Antiparkinson Drugs

Question 1

What are the 4 main symptoms of Parkinson’s? secondary sxs?

Answer 1

bradykinesia, resting tremor, rigidity, postural instability. secondary: depression, dementia, autonomic dysfunction

Question 2

What is the pathology?

Answer 2

loss of a lot of DA in neurons in the Substantia Nigra. Also Lewy inclusion bodies in neurons

Question 3

What drug is used to restore dopaminergic function?

Answer 3

Levodopa = L-DOPA

Question 4

1) what converts tyrosine to L-DOPA?

Answer 4

Tyrosine hydroxylase (TH)

Question 5

2) what converts L-DOPA to Dopamine?

Answer 5

aromatic-amino acid decarboxylase (AAD)

Question 6

what is the rate-limiting enzyme?

Answer 6

TH tyrosine hyroxylase

Question 7

3) which enzymes between Dopamine and Metabolites?

Answer 7

MAO-B (monoamine oxidase) and COMT (catechol O-methyltransferase)

Question 8

Does Dopamine cross the blood brain barrier?

Answer 8

no

Question 9

Does tyrosine increase dopamine levels? why/why not?

Answer 9

no because TH (tyrosine hydroxylase) is already saturated with normal tyrosine levels

Question 10

what happens when L-DOPA is administered alone?

Answer 10

the majority of it is converted to DA by AAD in peripheral tissues before entering the brain.

Question 11

What is administered with L-DOPA and why?

Answer 11

Carbidopa because it inhibits peripheral AAD and can’t cross the blood brain barrier…it stops L-DOPA from being converted to dopamine by AAD in peripheral tissues before the brain

Question 12

What is carbidopa?

Answer 12

a peripheral AAD inhibitor administered with Levodopa

Question 13

What does Carbidopa do to L-DOPA levels?

Answer 13

it permits more L-DOPA to enter the brain where it can be converted to DA by AAD in brain

Question 14

Therefore, Carbidopa (2):

Answer 14

1) increases the potency of L-DOPA (decreases required daily dose)
2) decreases production of DA in peripheral tissues, reducing peripheral side effects

Question 15

What are the peripheral side effects?

Answer 15

nausea, vomiting, postural hypotension

Question 16

What is the L-DOPA + Carbidopa drug?

Answer 16

Sinemet (like “cinema”)

Question 17

What is another name for vitamin B6?

Answer 17

pyridoxine

Question 18

What do high doses of pyridoxine do?

Answer 18

activates peripheral AAD which decreases L-DOPA levels

Question 19

how many patients actually respond to L-DOPA?

Answer 19

~2/3

Question 20

L-DOPA loses its effectiveness in about 5 years…why?

Answer 20

further loss of DA neurons and lack of new Da synthesis from L-DOPA

Question 21

What is the on-off phenomenon? why?

Answer 21

L-DOPA effectiveness is on-off. dietary reason, persistent loss of DA neurons

Question 22

What are the major side effects of L-DOPA (4)?

Answer 22

extrapyramidal dyskinesias, nausea and vomiting, postural hypotension, sleep disturbances

Question 23

What are the COMT inhibitors?

Answer 23

entacapone, tolcapone

Question 24

Which COMT inhibitors work in the periphery?

Answer 24

entacapone and tolcapone

Question 25

Which COMT inhibitors work in the CNS?

Answer 25

tolcapone

Question 26

How do COMT inhibitors work?

Answer 26

inhibit L-DOPA metabolism in peripheral tissues and/or DA metabolism in the brain (Tolcapone)

Question 27

Are COMT inhibitors used alone?

Answer 27

NO! Always used in combo with L-DOPA

Question 28

What are the side effects of COMT inhibitors?

Answer 28

diarrhea, increased sensitivity to L-DOPA

Question 29

What's special about Tolcapone?

Answer 29

hepatotoxicity, peripheral and central

Question 30

What's special about Entacapone?

Answer 30

peripheral COMT only, shorter duration

Question 31

What is the Levodopa + Carbidopa + Entacapone drug?

Answer 31

Stalevo

Question 32

What is Stalevo?

Answer 32

levodopa + carbidopa + entacapone

Question 33

What are the MAO-B Blockers?

Answer 33

Selegiline, Rasagiline

Question 34

Where do the MAO-B inhibitors work?

Answer 34

CNS (striatum)

Question 35

What is the mechanism of MAO-B blockers?

Answer 35

block DA metabolism by inhibiting MAO in striatum

Question 36

What does MAO-B do?

Answer 36

preferentially metabolizes DA

Question 37

What are the drug interactions with MAO-B blockers (2)?

Answer 37

1) contraindicated with Meperidine or Tricyclid antidepressants because of hyperthermic or hypertensive interactions 2) potential hypertension if used with L-DOPA

Question 38

What are the DA receptor agonists (3)?

Answer 38

Bromocriptine, Pramipexole, Ropinirole

Question 39

What are the older DA receptor agonists?

Answer 39

Bromocriptine

Question 40

What are the newer DA receptor agonists?

Answer 40

Pramipexole, Ropinirole

Question 41

What are the side effects of bromocriptine?

Answer 41

hypotension, nausea, dyskinesia

Question 42

Why are pramipexole and ropinirole better?

Answer 42

longer duration of action (less on and off) and good efficacy, side effects are less severe

Question 43

what are the side effects of pramipexole and ropinirole?

Answer 43

hypotension, nausea, dyskinesia, sleep disturbance, hallucination/confusion, risky behaviors. (less severe than bromocriptine)

Question 44

What are the muscarinic receptor antagonists?

Answer 44

Benztropine

Question 45

What does DA normally do to Ach?

Answer 45

DA released from nigrostriatal neurons activates D2 receptors on cholinergic neurons in the striatum and inhibits the release of Ach

Question 46

What does coordination of movement rely on?

Answer 46

balance of Ach and DA

Question 47

What happens to cholinergic activity in Parkinson's?

Answer 47

Reduced DA activity leads to cholinergic hyperactivity

Question 48

What do muscarinic receptor antagonists do (benztropine)?

Answer 48

counteract cholinergic hyperactivity in PD

Question 49

What are the side effects of benztropine?

Answer 49

anti-parasympathetic: dry mouth, reduced sweating, increased heart rate

Question 50

What is benztropine especially effective against?

Answer 50

tremor

Question 51

What antiviral agent works for Parkinsons?

Answer 51

Amantadine

Question 52

What does Amantadine do?

Answer 52

increases DA release

Question 53

Downsides of amantadine?

Answer 53

beneficial effects are not as pronounces as L-DOPA and tolerance occurs within weeks

Question 54

What are the side effects of Amantadine?

Answer 54

(usually mild) restlessness, depression, livedo reticularis (purplish mottled skin discoloration), edema, hypotension, hallucinations

Question 55

What is the DA precursor?

Answer 55

L-DOPA

Question 56

What is the peripheral AAD inhibitor?

Answer 56

Carbidopa

Question 57

What are the COMT inhibitors?

Answer 57

Entacapone, Tolcapone

Question 58

What are the MAO-B inhibitors?

Answer 58

Selegiline, Rasagiline

Question 59

What is the anti-viral agent?

Answer 59

Amantadine

Question 60

What is the muscarinic receptor antagonist?

Answer 60

Benztropine

Question 61

What are the DA receptor agonists?

Answer 61

Bromocriptine, Pramipexole, Ropinirole