Drugs used to Treat Parkinson's

Question 1

Provide brief description of parkinson’s

why?
symptoms?

Answer 1

dopamine deficiency in CNS

Symptoms:

• tremors (hand, feet, facial muscles)
• muscle rigidity
• bradykinesia: slowness in execution of movement
• akinesia: complete stopping of voluntary movement
• change in gait
• postural instability: loss of balance
• sleep disorders
• loss of cognitive function
• psychosis

Question 2

Describe pathophysiology of Parkinson’s

Answer 2

progressive loss of dopaminergic producing cells in substantia nigra

Question 3

Describe pathway for breakdown of tyrosine

Answer 3

tyrosine —–> dihydroxyphenylalanine —-> dopamine by DOPA decarboxylase

dopamine —–> NE by dopamine hydroxylase

NE——> epinephrine

COMT and MAO can inhibit both enzymes

Question 4

For what and how is selegiline used?

What is selegiline metabolized to?

SE?

Answer 4

parkinsons treatment - neuroprotective therapy

selective inhibitor of MAOb (derivitive found in CNS)

this treatment may slow progression of symptoms of Parkinson’s

it is metabolized to methamphetamine

SE: insomnia

Question 5

for what is rasagiline used?

Answer 5

neuroprotective therapy for parkinson’s

may slow progression of symptoms of Parkinson’s

is not metabolized to methamphetamine

Question 6

L DOPA plus carbidopa

what is notable about this drug?

what purpose does carbidopa serve?

SEs?

SE of sudden discontinuation?

Answer 6

L DOPA plus carbidopa is DRUG OF CHOICE for parkinson’s treatment

levo DOPA - prodrug - precursor of DA

dopamine does NOT enter CNS

DOPA can enter CNS, but is metabolized in gut by DOPA decarboxylase

carbidopa serves as DOPA decarboxylase inhibitor

side effects:

• nausea
• postural hypotension
• hallucinations
• confusion
• dyskinesia
• worsens closed-angle glaucoma
• something about effect for up to 5 years due to loss of endogenous DA?

Sudden discontinuation?
neuroleptic malignant syndrome:
-rigidity
-high fever
(similar to malignant hyperthermia caused by fluranes?)

Question 7

What are the two COMT inhibitors?

How are they used?

Answer 7

• entacapone
• tolcapone

these are never used alone, always with L-DOPA

Question 8

Where do dopamine agonists exert their effects?

Are they more or less selective than L-DOPA

Answer 8

act directly on dopamine receptors

not as selective as L-DOPA

Question 9

How does bromocryptine work?

SE?

Answer 9

stimulates DA2 receptors

SE:

• nausea
• hallucinations (semi-related to LSD)

Question 10

For what are pramipexole and ropinirole used?

Answer 10

restless leg syndrome

Question 11

how does rotigotine administer dopamine

Answer 11

patch

Question 12

how does apomorphine work?

administration?

Notable side effect?

Disorders of notable side effect?

Answer 12

D2 agonist via injection

Common SEs:

• nausea
• hypotension
• confusion

Notable SE:
-sudden sleep syndrome aka sleep attack

Disorders of impulse control:

• spending sprees
• compulsive gambling
• hypersexuality

Question 13

Name the two anticholinergics used in Parkinson’s treatment.

Why are they used?

MOA?

SEs?

Answer 13

• benztropine
• trihexyphenidyl

used to decrease the imbalance between DA and Ach that occurs in Parkinson’s

MOA: muscarinic blockers

SEs:

• memory loss
• hallucinations
• all common side effects of anti-muscarinics

Question 14

is amantadine an antiviral or antibacterial?

How does amantadine contribute in the treatment of Parkinson’s

SEs?

Answer 14

antiviral agent

used to increase release of stored DA from nerve endings

SEs:

• insomnia
• relestness

Question 15

name a few other therapies used in Parkinson’s treatment

Answer 15

surgery: may control tremor
deep brain stimulation
tissue tranplantation