Exam 3 Week 12 PP 3 Parkinson's Disease

Question 1

What is Parkinson’s Disease?

Answer 1

a progressive degenerative disease caused by death of dopaminergic (DA) neurons primarily in the substantia nigra pars compacta (SNpc)

Question 2

first signs of Parkinson’s Disease

Answer 2

loss of noradrenergic input into dorsal motor nucleus of X & locus coeruleus

Question 3

What occurs with normal aging?

Answer 3

Loss of dopaminergic neurons seen in SNpc with normal aging (50% decrease ages 20 to 60)

Question 4

Possible major factor in the accelerated development of PD

Answer 4

aging

Question 5

Progressive decline in DA in areas of the Mesolimbic system include what projections? (4)

how does it get there?

Answer 5

from the ventral tegmental area (VTA) to

1. -amygdala
2. -nucleus accumbens
3. -prefrontal cortex
4. -hippocampus

via medial forebrain bundle (MFB)

Question 6

Which connections are lost with continued decline with Parkinson’s? How does that manifest?

Answer 6

loss of connections in prefrontal, limbic cortex & hippocampus Loss of cognitive skills, memory and higher associative cognitive functioning

Question 7

Cardinal Signs of Parkinson’s

Answer 7

1. Resting Tremor
2. Bradykinesia
3. Rigidity
4. Postural Instability
5. Gait Abnormalities
6. Dysarthria
7. Dysphagia

Question 8

3 parts of bradykinesia

Answer 8

1. Hypokinesia-paucity of movement
2. Bradykinesia – slowed movement
3. Akinesia – problem initiating movement

Question 9

Define Rigidity and two types found in Parkinson’s

Answer 9

Increased muscle tone and resistance to movement

1. Lead pipe – sustained contaction
2. Cog-wheel – periodic breaks

Question 10

4 signs of gait abnormalities

Answer 10

1. Slow shuffling
2. No arm swing
3. Tendency for retropulsion – stepping backward
4. Festinating gait – rapid short steps

Question 11

Nonmotor impairments (6)

Answer 11

1. Cognitive decline (up to 80%)
2. Postural hypotension
3. Hallucinations
4. Autonomic changes
5. Fatigue & sleepiness
6. Pain

Question 12

What causes Parkinson’s?

Answer 12

God only knows, but….. some cases environmental or genetic causes are implicated. **Combination of factors

Question 13

Several approaches to the pharmacological management

Answer 13

1. Replacement therapy
2. Dopamine agonists
3. Blocking the enzymatic breakdown of dopamine
4. Anticholinergic interventions

(Pneumonic: Without drugs you may feel DRAB)

5. various other approches

Question 14

Disadvantages to dopamine replacement therapy (5)

Answer 14

L-DOPA

1. Rapidly metabolized peripherally so co-administered with carbidopa
2. L-DOPA requires intact dopaminergic neurons, the use of L-DOPA is less effective with the progression of the disease
3. relatively short half-life of L-DOPA (about 90 minutes) causes sudden ON-OFF shifts of symptoms late in therapy
4. side effect: dyskinesias may be due to dosing and its rapid metabolism
5. may accelerate DA neuron cell death secondary to increased free radicals or metabolic stres

Question 15

Reason L-dopa is used

Answer 15

Dopamine cannot cross blood brain barrier. L-dopa is a metabolic precursor- small enough to cross BBB

Question 16

Newer pharmacological therapy

Answer 16

Dopamine receptor agonists

Question 17

Benefits of Dopamine receptor agonists (4)

Answer 17

1. No requirement for DA neurons so longer effect
2. More selective action (D1 or D2 agonists)
3. Less dyskinesias
4. Not accelerate SNpc cell death

Question 18

Shared adverse reactions of Dopamine agonists & L-Dopa (4)

Answer 18

1. Dyskinesias – choreoform movements
2. Abnormal thinking – hold onto false beliefs
3. Hallucinations
4. Addictive behaviors – excessive gambling

Question 19

Role of Monoamine oxidase (MAO) inhibitors Catechol-O-methyl transferase (COMT) inhibitors

Answer 19

Inhibitors of dopamine metabolism

Question 20

One of the oldest pharmacological therapies of Parkinson’s

Answer 20

Anticholinergic agents (existed before L-dopa)

Question 21

Disadvantage of anticholinergic agents

Answer 21

strong Autonomic adverse reactions

Question 22

Rationale for using anticholinergic agents

Answer 22

-Striatal interneurons & PPN afferents to SN both cholinergic -Block muscarinic receptors

Question 23

Other drug therapies for Parkinson’s (3)

Answer 23

1. Amantadine- Antiviral may also have effects on catecholamine pathways but little efficacy
2. Anti-depressants- used for depression symptoms
3. NMDA receptor antagonists- Slow cell degeneration **May use any combination

Question 24

Surgical Interventions (4)

Answer 24

1. Pallidotomy
2. Ventrolateral thalamotomy
3. Deep brain stimulation
4. Fetal nigral transplantation

Question 25

Reasons Fetal nigral transplantation is not commonly used

Answer 25

Little efficacy despite positive MRI results & substantial adverse reactions noted in young patients

Question 26

What is deep brain stimulation?

Answer 26

Implanted pacemaker with leads to different brain regions Common targets are the thalamus, subthalamic nucleus, and globus pallidus.

Question 27

Advantage/ Disadvantage of deep brain stimulation

Answer 27

Advantage: Many patients show remarkable improvement Disadvantage: Behavioral adverse reactions

Question 28

Reason for Ventrolateral thalamotomy

Answer 28

lesioning of the VL nucleus is done with similar results to GPi lesions

Question 29

What does a Pallidotomy reduce

Answer 29

tremor & rigidity but not other symptoms

Question 30

What is Pallidotomy

Answer 30

Lesion of globus pallidus internus