Parkinson’s Disease

Question 1

WHAT IS THE PROBLEM IN PARKINSON’S DISEASE?

Answer 1

DEAD DOPAMINE NEURONS

Loss of dopamine synthesis

Loss of regulated release

Question 2

PARKINSON’S DISEASE

Disease of the elderly, average onset age:

Answer 2

60, about 1% of people over age 60 have it

Question 3

PARKINSON’S DISEASE

Genetic causes of Parkinson’s discovered in past 10 years show selective vulnerability of:

Answer 3

dopamine neurons

-Younger patients more likely to have genetic cause

Question 4

PARKINSON’S DISEASE

People who drink ________, work with pesticides or metals like iron and copper have higher risk of Parkinson’s

Answer 4

well water

Question 5

Tea and coffee drinkers have __________ risk of Parkinson’s

Answer 5

up five-times lower

Question 6

________ have lower risk of Parkinson’s

Answer 6

Smokers

Question 7

PARKINSON’S DISEASE

People who drink well water, work with pesticides or metals like _________ have higher risk of Parkinson’s

Answer 7

iron and copper

Question 8

L-Dopa

Answer 8

rx- direct precursor of dopamine
Carbidopa reduces dose of L-Dopa needed

(much L-Dopa destroyed in gut w/o carbi)

Question 9

Carbidopa

Answer 9

rx- Inhibits peripheral metabolism of L-Dopa

CAN”T cross BBB

Question 10

If _____ makes you better, you have Parkinsons

Answer 10

L-Dopa

Question 11

DRUG TREATMENT OF PARKINSON’S DISEASE

Answer 11

L-dopa – direct precursor of dopamine
Dopamine agonists
Dopamine “extenders”–carbidopa, MAO inhibitors and COMT inhibitors
Anticholinergic drugs
Amantadine - A glutamate antagonist
Drugs that may prevent progression

Question 12

The most important drug for Parkinson’s

Answer 12

L-DOPA

Question 13

L-DOPA

Answer 13

L-dopa is combined with carbidopa to block peripheral metabolism

Side effects – nausea, hypotension, depression, psychosis (up to 15%)

Long term complication – drug induced dyskinesias

Question 14

Healthy brain makes about _____ of dopamine

Answer 14

1 g

L-Dopa dose
Typical dose 125 mg q2h 8 times/day

Taking more than 1 g of L-Dopa can cause side effects

Question 15

Comtan

Answer 15

Keeps dopa around

Question 16

Ripineral

Answer 16

Direct dopa agonist

Smoothes out peaks and troughs of L-Dopa w/ a short half life

Question 17

L-Dopa half life

Answer 17

1 hour

Question 18

The tremor in parkinson’s is

Answer 18

A rest tremor

Question 19

Walking with parkinsons

Answer 19

Shuffling gait chasing the center of gravity

Question 20

Cognitive ability of Parkinson’s

Answer 20

normal

Question 21

Substantia Nigra name

Answer 21

has black pigment

Not born with pigment, it grows over time. PArk pts have no pigment

Question 22

Diagnostic feature of parkinsons

Answer 22

Lewy Bodies

Question 23

SN location

Answer 23

Base of skull

feeds axons to caudate and putamen (these stay normal)

Dopa deletion is worse in the Putamen

Question 24

Main output of BG

Answer 24

GPI/SNr

Question 25

Inhibitory Neurons

Answer 25

These dont see dopamine in PK, and they say "no movement allowed"

Question 26

Amantadine

Answer 26

Glu Antagonist

Question 27

Tyr--> L-Dopa--> Dopamine

Answer 27

enzyme not available in PK to do this synthesis

Question 28

Dopamine Receptor Agonists

Answer 28

Most D2-dopamine receptor agonists Developed for longer half lives Often started at time of diagnosis to delay need for L-DOPA Ropinirole (Requip) Pramipexole (Mirapex) Apomorphine – short acting

Question 29

Dopamine Receptor Agonists ADR

Answer 29

TOXICITY: Nausea, hallucinations, Sudden onset of sleep* – car accidents Pergolide – cardiac valve thickening – FDA withdrew drug EVENTUALLY, NEARLY EVERYONE ON A DOPAMINE AGONIST NEEDS L-DOPA

Question 30

Anticholinergics

Answer 30

Invention of antihistamines led to their use in Parkinson’s before dopamine and L-DOPA discovered Have some limited value in treating some patients with tremor Side effects: confusion, drowsiness, constipation, and urinary retention limit use in elderly Parkinson patients

Question 31

Amantadine

Answer 31

Beneficial effects discovered when Parkinson patients took amantadine for influenza symptoms – Dose 300 mg/day Mechanism uncertain - facilitate release of endogenous dopamine - glutamate antagonist

Question 32

Cost of Drugs

Answer 32

VERY steep

Question 33

Drugs that may prevent progression of Parkinson’s

Answer 33

Co-enzyme Q-10 at dose of 1200 mg/day or greater has passed early double blind study Creatine in doses of 10-20 gm/day may be beneficial Caffeine and Adenosine A2a antagonists are being tested Minocycline and Vitamin E have failed testing

Question 34

Surgical Therapy for Parkinson’s Disease

Answer 34

Deep brain stimulation—reversible thalamotomy or pallidotomy Thalamus Internal pallidum Subthalamic nucleus Fetal dopamine cell transplantation *When drugs arnt doing the trick