 3

The net effect of D1 stimulation and D2 inhibition is:

Answer 3

purposeful movement

Question 4

What is happening to the pathways in Parkinson’s?

Answer 4

The D1 pathway is inhibited and the D2 pathway is activated. This leads to reduced activity and movement inhibition

Question 5

When Parkinson’s s/s first appear destruction of what percentage of neurons in the substantia nigra has already occurred?

Answer 5

70%

by death 95%

Question 6

S/s of Parkinson’s include:

Answer 6

Bradykinesia, rigidity, impaired postural balance, tremor

Question 7

Pharmacologic goals in Parkinson’s management:

Answer 7

No curative agent
Symptomatic treatment only
Increase dopamine in brain

Question 8

Why can’t we just administer dopamine to these patients?

Answer 8

Dopamine will not cross the BBB

Question 9

The most effective treatment of Parkinson’s is and why?

Answer 9

Levodopa because it readily crosses the BBB via protein transport

Question 10

L-Dopa is converted to the dopamine in the CNS and where else, and what does this causes?

Answer 10

GI tract

Nausea

Question 11

When administered alone about how much levodopa reaches the CNS unchanged?

Answer 11

1-3%

Question 12

What is Levodopa often given with and why?

Answer 12

Carpidopa (Sinemet), it prevents breakdwon of Levodopa in the periphery. This causes more Levodopa to cross the BBB where it is then converted to dopamine

Question 13

Why is Levodopa not always used first?

Answer 13

Patients gain tolerance and become desensitized. They will require increased doses and may experience between on and off periods
(try to use prior to severe s/s though)

Question 14

AE of Levodopa:

Answer 14

Dyskinesia- uncontrollable rhythmic movements of head and trunk

Question 15

Dopamine receptor agonists MOA and include:

Answer 15

Directly target postsynaptic DA receptors
Bromocriptine (Parlodel)-ergot derivative (more AE)
Pramipexole (Mirapex)
Ropinirole (Requip)

Question 16

Advantages to dopamine receptor agonist include:

Answer 16

No enzymatic conversion

Longer half life= less blood level fluctuations

Question 17

AE of dopamine receptor agonists:

Answer 17

Sedation
Vivid dreams
Hallucinations
(schizophrenic like AE)

Question 18

MAO-B inhibitors used as an adjuvant to levodopa include:

Answer 18

Selegeline (Eldepryl)

Rasagiline (Azilect)

Question 19

Potentially toxic metabolic of selegeline:

Answer 19

Amphetamine, causes sleeplessness and confusion

Question 20

COMT inhibitors include and how do they work:

Answer 20

Inhibit COMT which breaks down dopamine and L-Dopa
Tolcapone (Tasmar)
Entacapone (Comtan)

Question 21

Where do Tolcapone and Entacapone work?

Answer 21

Tolcapone works centrally and peripherally

Entacapone works peripherally

Question 22

Tolcapone potential AE:

Answer 22

Hepatotoxicity

Question 23

What is Amatadine (Symmetrel) used for?

Answer 23

Treatment of levodopa-induced dyskinesias

may block excitatory NMDA receptors

Question 24

What type of drugs are Trihexyphenidyl (Artane) and benztropine (Congentin) and how are they used in the treatment of Parkinson’s?

Answer 24

Anticholinergics/muscarinic receptor antagonists

Used to decrease tremor

Question 25

Which adjuvant therapies of L-dopa work in the periphery and which centrally?

Answer 25

Entacapone, Talcapone, and Carbidopa work in the periphery to allow more L-dopa to cross the BBB. Once L-dopa has crossed the BBB, Talcapone, Selegeline, and Rasagiline work to inhibit its breakdown.