Anti Parkinson's Disease

Question 1

What are the common symptoms of Parkinson’s?

Answer 1

• Bradykinesia
• Rigidity
• Rest tremor
• Postural instability
• Gait disturbances (manner of walking)
• Expressionless face

Other symptoms

• Sleep disturbances
• Depression
• Psychosis
• Dementia

Question 2

What are the two neurotransmitters that are imbalanced?

Answer 2

Dopamine and Acetylcholine
Inhibitory —– Excitatory

Most drugs are focused on dopamine pathways

As long as there are functioning nerve terminals, symptoms can be partially controlled

Question 3

What is an example of a MAOI (monoamine oxidase inhibitors) and what system does it affect?

Answer 3

Levodopa-carbidopa (Sinemet)

• Reduces dopamine breakdown in neurons
• Impacts the dopamine system

Question 4

What’s an example of a anticholinergic agent for PD?

Answer 4

Benztropine (cogentin)

Question 5

What is levodopa, what special barrier can it cross, and how does it work?

Answer 5

• Levodopa is a precursor of dopamine
• It can cross the BBB but dopamine can’t
• Levodopa is taken up by dopaminergic terminals, and then converted to dopamine
• Aimed at increasing dopamine release from surviving DA neurons
• Prolongs quality of life and life expectancy
• Only works for 5-10 years then the disease progresses too far
• Levodopa is metabolized outside of CNS (GI, liver)

Question 6

What are the 2 combination therapy used for PD?

Answer 6

Carbidopa and Levodopa

Carbidopa does not cross BBB, but prevents levodopa breakdown in the periphery

Entacapone, Carbidopa, and Levodopa
- Inhibits COMT (inactivates levodopa) to allow more levodopa to enter the brain

Question 7

What is the wearing-off effect?

Answer 7

Occurs when subtherapeutic levels are reached near end of dosing interval

Question 8

What is the on-off phenomenon?

Answer 8

• Abrupt loss of drug effect even at high drug levels
• Lasts from minutes to hours
• Unknown reason

Question 9

What are some adverse effects of levodopa?

Answer 9

Nausea and vomiting
- CTZ

Dyskinesia
- Involuntary muscle movement

CV
- Hypotension and cardiac dysrhythmias

Psychosis
- Hallucinations, paranoid ideation

Question 10

What is dopaminergic therapy?

Answer 10

Regulation of dopamine

1st line of treatment for MD

• Mild/moderate symptoms
• Less effective than levodopa
• Younger patients

Question 11

Which neurotransmitters are broken down by MAO-A?

Answer 11

NE, and 5-HT

Question 12

What is selective MAO-B therapy?

Answer 12

When drugs like *selegiline are used to inhibit dopamine breakdown in neurons. *Amantadine are used indirectly and causes the release fo dopamine

Does not elicit “the cheese effect”

Causes an increase in the levels of dopaminergic stimulation in the CNS

Question 13

When should MAO-B therapy be used?

Answer 13

In combination with levodopa or levodopa-carbidopa

Acts as an adjunctive agent when response to levodopa is fluctuating on-off
- Delays the development of unresponsiveness to levodopa therapy

Question 14

What are the adverse effects of Selegiline?

Answer 14

Usually mild

• Nausea, abd pain, dry mouth
• Lightheadedness, dizziness, insomnia, confusion
• Doses higher than 10mg/day may cause more severe adverse effects

Question 15

What is amantadine and when should it be used?

Answer 15

Amantadine is a indirect acting drugs that causes the release of dopamine from the storage sites at the end of nerve cells

Question 16

What are the pros and cons of dopamine receptor agonists?

Answer 16

Pro:

• No conversion required
• No dietary protein restrictions
• Less dyskinesias

Cons:

• Hallucinations, postural hypotension
• Impulse control disorders (gambling, shopping, hypersexuality)

Question 17

What dietary restriction comes with levodopa?

Answer 17

Avoid high protein diets because amino acids reduce GI absorption and transport across BBB

Question 18

How do anticholinergics help with PD?

Answer 18

They block ACh to reduce:

• Muscle tremors
• Cogwheel rigidity
• Pill-rolling movement of fingers
• Bobbing of head at rest

Does not relieve bradykinesia (extremely slow movements)

Question 19

What is an example of an anticholinergic that helps PD?

Answer 19

Benztropine (Cogentin)

Question 20

What are adverse effects of anticholinergic therapy?

Answer 20

• Drowsiness, confusion, disorientation (CNS)
• Constipation, nausea, vomiting
• Urinary retention, pain on urination
• Blurred vision, dilated pupils, photophobia
  dry skin, fever
• Decreased salivation = dry mouth
• Vasodilation (central effect)

Mad as a hatter (confused
Blind as a bat (blurred vision)
Hot as a hare (fever)
Dry as a bone (salivation)
Red as a beet (vasodilation)