Pharmacology of Parkinson's Disease

Question 1

What is Amantidine (symmetrel)?

Answer 1

a drug that facilitates the release of endogenous dopamine

Question 2

Disorders of _____ may predispose pts to subsequent assault by chemicals in Parkinson’s Disease.

Answer 2

mitochondrial energy pathways

Question 3

How is dopamine broken down?

Answer 3

dopamine + MAO –> DOPAC + catchol-o-methyl transferase (COMT) –> HVA

Question 4

Neurotoxins such as the meperidine analog _____ can cause a Parkinson’s-like condition by killing dopamine neurons.

Answer 4

MPTP

Question 5

Name 3 anticholinergic drugs for Parkinson’s treatment.

Answer 5

1. Trihexyphenidyl (Artane)
2. Benztropine (Cogentin)
3. Diphenhydramine (Benadryl)

Question 6

Name 2 Catechol-o-methyl transferase inhibitors used to treat Parkinson’s.

Answer 6

1. Tolcapone (Tasmar)
2. Entacapone (Comtran)

Question 7

What drug facilitates the release of endogenous dopamine?

Answer 7

Amantidine (symmetrel)

Question 8

Name some possible environmental causes of Parkinsons.

Answer 8

• well water
• pesticides
• copper and iron exposures

Question 9

What is Sinemet?

Answer 9

L-DOPA combined with a peripheral decarboxylase inhibitor, carbidopa

Question 10

Collectively, what kind of drug are the following?

1. Tolcapone (Tasmar)
2. Entacapone (Comtan)

Answer 10

Catechol-o-methyl transferase inhibitors

Question 11

Name 5 dopamine receptor agonist drugs.

Answer 11

1. Bromocriptine (Parlodel)
2. Pergolide (Permax)
3. Pramipexole (Mirapex)
4. Ropinirole (Requip)
5. Cabergoline (Dostinex)

Question 12

Why are anticholinergic drugs used for Parkinson’s therapy? How effective are they? Why aren’t they used as often?

Answer 12

to treat the tremor; less effective than L-DOPA; anti-parasympathetic side effects

Question 13

Name 2 MAOIs used to treat Parkinson’s.

Answer 13

1. Selegiline, also called Deprenyl - (Eldepryl)
2. Rasagiline (Azilect)

Question 14

What is the significance of alpha-synuclein?

Answer 14

• it’s a mutated protein in the auto. dominant form of Parkinson’s
• is also found in the Lewy bodies in Parkinson’s patients w/o the mutation

Question 15

Why do some neurologists choose to start with a dopamine agonist, rather than L-DOPA?

Answer 15

there’s less risk of dyskinesia

Question 16

These drugs prevent the breakdown of L-DOPA and dopamine by COMT.

Answer 16

catchol-o-methyl transferase (COMT) inhibitors

Question 17

How is L-DOPA administered? How does it reach its target?

Answer 17

orally; crosses the BBB

Question 18

The first mutation found assoc. with Parkinson’s is a single aa change in the protein, ______.

Answer 18

alpha-synuclein

Question 19

Collectively, what kind of drug are the following:

1. Bromocriptine (Parlodel)
2. Pergolide (Permax)
3. Pramipexole (Mirapex)
4. Ropinirole (Requip)
5. Cabergoline (Dostinex)

Answer 19

dopamine receptor agonists

Question 20

Drug-induced Parkinsonism is a common side effect of _____ and other _____ drugs.

Answer 20

phenothiazines; neuroleptic

Question 21

What is the most important drug for Parkinson’s tx?

Answer 21

L-DOPA

Question 22

What seems to be the common physiological pathway in the pathology of Parkinson’s disease?

Answer 22

• destruction of dopamine cells in the pars compacta of the substantia nigra
• loss of the NT dopamine in the caudate and putamen

Question 23

How do catchol-o-methyl transferase (COMT) inhibitors work?

Answer 23

prevent the breakdown of L-DOPA and dopamine by COMT

Question 24

______ inhibits liver enzymes and has caused liver toxicity.

Answer 24

Tolcapone

Question 25

Tolcapone inhibits _____ enzymes and has caused _____ toxicity.

Answer 25

liver x2

Question 26

What are the cardinal features of Parkinson's Disease?

Answer 26

* tremor * rigidity * akinesia

Question 27

This is a drug that blocks decarboxylase in the intestines and peripheral organs but does not cross the BBB.

Answer 27

carbidopa

Question 28

What is carbidopa?

Answer 28

a drug that blocks decarboxylase (and levodopa breakdown) in the intestines and peripheral organs but does not cross the BBB

Question 29

These drugs directly stimulate the dopamine receptors in the caudate/putamen.

Answer 29

dopamine receptor agonists

Question 30

Collectively, what kind of drug are the following? 1. Selegiline, also called Deprenyl - (Eldepryl) 2. Rasagiline (Azilect)

Answer 30

they're MAOIs used to treat Parkinson's

Question 31

What do dopamine receptor agonists do?

Answer 31

directly stimulate the dopamine receptors in the caudate/putamen

Question 32

Collectively, what kind of drug are the following? 1. Trihexyphenidyl (Artane) 2. Benztropine (Cogentin) 3. Diphenhydramine (Benadryl)

Answer 32

they're anticholinergics used to treat Parkinson's

Question 33

How is dopamine synthesized?

Answer 33

tyrosine + tyrosine hydroxylase --\> L-dopa + DDC --\> dopamine

Question 34

Which receptor do most of the dopamine receptor agonists work at?

Answer 34

the dopamine D2 receptor

Question 35

How do MAOIs help Parkinson's disease?

Answer 35

they prevent the breakdown of dopamine