Parkinson's Disease and Levodopa Therapy

Podcast

Play an AI-generated podcast conversation about this lesson

Questions and Answers

What is the primary reason L-dopa is effective in treating Parkinson's disease?

It stimulates dopamine receptors directly

It increases the release of dopamine from neurons

It inhibits the breakdown of dopamine in the brain

It crosses the blood-brain barrier and is converted to dopamine (correct)

Which of the following is a potential neuroprotective effect of dopamine agonists?

Increasing dyskinesias

Reducing L-dopa effectiveness

May be neuroprotective (correct)

Enhancing dopamine receptors

What is the primary mechanism of action of COMT inhibitors?

Increasing dopamine release

Inhibiting dopamine receptors

Enhancing dopamine uptake

Blocking the breakdown of L-dopa in peripheral tissues (correct)

Which of the following antiparkinson agents is an antiviral agent that was discovered to have antiparkinson effects by chance?

Amantadine Signup and view all the answers

What is the primary purpose of combining L-dopa with carbidopa?

To increase the absorption of L-dopa Signup and view all the answers

What is the primary mechanism of action of MAO-B inhibitors?

Inhibiting monoamine oxidase type B Signup and view all the answers

Which of the following is a potential problem with anticholinergic agents?

All of the above Signup and view all the answers

What is the primary goal of coordinating rehabilitation sessions with drug therapy?

To optimize treatment timing Signup and view all the answers

What is the estimated percentage of the population above 60 years that is affected by Parkinson's disease?

1% Signup and view all the answers

What is the primary problem that leads to Parkinsonism?

Degeneration of dopamine-secreting neurons Signup and view all the answers

Why is direct administration of dopamine ineffective in treating Parkinson's disease?

Dopamine cannot cross the blood-brain barrier Signup and view all the answers

What is the purpose of carbidopa in L-DOPA therapy?

To prevent the premature conversion of L-DOPA to dopamine Signup and view all the answers

What is the term for the decreased response to L-DOPA towards the end of the dose cycle?

End of dose akinesia Signup and view all the answers

What is the purpose of inhaled L-DOPA (Inbrija)?

To treat 'off' episodes in patients already on L-DOPA therapy Signup and view all the answers

What is a possible reason for the diminished response to L-DOPA therapy in long-term use?

Disease progression Signup and view all the answers

What is the term for the fluctuations in response to L-DOPA within the dose cycle?

On-off phenomenon Signup and view all the answers

Study Notes

Parkinson Disease

Neurodegenerative disorder affecting 1% of the population over 60 years
Classical symptoms include rigidity, resting tremor, bradykinesia, and postural instability

Neurological Basis of Parkinsonism

Degeneration of dopamine-secreting neurons
Decreased dopamine results in increased acetylcholine
Other affected neurotransmitters include GABA, glutamate, 5-HT, and norepinephrine

Dopamine Replacement: Rationale for Levodopa Therapy

Attempt to increase dopamine content in basal ganglia
Levodopa (L-DOPA) is used as a precursor to dopamine, as it can cross the blood-brain barrier
L-DOPA is converted to dopamine in the brain

Use of Carbidopa

Carbidopa inhibits dopa decarboxylase, preventing premature conversion of L-DOPA to dopamine
L-DOPA and carbidopa are often contained in the same pill (e.g. Sinemet)

Problems with L-DOPA Therapy

Side effects: GI irritation, hypotension, psychotropic and behavioral effects, dyskinesias, and "freezing" of gait
Fluctuations in response: end-of-dose akinesia, on-off phenomenon
Diminished response in long-term use: benefits may be lost, or dyskinesias become intolerable, after 4 to 5 years

Inhaled L-DOPA

Inhaled form of L-DOPA available (Inbrija)
Used to treat "off" episodes in patients already taking levodopa/carbidopa

Other Parkinson Drugs

Dopamine Agonists

Act like dopamine, directly stimulating dopamine receptors
Longer t1/2, more stable responses
Can be used as initial treatment in early PD
May be neuroprotective
Common agents: apomorphine, bromocriptine, cabergoline, pramipexole, ropinerole, rotigotine
Problems: nausea, vomiting, confusion, hallucinations, postural hypotension, increased dyskinesia

COMT Inhibitors

Inhibit catechol-O-methyltransferase (COMT) enzyme, allowing more L-DOPA to reach the brain
May decrease fluctuations, increase "on time"
Two specific agents: tolcapone, entacapone
Can be combined with L-DOPA and carbidopa (Stalevo)
Problems: GI distress, orthostatic hypotension, increased dyskinesia

Anticholinergic Agents

Decrease acetylcholine influence, may help decrease rigidity and tremor
Common agents: benztropine mesylate, biperiden, diphenhydramine, trihexyphenidyl
Use limited by side effects

MAO-B Inhibitors

Inhibit monoamine oxidase type B, prolonging dopamine effects in the brain
Agents: selegiline, rasagiline
Combined with L-DOPA to increase and prolong effects
Problems: no major concerns
Possible neuroprotective effects

Amantadine

Blocks NMDA receptor in brain, decreasing influence of excitatory amino acids (glutamate)
Decreased chance of dyskinesias
Problems: orthostatic hypotension, psychotropic effects, skin discoloration

Anti-Parkinson Drugs: Impact of Rehabilitation

Coordinate rehab sessions with drug therapy
Optimal treatment time: 30 to 60 minutes after meds
Recognize synergistic effects of physical rehab and drug therapy

Studying That Suits You

Use AI to generate personalized quizzes and flashcards to suit your learning preferences.

Description

This quiz covers the basics of Parkinson's disease, its symptoms, and the neurological basis of parkinsonism, including the role of dopamine and other neurotransmitters.