Treatment of Parkinson's

Question 1

types of abnormal movements

Answer 1

tremor
chorea
athetosis
dystonia 
tics

Question 2

tremor

Answer 2

rhythmic oscillations in joints

when at rest often assoc. w/ Parkinson’s

Question 3

chorea

Answer 3

irregular jerkiness, esp at proximal muscles of limbs

Question 4

athetosis

Answer 4

slow & writhing abnormal movements

Question 5

dystonia

Answer 5

sustained (abnormal posture)

Question 6

tics

Answer 6

sudden, coordinated abnormal movements

Question 7

What are the effects of less DA in Parkinson’s disease?

Answer 7

less DA from Pars Compacta leads to more GLU from sub thalamic nucleus

Question 8

About Parkinson’s disease

(What is it?) tell me about the disease

Answer 8

(movement disorder)

• Tremors
• Rigidity
• Bradykinesia (slow movements) or akinesia (can’t initiate movement)
• Posture Instability

Question 9

What does Parkinson’s disease cause?

Answer 9

• degeneration of DA secreting neurons (sub migration PC)
• Imbalance b/w DA & ACh
• from toxin? (MPTP also knocks out same cells)
  
  • • Maybe from MAO-B producing a toxin

Question 10

What initiates the progression of Parkinson’s disease?

Answer 10

• DA (from sub migration) activate receptors that inhibit GABA output (inhibit an inhibitory pathway)
• ACh activates the same area that GABA inhibits. May be a imbalance b/w DA & ACh that’s important

Question 11

What is MPTP?

Answer 11

Methyl phenyl tetra hydropyridine

• a prodrug to the neurotoxin MPP+, which causes permanent symptoms of Parkinson’s disease
• destroys dopaminergic neurons in the substantia migration in the brain

Question 12

MPTP hypothesis

Answer 12

manufacturing MPPP turned into MPTP, which allowed a patient to respond well to the Parkinson’s treatment.

he then died due to MPPP being a bad batch!

Question 13

MPPP

Answer 13

Methyl phenyl proprionoxypiperidine
(DEA has labeled it as schedule I drug in the U.S.)

• heroine like drug (meperidine-like)
• quite addicting
• gives euphoria & peaceful sense

Question 14

Drugs that may induce PD

Answer 14

Serenace (haloperidol)
Stemetil (prochlorperazine)
Maxolon (metoclopramide)
Neulactil (pericyazine)
Risperidal (risperidone)

Question 15

DA/ACh imbalance in Parkinson’s

Answer 15

dopamine deletion blocks auto inhibition of ACh through muscarinic autoreceptors which lead to excessive ACh release

(higher levels of ACh cause dyskinesia)

Question 16

drugs used

Answer 16

Levodopa (MOST DRUG USED FOR THIS DISEASE)

• dopamine won’t cross BBB
• L-Dopa crosses BBB then gets converted to DA by dopa decarboxylase
• • “usually” reverses all effects of Parkinson’s
    * * but some do NOT respond
• Up to 98% is converted to DA in periphery
• • causes GI distress & arrythmia
• • given with a peripheral dopa decarboxylase inhibitor

Question 17

Tyrosine/dopamine

Answer 17

enzymes in body convert tyrosine into dopamine

hense., tyrosine plays a critical role for the production of dopamine

Question 18

Side effects of Levodopa w/ Carbidopa

Answer 18

1. Nausea/ vomiting
2. CV
3. Diskinesias
4. Depression & Anxiety
5. Loss of Efficacy
6. End-of-Dose Phenomenon

Question 19

Nausea/ vomiting

Answer 19

(less frequent w/ decarboxylase inhibitor)

Question 20

CV

Answer 20

(arrhythmia & postural hypotension)

Question 21

Diskinesias

Answer 21

(in about 80% of patients)
(include dystopias, myoclonus, tics, tremors)
(usually after 3 months to 10 years on L-Dopa)

Question 22

Depression & Anxiety

Answer 22

(w/ elderly & w/ decarboxylase inhibitors)

Question 23

Loss of Efficacy

Answer 23

(due to tolerance)

due to progression of disease

Question 24

End-of-loss Phenomenon

Answer 24

(due to plasma concentrations)

use sustained release or change timing of drug administration

Question 25

Drug holidays

Answer 25

removing patient from L-Dopa for days/weeks so that can respond to the drug again

they may now need less of the drug for response

NOT EFFECTIVE IN ALL CASES

Question 26

Dopamine Agonists

Answer 26

• Bromocryptine/ Pergolide (older, not used) OR
  Paramipexole (D3) OR Ropinirole (D2)
• Used w/ L-Dopa for synergistic effect or for early treatment in patients that don’t tolerate L-Dopa well

Question 27

Side effects of Dopamine Agonists

Answer 27

GI–> Nausea/ vomiting
CV–> Postural hypotension
CNS–> Confusion, hallucinations

Question 28

Rasagiline & Selegiline

Answer 28

(MAO-B inhibitor)

- Used w/ levodopa

Question 29

Entacapone & Tolcapone

Answer 29

(COMT inhibitors)

Question 30

Benztropine

Answer 30

(antimuscarinic)
- Balance ACh effects that’s strong in Parkinson’s
(used w/ L-Dopa)
(can reduce tremor & rigidity)

Question 31

Amantidine

Answer 31

(anti-viral w/ unknown mechanism)
- used w/ L-Dopa or anti-cholinergics
(helps reduce symptoms w/ mild side effects)

Question 32

Treatment

Answer 32

May start w/ selegiline or amantidine, then L-Dopa

Question 33

Newest Treatments

Answer 33

Mirapex (pramipexole), Requip (ropinirole)

Tasmar (tolcapone), Comtan (entacapone)

Question 34

Mirapex (pramipexole), Requip (ropinirole)

Answer 34

• Non-ergot DA agonists (type 2 autoreceptors)
• Less DA release > less MAO free radicals > less Parkinson’s - like damage
• Side effects:
  orthostatic hypotension, hallucinations, diskinesias, dry mouth

Question 35

Tasmar (tolcapone), Comtan (entacapone)

Answer 35

COMT inhibitors

• Side effects:
  liver damage, sleep disturbances, hallucinations, dizziness/hypotension