EXAM #3: ANTIPARKINSON'S DRUGS

Question 1

What is the aggregate found in PD?

Answer 1

Intracytoplasmic aggregates of alpha-synuclein

Question 2

When does PD typically onset?

Answer 2

50’s and 60’s

Question 3

What is PD characterized by from a pathologic standpoint?

Answer 3

Progressive loss of dopaminergic neurons in the basal ganglia

Question 4

What are the cardinal symptoms of PD?

Answer 4

1) Bradykinesia
2) Muscular rigidity
3) Resting tremor
4) Postural instability

Question 5

Specifically what dopaminergic neurons are lost in PD?

Answer 5

Dopaminergic neurons in the SN that project into the Striatum

Question 6

What is the definition of the Striatum i.e. what are the parts of the Basal Ganglia that compose the Striatum?

Answer 6

Putamen

Caudate Nucleus

Question 7

Describe the pathophysiology of PD.

Answer 7

• Alpha-synuclein accumulates into Lewy Bodies

- Lewy body formation generates free radicals

Question 8

What is the specific part of the Basal Ganglia that is degenerative in PD?

Answer 8

Substantia Nigra Pars Compacta

Question 9

What is the outcome of SN pars compacta degeneration in PD?

Answer 9

• OVERACTIVITY of the indirect pathway leading to:
  1) Inhibition of the VA/L thalamus
  2) Reduced excitatory input to the cortex
  3) Diminished execution of movement

Question 10

What is the role of ACh in PD?

Answer 10

• Imbalance of DA and ACh in PD

- Thus, there is too much ACh in PD

Question 11

What is the most common drug used to treat PD?

Answer 11

L-DOPA

Question 12

Why is L-DOPA given instead of DA?

Answer 12

DA cannot cross the BBB

Question 13

What enzyme converts L-DOPA into DA?

Answer 13

Dopa carboxylase

Question 14

What symptoms does L-DOPA specifically improve in PD?

Answer 14

Bradykinesia

Rigidity

Question 15

What drug is L-DOPA typically co-administered with?

Answer 15

Carbidopa

Question 16

What is the MOA of Carbidopa?

Answer 16

Carbidopa is an inhibitor of Dopa Decarboxylase in the periphery

Question 17

What is the effect of inhibiting Dopa Decarboxylase?

Answer 17

Inhibits the premature breakdown of L-DOPA in the periphery

Question 18

What are the adverse effects associated with L-DOPA adminstration?

Answer 18

1) Dyskinesias
2) Response fluctuations
- Wearing off reactions
- On-off phenomenon
3) GI disturbance
4) Postural hypotenion/ tachycardia
5) Behavioral disturbances

Question 19

What can be done to prevent the response fluctuations of L-DOPA?

Answer 19

Drug holidays i.e. periodic cessation

Question 20

What is the drug interaction of L-DOPA with Pyridoxine?

Answer 20

This is Vitamin B6, a DOPA decarboxylase cofactor that enhances L-DOPA metabolism in the periphery

Question 21

What is the drug interaction of L-DOPA with antipsychotics?

Answer 21

DA receptor blockade limits efficacy

Question 22

What is the drug interaction of L-DOPA with MAO-inhibitors?

Answer 22

Hypertensive response (NE)

Question 23

List the three DA receptor agonists.

Answer 23

Pramipexole
Ropinirole
Apomorphine

Question 24

What is the clinical use of Apomorphine?

Answer 24

Given subcutaneously for rescue of L-DOPA induced dyskinesias

Question 25

What is the MOA of the DA receptor agonists

Answer 25

D2 receptors agonsit

Question 26

What are the two MAO-B inhibitors used to treat PD?

Answer 26

Rasagiline

Selegiline

Question 27

What is the MOA of the MAO-B inhibitors?

Answer 27

Decreases breakdown of dopamine

Question 28

What is the major behavioral issue seen with the administration of DA agonsits?

Answer 28

Impaired impulse control leading to:

• Compuslive gambling
• Shopping
• Betting
• Sex

Question 29

What is the dose of MAO-B inhibitor that is needed to have a therapeutic effect in PD?

Answer 29

Low

Question 30

What are the two drugs used as COMT inhibitors in the treatment of PD?

Answer 30

Entacapone

Tolcapone

Question 31

What is the difference between Entacapone and Tolcapone?

Answer 31

Entacapone= peripheral COMT inhibitor ONLY

Tolcapone= central and peripheral COMT inhibition

Question 32

What is the MOA of COMT inhibitors?

Answer 32

Block peripheral breakdown of L-DOPA–used as an adjunct

Question 33

What is the MOA of Amantadine?

Answer 33

Increased DA release

Question 34

What class of drug is Amantadine?

Answer 34

Anti-viral

Question 35

What is the major adverse effect associated with Amantadine administration?

Answer 35

Livedo Reticularis

Question 36

What are the anticholinergic agents used to treat PD?

Answer 36

Benztropine

Trihexyphenidyl

Question 37

What is the MOA of Benztropine and Trihexyphenidyl?

Answer 37

Muscarinic antagonists

Question 38

What is the general picture of muscarininc antagonist overdose?

Answer 38

“Dry-picture”