Part II: Parkinson's

Question 1

Parkinson’s Disease is the

Answer 1

loss of nigrostriatal dopamine neurons which leads to loss of dopaminergic innervation of the basal ganglia

Question 2

What receptor is the most important therapeutic target in Parkinson’s

Answer 2

D2-like receptors (D2, D3, D4)

Question 3

Parkinson’s can be idiopathic or as a complication of (3 exogenous, 3 endogenous pathologies)

Answer 3

Influenza epidemic of 1918

Certain medications

MPTP toxicity

Neuro disorders: Progressive supranuclear palsy, shy-drager syndrome, CJD

Question 4

Other strategies include

Answer 4

Anticholinergics

Amantadine

Question 5

Dopamine production

Answer 5

L-Tyrosine to L-DOPA to Dopamine

Question 6

Rate Limiting step in dopamine production

Answer 6

L-tyrosine to L-DOPA via tyrosine Hydroxylase

Question 7

L-DOPA helps w/ reversing rigidity, tremor, bradykinesia and reduced facial expression. what are some adverse effects

Answer 7

GI upset

dyskinesia

Behavioral effects

on-off phenomena

Orthostatic hypotension

Brown discoloration of fluids

Mydriasis leading to glaucoma

Question 8

Where does L-DOPA degrade

Answer 8

in the gut

Question 9

Long term side effects of L-DOPA

Answer 9

hallucinations
paranoia
mania
anxiety
depression (more disease related)

Question 10

What drug is indicated for PD psychosis?

Answer 10

Pimavanserin (5-HT2c and 5-HT2a inverse agonist and antagonist)

Question 11

95% of L-DOPA is decarboxylated in the

Answer 11

decarboxylated by aromatic amino acid decarboxylase in the periphery and excreted in the urine

Question 12

What vitamin increases metabolism of L-DOPA?

Answer 12

Pyridoxine (B6)

Question 13

What drug blocks Aromatic Amino Acid Decarboxylase in the periphery that is similar to L-DOPA which decreases dose of L-DOPA required and decreases side effects?

Answer 13

Carbidopa

L-DOPA + Carbidopa= Sinemet

Question 14

In addition to Carbidopa, what are some other drugs used to increase dopaminergic activity thus increasing efficacy, decreasing L-DOPA dose, and decreasing the on-off effect?

Answer 14

COMT inhibitors: Tolcapone (hepatotox)
 and Entacapone (Peripheral only)

Question 15

What antiviral drug against influenza A is also used in Parkinson’s

Answer 15

Amantadine

Question 16

Which monoamine oxidase preferentially metabolizes DA

Answer 16

MAO-B

Question 17

MAO-B inhibitors?

Answer 17

Selegilene

Rasasgiline

Question 18

What are the MAO-I-B used for in tx of Parkinson’s

Answer 18

Adjunct to L-Dopa, increases efficacy, decreases L-DOPA dose, decreases on-off effect

Question 19

Contraindications of metabolism inibitors:

Answer 19

abrupt dicontinuation can result in neuroleptic malignant syndrome (fever, muscle rigidity, tachy, mental status changes)

closed-angle glaucoma

melanoma

breast feeding

Use w/ caution in:
Psychosis
Cardiac Disease
PUD
Open-angle glaucoma

Question 20

Dopamine Agonists Monotherapy

Answer 20

Pramipexole (D2/D3)

Ropinerole (D2/D3)

Rotigotine (D1/D2/D3 agonist), transdermal

Question 21

Dopamine Agonist Add-Ons

Answer 21

Bromocriptine (D2 agonist)
Apomorphine (Non-Ergot D1/D2 Agonists)

The thing with add on therapy is that D3 receptor activity confers greater efficacy and may mediate neuroprotective effects which is why D2 or non-D3 agonists aren’t used as monotherapy

Question 22

Anticholinergics can be used in the tx of parkinson’s. Which drugs?

Answer 22

Trihexyphenidyl
Benztropine
Procyclidine

Question 23

How do anticholinergics helps in the management of Parkinson’s?

Answer 23

Blocks actions of striatal cholinergic interneurons

Generally less effective than L-DOPA