Parkinson's Disease

Question 1

Parkinson’s Disease

Answer 1

• a neurodegenerative disorder associated with disruption of neurotransmission in the striatum
• characterized by dyskinesias as well as depression and psychosis with dimentia
• proper function of the striatum requires a balance between the neurotransmitters dopamine and acetylcholine
• an imbalance of these neurotransmitters results from the degeneration of the neurons that supply dopmaine to the striatum

Question 2

Dyskinesias

Answer 2

• tremor at rest
• rigidity
• postural instability
• bradykinesia (slowed movement)
• tremor

Question 3

Drug Therapy for Parkinson’s Disease

Answer 3

• Dopaminergic agents which promote the activation of dopamine receptors
• Anticholinergic agents which prevent the activation of cholinergic receptors

Question 4

Dopaminergic Agents

Answer 4

• levodopa
• Dopamine agnoists (pramipexole)
• MAO-B inhibitor (selegiline)
• Dopaminergic agnoists (amantadine)
• COMT inhibitors (entacapone, Tolcapone)

Question 5

Drug selection for initial treatment

Answer 5

• mild symptoms call for a MAO-B inhibitor
• More severe symptoms call for levodopa or a dopamine agonist
• management of motor fluctuations can be managed with all types

Question 6

Levodopa

Answer 6

• only given in combinaion with carbidopa or entacapone
• highly effective but benefits diminish over time
• orally administered and rapidly absorbed in the small intestine
• food will delay reabsorption as well as amino acids will compete for absorption
• high protein foods reduce effects
• once inside the body it is converted into dopamine
• side effects include nausea and vomiting, dyskinesias, increased heart functions, psychosis, and may darken sweat and urine

Question 7

Carbidopa

Answer 7

• no adverse effects on its own,
• increases available levodopa in the CNS and allows for 75% deccrease in levodopa dosage
• reduces cardiovascular and gi adverse effects
• effects come mainly from levodopa when given in combination

Question 8

Dopamine Agonists

Answer 8

• first line drugs for PD
• direct activation of receptors in striatum
• less effective than levodopa but has fewer side effects and does not compete with other substances for absorption
• two types are derivatives of ergot (less selective for dopamine receptors) and nonergot derivatives (highly selective for dopamine receptors)
• includes pramipexole

Question 9

Pramipexole (mirapex)

Answer 9

• used alone in early PD and with levodopa in advancing PD
• max benefits will take several weeks to develop
• adverse effects include nausea, dizziness, daytime solomence, insomnia, constipation, weakness, and hallucinations on its on, and orthostatic hypotension and dyskinesias when given with levodopa

Question 10

COMT Inhibitors

Answer 10

inhibit the metabolism of levodopa in the periphery

Question 11

Entacapone

Answer 11

• COMT inhibitor

- inhibits metabolism of levadopa, which in turn prolongs the time that levodopa is available to the brain

Question 12

MAO-B inhibitors

Answer 12

• considered second and third line drugs for the treatment of PD
• in combination with levodopa can reduce the wearing off effect

Question 13

Selegiline (eldpryl, Zelapar)

Answer 13

• can be used independently or with levodopa
• causes a modest improvement in motor function
• causes irreversible inhibition of MAO-B
• can suppress the destruction of dopamine derived from levodopa and prolong the effects of levodopa
• adverse effects include insomnia