Antiparkinson

Question 1

What is Parkinson’s Disease (PD)?

Answer 1

A progressive neurodegenerative disorder affecting motor function, characterized by tremor, rigidity, bradykinesia, and postural instability due to loss of dopaminergic neurons in the substantia nigra.

Question 2

What is the hallmark neurotransmitter deficiency in PD?

Answer 2

Dopamine, particularly in the substantia nigra pars compacta, leading to decreased stimulation of the motor cortex via basal ganglia circuits.

Question 3

What causes the resting tremor seen in Parkinson’s disease?

Answer 3

Increased inhibitory output from the basal ganglia to the thalamus due to dopamine depletion leads to excessive cholinergic activity and motor instability.

Question 4

What is the difference between the pyramidal and extrapyramidal systems?

Answer 4

The pyramidal system controls direct voluntary movement; the extrapyramidal system (involving basal ganglia) regulates posture, coordination, and involuntary movement. PD affects the extrapyramidal system.

Question 5

Which neurotransmitters are primarily involved in PD?

Answer 5

Dopamine (↓), acetylcholine (↑ relative), GABA, and glutamate.

Question 6

What environmental or iatrogenic factors can induce Parkinsonism?

Answer 6

Antipsychotics (e.g., haloperidol), MPTP neurotoxin, manganese exposure, reserpine, and some encephalitic or vascular conditions.

Question 7

What is MPTP and how is it related to Parkinsonism?

Answer 7

MPTP is a neurotoxin metabolized to MPP+, selectively destroying dopaminergic neurons in the substantia nigra—mimicking PD.

Question 8

What is the primary goal of pharmacologic PD treatment?

Answer 8

Restore dopamine/cholinergic balance in the basal ganglia—either by increasing dopamine or decreasing acetylcholine.

Question 9

Why does PD therapy focus on dopamine and acetylcholine balance?

Answer 9

Dopamine normally inhibits movement via basal ganglia circuits; when dopamine is lost, unopposed cholinergic activity leads to motor symptoms.

Question 10

Which part of the brain shows visible depigmentation in PD?

Answer 10

The substantia nigra, due to loss of melanin-containing dopaminergic neurons.

Question 11

What is levodopa (L-DOPA)?

Answer 11

A dopamine precursor that crosses the blood-brain barrier (BBB) and is converted to dopamine in the CNS.

Question 12

Why is carbidopa combined with levodopa (Sinemet)?

Answer 12

Carbidopa inhibits peripheral DOPA decarboxylase, preventing premature conversion of L-DOPA to dopamine outside the brain, which reduces side effects and increases CNS availability.

Question 13

What is the main adverse effect of L-DOPA in the periphery?

Answer 13

Nausea and vomiting, due to stimulation of the chemoreceptor trigger zone (CTZ), which is outside the BBB.

Question 14

What are ‘on-off’ phenomena in long-term L-DOPA use?

Answer 14

Sudden, unpredictable changes between mobility (‘on’) and immobility (‘off’) due to fluctuating dopamine levels and receptor sensitivity.

Question 15

What are ‘wearing-off’ effects with L-DOPA?

Answer 15

Gradual return of PD symptoms before the next dose due to progressive neuronal loss and loss of dopamine storage capacity.

Question 16

What is amantadine, and how does it help in PD?

Answer 16

An antiviral that enhances dopamine release, synthesis, and reuptake inhibition; also weak NMDA antagonist; used for mild symptoms or dyskinesia.

Question 17

How do COMT inhibitors like entacapone and tolcapone work?

Answer 17

Inhibit catechol-O-methyltransferase, reducing peripheral metabolism of L-DOPA, prolonging its plasma half-life and CNS action.

Question 18

What serious side effect is associated with tolcapone?

Answer 18

Hepatotoxicity—requires liver function monitoring.

Question 19

What is the role of selegiline (Eldepryl) in PD?

Answer 19

MAO-B inhibitor that reduces dopamine breakdown in the brain; used as an adjunct in early PD to prolong L-DOPA effects.

Question 20

What is a potential risk of combining MAO inhibitors with other medications?

Answer 20

Hypertensive crisis or serotonin syndrome if used with SSRIs or tyramine-containing foods (especially MAO-A inhibitors).

Question 21

What is bromocriptine and how does it work in PD?

Answer 21

Ergot-derived dopamine agonist that stimulates D2 receptors and acts as a partial D1 antagonist; used as adjunct therapy.

Question 22

Why was pergolide withdrawn from the market?

Answer 22

Associated with heart valve fibrosis due to ergot-related effects on serotonin receptors.

Question 23

What is pramipexole’s mechanism and advantage?

Answer 23

Non-ergot D3-preferring agonist, used in early PD monotherapy or as an adjunct to reduce motor fluctuations.

Question 24

What is ropinirole used for in PD?

Answer 24

A D2 agonist used in early or adjunct therapy to reduce L-DOPA dose and fluctuations.

Question 25

What are benefits of dopamine agonists compared to L-DOPA?

Answer 25

Longer half-life, lower risk of dyskinesia, no need for enzymatic conversion.

Question 26

What are side effects of dopamine agonists?

Answer 26

Nausea, hypotension, hallucinations, impulse control disorders (e.g., gambling, hypersexuality), somnolence.

Question 27

What is the mechanism of benztropine and its indication in PD?

Answer 27

Muscarinic acetylcholine receptor antagonist; used for tremor and rigidity, especially in younger patients or drug-induced PD.

Question 28

What symptoms are least responsive to anticholinergic therapy?

Answer 28

Bradykinesia and postural instability—anticholinergics are primarily helpful for tremor.

Question 29

What are common side effects of anticholinergic PD drugs?

Answer 29

Dry mouth, blurred vision, constipation, urinary retention, confusion—especially in elderly patients.

Question 30

What food or supplement interferes with L-DOPA absorption?

Answer 30

High-protein meals and vitamin B6 (pyridoxine), which enhances peripheral decarboxylation of L-DOPA.

Question 31

How is Parkinson’s disease diagnosed?

Answer 31

Clinical history and neurological exam—there is no definitive lab or imaging test; response to L-DOPA may support diagnosis.

Question 32

What is the average age of PD onset and course?

Answer 32

Onset typically in the 60s, with disease course spanning 10–25 years.

Question 33

What is the function of the basal ganglia in motor control?

Answer 33

Acts as a modulatory loop, balancing excitatory and inhibitory pathways to fine-tune motor output.

Question 34

What is the rationale behind combining dopamine agonists with L-DOPA?

Answer 34

Smooths motor fluctuations, allows lower L-DOPA dosing, and may delay dyskinesia onset.

Question 35

When is surgical treatment considered for PD?

Answer 35

In patients with motor fluctuations or dyskinesias not controlled by medication, including deep brain stimulation (DBS) of the subthalamic nucleus.

Question 36

What is the goal of DBS in PD?

Answer 36

Modulate dysfunctional circuits in the basal ganglia, improving motor symptoms and medication responsiveness.

Question 37

What type of Parkinsonism is caused by antipsychotics?

Answer 37

Iatrogenic Parkinsonism, due to dopamine receptor blockade—usually reversible upon drug cessation.

Question 38

What non-motor symptoms are common in PD?

Answer 38

Depression, anxiety, dementia, sleep disturbances, constipation, anosmia (loss of smell).

Question 39

What is the purpose of combining benserazide with L-DOPA (Madopar)?

Answer 39

Inhibits peripheral decarboxylation of L-DOPA, similar to carbidopa, but with longer duration of action.

Question 40

What are two investigational approaches in PD treatment?

Answer 40

Gene therapy (e.g., inserting enzymes for dopamine synthesis) and stem cell therapy (dopaminergic neuron regeneration)—results are currently inconclusive.